Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation during First Complete Remission Following Imatinib-Combined Chemotherapy in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Authors: Mizuta Shuichi , Yanada Masamitsu , Sugiura Isamu , Yagasaki Fumiharu , Yujiri Toshiaki , Takeuchi Makoto , Hatta Yoshihiro , Kimura Yukihiko , Ueda Yasunori , Kanamori Heiwa , Usui Noriko , Akiyama Hideki , Miyazaki Yasushi , Ohtake Shigeki , Jinnai Itsuro , Matsuo Keitaro , Naoe Tomoki , Ohno Ryuzo 
Published: April 2020

Abstract
The treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has been changed dramatically since the introduction of imatinib. We previously reported a 96% complete remission (CR) rate in newly diagnosed patients treated with imatinib-combined chemotherapy (Yanada et al. J Clin Oncol2006;24:460–466), and showed that the combination therapy is useful in terms of providing patients with a better chance for receiving allogeneic hematopoietic stem cell transplantation (HSCT) in first CR. However, little is known about the outcome after allogeneic HSCT in such patients. To address this issue, we analyzed detailed data from 60 patients who underwent allogeneic HSCT in first CR following a uniform treatment protocol consisting of imatinib and chemotherapy. The median age of the studied patients was 37 years (range, 15–64 years), with 32 males and 28 females. Donors were HLA-matched related (n=24), matched unrelated (n=21), mismatched cord blood (n=9), and mismatched related (n=6). All 52 patients aged less than 55 years received a myeloablative conditioning regimen, whereas 6 of 8 patients aged 55 years or older received a reduced intensity conditioning (RIC) regimen. Grade 2–4 acute graft-versus-host disease (GVHD) was recorded in 20 patients, and chronic GVHD was recorded in 32 patients, 17 of whom had the extensive form. During a median follow-up of 2.6 years (maximum, 4.6 years) after transplantation, relapse and death in first CR occurred in 9 and 15 patients. The probabilities for overall survival (OS) and relapse-free survival (RFS) were 64% and 53%, respectively, at 3 years. Patients younger than 40 years had a trend toward better RFS than those at 40 to 54 years (60% vs. 38% at 3 years, p=0.16). Unexpectedly, all of the 8 patients aged 55 years or older remained alive in first CR. In relation to the donor type, RFS did not differ among patients allografted from a matched related donor, a matched unrelated donor, and mismatched cord blood (52% vs. 59% vs. 56% at 3 years, p=0.92). For risk factor analysis, the following variables were examined: donor type (sibling vs. unrelated vs. cord blood), age group (&lt;40 years vs. 40–54 years vs. ≥55 years), minimal residual disease status at time of HSCT (quantitative real-time PCR negative vs. positive), type of conditioning regimen (RIC vs. myeloablative conditioning), performance status at time of HSCT, and bcr/abl isotype (major vs. minor). Multivariate analysis revealed that only the presence of major bcr/abl was significantly associated with inferior RFS (HR, 3.70; 95% CI, 1.34–10.2; p=0.012).
Conclusion: In patients with Ph+ ALL who were initially treated with imatinibcombined chemotherapy, the outcome after allogeneic HSCT in first CR was favorable irrespective of the donor type. Cord blood transplantation and RIC transplantation might be attractive options for those without a suitable donor and for those unfit for conventional myeloablative conditioning, respectively. Prospective studies are warranted to confirm the roles of these forms of transplantation, especially RIC for patients between 40 and 54 years of age.