| 1. |
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| 2. |
- Abelsson, J, et al.
(författare)
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The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries.
- 2012
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Ingår i: Bone Marrow Transplantation. - : Nature Publishing Group. - 0268-3369 .- 1476-5365. ; 47:3, s. 380-386
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Tidskriftsartikel (refereegranskat)abstract
- Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectively (P<0.001). When adjustment for age differences was made, the survival of the patients treated with RIC was significantly better (P=0.003). Among the RIC patients, the survival was significantly (P=0.003) better for the patients with age <60 years (a 10-year survival close to 80%) than for the older patients. The type of stem cell donor did not significantly affect the survival. No significant difference was found in TRM at 100 days between the MAC- and the RIC-treated patients. The probability of survival at 5 years was 49% for the MAC-treated patients and 59% in the RIC group (P=0.125). Patients treated with RIC experienced significantly less aGVHD compared with patients treated with MAC (P<0.001). The OS at 5 years was 70, 59 and 41% for patients with Lille score 0, 1 and 2, respectively (P=0.038, when age adjustment was made). Twenty-one percent of the patients in the RIC group were given donor lymphocyte infusion because of incomplete donor chimerism, compared with none of the MAC-treated patients (P<0.002). Nine percent of the patients needed a second transplant because of graft failure, progressive disease or transformation to AML, with no significant difference between the groups. Our conclusions are (1) allo-SCT performed with RIC gives a better survival compared with MAC. (2) age over 60 years is strongly related to a worse outcome and (3) patients with higher Lille score had a shorter survival.
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| 3. |
- Barkholt, L., et al.
(författare)
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Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe
- 2006
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 17:7, s. 1134-1140
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Tidskriftsartikel (refereegranskat)abstract
- Background: An allogeneic antitumour effect has been reported for various cancers. We evaluated the experience of allogeneic haematopoietic stem cell transplantation (HSCT) for renal cell carcinoma (RCC) in 124 patients from 21 European centres. Patients and methods: Reduced intensity conditioning and peripheral blood stem cells from an HLA-identical sibling (n = 106), a mismatched related (n = 5), or an unrelated (n = 13) donor were used. Immunosuppression was cyclosporine alone, or combined with methotrexate or mycophenolate mofetil. Donor lymphocyte infusions (DLI) were given to 42 patients. The median follow-up was 15 (range 3-41) months. Results: All but three patients engrafted. The cumulative incidence of moderate to severe, grades II-IV acute GVHD was 40% and for chronic GVHD it was 33%. Transplant-related mortality was 16% at one year. Complete (n = 4) or partial (n = 24) responses, median 150 (range 42-600) days post-transplant, were associated with time from diagnosis to HSCT, mismatched donor and acute GVHD II-IV. Factors associated with survival included chronic GVHD (hazards ratio, HR 4.12, P < 0.001), DLI (HR 3.39, P < 0.001), < 3 metastatic sites (HR 2.61, P = 0.002) and a Karnofsky score > 70 (HR 2.33, P = 0.03). Patients (n = 17) with chronic GVHD and given DLI had a 2-year survival of 70%. Conclusion: Patients with metastatic RCC, less than three metastatic locations and a Karnofsky score > 70% can be considered for HSCT. Posttransplant DLI and limited chronic GVHD improved the patient survival.
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| 4. |
- Brissot, Eolia, et al.
(författare)
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Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia.
- 2015
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 100:3, s. 392-399
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine the impact of tyrosine-kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the Acute Leukemia Working Party of EBMT included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using an human leucocyte antigen-identical sibling or human leucocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred ninety patients received tyrosine-kinase inhibitors before transplant, 329 at induction and 274 at consolidation. The Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at 5 years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P=.04) and was associated with lower relapse incidence (HR=0.5; P=.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitors administration to be a significant factor for improved leukemia-free survival (HR=0.44; P=.002) and overall survival (HR=0.42; P=.004), and a lower relapse incidence (HR=0.40; P=.01). In conclusion, over the past decade, tyrosine-kinase inhibitors administration before allogeneic stem cell transplantation has significantly improved the long term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine-kinase inhibitors in the post-transplant setting.
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| 5. |
- Burman, Joachim, et al.
(författare)
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Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis : the Swedish experience
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - London, United Kingdom : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 85:10, s. 1116-1121
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.Methods: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.Results: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).Conclusions: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.
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| 6. |
- Chalandon, Y., et al.
(författare)
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Outcome of patients developing GVHD after DLI given to treat CML relapse: a study by the chronic leukemia working party of the EBMT
- 2010
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 45:3, s. 558-564
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Tidskriftsartikel (refereegranskat)abstract
- We studied GVHD after donor lymphocyte infusion (DLI) in 328 patients with relapsed CML between 1991 and 2004. A total of 122 patients (38%) developed some form of GVHD. We analyzed GVHD by clinical presentation (acute or chronic GVHD) and onset time after the first DLI (early (<= 45 days) or late (>45 days)). There was a significant overlap between onset time and clinical presentation. Some form of GVHD occurred at a median of 104 days, acute GVHD at 45 days and chronic GVHD at 181 days after DLI. The clinical presentation was acute GVHD in 71 patients, of whom 31 subsequently developed chronic GVHD subsequently. De novo chronic GVHD was seen in 51 patients. OS for all patients was 69% (95% confidence interval (CI) 63-75) at 5 years, DLI-related mortality was 11% (95% CI 8-15) and disease-related mortality was 20% (95% CI 16-25). Risk factors for developing GVHD after DLI were T-cell dose at first DLI, the time interval from transplant to DLI and donor type. In time-dependent multivariate analysis, GVHD after DLI was associated with a risk of death of 2.3-fold compared with patients without GVHD. Clinical presentation as acute GVHD and early onset GVHD were associated with increased mortality.
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| 7. |
- Daikeler, Thomas, et al.
(författare)
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Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party.
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; Aug 11:118(6), s. 1693-8
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Tidskriftsartikel (refereegranskat)abstract
- To specify incidence and risk factors for secondary autoimmune diseases (AD) after HSCT for a primary AD, we retrospectively analysed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least one secondary AD (cases) and those without (controls). After autologous HSCT, 29 amongst 347 patients developed at least one secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 amongst 16 patients. The observed secondary AD included: autoimmune hemolytic anemia (n=3), acquired haemophilia (n=3), autoimmune thrombocytopenia (n=3), antiphospholipid syndrome (n=2), thyroiditis (n=12), blocking TSHR-ab (n=1), Graves' disease (n=2), myasthenia gravis (n=1), rheumatoid arthritis (n=2), sarcoidosis (n=2), vasculitis (n=1), psoriasis (n=1) and psoriatic arthritis (n=1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8+/-2 % at 5 years, lupus erythematosus as primary AD and antithymocyte-globulin use plus CD34+ graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26/29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, haemophilia) and 1 death was HSCT related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.
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| 8. |
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| 9. |
- Dykes, Josefina, et al.
(författare)
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Rapid and effective CD3 T-cell depletion with a magnetic cell sorting program to produce peripheral blood progenitor cell products for haploidentical transplantation in children and adults.
- 2007
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Ingår i: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 47:11, s. 2134-2142
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Effective T-cell depletion is a prerequisite for haploidentical peripheral blood progenitor cell (PBPC) transplantation. This study was performed to investigate the performance of magnetic cell sorting–based direct large-scale T-cell depletion, which is an attractive alternative to standard PBPC enrichment procedures. STUDY DESIGN AND METHODS: PBPCs were harvested from 11 human leukocyte antigen (HLA)-haploidentical donors. T cells labeled with anti-CD3–coated beads were depleted with a commercially available magnetic separation unit (CliniMACS, Miltenyi Biotec) with either the Depletion 2.1 (D2.1, n = 11) or the novel Depletion 3.1 (D3.1, n = 12) program. If indicated, additional CD34+ selections were performed (n = 6). Eleven patients received T-cell-depleted grafts after reduced-intensity conditioning. RESULTS: The median log T-cell depletion was better with the D2.1 compared to the D3.1 (log 3.6 vs. log 2.3, p < 0.05) and was further improved by introducing an immunoglobulin G (IgG)-blocking step (log 4.5 and log 3.4, respectively). The D3.1 was superior to the D2.1 (p < 0.05) in median recovery of CD34+ cells (90% vs. 78%) and in median recovery of CD3– cells (87% vs. 76%). The median processing times per 1010 total cells were 0.90 hours (D2.1) and 0.35 hours (D3.1). The transplanted grafts (directly T-cell–depleted products with or without positively selected CD34+ cells) contained a median of 10.5 × 106 per kg CD34+, 0.93 × 105 per kg CD3+, and 11.6 × 106 per kg CD56+. Rapid engraftment was achieved in 10 patients. The incidences of acute graft-versus-host disease were less than 10 percent (Grade I/II) and 0 percent (Grade III/IV). CONCLUSION: The novel D3.1 program with IgG blocking enables highly effective, time-saving large-scale T-cell depletion. Combining direct depletion techniques with standard CD34+ selection enables the composition of grafts optimized to the specific requirements of the patients.
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| 10. |
- Gelder, Marion E Meijer-Van, et al.
(författare)
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Long-term survival of patients with CLL after allogeneic transplantation : A report from the European Society for Blood and Marrow Transplantation
- 2017
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 52:3, s. 372-380
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Tidskriftsartikel (refereegranskat)abstract
- Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.
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| 11. |
- Ghatnekar, Ola, et al.
(författare)
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Direct hospital resource utilization and costs of treating patients with multiple myeloma in Southwest Sweden: a 5-year retrospective analysis.
- 2008
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918. ; 30:9, s. 1704-1713
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Approximately 570 patients are diagnosed with multiple myeloma (MM) in Sweden each year. Few studies have estimated the cost of treatment for these patients. OBJECTIVE: The purpose of this study was to retrospectively investigate the direct hospital resource utilization and costs associated with the treatment of patients with MM in southwest Sweden. METHODS: Patients aged > or =18 years who initiated first-line chemotherapy in the year 2001 at hospitals in southwestern Sweden were included in this retrospective chart review. Direct hospital-based resources and their corresponding costs (year-2006 euros) for each patient were calculated until the patient's death, or until December 31, 2005. Costs for outpatient and terminal stage care related to MM were not included. RESULTS: Ninety-four patients were included; 20 were still alive at study completion. Mean age at diagnosis was 76 years and patients were followed for a mean of 32.7 months; 55% were males and 74% had at least 1 comorbidity. First-, second-, and third-line treatment lasted a mean of 24.3, 5.8, and 2.6 months, and included 2.8, 2.6, and 3.1 chemotherapy drugs per patient, respectively. Of the 80 patients who received first-line chemotherapy, 72 were prescribed melphalan and 55 patients received a combination of melphalan and prednisone, as recommended by Swedish treatment guidelines. The mean total cost per patient was euro88,199, or euro2770 per patient-month. Therapy-induced and comorbidity-related events constituted 42% of total costs, as much as autologous stem-cell transplantation and inpatient care together. Chemotherapy, bisphosphonate, and blood cell-enhancement drugs each amounted to only 2% of total costs, but chemotherapy drugs increased from euro29/month in first-line therapy to euro453/month in third-line therapy. CONCLUSIONS: The cost of treating Swedish patients with MM varied greatly between individuals but, overall, chemotherapy drugs constituted only a minor part of the total monthly cost (2%), whereas costs for inpatient stays and therapy-induced adverse events or comorbidity-related events accounted for 35% and42%, respectively. There was no significant differencein monthly cost between treatment lines.
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| 12. |
- Gimsing, P, et al.
(författare)
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Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial.
- 2015
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 50:10, s. 1306-1311
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Tidskriftsartikel (refereegranskat)abstract
- Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT and median OS was almost 5.5 years with acceptable toxicity. A recent prospective randomized study confirms salvage ASCT to be an effective treatment.Bone Marrow Transplantation advance online publication, 29 June 2015; doi:10.1038/bmt.2015.125.
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| 13. |
- Haraldsson, André, et al.
(författare)
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Implementing safe and robust Total Marrow Irradiation using Helical Tomotherapy – A practical guide
- 2019
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Ingår i: Physica Medica. - : Elsevier BV. - 1120-1797. ; 60, s. 162-167
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Tidskriftsartikel (refereegranskat)abstract
- Total Marrow Irradiation (TMI) with Helical Tomotherapy is a radiotherapy treatment technique that targets bone marrow and sanctuary sites prior to stem cell or bone marrow transplantation (SCT/BMT). TMI is a complex procedure that involves several critical steps that all need to be carefully addressed for a successful implementation, such as dose homogeneity in field junctions, choice of target margins, integrity of treatment and back-up planning. In this work we present our solution for a robust and reproducible workflow throughout the treatment chain and data for twenty-three patients treated to date. Material & Methods: Patients were immobilized in a whole body vacuum cushion and thermoplastic mask. CT-scanning and treatment were performed in two parts with field matching at the upper thigh. Target consisted of marrow containing bone and sanctuary sites. Lungs, kidneys, bowel, heart and liver were defined as organs at risk (OAR). A fast surface scanning system was used to position parts of the body not covered by the imaging system (MVCT) as well as to reduce treatment time. Results: All patients completed their treatment and could proceed with SCT/BMT. Doses to OARs were significantly reduced and target dose homogeneity was improved compared to TBI. Robustness tests performed on field matching and patient positioning support that the field junction technique is adequate. Replacing MVCT with optical surface scanning reduced the treatment time by 25 min per fraction. Conclusion: The methodology presented here has shown to provide a safe, robust and reproducible treatment for Total Marrow Irradiation using Tomotherapy.
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| 14. |
- Haraldsson, André, et al.
(författare)
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Organ sparing total marrow irradiation compared to total body irradiation prior to allogeneic stem cell transplantation
- 2021
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 107:4, s. 393-407
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Total body irradiation (TBI) is commonly used prior to hematopoietic stem cell transplantation (HSCT) in myeloablative conditioning regimens. However, TBI may be replaced by total marrow irradiation (TMI) at centres with access to Helical TomoTherapy, a modality that has the advantage of delivering intensity-modulated radiotherapy to long targets such as the entire bone marrow compartment. Toxicity after organ sparing TMI prior to HSCT has not previously been reported compared to TBI or with regard to engraftment data. Methods: We conducted a prospective observational study on 37 patients that received organ sparing TMI prior to HSCT and compared this cohort to retrospective data on 33 patients that received TBI prior to HSCT. Results: The 1-year graft-versus-host disease-free, relapse-free survival (GRFS) was 67.5% for all patients treated with TMI and 80.5% for patients with matched unrelated donor and treated with TMI, which was a significant difference from historical data on TBI patients with a hazard ratio of 0.45 (P =.03) and 0.24 (P <.01). Engraftment with a platelet count over 20 [K/µL] and 50 [K/µL] was significantly shorter for the TMI group, and neutrophil recovery was satisfactory in both treatment cohorts. There was generally a low occurrence of other treatment-related toxicities. Conclusions: Despite small cohorts, some significant differences were found; TMI as part of the myeloablative conditioning yields a high 1-year GRFS, fast and robust engraftment, and low occurrence of acute toxicity.
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| 15. |
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| 16. |
- Johnsen, Hans E., et al.
(författare)
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Improved Survival for Multiple Myeloma in Denmark Based on Autologous Stem Cell Transplantation and Novel Drug Therapy in Collaborative Trials: Analysis of Accrual, Prognostic Variables, Selection Bias, and Clinical Behavior on Survival in More Than 1200 Patients in Trials of the Nordic Myeloma Study Group
- 2010
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Ingår i: Clinical Lymphoma, Myeloma & Leukemia. - 2152-2650. ; 10:4, s. 290-296
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Tidskriftsartikel (refereegranskat)abstract
- Background: An unexplained survival difference was observed in the Nordic Myeloma Study Group (NMSG) high-dose therapy trial 5/94 in Denmark compared with Sweden and Norway; however, this difference was eliminated in the subsequent NMSG trial 7/98. It was hypothesized that a detailed analysis of potential explanations would reveal important information for future designs of clinical trials for multiple myeloma (MM) patients in Denmark. Patients and Methods: The analysis is based on 3 consecutive clinical trials coordinated by NMSG from 1990 to 2000: NMSG 4/90 including 583 patients, NMSG 5/94 including 274 patients and NMSG 7/98 including 414 patients with newly diagnosed MM. Event-free and total survival rates were calculated according to the Kaplan-Meier method, and survival comparisons were made by the log-rank test. The Cox proportional hazards regression model was used to estimate the prognostic importance of selected variables. Results: The analysis revealed no differences in disease stages, prognostic variables, or inclusion bias at diagnosis between the 3 consecutive NMSG trials. However, the number of initial treatment failures was low, and post-relapse survival was superior in Swedish patients as compared to Danish patients. These differences were explained by a defensive clinical practice in Denmark during 1994-1997 for patients with poor risk refractory or relapsed disease. Conclusion: These initially observed differences were subsequently eliminated most likely as a consequence of international collaboration improving diagnosis, research infrastructure, clinical training, and education as planned within the European Myeloma Network (EMN).
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| 17. |
- Johnsen, Hans E., et al.
(författare)
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Multiparametric Flow Cytometry Profiling of Neoplastic Plasma Cells in Multiple Myeloma
- 2010
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Ingår i: Cytometry Part B - Clinical Cytometry. - : Wiley. - 1552-4949. ; 78B:5, s. 338-347
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim: The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary aim of this study was to perform global analysis of CD expression on the PC compartment and subsequently to evaluate the prognostic impact. Secondary aims were to study the diagnostic and predictive impact. Design and methods: The design included a retrospective analysis of MFC data generated from diagnostic bone marrow (BM) samples of 109 Nordic patients included in clinical trials within NMSG. Whole marrow were analyzed by MFC for identification of end-stage CD45(-)/CD38(++) neoplastic PC and registered the relative numbers of events and mean fluorescence intensity (MFI) staining for CD19, CD20, CD27, CD28, CD38, CD44, CD45, CD56, and isotypes for cluster analysis. Results: The median MFC-PC number was 15%, and the median light microscopy (LM)-PC number was 35%. However, the numbers were significant correlated and the prognostic value with an increased relative risk (95% Cl) of 3.1 (1.7-5.5) and 2.9 (1.4-6.2), P < 0.0003 and P < 0.004 of MFC-PC and LM-PC counts, respectively. Unsupervised clustering based on global MFI assessment on PC revealed two clusters based on CD expression profiling. Cluster I with high intensity for CD56, CD38, CD45, right-angle light-scatter signal (SSC), forward-angle light-scatter signal (FSC), and low for CD28, CD19, and a Cluster II, with low intensity of CD56, CD38, CD45, SSC, FSC, and high for CD28, CD19 with a median survival of 39 months and 19 months, respectively (P = 0.02). Conclusions: The MFC analysis of MM BM samples produces diagnostic, prognostic, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). (C) 2010 International Clinical Cytometry Society
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| 18. |
- Juliusson, Gunnar, 1954-, et al.
(författare)
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Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma
- 2000
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Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 109:1, s. 89-96
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-three patients with advanced and heavily pretreated myeloma were treated with thalidomide. Starting dose was 200 mg/d, and 20 patients had dose escalations up to 400 (n = 5), 600 (n = 12) or 800 mg/d (n = 3), usually in divided doses. Nineteen patients were refractory to recent chemotherapy, and four had untreated relapse after prior intensive therapy. Ten out of 23 patients (43%) achieved partial response (PR, nine with refractory and one with relapsed disease), six patients had minor response or stabilization of the disease and four had disease progression. Another three patients died early from advanced myeloma at less than 3 weeks of thalidomide therapy. Of the 10 patients with PR, seven had a better response than after any prior therapy, despite vincristine-doxorubicin-dexamethasone (VAD)-based treatment in all but one and high-dose melphalan with autologous stem cell support in four. Time to achieve PR was rapid in patients receiving thalidomide in divided doses (median 31 d). Responses also included reduced bone marrow plasma cell infiltration and improved general status. Normalized polyclonal gammaglobulin levels were seen in four cases. Six out of 10 patients with PR remained in remission with a median time on treatment of 23 weeks (range 15- 50 weeks). Sedation was common but usually tolerable, and some patients continued full- or part-time work. Four patients had skin problems, three patients had pneumonia, one hypothyrosis, one sinus bradycardia and one minor sensory neuropathy. Thalidomide may induce good partial remissions in advanced refractory myeloma with tolerable toxicity, and should be evaluated in other settings for myeloma patients. Divided thalidomide doses seem to reduce time to achieve remission and may improve response rate.
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| 19. |
- Kisch, Annika, et al.
(författare)
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Being a haematopoietic stem cell donor for a sick sibling : Adult donors' experiences prior to donation
- 2015
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Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 19:5, s. 529-535
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is a lack of knowledge about sibling stem cell donors' experiences pre-donation and the waiting period before the donation might have been long. The donors and their corresponding sibling recipients were simultaneously included in two different interview studies. The results from the recipient study have been presented in a separate paper. PURPOSE: The aim was to explore the experiences of being a stem cell donor for a sibling, prior to donation. METHOD: Ten adult sibling donors were interviewed prior to stem cell donation. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis. RESULTS: The main theme Being a cog in a big wheel describes the complex process of being a sibling donor prior to donation, covering a mixture of emotions and thoughts. The four subthemes Being available, Being anxious, Being concerned and Being obliged cover the various experiences. The sibling donors' experiences are influenced by the quality of the relationship with the sick sibling. CONCLUSIONS: Sibling stem cell donors go through a complex process once they have accidentally got involved in. They have been asked to become a donor; it was not a voluntary choice. In caring for sibling stem cell donors the nurses should be aware of the complexity of the process they experience and take into consideration their personal situation and needs. Providing optimal care for both sibling donors and their corresponding recipients is a challenge, and further improvement and exploration are needed.
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| 20. |
- Kisch, Annika, et al.
(författare)
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Factors associated with changes in quality of life in patients undergoing allogeneic haematopoietic stem cell transplantation
- 2012
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Ingår i: European Journal of Cancer Care. - : Blackwell Munksgaard. - 0961-5423 .- 1365-2354. ; 21:6, s. 735-746
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Tidskriftsartikel (refereegranskat)abstract
- Factors associated with changes in quality of life in patients undergoing allogeneic haematopoietic stem cell transplantation It is well known that patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) experience changes in quality of life. We investigated factors associated with quality of life changes in adult HSCT patients. The Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) scale, supplemented with the Functional Assessment of Chronic Illness Therapy - Spiritual Well-being (FACIT-Sp) subscale, was administered on three occasions, immediately before transplantation, 100 days and 12 months after transplantation. Analyses of nine selected factors were made where changes in quality of life were found. Seventy-five patients were included and 40 of these completed the study. Emotional well-being was found to improve between the baseline and 100 days, while all other dimensions deteriorated, including overall quality of life. Physical and social/family well-being deteriorated between the baseline and the 12-month follow-up, while emotional well-being improved. The main factors associated with deteriorating quality of life over time were found to be significant infections, female gender and transplantation with stem cells from a sibling donor. In our further studies we aim to focus on the relationships between patients and sibling donors in order to improve the care. Careful attention must be paid to continuous adequate information during the transplantation procedure.
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| 21. |
- Kisch, Annika, et al.
(författare)
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Having a sibling as donor : patients’ experiences immediately before allogeneic hematopoietic stem cell transplantation
- 2014
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Ingår i: European Journal of Oncology Nursing. - : Elsevier. - 1462-3889 .- 1532-2122. ; 18:4, s. 436-442
-
Tidskriftsartikel (refereegranskat)abstract
- Background Allogeneic haematopoietic stem cell transplantation (HSCT) offers a potential cure for a variety of diseases but is also associated with significant risks. With HSCT the donor is either a relative, most often a sibling, or an unrelated registry donor. Purpose The aim was to explore patients’ experiences, immediately before transplantation, regarding having a sibling as donor. Method Ten adult patients with sibling donors were interviewed before admission for HSCT. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis. Results The main theme Being in no man’s land is a metaphor for the patients’ complex situation with its mixture of emotions and thoughts prior to transplantation. The three subthemes Trust in the sibling donor, Concern about others and Loss of control cover the various experiences. The patient’s experiences are influenced by their personal situation and the quality of the relationship with the sibling donor. While patients feel secure in having a sibling donor, they are dependent for their survival on the cell donation and feel responsible for the donor’s safety during donation. These emotions intensify the patients’ sense of dependency and loss of control. Conclusions In caring for HSCT patients the nurses should be aware of the complexity of the patients’ situation and keep in mind that having a sibling donor might imply extra pressure, including a sense of responsibility. Caring for both patients and sibling donors optimally is a challenge, which needs further improvement and exploration.
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| 22. |
- Kisch, Annika, et al.
(författare)
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Potential adult sibling stem cell donors’ perceptions and opinions regarding an information and care model
- 2013
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Ingår i: Bone Marrow Transplantation. - : Nature Publishing Group. - 0268-3369 .- 1476-5365. ; 48:8, s. 1133-1137
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Tidskriftsartikel (refereegranskat)abstract
- The first international recommendations and guidelines for the care of sibling stem cell donors were established in 2010, and have not yet been evaluated. However, a model for information and care of adult potential sibling stem cell donors (the IC model) developed and introduced at the Skåne University Hospital, Lund, Sweden, in 2005 conforms closely to them. The IC model aims to protect the privacy of potential donors, support and respect their free choice, and identify quickly those unwilling or unable to donate and thus minimize delay in seeking alternative donors. To evaluate the IC model a questionnaire survey in 2010 gathered the perceptions and views on information provision; influences over decision making; and care provision under the IC model of 148 adult siblings informed about SCT donation, and asked to undergo HLA-typing since September 2005 at the hospital. The results suggest the IC model works well but highlights areas for improvement, such as in delivery of HLA typing results to non-matched siblings, and a need to further prevent complicating influence from health professionals and relatives on the decision to undergo HLA typing. Thus improved, the IC model could provide the groundwork for other SCT units seeking to implement the recommendations and guidelines.
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| 23. |
- Kisch, Annika, et al.
(författare)
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Potential adult sibling stem cell donors’ perceptions and opinions regarding an information and care model
- 2013
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Ingår i: Bone Marrow Transplantation. - : Nature Publishing Group. - 0268-3369 .- 1476-5365. ; 48:S2, s. S471-S472
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The first international recommendations and guidelines for the care of sibling stem cell donors were established in 2010 and have not yet been evaluated. However, a model for information and care of adult potential sibling stem cell donors (the IC model) developed and introduced at Skåne University Hospital, Lund, Sweden, in 2005 conforms closely to them. The IC model aims to protect the privacy of potential donors, support and respect their free choice, and identify quickly those unwilling or unable to donate and thus minimize delay in seeking alternative donors. All contacts with potential sibling donors are handled by the SCT (Stem Cell Transplantation) team. If the sibling is unwilling or unable to donate, HLA (Human Leukocyte Antigen) typing is not performed and the patient is told only that there is no possible donor among the siblings. To protect the sibling donor’s privacy, the physician and nurse assigned to the donor are never those responsible for the patient.Objectives: The main aim of the present study was to evaluate the IC model by surveying adult potential sibling stem cell donors’ perceptions and views regarding the provision of information, staff and relatives’ influence over decision making, and the care provision by health professionals around the time of the decision whether to undergo HLA typing.Methods: A questionnaire survey containing 30 questions was performed in 2010 gathering the perceptions and views on information provision; influences over decision making; and care provision under the IC model of 148 adult siblings informed about SCT donation and asked to undergo HLA typing since September 2005 at the hospital. The questionnaire responses were analysed using descriptive statistical methods.Results: The results suggest the IC model works well but highlights areas for improvement, such as in delivery of HLA typing results to non-matched siblings and a need to further prevent complicating influence from health professionals and relatives on the decision to undergo HLA typing.Conclusion: The majority of the siblings was satisfied with the information and care provided, and found the aspects of information, care provision and support important. The IC model could provide the groundwork for other SCT units seeking to implement handling of potential adult sibling stem cell donors according to the international recommendations and guidelines published after the IC model was developed and introduced.
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| 24. |
- Lazarevic, Vladimir Lj, et al.
(författare)
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Relatively favorable outcome after allogeneic stem cell transplantation for BCR-ABL1-positive AML : A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)
- 2018
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 93:1, s. 31-39
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR-ABL1-positive acute myeloid leukemia (AML). Fifty-seven patients (median age, 48 years, range: 19-67) with BCR-ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR-ABL1/ABL<104) at time of SCT in 36.1% (14/40). After SCT, 16 (61.5%) out of 26 patients with MRD positive at transplantation reached MRD negativity. After a median follow-up of 6.3 years (0.7-14.2), NRM, RI, LFS, OS, and GRFS at 5 years were 18.1%, 37%, 44.2%, 53.8%, and 32.1%, respectively. The cumulative incidence of acute GvHD grade II-IV was 16.4%, incidence of chronic GvHD 24.9%, and of extensive cGvHD 21.4%, respectively. In patients who received SCT in CR1, 5-yr NRM, RI, LFS, OS, and GRFS were 15.9%, 36.4%, 46.5%, 59.4%, and 34.9%, respectively. Univariate analysis showed that age (<50 vs. ≥50 years) was associated with RI (5-yr: 22.7 vs. 50%), LFS (5-yr: 61.9 vs. 31.8%), and GRFS (5-yr: 52.4 vs. 18.2%), whereas MRD-negative status before SCT was associated with an improved GRFS (38.9 vs. 16.7%). We conclude that the outcome of patients <50 years of age with BCR-ABL1-positive AML receiving allogeneic SCT in CR is relatively favorable, possibly reflecting the beneficial effect of the use of TKI.
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| 25. |
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| 26. |
- Lenhoff, Stig
(författare)
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Granulopoietic growth factors. Cytokine and cellular regulation of GM-CSF and G-CSF production.
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Granulocyte-macrophage- (GM-) and granulocyte- (G-) colony stimulating factor (CSF) are important cytokines in the regulation of hematopoiesis and for the function of mature blood cells. They are also involved in the cytokine network regulating the inflammatory and immune response. The aim of this study was to investigate the regulation of GM- and G-CSF production at the cellular level. The studies focused on the secretion by monocytes derived from peripheral blood of healthy subjects and by endothelial cells derived from human umbilical cord veins. The cells were cultured in vitro and the production of GM-CSF and G-CSF measured by immunoassays or RT-PCR. The results show that GM-CSF and G-CSF secretion can be separately modulated within the same cell system, and furthermore that there are differences in the regulation of GM- and G-CSF secretion between the different cell types. G/GM-CSF secretion by endothelial cells is regulated by the presence or absence of a stimulus in a "switch-on - switch-off" manner, with interleukin (IL-) 1 being the most effective stimulus. No factors down-regulate G/GM-CSF secretion by endothelial cells. However, corticosteroids and the addition of neutrophils enhance G-CSF secretion by activated endothelial cells. Secretion by monocytes is induced by endotoxin and IL-1. Activated monocytes continue to secrete G/GM-CSF also when stimulus is removed. However, the secretion eventually ceases due to the effect of down-regulatory factors. Monocytes inhibit by the secretion of IL-10 in an autocrine manner GM-CSF secretion but not G-CSF secretion. The addition of T-lymphocytes increases the production of monocyte-derived IL-10. Furthermore, corticosteroids selectively down-regulate GM-CSF but not G-CSF secretion by monocytes. IL-4 and IL-13 down-regulate GM-CSF and G-CSF secretion by monocytes to the same extent. Neutrophils and mononocytes modulate the biological activity of secreted GM- and G-CSF by absorption of the cytokines. The interpretation of the results is that G/GM-CSF secreted by monocytes function in the local compartment, and the production is therefore regulated in a more complex manner. Endothelial cells are by their production of especially G-CSF responsible for the long-range activity.
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| 27. |
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| 28. |
- Lenhoff, Stig, et al.
(författare)
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Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation
- 2006
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Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 91:9, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives. From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation. Design and Methods. The prospective population was formed of 397 patients and the historic population of 313 patients. Both populations were calculated to comprise more than 75% of the expected number of new cases. Results. After a median follow-up of 7 years survival was longer in the prospective population than in the historic one (median 60 versus 39 months; p=0.0002). When comparing only patients eligible for intensive therapy the median survival was 63 versus 44 months (p < 0.0001). Attaining a complete response was associated with prolonged event-free survival but not overall survival. The pattern of relapse after transplantation was heterogeneous but could be divided into four major groups; insidious, classical, plasmacytoma form and transformed disease. The median survival after relapse was 29 months. The relapse pattern and time to relapse predicted outcome. Patients relapsing with an insidious or classical form of disease with skeletal events only, or after a long lasting first response were likely to respond well to conventional salvage therapy. In contrast, relapse with multiple symptoms, transformed disease or a short duration of first response implied bad prognosis. Interpretation and conclusions. The relapse pattern after autologous transplantation is heterogeneous and response to salvage therapy is variable. The degree of response and event-free survival after transplantation are not reliable surrogate markers for survival.
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| 29. |
- Lim, Hooi Ching, et al.
(författare)
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Development of acoustically isolated extracellular plasma vesicles for biomarker discovery in allogeneic hematopoietic stem cell transplantation
- 2021
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Ingår i: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Infection and graft-versus-host disease (GvHD) are the major causes for mortality and morbidity of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Plasma-derived extracellular vesicles (EVs) contain disease-related proteins, DNAs and RNAs, and have recently been suggested as potential biomarker candidates for transplantation complications. However, EV isolation from small plasma volumes in clinical biomarker studies using conventional methods is challenging. We therefore investigated if EVs isolated by novel automated acoustic trapping could be developed as potential biomarkers for allo-HSCT complications by performing a clinical proof-of-principle study. Results: Plasma samples were collected from twenty consecutive patients with high-risk/relapsed hematologic malignancies undergoing allo-HSCT before transplantation and post-transplant up to 12 weeks. EVs were isolated from small plasma sample volumes (150 μl) by an automated, acoustofluidic-based particle trapping device, which utilizes a local λ/2 ultrasonic standing wave in a borosilicate glass capillary to capture plasma EVs among pre-seeded polystyrene microbeads through sound scatter interactions. We found that EVs could be reliably isolated from all plasma samples (n = 173) and that EV numbers increased more than 2-fold in the majority of patients after transplantation. Also, sufficient quantities of RNA for downstream microRNA (miRNA) analysis were obtained from all samples and EV miRNA profiles were found to differ from whole plasma profiles. As a proof of principle, expression of platelet-specific miR-142-3p in EVs was shown to correlate with platelet count kinetics after transplantation as expected. Importantly, we identified plasma EV miRNAs that were consistently positively correlated with infection and GvHD, respectively, as well as miRNAs that were consistently negatively correlated with these complications. Conclusions: This study demonstrates that acoustic enrichment of EVs in a clinical biomarker study setting is feasible and that downstream analysis of acoustically-enriched EVs presents a promising tool for biomarker development in allo-HSCT. Certainly, these findings warrant further exploration in larger studies, which will have significant implications not only for biomarker studies in transplantation but also for the broad field of EV-based biomarker discovery.
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| 30. |
- Lisak, Mikael, et al.
(författare)
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Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Cyclosporine-A (CsA) is used to prevent acute graft-versus-host disease (aGvHD). European Society for Blood and Marrow transplantation (EBMT) recommends a CsA target serum concentration of 200–300µg/L during the first month after allogeneic hematopoietic stem cell transplantation (HSCT). With this study, we investigated whether a median CsA concentration > 200µg/L (CsAhigh) the first month after HSCT, compared to ≤ 200µg/L (CsAlow), increased the relapse risk of acute myloid leukemia (AML), using unrelated donors (URD) and antithymocyte globulin (ATG). Data was collected from 157 patients with AML, transplanted 2010–2016. The cumulative incidence of relapse (CIR) at 60months was 50% in the CsAhigh versus 32% in the CsAlow group (p = 0.016). In univariate analysis, CsAhigh versus CsAlow (p = 0.028), 10-unit increase of CsA as a continuous variable (p = 0.017) and high risk disease (p = 0.003) were associated with higher CIR. The results remained after adjusting for disease risk. Death following relapse occurred more frequently in the CsAhigh group (p = 0.0076). There were no significant differences in rates of aGvHD, chronic GvHD (cGvHD), EBV/CMV-infections or overall survival (OS) between the two groups. In conclusion, we found that a median CsA concentration > 200µg/L, the first month after HSCT, results in higher CIR of AML when combined with ATG.
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| 31. |
- Lubking, Anna, et al.
(författare)
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Allogeneic stem cell transplantation for chronic myeloid leukemia in the TKI era : population-based data from the Swedish CML registry
- 2019
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 54:11, s. 1764-1774
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Tidskriftsartikel (refereegranskat)abstract
- Two decades after the introduction of tyrosine kinase inhibitors (TKI), a sizeable portion of patients with chronic myeloid leukemia (CML) in chronic phase (CP) still undergo allogeneic stem cell transplantation (allo-HSCT). We investigated the indications for allo-HSCT, clinical outcome, management of relapse, and post-transplant TKI treatment in a population-based setting using the Swedish CML registry. Of 118 CML patients transplanted between 2002 and 2017, 56 (47.4%) received allo-HSCT in first CP, among whom TM resistance was the most common transplant indication (62.5%). For patients diagnosed with CML in CP at <65 years of age, the cumulative probability of undergoing allo-HSCT within 5 years was 9.7%. Overall 5-year survival was 96.2%, 70.1% and 36.9% when transplanted in first CP, second or later CP, and in accelerated phase or blast crisis, respectively. Risk factors for relapse were EBMT score >2 and reduced intensity conditioning, and for death, CP > 2 at time point of allo-HSCT only. Non-relapse mortality for patients transplanted in CP was 11.6%. Our data indicate that allo-HSCT still constitutes a reasonable therapeutic option for patients with CML in first CP, especially those resistant to TKI treatment, providing high long-term survival and low non-relapse mortality.
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| 32. |
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| 33. |
- Lübking, Anna, et al.
(författare)
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Young woman with mild bone marrow dysplasia, GATA2 and ASXL1 mutation treated with allogeneic hematopoietic stem cell transplantation
- 2015
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Ingår i: Leukemia Research Reports. - : Elsevier. - 2213-0489. ; 4:2, s. 72-75
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous mutations in GATA2 underlie different syndromes, previously described as monocytopenia and mycobacterial avium complex infection (MonoMAC); dendritic cell, monocytes, B- and NK lymphocytes deficiency (DCML); lymphedema, deafness and myelodysplasia (Emberger syndrome) and familiar myelodysplastic syndrome/acute myeloid leukemia (MDS / AML). Onset and severity of clinical symptoms vary and preceding cytopenias are not always present. We describe a case of symptomatic DCML deficiency and rather discrete bone marrow findings due to GATA2 mutation. Exome sequencing revealed a somatic ASXL1 mutation and the patient underwent allogeneic stem cell transplantation successfully. © 2015.
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| 34. |
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| 35. |
- Machowicz, Rafal, et al.
(författare)
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Allogeneic hematopoietic stem cell transplantation for adult HLH : a retrospective study by the chronic malignancies and inborn errors working parties of EBMT
- 2022
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Ingår i: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 57:5, s. 817-823
-
Tidskriftsartikel (refereegranskat)abstract
- Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited. We obtained data about 87 adult (>= 18 years of age) patients retrospectively reported to the EBMT. The median survival time was 13.9 months. The three and five-year overall survival (OS) was 44% (95% CI 33-54%). Among 39 patients with a follow-up longer than 15 months, only three died. Relapse rate was 21% (95% CI 13-30%), while NRM reached 36% (95% CI 25-46%). Younger patients (<30 years of age) had better prognosis, with an OS of 59% (95% CI 45-73%) at three and five years vs 23% (95% CI 8-37%) for older ones. No difference in survival between reduced and myeloablative conditioning was found. To our knowledge, this is the largest report of adult HLH patients who underwent allo-HSCT. Patients who survive the first period after this procedure can expect a long disease-free survival. Both reduced intensity and myeloablative conditioning have therapeutic potential in adult HLH.
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| 36. |
- Malmberg, Erik, et al.
(författare)
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Minimal residual disease assessed with deep sequencing of NPM1 mutations predicts relapse after allogeneic stem cell transplant in AML
- 2019
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 60:2, s. 409-417
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical outcome; 3-year relapse-free survival 20% vs 85% (p <.001), HR 45 (95% CI 2–1260), and overall survival 20% vs 89% (p <.001), HR 49 (95% CI 2–1253). Thus, the new methodology deep sequencing is an applicable and predictive tool for MRD assessment in AML.
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| 37. |
- Mellqvist, Ulf-Henrik, et al.
(författare)
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Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:23, s. 4647-4654
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared with 20 months for the control group (P = .05). Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after randomization (P = .007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the andgt;= VGPR category at randomization. Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL. This trial was registered at www.clinicaltrials.gov as #NCT00417911.
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| 38. |
- Mellqvist, Ulf-Henrik, et al.
(författare)
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Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma - Results of a randomized comparison with vincristine, doxorubicin
- 2008
-
Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 112:1, s. 129-135
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Today, intensive therapy that includes high-close melphalan with autologous stein cell transplantation (ASCT) is considered standard therapy in younger patients with newly diagnosed myeloma. When the current trial was initiated, combined vincristine, doxorubicin, and dexamethasone (VAD) was the most commonly used induction therapy before ASCT and yielded rapid major responses without interfering with stein cell harvest. However, the administration of VAD demands a central venous access, and well-described toxicities are associated with the therapy. This randomized trial, which was initiated in 2001 by the Nordic Myeloma Study Group, was an attempt to bring a larger portion of patients to ASCT more quickly. METHODS. Patients were randomized to receive either 3 cycles of VAD or 2 courses of cyclophosphamide plus dexamethasone (Cy-Dex) (cyclophosphamide at a dose of 1000 mg/m(2) on Day 1 and dexamethasone at a dose of 40 mg per day on Days 1-4 and 9-12, repeated on Day 22) as initial therapy followed by stein cell mobilization, harvest, and finally ASCT. RESULTS. No significant difference was observed in the proportion of patients undergoing ASCT (VAD [86%] vs Cy-Dex [87%]). During the first 4 months after the initiation of therapy, the mortality rates were 5.8% for VAD and 1.9% for Cy-Dex (P =.08). The response rates after ASCT were comparable (partial response or better: VAD: 80% vs Cy-Dex: 81%). In both groups, the median event-free survival was 29 months, and the overall survival rate at 3 years was 75%. CONCLUSIONS. The current results indicated that Cy-Dex before ASCT has efficacy comparable to that of VAD. It also demonstrated that a short course of alkylater therapy using cyclophosphamide does not affect stem cell harvest or transplantation.
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| 39. |
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| 40. |
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| 41. |
- Mitchell, Jonathan S., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 42. |
- Morris, Curly, et al.
(författare)
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Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide
- 2014
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Ingår i: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 54:10, s. 2514-2522
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDimethyl sulfoxide (DMSO) is essential for the preservation of liquid nitrogen-frozen stem cells, but is associated with toxicity in the transplant recipient. Study Design and MethodsIn this prospective noninterventional study, we describe the use of DMSO in 64 European Blood and Marrow Transplant Group centers undertaking autologous transplantation on patients with myeloma and lymphoma and analyze side effects after return of DMSO-preserved stem cells. ResultsWhile the majority of centers continue to use 10% DMSO, a significant proportion either use lower concentrations, mostly 5 or 7.5%, or wash cells before infusion (some for selected patients only). In contrast, the median dose of DMSO given (20mL) was much less than the upper limit set by the same institutions (70mL). In an accompanying statistical analysis of side effects noted after return of DMSO-preserved stem cells, we show that patients in the highest quartile receiving DMSO (mL and mL/kg body weight) had significantly more side effects attributed to DMSO, although this effect was not observed if DMSO was calculated as mL/min. Dividing the myeloma and lymphoma patients each into two equal groups by age we were able to confirm this result in all but young myeloma patients in whom an inversion of the odds ratio was seen, possibly related to the higher dose of melphalan received by young myeloma patients. ConclusionWe suggest better standardization of preservation method with reduced DMSO concentration and attention to the dose of DMSO received by patients could help reduce the toxicity and morbidity of the transplant procedure.
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| 43. |
- Mylin, Anne K., et al.
(författare)
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Serum YKL-40 concentrations in newly diagnosed multiple myeloma patients and YKL-40 expression in malignant plasma cells
- 2006
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Ingår i: European Journal of Haematology. - 1600-0609. ; 77:5, s. 416-424
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: A potential role in cancer biology is suggested for YKL-40 (CHI3L1, HC gp-39). The purpose of this study was to evaluate the clinical value of serum YKL-40 (sYKL-40) in multiple myeloma (MM) and to examine YKL-40 expression in malignant plasma cells (MM PCs). Methods: sYKL-40 was measured by enzyme-linked immunosorbent assay (ELISA) in 82 patients with newly diagnosed MM. YKL-40 expression in immunophenotypically defined plasma cells was investigated by double-labelled immunohistochemistry in 21 MM patients and by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in cDNA archives generated by global RT-PCR in seven controls, 14 patients with monoclonal gammopathy of undetermined significance (MGUS), 45 MM patients, nine patients with extramedullary myeloma (exMM), and seven human myeloma cell lines (HMCLs). Results: sYKL-40 was elevated above a constructed reference range for healthy controls in 29% of the patients investigated. Patients with elevated sYKL-40 had reduced overall survival and event-free survival when compared to patients with normal sYKL-40, but sYKL-40 level was defeated by beta(2)-microglobulin in the multivariate analyses. Intramedullary MM PCs lacked significant expression of YKL-40, but high levels of YKL-40 expression were seen in extramedullary MM PCs from one exMM patient and in six HMCLs. Further investigations of other bone marrow (BM) cells showed YKL-40 expression in megakaryocytes, neutrophils and adherent cells from long-term BM cultures. Conclusions: In newly diagnosed MM-patients, a sYKL-40 elevated above the reference range predicts a poor clinical outcome, and YKL-40 is expressed by other BM cells than MM PCs. At this point, routine measurements of sYKL-40 are not warranted, but YKL-40 should be considered as a potential player in the pathophysiology of MM.
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| 44. |
- Nilsson, Christer, et al.
(författare)
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Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 25:9, s. 1770-1778
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Tidskriftsartikel (refereegranskat)abstract
- Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML.
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| 45. |
- Nilsson, Therese, et al.
(författare)
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A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differences.
- 2003
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 120:6, s. 960-969
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Tidskriftsartikel (refereegranskat)abstract
- The cytogenetic features (ploidy, complexity, breakpoints, imbalances) were ascertained in 783 abnormal multiple myeloma (MM) cases to identify frequently involved chromosomal regions as well as a possible impact of age/sex. The series included MM patients from the Mitelman Database of Chromosome Aberrations in Cancer and from our own laboratory. Hyperdiploidy was most common, followed by hypodiploidy, pseudodiploidy and tri-/tetraploidy. Most cases were complex, with a median of eight changes per patient. The distribution of modal numbers differed between younger and older patients, but was not related to sex. No sex- or age-related differences regarding the number of anomalies were found. The most frequent genomic breakpoints were 14q32, 11q13, 1q10, 8q24, 1p11, 1q21, 22q11, 1p13, 1q11, 19q13, 1p22, 6q21 and 17p11. Breaks in 1p13, 6q21 and 11q13 were more common in the younger age group. The most frequent imbalances were + 9, - 13, + 15, + 19, + 11 and - Y. Trisomy 11 and monosomy 16 were more common among men, while -X was more frequent among women. Loss of Y as the sole change and + 5 were more common in elderly patients, and - 14 was more frequent in the younger age group. The present findings strongly suggest that some karyotypic features of MM are influenced by endogenous and/or exogenous factors.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Peccatori, J, et al.
(författare)
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Prognostic factors for survival in patients with advanced renal cell carcinoma undergoing nonmyeloablative allogeneic stem cell transplantation
- 2005
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Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 104:10, s. 2099-2103
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. The objective of this study was to identify prognostic factors for predicting survival in patients with advanced renal cell carcinoma (RCC) who had undergone an allogeneic stem cell transplantation after failure on immunotherapy. METHODS. The authors Studied 70 patients with advanced RCC Who underwent allogeneic transplantation with a fludarabine-based, reduced-intensity regimen. Ten parameters were analyzed at the time of transplantation for their power to predict Survival. Clinical features were examined first univariately; then, variables that were correlated significantly with Survival in the univariate analysis were included in a multivariate Cox regression model. RESULTS. Factors that were found to be associated significantly with limited survival were performance Status, the number of metastatic sites, the presence of mediastinal metastasis, hemoglobin level, C-reactive protein (CRP) level, lactate dehydrogenase (LDH) level, and neutrophil counts. All these variables were included in a multivariate Cox regression model, and three were retained in the final model. Patients were classified according to the score estimated by the final Cox model in two groups (above or below the median Value): The median Survival was 3.5 months for patients who had a poor prognosis patients versus 23 months for patients who had a good prognosis. CONCLUSIONS. The Current findings suggested that three easily available parameters (performance status, CRP level, and LDH level) could be used to stratify patients with advanced RCC who are candidates for allografting and to assist clinicians in decision-making and selection of an appropriate treatment program.
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| 50. |
- Roer, O, et al.
(författare)
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Quality assessment of autografting by probability evaluation: model estimation by clinical end-points in newly diagnosed multiple myeloma patients
- 2006
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Ingår i: Cytotherapy. - : Elsevier BV. - 1477-2566 .- 1465-3249. ; 8:1, s. 79-88
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Tidskriftsartikel (refereegranskat)abstract
- Background Pre-transplant clinical evaluation of autografting is an important step in predicting post-transplant support, complications and safety. Today, unfavorable outcomes such as early death or graft failure are rare, making them unsuitable for quality assessment of supportive autografting. However, end-points constructed from frequently occurring clinical events may estimate clinically relevant prognostic models. Methods The present retrospective analysis was based on two consecutive clinical trials in the Nordic area, including up to 640 newly diagnosed multiple myeloma patients. Results In the model, the efficacy (time on antibiotics and use of transfusions) was influenced by pre-transplant variables, including sex, nationality, serum creatinine, hemoglobin, disease stage at diagnosis, response following induction therapy, length of priming and average graft CD34(+) cell number per day of harvest. The toxicity end-point (time to blood cell recovery) was influenced by nationality, marrow plasma cell percentage, serum creatinine, M-component isotype, response to induction therapy, length of priming and graft CD34(+) cell number. The safety (early disease recurrence or death) was influenced by serum creatinine, hemoglobin, treatment response and CD34(+) cell number. Discussion In conclusion, the model illustrates that intervention strategies in quality assessment of autografting may benefit from probability estimates of graded clinical end-points.
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