Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of patients with mixed-lineage-leukemia-rearranged acute leukemia: Results from a prospective, multi-center study.

The purpose of this study is to define the role for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mixed-lineage-leukemia (MLL)-rearranged acute leukemia, which is now poorly understood. A prospective, multi-center cohort study to determine whether allo-HSCT could decrease relapse rates and improve long-term survival of MLL+ leukemia patients was performed. Fifty-six consecutive patients diagnosed with MLL-rearranged acute leukemia undergoing allo-HSCT from two transplant centers in China were enrolled between October 2007 and October 2012. The trial was registered at www.chictr.org as # ChiCTR-ONC-12002739. The incidences of grades II to IV acute graft versus host disease (aGVHD) and of grades III and IV aGVHD were 28.8% (CI, 16.87-40.8%), and 14.2% (CI, 5.4-23.0%), respectively. The cumulative incidences for chronic GVHD (cGVHD) at 2 years after HSCT were 35.2% (CI, 21.2-49.2%). Up to April 30, 2013, 12 patients had relapsed and 11 died from relapse, and 37 patients were still alive without disease recurrence. The relapse and NRM rates at 3 years were 25.3% (CI, 12.7-37.9%) and 18.0% (CI, 2.6-33.4%), respectively. The probalities of overall survival and leukemia free survival were 61.8% (CI, 46.0-77.6%) and 56.3% (CI, 38.1-74.5%) at 3 years, respectively. Patients transplanted during their hematological first complete remission (CR1) had a lower relapse rate (17.9% vs. 48.1%, P = 0.03) compared with patients transplanted beyond CR1. The median overall survival for the 29 patients not receiving allo-HSCT during the study period was 145 days from diagnosis. This study showed that allo-HSCT could be a valuable treatment choice for MLL+ acute leukemia.

Partially matched related donor transplantation can achieve outcomes comparable with unrelated donor transplantation for patients with hematologic malignancies.

PURPOSE: The study aimed to compare the outcomes of patients undergoing hematopoietic stem cell transplantation (HSCT) from partially matched related donors (PMRD) and unrelated donors (URD) for hematologic malignancies without the use of in vitro T cell depletion. EXPERIMENTAL DESIGN: HSCT was done on 297 consecutive patients from URDs (n = 78) and PMRDs (n = 219) during the same time period. Incidences of graft-versus-host disease (GVHD), relapse, nonrelapse mortality, overall survival, and leukemia-free survival between the PMRD and URD groups were compared. RESULTS: All patients achieved full engraftment. The cumct65ulative incidences of grades II to IV acute GVHD in the PMRD and URD cohorts were 47% [95% confidence interval (95% CI), 33-62%] versus 31% (CI, 20-42%; P = 0.033), with a relative risk of 1.72 (95% CI, 1.01-2.94; P = 0.046). The incidence of chronic GVHD did not differ significantly between the two cohorts (P = 0.17). The 2-year incidences of nonrelapse mortality and relapse were 20% (CI, 15-26%) versus 18% (CI, 10-27%), with P = 0.98, and 12% (CI, 8-16%) versus 18% (CI, 10-27%), with P = 0.12, for the PMRD versus the URD cohort, respectively. The 4-year overall survival and leukemia-free survival were 74% (CI, 67-80%) versus 74% (CI, 62-85%), with P = 0.98, and 67% (CI, 59-75%) versus 61% (CI, 47-74%), with P = 0.74, respectively. CONCLUSIONS: Our comparisons show that every major end point, including relapse, nonrelapse mortality, overall survival, and leukemia-free survival, was comparable between the PMRD and the URD groups.

HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for chronic myeloid leukemia: improved outcomes in patients in accelerated phase and blast crisis phase.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only proven curative therapy for chronic myeloid leukemia (CML), but lack of human leukocyte antigen (HLA)-matched sibling or unrelated donors has restricted its application. Recently, we developed an effective method for haploidentical allo-HSCT achieving comparable outcomes to HLA-identical transplantation. AIM: To evaluate the outcomes of CML patients who underwent haploidentical allo-HSCT. METHODS: Ninety-three patients were treated with a modified busulfan (BU)/cyclophosphamide (CY) 2 regimen, including antithymocyte globulin followed by unmanipulated blood and marrow transplantation. RESULTS: Our data showed that the cumulative incidence of acute graft-versus-host disease (GVHD) was 64.52%, and grade III-IV was 26.45%, 61.79% had chronic GVHD, and 28.93% had extensive chronic GVHD. Non-relapse mortality varied at 8.72% (100 days), 20.72% (1 year) and 20.72% (2 years). Probability of 1-year and 4-year leukemia-free survival was similar in chronic phase (CP) 1, CP2/CR2, accelerated phase, and blast crisis patients. Probability of 4-year overall survival varied as 76.5% (CP1), 85.7% (CP2/CR2), 73.3% (accelerated phase), and 61.5% (blast crisis). Multivariate analysis indicated that factors affecting transplantation outcomes were HLA-B+DR mismatches versus others for II-III acute GVHD and III-IV acute GVHD, the stage of disease at transplantation for relapse, and the time from diagnosis to transplantation for leukemia-free survival, overall survival, and transplantation-related mortality. In our protocol, survival of HSCT for advanced CML was similar to stable stage. CONCLUSIONS: For patients lacking an HLA-identical related donor, haploidentical relatives are alternative HSCT donors.