Measurable residual disease (MRD) at the time of allogeneic hematopoietic cell transplantation (allo-HCT) is an important prognostic factor during first and second complete remission in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), according to research published in Blood Advances.
MRD at the time of allo-HCT is a prognostic factor for treatment response in patients with first complete remission (CR1) of Ph+ ALL. The study authors sought to determine whether MRD is a strong prognostic factor during second complete remission (CR2).
The authors evaluated MRD as a prognostic factor in patients undergoing allo-HCT either during CR1 or CR2 by analyzing data in the Japan Society for Hematopoietic Cell Transplantation (JSHCT) registration database from 1625 patients aged 16 and older with Ph+ ALL.
Out of the 1523 patients undergoing transplantation in CR1, 1111 (73%) were MRD negative. Of the 102 patients undergoing transplantation in CR2, 61 (60%) were MRD negative.
At 4 years, overall survival was 70% for patients who were MRD negative at CR1 and 54% for patients MRD positive at CR1. Overall survival at CR2 was 47% for patients who were MRD negative and 31% for patients who were MRD positive. At 4 years, the adjusted leukemia-free survival was 64% for patients who were MRD negative at CR1 and 52% for patients who were MRD negative at CR2.
The authors did not observe a significant difference in the relapse rate in patients in CR1 who were MRD negative and those in CR2 who were MRD negative. Graft-vs-host disease is a common complication of allo-HCT, but high survival rates can be achieved in patients who are MRD negative during CR1.
The study was limited by its retrospective nature and the small number of patients undergoing transplantation during CR2.
New drugs, namely tyrosine kinase inhibitors, may affect the timing of transplantation, as these drugs provide more therapeutic options for ALL. The authors concluded that achieving MRD negative status before allo-HCT is desirable for patients with Ph+ ALL.
Nishiwaki S, Akahoshi Y, Mizuta S, et al. Measurable residual disease affects allogeneic hematopoietic cell transplantation in Ph+ ALL during both CR1 and CR2. Blood Adv. 2021;5(2):584-592. doi:10.1182/bloodadvances.2020003536