Predictive factors for outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for hematological malignancies: a 10-year retrospective analysis from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

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 (Po0.001).In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (Po0.001 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 o6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR ¼ 1.1), whereas there was a suggestion for higher relapse risk in patients given X6 mg/kg ATG (HR ¼ 1.4, P ¼ 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. INTRODUCTIONThe use of PBSC instead of BM in patients receiving grafts from HLA-matched donors after myeloablative conditioning has been associated with faster hematological recovery, lower relapse risk in patients with advanced disease (due to higher immune-mediated graft-versus-tumor (GVT) effects), but also higher incidence extensive chronic GVHD. 1-4 These observations prompted several groups of investigators to study in vivo T-cell depletion of the graft with antithymocyte globulin (ATG) or alemtuzumab as a way to reduce severe GVHD in patients given PBSC after highdose myeloablative conditioning regimen. [5][6][7] These studies demonstrated that the use of ATG or alemtuzumab was successful at preventing severe GVHD without apparently increasing the relapse incidence (RI). [5][6][7] In contrast to patients given grafts after myeloablative conditioning who benefit from both the high-dose chemo/radiotherapy given as part of the conditioning regimen and the GVT effect for tumor eradication,

Section: Discussionsupporting

confidence: 79%

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

Baron

Labopin

Blaise³

et al. 2014

“…31 Although the development of RIC regimens has allowed patients who are ineligible for standard allo-HSCT to benefit from allogeneic therapy, NRM remains a significant obstacle to its success. While the association between low performance status (ECOG 41) and advanced disease status with early NRM has been previously reported by us and other groups in allo-RIC regimens, 8,24,32,33 this is the first observation, to the best of our knowledge, that CsA/ MTX GVHD prophylactic regimen showed a relevant trend to a higher early NRM for patients who underwent HLA-identical sibling peripheral blood allo-RIC. Nonetheless, it is well know that MTX has several potentially relevant toxicities (pulmonary, hepatic, gastrointestinal and hematopoietic toxicity).…”

Section: Discussionmentioning

confidence: 70%

MTX or mycophenolate mofetil with CsA as GVHD prophylaxis after reduced-intensity conditioning PBSCT from HLA-identical siblings

Piñana

Valcárcel

Fernández‐Avilés

et al. 2010

Mycophenolate mofetil (MMF) in combination with CsA seems to lead to earlier post transplant hematological recovery and less mucositis than MTX, with a similar incidence of GVHD. In this study we analyzed the post transplant outcomes of two cohorts of patients who underwent an HLA-identical sibling reduced intensity conditioning transplantation (allo-RIC) with GVHD prophylaxis consisting of CsA in combination with either MMF or a short course of MTX. We included 145 consecutive allo-RIC transplants performed between April 2000 and August 2007. The median follow-up for survivors was 41 months (4-105 months). The study group included 91 males. Median age was 55 years (range 18-71 years). Diagnoses included myeloid (n ¼ 65) and lymphoid (n ¼ 80) malignancies. GVHD prophylaxis consisted of CsA/MMF in 52 and CsA/MTX in 93 patients. The conditioning regimen was based on fludarabine in combination with BU (n ¼ 59) or melphalan (n ¼ 86). The occurrence of grade 2-4 mucositis was higher in the CsA/MTX group than in the CsA/MMF group (57 vs 23%, P ¼ 0.001). The cumulative incidence of acute and chronic GVHD was similar, 48 vs 50% and 71 vs 68%, respectively (P40.7). The 2-year relapse and OS were similar in the CsA/MTX and CsA/MMF groups (29 vs 21%, P ¼ 0.3 and 52 vs 51%, P ¼ 0.7, respectively). Our results support further prospective studies comparing the use of the CsA/MMF combination with CsA/MTX as GVHD prophylaxis in HLA-identical sibling donor allo-RIC recipients.

“…4,8,[22][23][24][25][26][27][28][29] Of the larger studies, a French registry study of 1108 RIC HSCT patients reported that MN ABO incompatibility was associated with reduced OS. 30 In the RIC subgroup of the largest registry study to date, Kimura et al 2 reported increased transplantrelated mortality (TRM) for MN, MJ and BD ABO-mismatched patients. Recently, ABO mismatch was found to have no effect on OS, nonrelapse mortality or GVHD in 2 studies of 310 patients 31 and 503 patients 3 undergoing RIC allograft, but both noted increased transfusion requirements in patients with MJ/BD mismatch.…”

Section: Introductionmentioning

confidence: 99%

Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity conditioned haematopoietic SCT

Brierley

Littlewood

Peniket

et al. 2015

The impact of ABO incompatibility on clinical outcomes following haematopoietic SCT (HSCT) remains controversial. This retrospective study assessed the effect of ABO mismatch on transplant outcomes and transfusion requirements in 594 patients undergoing reduced-intensity conditioned (RIC) HSCT with alemtuzumab in three UK transplant centres. We found no significant effects of minor, major or bidirectional ABO mismatch on overall survival, relapse-free survival, nonrelapse mortality or relapse incidence. Although the rate of acute GVHD was unaffected by ABO mismatch, the incidence of extensive chronic GVHD was higher in patients with minor and major mismatch compared with those who were ABO matched (hazard ratio (HR) 1.74, P = 0.032 for minor, HR 1.69 P = 0.0036 for major mismatch). Red cell and platelet transfusion requirements in the first 100 days post transplant did not differ by ABO mismatch. In this large UK series, ABO mismatch in RIC HSCT has no clinically significant effect on survival outcomes but appears to modify susceptibility to extensive chronic GVHD.Bone Marrow Transplantation (2015) 50, 931-938;