Allogeneic transplantation for Ph1 acute lymphoblastic leukemia with posttransplantation cyclophosphamide

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Abstract

Allogeneic blood or marrow transplantation (alloBMT) is standard of care for adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph1 ALL) in first complete remission (CR1). The routine pretransplant and posttransplant use of tyrosine kinase inhibitors (TKIs) has dramatically improved outcomes, but the optimal conditioning regimen, donor type, and TKI remain undefined. The bone marrow transplant database at Johns Hopkins was queried for adult patients with de novo Ph1 ALL who received alloBMT using posttransplantation cyclophosphamide (PTCy) as a component of graft-versus-host disease (GVHD) prophylaxis from 2008 to 2018. Among transplants for Ph1 ALL, 69 (85%) were performed in CR1, and 12 (15%) were performed in second or greater remission (CR21). The majority of transplants (58%) were HLA haploidentical. Nearly all patients (91.4%) initiated TKI posttransplant. For patients in CR1, the 5-year relapse-free survival (RFS) was 66%. The use of nonmyeloablative conditioning, absence of measurable residual disease (MRD) according to flow cytometry at transplant, and the use of dasatinib vs imatinib at diagnosis were associated with improved overall survival (OS) and RFS. Neither donor type nor recipient age $60 years affected RFS. When analyzing all transplants, alloBMT in CR1 (vs CR21) and the absence of pretransplant MRD were associated with improved RFS. Most relapses were associated with the emergence of kinase domain mutations. The cumulative incidence of grade 3 to 4 acute GVHD at 1 year was 9%, and moderate to severe chronic GVHD at 2 years was 8%. Nonmyeloablative alloBMT with PTCy for Ph1 ALL in an MRD-negative CR1 after initial treatment with dasatinib yields favorable outcomes.

Original languageEnglish (US)
Pages (from-to)5078-5088
Number of pages11
JournalBlood Advances
Volume4
Issue number20
DOIs
StatePublished - Oct 20 2020

ASJC Scopus subject areas

  • Hematology

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