Timing of achieving MRD negativity for B-ALL patients with IKZF1 alterations in CR1 may dictate transplant decision: Autologous versus Allogeneic HSCT

Acute lymphoblastic leukemia (ALL), especially B-cell acute lymphoblastic leukemia (B-ALL), poses a significant threat to the health of both children and adults. In the adult population, B-ALL accounts for ~75% of all ALL cases [1]. Alterations in the Ikaros family zinc finger 1 (IKZF1) gene are frequently detected in B-ALL patients and are strongly associated with poor prognosis, including a higher risk of relapse and resistance to conventional chemotherapy [2]. In the treatment of B-ALL, autologous HSCT (auto-HSCT) offers benefits such as lower transplant-related mortality and absence of graft-versus-host disease (GVHD), potentially enhancing quality of life, which has comparable outcomes with allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients in the first complete remission (CR1) who achieve negative minimal residue disease (MRD) after three cycles of chemotherapy [3, 4]. However, the optimal choice based on MRD status between auto-HSCT and allo-HSCT for B-ALL patients with IKZF1 mutations remains unclear. Our study aims to address this issue.

In this correspondence, we retrospectively analyzed 44 B—ALL patients with IKZF1 alterations in CR1 who underwent HSCT between Feb 2018 and July 2023 in the Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences. Among them, 12 received auto-HSCT and 32 received allo-HSCT. The baseline characteristics of the patients are presented in Table S1. The median follow-up period was 22 months. The assessment of MRD was based on molecular biology, immunological and cytogenetic testing. MRD was evaluated using multiparameter flow cytometry (MFC) following the standardized protocols of EuroFlow [5] or reverse-transcription polymerase chain reaction (RT-PCR) after each chemotherapy session. MRD negativity was defined as less than 0.01% leukemic blasts by MFC or BCR-ABL levels in the bone marrow specimens less than the detection limit of RT-PCR. Patients with positive MRD after three treatments were recommended for allo-HSCT. For patients with negative MRD, auto-HSCT was provided as an alternative. This study was approved by our center’s Medical Ethics Committee and all patients signed informed consent. Maintenance therapy referred to our previous research [3]. Statistical analyses were done using the R software version 4.3.0. The COX regression model was applied for both univariate and multivariate analyses. Categorical data were compared by the x² test or Fisher’s exact, whereas continuous variables were compared using the T-test or Kruskal-Wallis test. Kaplan-Meier methods were used to estimate probability of leukemia-free survival (LFS) and overall survival (OS). The cumulative incidence of relapse was calculated using competing risk analysis, taking into account the competing risks for death.