Favorable Outcomes of Autologous Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in First Remission: On Behalf of the Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT)
Authors: Kato Harumi , Kawase Takakazu , Kako Shinichi , Mizuta Shuichi , Ohashi Kazuteru , Kurokawa Mineo , Iwato Koji , Mori Takehiko , Suzuki Ritsuro , Sakamaki Hisashi , Morishima Yasuo , Tanaka Junji 
Published: October 2019

Abstract
Abstract 2021

Background:
Postremission treatment for adult Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-)ALL] in first remission remains elucidated and the role of autologous stem cell transplantation (auto-SCT) is still controversial in the application for Ph(-)ALL patients. We retrospectively analyzed the consolidative role of auto-SCT as a postremission therapy for adult Ph(-)ALL in first remission.

Patients and Methods:
Among 1962 adult Ph(-)ALL patients registered in the JSHCT database, we selected cases receiving auto-SCT with myeloablative preparative regimens in first complete remission from 1983 to 2009.

Results:
A total of 155 patients with 86 male patients were analyzed. The median age was 25 years (range: 16 to 74) and 79% of patients were less than 45 years of age at transplant. The number of patients having white blood cell (WBC) count <30000/ul and ≥30000/ul at diagnosis was 81 and 21, respectively. The number of patients showing B- and T-cell phenotypes was 80 and 21, respectively. Cytogenetic data were available in 96 patients, of which 69 patients had normal karyotypes. Most patients (84%) underwent auto-SCT before 2002, and 42 out of 155 patients received TBI combined conditioning regimens. With a median follow-up of 10 years, the 10-year overall survival rate of all 155 patients was 41% (95%CI: 33 to 49). Among patients younger than 45 years, the survival rate of adolescent and young adult (AYA) patients (aged 24 years or less) was comparable to that of patients aged 25 to 44 years (p= 0.110). Cumulative incidence of relapse and non-relapse mortality (NRM) at 10 year after auto-SCT was 47% (95%CI: 39 to 55) and 10% (95%CI: 6 to 16), respectively. In univariate analysis, factors associated with worse overall survival were age 45 years or more [Hazard ratio (HR): 1.67, p=0.038] and usage of conditioning regimens without total body irradiation (TBI) (HR: 1.51, p=0.110). Factors associated with decreasing relapse rates were usage of TBI conditioning regimens (HR: 0.35, p=0.069) and transplant year 2000 and later (HR: 0.35, p=0.141). In multivariate analysis, factors correlated with increasing the overall survival rate and decreasing the relapse rate were age less than 45 years [HR: 0.59 (95%CI: 0.36 to 0.96), p=0.034] and usage of TBI conditioning regimens [HR: 0.55 (95%CI: 0.31 to 0.99), p=0.048], respectively. There were no significant factors associated with NRM in univariate and multivariate analyses.
We next performed comparison of auto-SCT with allogeneic stem cell transplantation (allo-SCT) in adult Ph(-)ALL patients. Patients undergoing allo-SCT were selected from the same JSHCT database. A total of 921 patients were identified as cases receiving allo-SCT with myeloablative preparative regimens in first complete remission. With a median follow-up of 4.95 years, the 4-year overall survival rate was 63% (95%CI: 51 to 59). Allo-SCT yielded better overall survival rate than that of auto-SCT (63% vs. 48% at 4 year, p=0.0004). In subset analyses, we limited analyses to the groups of patients younger than 45 years and receiving TBI regimens followed by auto-SCT (n=31) or allo-SCT (n=685). There were no differences in baseline patients' characteristics between the two groups except age [auto-SCT: 20 years (range: 16 to 40) vs. allo-SCT: 28 years (range: 16 to 44), p<0.001]. The 4-year overall survival rates in patients undergoing auto-SCT and allo-SCT were 71% (95%CI: 52 to 84) and 66% (95% CI: 62 to 70), respectively (p=0.510, Figure. 1). No statistically significant factors were found in the analyses of relapse and NRM.

Conclusions:
Our analyses demonstrated that auto-SCT produced excellent results showing a plateau in long-term survival and that clinical outcome of auto-SCT was comparable to that of allo-SCT in some part of patients. Candidates who obtained most benefit from auto-SCT was those younger than 45 years and well tolerated with TBI combined myeloablative conditioning regimens. Since optimal timing of postremission therapy is critical for adult Ph(-)ALL patients, auto-SCT in first complete remission could be one of promising treatment strategies for the patients.

Disclosures:
No relevant conflicts of interest to declare.