| 1. |
- Arai, Sally, et al.
(author)
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Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation : a report from the Center for International Blood and Marrow Transplant Research.
- 2015
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:2, s. 266-74
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Journal article (peer-reviewed)abstract
- Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.
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| 2. |
- Ayas, Mouhab, et al.
(author)
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Allogeneic hematopoietic cell transplantation for fanconi anemia in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome, or acute leukemia.
- 2013
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 31:13, s. 1669-76
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Journal article (peer-reviewed)abstract
- PURPOSE Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. PATIENTS AND METHODS We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Results Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. CONCLUSION Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.
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| 3. |
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| 4. |
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| 5. |
- Bizzetto, Renata, et al.
(author)
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Outcomes after related and unrelated umbilical cord blood transplantation for hereditary bone marrow failure syndromes other than Fanconi anemia
- 2011
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:1, s. 134-141
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Journal article (peer-reviewed)abstract
- BACKGROUND: Allogeneic stem cell transplantation is the only curative option for patients with hereditary bone marrow failure syndromes. Umbilical cord blood is an alternative source of stem cells for allogeneic transplantation. DESIGN AND METHODS: This multicenter, retrospective study is based on data reported to the Eurocord Registry about patients with hereditary bone marrow failure syndrome who underwent umbilical cord blood transplantation. RESULTS: Sixty-four patients with hereditary bone marrow failure syndromes were transplanted from related (n = 20) or unrelated donors (n = 44). Diagnoses were Diamond-Blackfan anemia (21 patients), congenital amegakaryocytic thrombocytopenia (16 patients), dyskeratosis congenita (8 patients), Shwachman-Diamond syndrome (2 patients), severe congenital neutropenia (16 patients) and unclassified (1 patient). In the group of patients who received grafts from related donors, all patients but one received an HLA-matched sibling transplant. The median number of total nucleated cells infused was 5 × 10⁷/kg. The cumulative incidence of neutrophil recovery at 60 days was 95%. Two patients had grade II-IV acute graft-versus-host disease, while the 2-year cumulative incidence of chronic graft-versus-host disease was 11%. The 3-year overall survival rate was 95%. In the group of patients who received grafts from unrelated donors, 86% had HLA-mismatched grafts and three received two umbilical cord blood units. The median number of total nucleated cells infused was 6.1 × 10⁷/kg. The cumulative incidence of neutrophil recovery at day 60 in this group was 55%. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease was 24%, while the 2-year cumulative incidence of chronic graft-versus-host disease was 53%. The 3-year overall survival rate was 61%; better overall survival was associated with age less than 5 years (P = 0.01) and 6.1 × 10⁷/kg or more total nucleated cells infused (P = 0.05). CONCLUSIONS: In patients with hereditary bone marrow failure syndromes, related umbilical cord blood transplantation is associated with excellent outcomes while increasing cell dose and better HLA matching might provide better results in unrelated umbilical cord blood transplantation.
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| 6. |
- Brissot, Eolia, et al.
(author)
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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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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 100:3, s. 392-399
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Journal article (peer-reviewed)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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| 7. |
- Cornelissen, Jan J., et al.
(author)
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The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach
- 2012
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In: Nature Reviews Clinical Oncology. - : Springer Science and Business Media LLC. - 1759-4782 .- 1759-4774. ; 9:10, s. 579-590
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Research review (peer-reviewed)abstract
- Allogeneic haematopoietic stem-cell transplantation (HSCT) is frequently applied as part of the treatment in patients with acute myeloid leukaemia (AML) in their first or subsequent remission. Allogeneic HSCT reduces relapse, but nonrelapse mortality and morbidity might counterbalance this beneficial effect. Here, we review recent studies reporting new disease-specific prognostic markers, in addition to allogeneic-HSCT-related risk factors, which can be assessed at specific time points during treatment. We propose risk assessment as a dynamic process during treatment, incorporating both disease-related and transplant-related factors for the decision to proceed either to allogeneic HSCT or to apply a nontransplant strategy. We suggest that allogeneic HSCT might be favoured if the projected disease-free survival is expected to improve by at least 10% based on an individual's risk assessment. The approach requires initial disease risk assessment, identifying a sibling or unrelated donor soon after diagnosis and the incorporation of time-dependent risk factors, all within the context of an integrated therapeutic management approach.
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| 8. |
- Daikeler, Thomas, et al.
(author)
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New autoimmune diseases after cord blood transplantation : a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation
- 2013
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:6, s. 1059-1064
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Journal article (peer-reviewed)abstract
- To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% +/- 1% at 1 year and 6.6% +/- 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n = 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs.
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| 9. |
- Engert, Andreas, et al.
(author)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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In: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Journal article (peer-reviewed)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 10. |
- Gadalla, Shahinaz M, et al.
(author)
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Outcomes of allogeneic hematopoietic cell transplant in patients with dyskeratosis congenita.
- 2013
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In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 19:8, s. 1238-1243
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Journal article (peer-reviewed)abstract
- We describe outcomes after allogeneic transplantation in 34 patients with dyskeratosis congenita transplanted between 1981 and 2009. The median age at transplantation was 13 years (range 2 - 35). Approximately 50% of transplants were from related donors. Bone marrow was the predominant source of stem cells (n=24/34). The day-28 probability of neutrophil recovery was 73% and the day-100 platelet recovery was 72%. The day-100 probability of grade II-IV acute GVHD and the 3-year probability of chronic GVHD were 24% and 37%, respectively. The 10-year probability of survival was 30%; 14 patients were alive at last follow-up. Ten deaths occurred within 4 months from transplantation due to graft failure (n=6) or other transplant-related complications; 9 of these patients had been transplanted from mismatched related or from unrelated donors. Another 10 deaths occurred after 4 months; 6 of them occurred more than 5 years from transplantation, 4 of these were attributed to pulmonary failure. Transplant-regimen intensity and transplants from mismatched related or unrelated donors were associated with early mortality. Transplantation of grafts from HLA-matched siblings with cyclophosphamide-containing non-radiation regimens was associated with early low toxicity. Late mortality was attributed mainly to pulmonary complications and likely related to the underlying disease.
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| 11. |
- Locasciulli, Anna, et al.
(author)
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Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT)
- 2007
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 92:1, s. 11-18
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: The treatment of acquired aplastic anemia (AA) is based on allogeneic bone marrow transplantation (BMT) and immunosuppressive therapy. The aim of this study was to assess the outcome of children and adults with AA treated in the last decade, and to determine whether results have improved in two sequential time periods,1991-1996 and 1997-2002. DESIGN AND METHODS: Two-thousands and seventy-nine consecutive patients with AA, classified according to first-line treatment: BMT (n=1567) or immunosuppressive therapy (n= 912), the patients for the two sequential time periods were studied. Analyses included variables related to patients, disease and transplant. RESULTS: The actuarial 10-year survival was 73% and 68% for BMT or immunosuppressive treatment, respectively (p=0.002). BMT outcome improved significantly with time (69% and 77%, p=001) for both matched sibling donor (MSD) (74% and 80%; p=0.003 ), alternative donor (38% and 65% p=0.0001), and was better in children (79% versus 68%, p<0.0001). Multivariate analysis: favorable predictors (p<0.001) were younger age, transplant beyond 1996, MSD, a short interval diagnosis-transplant , no irradiation. IS: no significant improvement over time (69% and 73% p=0.29). Survival was significantly better in children (81% versus 70%, p=0.001), especially in vSAA(83% versus 62%, p=0.0002). Combined IS was superior to single drug treatment (77% versus 62%, p=0.002). Multivariate analysis: significant predictors of survival: age > or =16 years (p=0.0009), longer interval between diagnosis -treatment (p=0.04), single drug versus combined IS (p=0.02). INTERPRETATION AND CONCLUSIONS: Outcome has improved in subsets of AA patients: those receiving first- line BMT and children with vSAA treated with IS. Age remains a major predictor for both treatments. Early intervention is associated with a significantly better outcome and is strongly recommended, whatever the first-line therapy.
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| 12. |
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| 13. |
- McClune, Brian L., et al.
(author)
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Allotransplantation for Patients Age >= 40 Years with Non-Hodgkin Lymphoma : Encouraging Progression-Free Survival
- 2014
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:7, s. 960-968
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Journal article (peer-reviewed)abstract
- Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood and Marrow Transplant Research data on 1248 patients age >= 40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age >= 65; P = .0008). Fewer patients aged >= 65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% [95% confidence interval (CI), 19% to 26%] for age 40 to 54, 27% [95% CI, 23% to 31%] for age 55 to 64, and 34% [95% CI, 24% to 44%] for age >= 65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% [95% CI, 50% to 58%] for age 40 to 54; 40% [95% CI, 36% to 44%] for age 55 to 64, and 39% [95% CI, 28% to 50%] for age >= 65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age >= 55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age >= 55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Nagler, Arnon, et al.
(author)
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Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission: a retrospective analysis from the Acute Leukemia Working Party of EBMT
- 2012
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In: European Journal of Haematology. - : John Wiley and Sons. - 0902-4441 .- 1600-0609. ; 89:3, s. 206-213
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Journal article (peer-reviewed)abstract
- Reduced-intensity conditioning (RIC)-alloSCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-alloSCT. We used the European Group for Blood and Marrow Transplantation (EBMT) ALWP data to compare the outcome of mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n = 107) for acute myelogenous leukemia (AML) patients with complete remission that underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the disease status, and the time from diagnosis were similar between the two groups. Engraftment was achieved in 99% and 93% in the PBSC and BM groups, respectively (P andlt; 0.0001). The day of engraftment was significantly earlier for the PBSC vs. the BM group, 15 (159) and 19 (569), respectively (P andlt; 0.001). Acute GVHD, severe GVHD (grade IIIIV) and chronic GVHD did not differ between the groups. leukemia-free survival (LFS), relapse, and non-relapsed mortality (NRM) were 51 +/- 2%, 32 +/- 1%, and 17 +/- 1% vs. 50 +/- 6%, 38 +/- 6%, and 12 +/- 3% for the PBSC and BM groups, respectively. Our results indicate faster engraftment, but no difference in GVHD, LFS, relapse, and NRM when comparing PBSC to BM grafts from sibling donors following RIC conditioning. This is the first study comparing PBSC to BM grafts in the RIC setting, analyzing a homogeneous population of patients with AML in remission. Whether PBSC should be preferred for advanced phases of the disease, where the outcome is dominated by relapse incidences, needs further investigation.
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| 18. |
- Robin, Marie, et al.
(author)
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Antilymphocyte globulin for matched sibling donor transplantation in patients with myelofibrosis
- 2019
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In: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 104:6, s. 1230-1236
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Journal article (peer-reviewed)abstract
- The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft-versus-host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n= 287). The cumulative incidences of grade II-IV acute graft-versus-host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft-versus-host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft-versus-host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P= 0.010) while it did not decrease the risk of chronic graft-versus-host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P-values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft-versus-host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft-versushost disease without increasing the risk of relapse.
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| 19. |
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| 20. |
- Schmid, Christoph, et al.
(author)
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Outcome and risk factor analysis of molecular subgroups in cytogenetically normal AML treated by allogeneic transplantation.
- 2015
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 126:17, s. 2062-2069
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Journal article (peer-reviewed)abstract
- Patients with cytogenetically normal acute myeloid leukemia (CN-AML) can be subdivided by molecular mutations. However, data on the influence of combinations of different aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) is limited. Therefore, we performed a retrospective registry analysis on 702 adults with CN-AML undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double negative patients were evaluated for mutations of the CCAAT/enhancer binding protein α gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. 2y-OS from HSCT was 81±5% in NPM1(mut)/FLT3(wt) (n=68), 75±3% in NPM1(wt)/FLT3(wt) (n=290), 66±3% in NPM1(mut)/FLT3-ITD (n=269) and 54±7% in NPM1(wt)/FLT3-ITD (n=75; p=0.003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) (n=13, 2y-OS:100%), and with a triple negative genotype (n=138, 2y-OS:77±3%). In a Cox-model of predefined factors, older age, presence of FLT3-ITD and >1 course of chemotherapy to reach CR were associated with inferior outcome. 2y-OS/LFS were 88±3%/79±4% in patients without any, 77±2%/73±3% with one, and 53±4%/50±4 with>=2 risk factors (p=0.002 for LFS, p=0.003 for OS). Hence, FLT3-ITD proofed to be the decisive molecular marker for outcome after HSCT for CN-AML in CR1, regardless of NPM1 mutational status, variations of transplant protocols, or development of GvHD. Age, FLT3-ITD and response to induction chemotherapy allow for a prognostic risk classification.
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| 21. |
- Socie, Gerard, et al.
(author)
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Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT)
- 2007
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 109:7, s. 2794-2796
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Journal article (peer-reviewed)abstract
- Previous studies suggested a link between the use of G-CSF and increased incidence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST) for severe aplastic anemia (SAA). This European survey included 840 patients who received a first-line IST with (43%) or without (57%) G-CSF. The incidences of MDS/AML in patients who did or did not receive G-CSF were 10.9% and 5.8%, respectively. A significantly higher hazard (1.9) of MDS/AML was associated with use of G-CSF. Relapse of aplastic anemia was not associated with a worse outcome in patients who did not receive G-CSIF as first therapy, whereas relapse was associated with a significantly worse outcome in those patients who received G-CSF. These results emphasize the necessity of the current European randomized trial comparing IST with or without G-CSF and to alert physicians that adding G-CSIF to IST is currently not standard treatment for SAA.
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| 22. |
- Stern, Martin, et al.
(author)
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Influence of donor/recipient sex matching on outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia
- 2006
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In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1534-6080 .- 0041-1337. ; 82:2, s. 218-226
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Journal article (peer-reviewed)abstract
- Background. Increased risk of transplant related mortality in male recipients of female hematopoietic stem cell grafts and in vitro reactivity of lymphocytes against H-Y encoded gene products in females with rejected male grafts have been documented. An increased rejection of male grafts in female recipients is not reported for solid organ or stem cell transplants and the role of H-Y as transplantation antigen has been controversial. Methods. Data from 1481 patients with a hematopoietic stem cell transplant for aplastic anemia reported from 154 centers in 28 countries were analyzed. Outcome was compared between patients with donors of the same or opposite Sex. Results. Survival at 5 years was significantly better in patients with donors from the same sex: 68% vs. 60% (P=0.001). Male patients with female donors had a decreased survival (relative risk of death 1.52, P < 0.001) and an increased risk of severe graft-versus-host disease (relative risk 1.33, P=0.03) compared to recipients of sex-matched grafts. Female patients with male donors had a decreased survival (relative risk of death 1.44, P=0.01) and an increased risk of rejection (relative risk 2.20, P=0.01) compared to recipients of sex-matched grafts. In a subgroup analysis, the negative effects of donor/recipient sex-mismatching appeared confined to patients receiving conditioning regimens not containing antithymocyte globulin. Conclusions. These data confirm H-Y as a clinically relevant transplantation antigen, in both the graft-versus-host and the host-versus-graft direction. Wherever possible, donor-recipient sex-matching should be integrated into donor selection algorithms.
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| 23. |
- Tichelli, Andre, et al.
(author)
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Late cardiovascular events after allogeneic hematopoietic stem cell transplantation: a retrospective multicenter study of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation
- 2008
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 93:8, s. 1203-1210
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Journal article (peer-reviewed)abstract
- Background Long-term outcome after hematopoietic stem cell transplantation including late transplant-related events is of increasing interest. The aim of this study was to evaluate the incidence of cardiovascular events after allogeneic HSCT and to search for their risk factors. Design and Methods This is a retrospective mutlicenter European Group of Blood and Marrow Transplantation (EBMT) analysis, including 548 long-term survivors treated in ten EBMT transplant centers, who underwent hematopoietic stem cell transplantation between 1990 and 1995 and survived >= 1 year after the transplant. All arterial events occurring after hematopoietic stem cell transplantation (cerebral, coronary, peripheral) were reported. Results Twenty (3.6%) out of 548 patients had a cardiovascular event in at least one arterial territory. The median age at occurence of cardiovascular events was 54 years (range, 41-70). The cumulative incidence of a first arterial event 15 years after hematopoietic stem cell transplantation was 6% (95% CI, 3%-10%). The cumulative incidence for patients with a high global cardiovascular risk score, defined as having >= 50% of the risk factors (arterial hypertension, diabetes, dyslipidemia, increased body-mass index, physical inactivity, smoking) was 17%, as compared to 4% in those with a low risk score. In multivariate analysis age older than 30 years at last follow-up, and a high global cardiovascular risk score were associated with, respectively, 6.4-fold and 9.8-fold increases in the risk of an arterial event. Conclusions Long-term survivors after allogeneic hematopoietic stem cell transplantation are likely to have an increased risk of premature cardiovascular accidents.
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| 24. |
- Urbano-Ispizua, Alvaro, et al.
(author)
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The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen
- 2015
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:10, s. 1746-1753
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Journal article (peer-reviewed)abstract
- The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR],.51; P = 3.049) and in MCL (RR,.41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR,.14; P = .007; and RR,.15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.
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- Warlick, Erica, et al.
(author)
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Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era
- 2012
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 119:17, s. 4083-4090
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Journal article (peer-reviewed)abstract
- Tyrosine kinase inhibitors (TKIs) and reduced intensity conditioning (RIC)/nonmyeloablative (NMA) conditioning hematopoietic cell transplants (HCTs) have changed the therapeutic strategy for chronic myelogenous leukemia (CML) patients. We analyzed post-HCT outcomes of 306 CML patients reported to the Center for International Blood and Marrow Transplant Research aged 40 years and older undergoing RIC/NMA HCT from 2001 to 2007: 117 (38%) aged 40 to 49 years, 119 (39%) 50 to 59 years, and 70 (23%) 60 years or older. The majority (74%) had treatment with imatinib before HCT. At HCT, most patients aged 40 to 49 years were in chronic phase (CP) 1 (74%), compared with 31% aged 60 years or older. Siblings were donors for 56% aged 40 to 49 years; older cohorts had more unrelated donors. The majority received peripheral blood grafts and RIC across all age groups. 3 year overall survival (54%, 52%, and 41%), day + 100 grade II-IV acute GVHD (26%, 32%, and 32%), chronic GVHD (58%, 51%, and 43%), and 1-year treatment-related mortality (18%, 20%, and 13%) were similar across ages. The 3-year relapse incidence (36%, 43%, and 66%) and disease-free survival (35%, 32%, and 16%) were inferior in the oldest cohort. Importantly, for CP1 patients, relapse and disease-free survival were similar across age cohorts. Allogeneic RIC HCT for older patients with CML can control relapse with acceptable toxicity and survival in TKI-exposed CML, especially if still in CP1.
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