Unmanipulated haploidentical hematopoietic stem cell transplantation using very low-dose antithymocyte globulin and methylprednisolone in adults with relapsed/refractory acute leukemia

Ann Hematol. 2020 Jan;99(1):147-155. doi: 10.1007/s00277-019-03865-x. Epub 2019 Nov 30.

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) could be the only curative therapy for patients with relapsed/refractory acute leukemia (RRAL). Many reports have described unmanipulated haploidentical HSCT (HID-HSCT) using high-dose antithymocyte globulin (ATG). However, the transplant outcomes of HID-HSCT using very low-dose ATG (thymoglobulin, 2-2.5 mg/kg) and methylprednisolone (mPSL, 1 mg/kg) for patients with RRAL have not been reported. We compared the outcomes of 46 patients with RRAL who underwent HID-HSCT using very low-dose ATG (thymoglobulin) and mPSL with the outcomes of 72 patients who underwent non-HID-HSCT. Patient characteristics differed regarding conditioning intensity (myeloablative; 19.6% in HID-HSCT vs. 61.1% in non-HID-HSCT, P < 0.001) and having undergone multiple HSCT (26.1% vs. 11.1%, P = 0.045). However, we found no significant differences in the 1-year overall survival (OS, 31.7% vs. 29.1%; P = 0.25), disease-free survival (DFS, 20.5% vs. 23.7%; P = 0.23), cumulative incidence of relapse (CIR, 40.0% vs. 42.8%; P = 0.92), non-relapse mortality (NRM, 39.5% vs. 33.5%; P = 0.22), or 100-day grade II-IV acute graft-versus-host disease (32.6% vs. 34.7%; P = 0.64) following HID-HSCT vs. non-HID-HSCT, respectively. Subgroup analysis stratified by disease and intensity of conditioning regimen demonstrated the same results between HID-HSCT and non-HID-HSCT. Furthermore, multivariate analysis showed that HID-HSCT was not an independent prognostic factor for OS (hazard ratio (HR) = 0.95 [95% confidence interval (CI), 0.58-1.58]), DFS (HR = 1.05 [95%CI, 0.67-1.68]), CIR (HR = 0.84 [95%CI, 0.48-1.47]), or NRM (HR = 1.28 [95%CI, 0.66-2.46]). In summary, transplant outcomes for RRAL were comparable in the HID-HSCT and non-HID-HSCT groups. HID-HSCT using very low-dose ATG and mPSL for RRAL may be a viable alternative to non-HID-HSCT.

Keywords: Haploidentical hematopoietic stem cell transplantation; Relapsed/refractory acute leukemia; Very low-dose antithymocyte globulin.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Antilymphocyte Serum / administration & dosage*
  • Cyclophosphamide / administration & dosage
  • Female
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / prevention & control
  • Graft vs Leukemia Effect*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute / blood
  • Leukemia, Myeloid, Acute / therapy*
  • Lymphocyte Depletion*
  • Male
  • Methylprednisolone / administration & dosage*
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Recurrence

Substances

  • Antilymphocyte Serum
  • Cyclophosphamide
  • Methylprednisolone