Thiotepa, Busulfan, and Fludarabine Conditioning Regimen in T Cell-Replete HLA-Haploidentical Hematopoietic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2019 Jul;25(7):1407-1415. doi: 10.1016/j.bbmt.2019.02.025. Epub 2019 Mar 11.

Abstract

We report the outcomes of 51 patients who underwent unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) and antithymocyte globulin (ATG), from peripheral blood stem cells (PBSCs) or bone marrow, after receipt of a TBF (thiotepa, busulfan, and fludarabine) conditioning regimen. Their median age was 55 years (range, 16 to 72 years). Hematologic diagnoses included acute leukemias (n = 31), lymphoid neoplasm (n = 12), myeloproliferative neoplasm (n = 5), and myelodysplastic syndromes (n = 3). Thirty-seven patients (73%) were in complete remission. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate for all patients, associated with ATG in 39 patients (76.5%). The median time to neutrophil engraftment was 17 days (range, 12 to 34 days). The cumulative incidences of grade II-IV and grade III-IV acute GVHD were 27.5% and 14%, respectively. In patients receiving a PBSC graft and ATG prophylaxis, grade II-IV aGVHD occurred in 16% of patients. The use of ATG and a lower thiotepa dose (5 mg/kg versus 10 mg/kg) were associated with a reduced cumulative incidence of grade II-IV acute GVHD (P = .03 and .005, respectively). The 2-year cumulative incidence of chronic GVHD was 29% and was significantly reduced to 13% with the lower thiotepa dose (P = .002). After a median follow-up of 25 months (range, 12 to 62 months), the cumulative incidences of nonrelapse mortality, relapse, overall survival (OS), disease-free survival (DFS), and GVHD-free, relapse-free survival (GFRFS) were 20%, 22.5%, 67%, 58%, and 51%, respectively. Pretransplantation disease status (complete remission versus others) was the main factor associated with OS, DFS, and GFRFS. In conclusion, the TBF conditioning regimen is an appealing platform in the haplo-HSCT setting with PT-Cy in terms of engraftment rate, toxicity, and disease control. We found no benefit of a thiotepa dose of 10 mg/kg compared with a dose of 5 mg/kg. ATG reduced the risk of acute GVHD without comprising outcomes.

Keywords: Antithymocyte globulin; Conditioning; Graft-versus-host disease; Haploidentical transplantation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Busulfan / administration & dosage*
  • Cyclosporine / administration & dosage
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease* / metabolism
  • Graft vs Host Disease* / mortality
  • Graft vs Host Disease* / pathology
  • Graft vs Host Disease* / prevention & control
  • HLA Antigens
  • Hematologic Neoplasms* / metabolism
  • Hematologic Neoplasms* / mortality
  • Hematologic Neoplasms* / pathology
  • Hematologic Neoplasms* / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Retrospective Studies
  • Survival Rate
  • T-Lymphocytes* / metabolism
  • T-Lymphocytes* / pathology
  • Thiotepa / administration & dosage*
  • Transplantation Conditioning*
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*

Substances

  • HLA Antigens
  • Cyclosporine
  • Thiotepa
  • Vidarabine
  • Busulfan
  • Mycophenolic Acid
  • fludarabine