Comparative Survival of Haploidentical and Matched Related Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia
Authors: Huan Chen , Liu Kai-Yan , Lan-ping Xu , Dai-hong Liu , Chen Yu-hong , Wei Han , Xiao-hui Zhang , Yu Wang , Ya-zhen Qin , Yan-rong Liu , Huang Xiao Jun 
Published: April 2020

Abstract
Purpose
The role of haploidentical related allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia( Ph+ ALL) is still not clear in the imatinib era, and limited data are available from the literature. We aimed to investigate the long-term survival between the haploidentical and matched related transplant in Ph+ ALL patients, and to analyze factors affecting relapse rate in different donor-type with maintenance therapy of imatinib post-transplant. Patients and methods The study population included Ph+ ALL patients receiving allo-HSCT from either haploidentical or matched related donor, and with maintenance therapy of imatinib post-HSCT. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were&gt;1.0 ± 109/L and platelet counts were&gt;50.0 ± 109/L, or if they displayed a high BCR-ABL transcript levels (∼10-2 after initial engraftment) or elevated BCR-ABL transcript levels in two consecutive tests. The imatinib treatment was scheduled for 3-12 months, or BCR-ABL transcript levels were negative at least for three consecutive tests and complete molecular remission was sustained for at least 3 months). Imatinib-resistant defined as: (1) transcript levels of BCR-ABL increased in two consecutive tests at least one-month interval; or (2) detection of point mutations in the BCR-ABL kinase domain (KD) after transplant. Results The total 120 consecutive Ph+ ALL patients received allo-HSCT and maintenance therapy of imatinib post-HSCT in our center between May 2005 to September 2012. Of these, 115 patients receiving a haploidentical (n=81) and matched related (n=34) graft were analyzed. 24 patients were identified as imatinib-resistant during post-transplant period, 13 in haploidentical group and 11 in matched related group. The 5-year cumulative incidence of relapse£¨CIR£©and non-relapse mortality (NRM) among the haploidentical group and matched related group were no different ( 18.2% vs.26.0%, p=0.212; 9.4% vs.7.2%, p=0.687). At a median follow-up of 37.5 months, the 5-year DFS and OS were 72.2% and 81.5% for the haploidentical group, compared with 68.5% and 79.5% for matched related group (p = 0.265, 0.419, respectively). Multivariate analysis showed that RT-PCR-BCR-ABL positive pre-transplant was significant factor for OS in haploidentical transplant (P=0.046). Remission status (&gt;CR1) at HCT was a significant predictor to CIR in matched related group (p=0.020), but it wasn't a significant factor to impact on CIR in haploidentical transplant group. Imatinib-resistant was a significant factor to affect DFS, OS and CIR in both donor-type groups. Conclusion In the imatinib era, haploidentical HSCT for Ph+ALL achieves identical long-term survival compared with matched related HCT. Remission status (&gt;CR1) at the transplant does not significantly impact on relapse in haploidentical transplant. Imatinib-resistant is a worse predictor to long-term survival and relapse rate in both donor-type group after HCT.

Disclosures
No relevant conflicts of interest to declare.