Prognostic factors of unrelated donor hematopoietic stem cell transplantation for treatment of Ph chromosome positive acute lymphocyte leukemia

Abstract

Objective To analyze prognostic factors for the clinical outcome of unrelated donor hematopoietic stem cell transplantation (URD-HSCT) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) following imatinil-based therapy.Method From February 2002 to February 2012,25 patients with Ph+ ALL receiving URD-HSCT were enrolled in the study.There were 17 cases in the first CR (CR1),and 8 cases beyond CR2.Nine patients expressed major BCR/ABL (M) and 16 expressed minor BCR/ABL (m).All the patients were administrated with imatinib before transplantation.Graft versus host disease (GVHD) prophylaxis protocol included cyclosporine A (CSA),short term methotrexate (MTX),antithymocyte globulin (ATG) and mycophenolate mofetil (MMF).Results The median time of ANC ≥0.5 × 109/L was 12 (10-20) days,and that of PLT ≥20× 109/L was 12 (10-36) days.Thirty days after URD-HSCT,all patients achieved full donor chimerism.The median follow-up duration post-transplantation was 20.5 (3 to 93) months.The 2-year overall survival (OS) and leukemia-free survival (LFS) was (55.3 ± 10.9) ％ and (49.1 ± 12.2) ％,respectively.The cumulative incidence of relapse and aGVHD was (29.6 ± 9.4) ％ and (48.0-± 10.6) ％,respectively.The uninvariate analysis revealed that the OS and LFS were higher in CR1 group pre-HSCT than in non-CR1 group (77.1％ vs.20％,P =0.028;74.1％ vs.0,P=0.030),lower in major BCR/ABL than in minor BCR/ABL group (22.2％ vs.80.2％,P=0.010; 13.9％ vs.78.3％,P =0.015).The median age at HSCT,gender,WBC at diagnosis,conditioning regimen,stem-cell source and HLA typing didn't significantly influence the outcome of URD-HSCT.The multivariate analysis revealed that both the status of disease Pre-HSCT and BCR/ABL subtype were the unfavorable factors for OS [P=0.038,Exp(B) =3.823; P =0.023,Exp(B) =4.829].Conclusion The status of disease Pre-HSCT and BCR/ABL subtype were the major prognostic factors.The outcome of URD-HSCT done in CR1 was desirable and we should pay more attention to monitoring in the minor BCR/ABL patients after URD-HSCT. Key words: Hematopoietic Stem cell transplantation; Philadelphia chromosome; Leukemia,lymphocytic, acute; Prognosis; Fusion proteins, bcr-abl