Several recently published studies have suggested that patients who undergo ABO mismatched hematopoietic stem cell transplantation may be at increased risk for relapse, graft-versus-host disease, transplant-related mortality, and/or all-cause mortality. To investigate this issue further, we analyzed potential associations between the donor-recipient ABO mismatch pattern and the above outcome measures among 240 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation at our institution. Our analyses uncovered no significant associations between donor-recipient ABO mismatch pattern and overall survival, event-free survival, transplant-related mortality, incidence of acute graftversus-host disease (GVHD), or incidence of chronic GVHD. Our data do not support recent assertions that donor-recipient ABO mismatching is a major risk factor for patients undergoing allogeneic transplant, nor do they support recent assertions that ABO matching should be an important consideration in selecting allogeneic hematopoietic stem cell donors.
BACKGROUND:A recently published study has reported that donor-recipient Rhesus (Rh)-mismatched allogeneic hematopoietic stem cell transplantation independently led to significantly poorer survival. This suggests that donor-recipient Rh mismatching is a risk factor in allogeneic hematopoietic stem cell transplantation and should be a criterion for donor selection. STUDY DESIGN AND METHODS:To further evaluate this issue, 258 consecutive patients who underwent myeloablative or submyeloablative allogeneic hematopoietic stem cell transplantation at our institution were analyzed to determine the association between the Rh mismatch pattern and 5-year actuarial survival. Secondary endpoints analyzed were the association of donor-recipient Rh mismatch and event-free survival, transplant-related mortality, incidence of acute graftversus-host disease (GVHD), and incidence of chronic GVHD. RESULTS: In our analysis, there were no significant associations between donor-recipient Rh mismatch pattern and overall survival, event-free survival, transplant-related mortality, incidence of acute GVHD, or incidence of chronic GVHD. On multivariate Cox proportional hazard analyses, the donor-recipient Rh mismatch pattern was not independently predictive of overall survival. CONCLUSION: Donor-recipient Rh mismatch is not a risk factor in allogeneic hematopoietic stem cell transplantation and does not affect transplant outcomes. D onor-recipient ABO mismatch in allogeneic hematopoietic stem cell transplantation can result in hemolytic anemia, delayed red blood cell (RBC) engraftment and pure RBC aplasia.1 Most of the largest studies, however, show no significant associations between donor-recipient ABO mismatch pattern and overall survival, event-free survival, treatment-related mortality, incidence of acute graftversus-host disease (GVHD), or chronic GVHD. 2,3Donor-recipient Rh mismatch in allogeneic hematopoietic stem cell transplantation can result in hemolytic anemia. 4 Less is known about transplant outcomes and donor-recipient Rh mismatching than ABO mismatching. Recently, a single institution analysis of donor-recipient Rh-mismatched patients undergoing allogeneic hematopoietic stem cell transplantation found a significantly poorer survival than for Rh-matched patients. On multivariate analysis, Rh mismatch between donor and recipient was an independent risk factor for poorer survival (p = 0.02). 5 The etiology of the poorer survival has not been formally studied but was postulated to be related to cellular immunologic mechanisms.We undertook to investigate this issue in a larger study by formally defining a single primary statistical endpoint, that is, the effect of Rh-mismatched allogeneic hematopoietic stem cell transplant on overall survival, before the initiation of the analysis. In addition, formal statistical multiple comparison adjustment techniques were used to lessen the chance of false-positive
Introduction: We previously reported that reduced intensity conditioning (RIC) regimens are safe for patients with XIAP deficiency. XIAP is ubiquitously expressed, and emerging evidence suggests that XIAP is a critical regulator of inflammasome activity and necroptotic cell death downstream of TNFR signaling. It is unknown if there may be an increased risk of death due to inflammatory problems following allogeneic hematopoietic cell transplantation (HCT) such as acute GVHD. Methods: We conducted a retrospective analysis of transplant outcomes of 15 XIAP deficient patients who underwent RIC HCT with alemtuzumab (proximal, distal, or intermediate schedule), fludarabine (150 mg/M2), and melphalan (140 mg/M2) at our center. Twelve patients received bone marrow grafts from either matched related (n = 3) or unrelated (n = 9) donors, and 3 patients received bone marrow grafts from mismatched unrelated donors. Acute GVHD prophylaxis consisted of methylprednisolone and a calcineurin inhibitor. Kaplan Meier survival curves were generated and the outcomes of patients with and without acute GVHD were compared using the log rank test. Results: Fifteen patients with XIAP deficiency underwent allogenic RIC HCT. All patients engrafted. There were no occurrences of severe toxicities such as hepatic veno-occlusive disease, and all patients survived beyond 100 days. All three patients who received mismatched donor grafts died with acute or chronic GVHD and associated infections or PTLD. Two additional patients who received grafts from matched sibling donors developed acute GVHD following donor lymphocyte infusion (intervention for mixed chimerism) and died with acute GVHD and multiple organ failure or chronic GVHD and infection. Only one patient who developed upfront acute GVHD survived, and acute GVHD in this patient developed in the setting of mixed chimerism. Overall long term survival probability of patients who did not develop acute GVHD was 100% versus 17% for patients who developed acute GVHD (all grades) (P = .004). Discussion: We observed very high late mortality in patients with XIAP deficiency treated with RIC HCT who received mismatched grafts and/or developed GVHD. It is possible that host XIAP-deficient tissues, which likely remain susceptible to abnormal inflammatory responses following transplant, may alter the natural history of acute and chronic GVHD in patients with XIAP deficiency. A multi-center survey is indicated to better determine if there is an increased risk of death due to acute GVHD following HCT in patients with XIAP deficiency, as this would alter decisions to pursue mismatched HCT or perform donor lymphocyte infusions.
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