Outcomes of Adults with Acute Lymphoblastic Leukemia After Autologous Hematopoietic Stem Cell Transplantation and the Significance of Pretransplantation Minimal Residual Disease

Abstract

Background:The postremission therapies for adult patients generally contain consolidation chemotherapy, allogeneic hematopoietic stem cell transplantation and autologous hematopoietic stem cell transplantation (auto-HSCT). Because of the various results from different centers, the optimal therapy for adult acute lymphoblastic leukemia (ALL) patients is still uncertain. This study aimed to better understand predictive factors and role of auto-HSCT in the postremission therapy for adult ALL patients.Methods:The outcomes of 135 adult patients with ALL, who received the first auto-HSCT in Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 1994 to February 28, 2014, were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method and simultaneous effects of multiple covariates were estimated with the Cox model.Results:Overall survival (OS) and disease-free survival (DFS) at 5 years for the whole cohort were 59.1 ± 4.5% and 59.0 ± 4.4%, respectively. The cumulative nonrelapse mortality and relapse rate at 5 years were 4.5 ± 0.03% and 36.6 ± 0.19%. For both OS and DFS, acute T-cell lymphoblastic leukemia, high lactate dehydrogenase (LDH) at diagnosis, blast cell proportion ≥5% on the 15th day of induction therapy, and extramedullary infiltration before HSCT were the poor prognosis factors. In addition, age ≥35 years predicted poor DFS. Only T-ALL and high LDH were the independent undesirable factors associated with OS and DFS in Cox regression model. For 44 patients who had results of pretransplantation minimal residual disease (MRD), positive MRD (MRD ≥0.01%) indicated poor OS (P = 0.044) and DFS (P = 0.008). Furthermore, for the standard risk group, the patients with negative MRD (MRD <0.01%) had better results (OS at 18 months was 90.0 ± 9.5%, while for the patients with positive MRD OS was 50.0 ± 35.4%, P = 0.003; DFS at 18 months was 90.0 ± 9.5%, while for the positive MRD group DFS was 0%, P < 0.001).Conclusions:This study confirmed that auto-HSCT combined with posttransplantation maintenance chemotherapy could be an option for adult ALL patients and pretransplantation MRD may play a significant role in the direction of therapy for adult ALL patients.

Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy

“…Although this study was limited by a small sample size and lack of detailed MRD data, OS and DFS were similar in the allo-HCT and auto-HCT cohorts, suggesting that auto-HCT may be a safe and effective alternative for patients with MRD-negative Ph+ ALL and without a matched sibling donor [32]. Regardless of Ph status, MRD-positivity before auto-HCT is associated with high rates of relapse and worse DFS and OS [33]. These recommendations should be considered speculative without confirmation in a well-characterized MRD-negative population.…”

Comparison of autologous and allogeneic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

“…Patients newly diagnosed in our center were given a standard induction regimen VDCP (vincristine [10] and one kind of TKIs (imatinib 400-600 mg•d −1 or dasatinib 100-120 mg•d −1 or nilotinib 600-800 mg•d −1 ) was administered once the Philadelphia chromosome or the fusion gene of BCR/ABL was demonstrated. The third-generation TKIs would be given to patients who harbored BCR-ABL T315I mutation.…”

Optimizing Autologous Hematopoietic Stem Cell Transplantation for Acute Leukemia

“…This study showed that pretransplant chemotherapy intensification is not associated with significantly better outcome compared with standard-dose chemotherapy in elderly patients. 34 26,29 After one or two consolidation courses, stem cell mobilization can be conducted. A total of three to four cycles of consolidation chemotherapy should be applied before ASCT.…”