Favorable outcome of haploidentical hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia: a multicenter study in Southwest China.

Li Gao,Sanbin Wang,Yi Su,Zhong Yuan,Cheng Zhang,Xi Zhang,Lei Gao,Yao Liu,Bin Li,Tonghua Yang

doi:10.1186/s13045-015-0186-5

Abstract

BackgroundSince the introduction of tyrosine kinase inhibitors (TKIs) into combination chemotherapy regimens, the majority of newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients have achieved complete remission (CR). However, without allogeneic hematopoietic stem cell transplantation (HSCT), long-term outcomes in adults remain unsatisfactory. Indeed, haploidentical HSCT has become a common treatment for adult patients who lack an HLA-matched donor, though limited data are available on the efficacy of haploidentical HSCT in Ph+ ALL patients.MethodsWe analyzed the clinical outcomes of 82 Ph+ ALL patients who underwent haploidentical HSCT (n = 47) or HLA-matched HSCT (n = 35). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess BCR-ABL expression. All of the patients were treated with an imatinib-based regimen before undergoing HSCT. Imatinib treatment was resumed in the patients’ posttransplantation following detection of BCR-ABL transcripts.ResultsAll of the patients achieved neutrophil and platelet engraftment, with the exception of five patients who died prior to engraftment. Haploidentical HSCT was associated with higher incidences of acute graft-versus-host disease (GVHD) (51.1 vs. 25.7 %, p < 0.05) and chronic GVHD (48.9 vs. 25.7 %, p < 0.05) compared with HLA-matched HSCT, but there was no difference in the incidence of either grades III–IV acute GVHD or extensive chronic GVHD. The incidence of cytomegalovirus (CMV) infection was significantly higher in the patients treated with haploidentical HSCT than in those treated with HLA-matched HSCT (38.3 vs. 14.3 %, p < 0.05). Haploidentical HSCT was associated with a significantly lower relapse rate compared with HLA-matched HSCT (44.8 vs. 19.1 %, p < 0.05). There were no differences in non-relapse mortality (NRM), leukemia-free survival (LFS), or overall survival (OS) between the patients who received HLA-matched HSCT and those who underwent haploidentical HSCT.ConclusionsOur data indicate that the incidence of NRM after HSCT is similar between the patients who receive HLA-matched donor cells and those who receive haploidentical donor cells and that haploidentical HSCT reduces the relapse rate. Haploidentical HSCT represents an encouraging treatment option for Ph+ ALL patients who lack a suitable HLA-matched donor.

Highlights

25–30 % of adults and 3 % of children with acute lymphoblastic leukemia (ALL) express the oncogenic BCR-ABL protein, which results from a 9;22 chromosomal translocation known as the Philadelphia (Ph) chromosome [1]
The patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) were conditioned with 9.0–10.5 Gy total-body irradiation (TBI) on days −7 and −6, 6 g/m2/day intravenous arabinosylcytosine (Ara-C) on days −5 to −3, 45 mg/kg/day intravenous CY on days −3 to −2, and 2.5 mg/kg/day intravenous anti-thymocyte globulin (ATG) (Sanofi, SangStat, Lyon, France) on days −5 to −2
Despite an initial favorable response to treatment, the long-term outcome is unsatisfactory in adults when tyrosine kinase inhibitors (TKI)/chemotherapy combinations are used without alloHSCT

Summary

Introduction

25–30 % of adults and 3 % of children with acute lymphoblastic leukemia (ALL) express the oncogenic BCR-ABL protein, which results from a 9;22 chromosomal translocation known as the Philadelphia (Ph) chromosome [1]. The introduction of tyrosine kinase inhibitors (TKIs) into the standard combination chemotherapy regimens for newly diagnosed Ph+ ALL allows over 95 % of patients to achieve CR [5, 6], Ph+ ALL remains an unfavorable prognostic subgroup with an unacceptably high relapse rate. Our current study compares the outcomes of patients who have been diagnosed with Ph+ ALL and treated with HSCT using cells from either haploidentical donors or matched donors. Since the introduction of tyrosine kinase inhibitors (TKIs) into combination chemotherapy regimens, the majority of newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients have achieved complete remission (CR). Without allogeneic hematopoietic stem cell transplantation (HSCT), long-term outcomes in adults remain unsatisfactory. Haploidentical HSCT has become a common treatment for adult patients who lack an HLA-matched donor, though limited data are available on the efficacy of haploidentical HSCT in Ph+ ALL patients

Methods

Results

Conclusion