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| 2. |
- Mellgren, Karin, 1962, et al.
(author)
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Chimerism analysis in clinical practice and its relevance for the detection of graft rejection and malignant relapse in pediatric hematopoietic stem cell transplant patients
- 2015
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In: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 19:7, s. 758-766
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Journal article (peer-reviewed)abstract
- Chimerism and clinical outcome data from 244 hematopoietic stem cell transplants in 218 children were retrospectively analyzed to assess their relevance for the detection of graft rejection and malignant relapse. Patients transplanted for a non-malignant disease had significantly higher proportions of residual recipient T cells in peripheral blood at one, three, and sixmonths compared with patients transplanted for malignant disease. Recipient T-cell levels were below 50% at onemonth after transplantation in most patients (129 of 152 transplants). Graft rejection occurred more frequently in the group of patients with high levels of recipient cells at onemonth (10 graft rejections in the 23 patients with recipient T cells >50% at onemonth as compared to seven graft rejections occurred in 129 patients with recipient T cells <50% (p<0.001). Multilineage chimerism data in 87 children with leukemia at one, three, and sixmonths after transplantation were not correlated with subsequent relapse of malignant disease. In conclusion, early analysis of lineage-specific chimerism in peripheral blood can be used to identify patients who are at high risk of graft rejection. However, the efficacy of early chimerism analysis for predicting leukemia relapse was limited.
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| 3. |
- Ifversen, Marianne, et al.
(author)
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Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia : The NOPHO ALL2008 experience
- 2019
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 184:6, s. 982-993
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Journal article (peer-reviewed)abstract
- The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD >= 5% at end of induction or >= 10(-3) at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD >= 5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD >= 10(-3). After a median follow-up of 5 center dot 5 years, the cumulative incidence of relapse was 23 center dot 5% (95% confidence interval [CI]: 10 center dot 5-47 center dot 7) for MRD-positive versus 5 center dot 1% (95% CI: 1 center dot 3-19 center dot 2), P = 0 center dot 02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9 center dot 1, 95% CI: 1 center dot 6-51 center dot 0, P = 0 center dot 012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85 center dot 6% (95% CI: 75 center dot 4-97 center dot 2) and 67 center dot 4% (95% CI: 50 center dot 2-90 center dot 5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.
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| 4. |
- Ringden, Olle, et al.
(author)
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The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Inherited Diseases Is Influenced by HLA Match, Year of Transplantation, and Immunized Female Donor
- 2019
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In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 103:6, s. 1247-1252
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Journal article (peer-reviewed)abstract
- Background For many inborn errors of metabolism (IEM), allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure.Methods We report the outcome in 160 patients with inherited diseases, who were treated with HSCT in 3 decades. Median age was 3 years (range 0.1-63). Grafts were from matched related donors (MRDs, 56), matched unrelated donors (MUDs, 66), or HLA-mismatched donors (38).Results Graft failure (GF) occurred in 26 patients (16%), severe acute graft-versus-host disease (GVHD) in 9 (6%), and chronic GVHD in 23 (12%). Ten-year survival was 64% before the year 2000 and 86% after that (P = 0.01). Ten-year survival for MRD grafts was 90%, as opposed to 79% for MUD grafts and 56% for HLA-mismatched grafts (P = 0.03). In multivariate analysis, GF was associated with having an HLA-mismatched donor (P < 0.05) or MUD (P = 0.015) and with reduced-intensity conditioning (P < 0.01). Death was associated with year of transplant (P = 0.015), having an HLA-mismatched donor (P < 0.001), and being a male recipient from an immune female donor (P = 0.05).Conclusions The outcome after HSCT for IEM depends on HLA match, year and immune female donor.
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| 5. |
- Sadeghi, Behnam, et al.
(author)
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Long-Term Follow-Up of a Pilot Study Using Placenta-Derived Decidua Stromal Cells for Severe Acute Graft-versus-Host Disease
- 2019
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 54, s. 300-300
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Journal article (peer-reviewed)abstract
- There is a need for effective therapy with few side effects for severe acute graft-versus-host disease (GVHD). The placenta protects the fetus from the mother's haploidentical immune system during pregnancy. We found that maternal stromal cells from the fetal membrane, so-called decidua stromal cells (DSCs), are more immunosuppressive than other sources of stromal cells. We prospectively treated 21 patients (median age, 49 years; range, 1.6 to 72 years) for grade II-IV acute GVHD. All 21 patients had biopsy-proven gastrointestinal GVHD. The majority of patients were either steroid-refractory or had progressive GVHD, 11 patients after >7 days or with progression after 3 days, and 10 were refractory to steroids after >3 days. We used an improved protocol in which DSCs were thawed and infused in a buffer with 5% human albumin. DSCs were given at a median dose of 1.2 (range, 0.9 to 2.9) x 10(6) cells/kg body weight with a median of 2 (range, 1 to 6) doses, given 1 week apart. The median viability of thawed DSCs was 93% (range, 69% to 100%), and the median cell passage number was 4 (range, 2 to 4). Complete resolution of GVHD was seen in 11 patients, with a partial response in the other 10. The cumulative incidence of chronic GVHD was 52%. GVHD was mild in 6 patients, moderate in 4 patients, and severe in 1 patient based on National Institutes of Health chronic GVHD severity scoring. Nine patients died, including 3 from relapse and 1 each from acute GVHD and septicemia, Zygomycetes infection, liver insufficiency, cerebral hemorrhage, multiple organ failure, and chronic GVHD with obstructive bronchiolitis. Four-year transplantation-related mortality was 28.6%, and overall survival was 57%. Survival was similar (P= .33) to that for all 293 patients who underwent allogeneic hematopoietic cell transplantation during the same period (2012 to 2015), with 66% overall survival. DSC infusion is a novel therapy for acute GVHD grade II-IV, and a randomized trial is currently underway.
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| 6. |
- Svenberg, Petter, et al.
(author)
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Improved overall survival for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation - A comparison of the last two decades.
- 2016
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In: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 20:5, s. 667-74
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Journal article (peer-reviewed)abstract
- Pediatric protocols for allogeneic hematopoietic SCT have been altered during the last two decades. To compare the outcomes in children (<18 yr old), who underwent SCT at our center during 1992-2002 (P1) and 2003-2013 (P2). We retrospectively analyzed 188 patients in P1 and 201 patients in P2. The most significant protocol changes during P2 compared with P1 were a decrease in MAC protocols, particularly those containing TBI, an increase in RIC protocols, and altered GvHD prophylaxis. In addition, P2 had more patients with nonmalignant diagnoses (p = 0.002), more mismatched (MM) donors (p = 0.01), and more umbilical CB grafts (p = 0.03). Mesenchymal or DSCs were used for severe acute GvHD during P2. Three-yr OS in P1 was 58%, and in P2, it was 78% (p < 0.001). Improved OS was seen in both malignant disorders (51% vs. 68%; p = 0.05) and nonmalignant disorders (77% vs. 87%; p = 0.04). Multivariate analysis showed that SCT during P2 was associated with reduced mortality (HR = 0.57; p = 0.005), reduced TRM (HR = 0.57; p = 0.03), unchanged relapse rate, similar rate of GF, less chronic GvHD (HR = 0.49; p = 0.01), and more acute GvHD (HR = 1.77, p = 0.007). During recent years, OS has improved at our center, possibly reflecting the introduction of less toxic conditioning regimens and a number of other methodological developments in SCT.
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| 7. |
- Tesi, Bianca, et al.
(author)
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Successful Hematopoietic Stem Cell Transplantation in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Gene Mutation
- 2016
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In: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 36:5, s. 480-489
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Journal article (peer-reviewed)abstract
- Purpose: Autosomal recessive mutations in LRBA, encoding for LPS-responsive beige-like anchor protein, were described in patients with a common variable immunodeficiency (CVID)-like disease characterized by hypogammaglobulinemia, autoimmune cytopenias, and enteropathy. Here, we detail the clinical, immunological, and genetic features of a patient with severe autoimmune manifestations. Methods: Whole exome sequencing was performed to establish a molecular diagnosis. Evaluation of lymphocyte subsets was performed for immunological characterization. Medical files were reviewed to collect clinical and immunological data. Results: A 7-year-old boy, born to consanguineous parents, presented with autoimmune hemolytic anemia, hepatosplenomegaly, autoimmune thyroiditis, and severe autoimmune gastrointestinal manifestations. Immunological investigations revealed low immunoglobulin levels and low numbers of B and NK cells. Treatment included immunoglobulin replacement and immunosuppressive therapy. Seven years after disease onset, the patient developed severe neurological symptoms resembling acute disseminated encephalomyelitis, prompting allogeneic hematopoietic stem cell transplantation (HSCT) with the HLA-identical mother as donor. Whole exome sequencing of the patient uncovered a homozygous 1 bp deletion in LRBA (c.7162delA:p.T2388Pfs*7). Importantly, during 2 years of follow-up post-HSCT, marked clinical improvement and recovery of immune function was observed. Conclusions: Our data suggest a beneficial effect of HSCT in patients with LRBA deficiency.
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| 8. |
- Törnquist, Alba Lucia, et al.
(author)
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Visual evoked potentials after hematopoietic allogeneic stem cell transplantation in childhood
- 2017
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In: Clinical Neurophysiology Practice. - : Elsevier. - 2467-981X. ; 2, s. 67-71
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To study visual pathway pathology detected by visual evoked potentials (VEPs) in patients treated with hematopoietic stem cell transplantation (HSCT) in childhood and to determine the impact of adverse ocular findings, somatic diseases, and conditioning regimens on the VEP results.METHODS: Ophthalmological assessments including pattern VEPs were performed in 47 of 79 patients at a median age of 15 years (range 3-21 years) in median 6 years (1-17 years) after HSCT. Somatic data were extracted from medical records.RESULTS: Eight patients of 47 (17%) demonstrated pathological VEPs with prolonged latencies bilaterally (n = 3) or unilaterally (n = 5) at their latest VEP test at an age of 12-18 years. A subnormal visual acuity was present in 8/11 eyes with pathological VEPs: one eye had cataract, six eyes had cataract surgery where of two had developed secondary cataracts. One eye had residual retinopathy of prematurity. Pathological VEPs were associated with decreased visual acuity (p = 0.00019) but not linked to gender, malignant diagnosis or conditioning.CONCLUSION: VEP recordings showed an association with decreased visual acuity but no relationship with irradiation or chemotherapy in the present study.SIGNIFICANCE: VEP recordings might be of clinical value for children with an unexplained subnormal visual acuity undergoing HSCT.
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| 9. |
- Vaht, Krista, 1973, et al.
(author)
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High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia : A Nationwide Swedish Cohort Study
- 2019
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In: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 25:10, s. 1970-1974
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Journal article (peer-reviewed)abstract
- Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged >= 40 years had a higher transplant-related mortality (29.4% versus 7.8%; P= .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (A=.022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged >= 40 years is problematic, and clinical trials addressing this issue are warranted. (C) 2019 American Society for Transplantation and Cellular Therapy.
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| 10. |
- Vaht, Krista, 1973, et al.
(author)
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Low response rate to ATG-based immunosuppressive therapy in very severe aplastic anaemia : A Swedish nationwide cohort study
- 2018
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In: European Journal of Haematology. - : Munksgaard Forlag. - 0902-4441 .- 1600-0609. ; 100:6, s. 613-620
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Journal article (peer-reviewed)abstract
- Objectives: Antithymocyte globulin (ATG)-based immunosuppression remains a cornerstone in aplastic anaemia (AA) treatment. However, most ATG studies are not population-based and knowledge about real-world results concerning response and outcome could offer important information for treating physicians.Methods: We have recently performed a nationwide retrospective cohort study on all AA patients diagnosed in Sweden in 2000–2011 and now present treatment and outcome data on patients receiving first-line ATG. In total, 158 patients showed a 47.0% response rate which was similar in all age groups (range 41.5%-51.7%) with no difference regarding ATG formulation. The response was significantly associated with severity grade—especially at time of treatment initiation: very severe (VSAA) 22.7%; severe (SAA) 54.5% (P <.001); and non-severe 88.5% (P <.001). A logistic regression-based predictive model indicated that VSAA patients with an absolute reticulocyte count <25 × 109/L had only a 19% probability of response. In a multivariable analysis, age and VSAA at the time of treatment were the independent factors for inferior survival.Conclusions: Real-world VSAA patients respond poorly to ATG which indicates the need for a different treatment approach. Our findings suggest that age alone should not be a discriminating factor for administering ATG treatment.
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