Abstract

Relapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Multiparameter flow cytometry and polymerase chain reaction assays were applied for MRD monitoring. Recombinant human IFN-α-2b injections were administered subcutaneously twice weekly in every 4 weeks cycle. Twenty-four (35.3%), 5 (7.4%), 6 (8.8%), and 13 (19.1%) patients achieved MRD negativity at 1, 2, 3, and > 3 months, respectively, after treatment. Seven patients showed grade ≥ 3 toxicities after IFN-α treatment. The 4-year cumulative incidence of total acute graft-versus-host disease (aGVHD), severe aGVHD, total chronic GVHD (cGVHD), and severe cGVHD after treatment was 14.7%, 2.9%, 40.0%, and 7.5%, respectively. The 4-year cumulative incidences of relapse and non-relapse mortality after treatment was 31.9% and 6.0%, respectively. The 4-year probabilities of disease-free survival and overall survival after IFN-α treatment were 62.1% and 71.1%, respectively. Thus, preemptive IFN-α treatment could protect against relapse and improve long-term survival for ALL patients who had MRD after allo-HSCT. The study was registered at https://clinicaltrials.gov as #NCT02185261 (09/07/2014).

Highlights

  • Relapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation

  • Multiparameter flow cytometry (MFC) identified cells with leukemia-associated immunophenotypes (LAIPs) and polymerase chain reaction (PCR) assays detected leukemia-associated genetic abnormalities, both could be applied for monitoring minimal residual disease (MRD) in leukemia patients

  • These results identify the undefined role of this intervention strategy in ALL patients following allo-HSCT

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Summary

Introduction

Relapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Chemotherapy plus donor leukocyte infusion (Chemo-DLI) was the most effective preemptive intervention for ­MRD6,7, it may lead to some severe complications (e.g., graft-versus-host disease [GVHD] and pancytopenia)[8]. It was out of choices for some patients because of related donor refusal or unavailability of the second donation from an unrelated donor. We further confirmed that preemptive IFN-α treatment can clear the MRD effectively in patients with acute leukemia and high-risk myelodysplastic syndrome after allo-HSCT4,20–22. The long-term efficacy of preemptive IFN-α treatment remains unknown in ALL patients following allo-HSCT

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