Fludarabine, busulfan, and low-dose TBI conditioning versus cyclophosphamide and TBI in allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia

Leuk Lymphoma. 2019 Mar;60(3):639-648. doi: 10.1080/10428194.2018.1493734. Epub 2018 Aug 30.

Abstract

The optimal conditioning regimen for adults undergoing transplantation for acute lymphoblastic leukemia (ALL) remains undetermined. Cyclophosphamide and total body irradiation (Cy/TBI) has emerged as a standard myeloablative regimen but is associated with significant toxicity. We compared outcomes between patients undergoing transplant for ALL at centers using Cy/TBI as standard of care and another center using fludarabine, busulfan, and low-dose TBI (400 cGy) in combination with anti-thymocyte globulin as its standard. Among 146 patients (74 Cy/TBI and 72 Flu/Bu/TBI) there were no significant differences in overall or progression-free survival between groups. Non-relapse mortality was similar (12% vs. 16.7% for Cy/TBI and Flu/Bu/TBI, respectively, p = .62) despite the Flu/Bu/TBI group having significantly worse performance status. Flu/Bu/TBI resulted in significantly lower cumulative incidence of relapse compared with Cy/TBI (2-year point estimate 18.5% vs. 31.5%, p = .05). These results demonstrate similar outcomes for patients receiving Flu/Bu/TBI versus Cy/TBI. Flu/Bu/TBI may allow the possibility of providing myeloablative conditioning to patients with poor performance status.

Keywords: Acute lymphoblastic leukemia; allogeneic transplantation; conditioning; instrumental variable analysis; myeloablative; total body irradiation.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / administration & dosage
  • Combined Modality Therapy
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • Recurrence
  • Survival Analysis
  • Transplantation Conditioning* / adverse effects
  • Transplantation Conditioning* / methods
  • Transplantation, Homologous
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Whole-Body Irradiation*
  • Young Adult

Substances

  • Vidarabine
  • Busulfan
  • fludarabine