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- Spyridonidis, A., et al.
(författare)
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Outcomes and prognostic factors of adults with acute lymphoblastic leukemia who relapse after allogeneic hematopoietic cell transplantation. An analysis on behalf of the Acute Leukemia Working Party of EBMT
- 2012
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 26:6, s. 1211-1217
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Tidskriftsartikel (refereegranskat)abstract
- To describe outcomes, treatment and prognostic factors that influence survival of adult patients with acute lymphoblastic leukemia (ALL), who relapsed after allogeneic hematopoietic cell transplantation (HCT), we retrospectively analyzed 465 ALL adult patients from European Group for Blood and Marrow Transplantation (EBMT) centers who relapsed after a first HCT performed in complete remission (CR1 65%, CR2/3 35%). Salvage treatments were: supportive care (13%), cytoreductive therapy (43%), donor lymphocyte infusion without or with prior chemotherapy (23%) and second HCT (20%). Median time from HCT to relapse was 6.9 months, median follow-up was 46 months and median survival after relapse was 5.5 months. Estimated 1-, 2- and 5-year post-relapse survival was 30 +/- 2%, 16 +/- 2% and 8 +/- 1%, respectively. In a multivariate analysis, adverse factors for survival were: late CR (CR2/3) at transplant (P<0.012), early relapse after transplant (<6.9 months, P <0.0001) and peripheral blast percent at relapse (P <0.0001). On the basis of multivariate model for survival, three groups of patients were identified with estimated 2 year survival of 6 +/- 2, 17 +/- 3 and 30 +/- 7%. Outcome of ALL patients relapsing after HCT is dismal and there is a need for new therapies. Our study provides the standard expectations in ALL relapse and may help in the decision of post-relapse therapy.
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| 8. |
- Baron, F, et al.
(författare)
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Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation
- 2012
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Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 26:12, s. 2462-2468
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Tidskriftsartikel (refereegranskat)abstract
- This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR) 0.7, P = 0.02) translating into a trend for better overall survival (OS; HR 1.3; P = 0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR 0.4, P andlt; 0.0.001) owing to high risk of nonrelapse mortality (NRM; HR 5.2, P andlt; 0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR 0.72; P = 0.07) translating into a better OS (HR 1.8; P andlt; 0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR 0.65; P = 0.02) but also with higher NRM (HR 3.5; P andlt; 0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P andlt; 0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR 0.65; P = 0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. Leukemia (2012) 26, 2462-2468; doi: 10.1038/leu.2012.135
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| 9. |
- Baron, F., et al.
(författare)
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Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor : a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation
- 2014
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Ingår i: Bone Marrow Transplantation. - : Nature Publishing Group. - 0268-3369 .- 1476-5365. ; 49:3, s. 389-396
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Tidskriftsartikel (refereegranskat)abstract
- The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult patients with de novo AML in first CR (CR1) given PBSC from HLA-identical siblings after chemotherapy-based RIC. A total of 554 patients did not receive any form of in vivo T-cell depletion (control group), whereas antithymocyte globulin (ATG) and alemtuzumab were given in 444 and 252 patients, respectively. The incidences of grade II-IV acute GVHD were 21.4, 17.6 and 10.2% in control, ATG and alemtuzumab patients, respectively (P less than 0.001). In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (P less than 0.001 each), but a similar risk of relapse, and of nonrelapse mortality, and similar leukemia-free survival and OS. Further, among patients given BU-based RIC, the use of less than 6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR=1.1), whereas there was a suggestion for higher relapse risk in patients given greater than= 6 mg/kg ATG (HR=1.4, P=0.08). In summary, these data suggest that a certain amount of in vivo T-Cell depletion can be safely used in the conditioning of AML patients in CR1 given PBSC after chemotherapy-based RIC.
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| 11. |
- Chevallier, P, et al.
(författare)
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Impact of cytogenetics risk on outcome after reduced intensity conditioning allo-SCT from an HLA-identical sibling for patients with AML in first CR: a report from the acute leukemia working party of EBMT
- 2012
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Ingår i: Bone Marrow Transplantation. - : Nature Publishing Group. - 0268-3369 .- 1476-5365. ; 47:11, s. 1442-1447
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Tidskriftsartikel (refereegranskat)abstract
- So far the impact of cytogenetics risk on outcome in the context of reduced intensity conditioning (RIC) allo-SCT has been poorly studied. We have identified 378 AML patients in first CR who underwent RIC allo-SCT from an HLA-matched sibling donor between 2000 and 2007 reported to the European Group for Bone and Marrow Transplantation and for whom detailed cytogenetics data were available (good risk: n = 21; intermediate risk: n = 304; and poor risk: n = 53). With a median follow-up of 24 months (range: 1-93), 2-year non-relapse mortality, relapse rate (RR), leukemia-free survival (LFS) and OS were 14%, 31%, 55% and 61%, respectively. Cytogenetics was significantly associated with RR (good risk: 10%; intermediate risk: 28%; and poor risk: 55% at 2 years, Pandlt;0.0001) and LFS (good risk: 64%; intermediate risk: 57%; and poor risk: 38% at 2 years, P = 0.003). In a multivariate analysis, RR and LFS were significantly higher and lower, respectively, in the high-risk cytogenetics group (P = 0.001, P = 0.004) and in patients with a higher WBC at diagnosis (andgt;10 x 10(9)/L) (Pandlt;0.001, P = 0.004). As documented in the setting of myeloablative allo-SCT, patients with poor cytogenetics had increased RR and decreased LFS after RIC allo-SCT, requiring new prospective strategies to improve results in this subgroup.
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| 16. |
- Cornelissen, Jan J., et al.
(författare)
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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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Ingår i: Nature Reviews Clinical Oncology. - : Springer Science and Business Media LLC. - 1759-4782 .- 1759-4774. ; 9:10, s. 579-590
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Forskningsöversikt (refereegranskat)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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| 17. |
- Nagler, Arnon, et al.
(författare)
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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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Ingår i: European Journal of Haematology. - : John Wiley and Sons. - 0902-4441 .- 1600-0609. ; 89:3, s. 206-213
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Tidskriftsartikel (refereegranskat)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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