Reduced intensity conditioning regimens including alkylating chemotherapy do not alter survival outcomes after allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia compared to low-intensity non-myeloablative conditioning

J Cancer Res Clin Oncol. 2019 Nov;145(11):2823-2834. doi: 10.1007/s00432-019-03014-x. Epub 2019 Aug 29.

Abstract

Purpose: The optimal dose intensity for conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) for chronic lymphocytic leukemia (CLL) is unknown.

Methods: We retrospectively compared outcomes of patients who received a first alloHCST after non-myeloablative (NMA) and reduced intensity conditioning (RIC). Data of 432 patients with a median age of 55 years were included, of which 86 patients underwent NMA and 346 RIC.

Results: The median follow-up after alloHSCT was 4.3 years. Compared to the RIC group, more NMA patients had purine-analog-sensitive disease, were in complete remission and received matched related donor transplantation. After RIC, the probabilities for 5-year OS, EFS, CIR, and NRM were 46%, 38%, 28%, and 35% and after NMA the respective probabilities were 52%, 43%, 25%, and 32%. In multivariate analysis, remission status prior to conditioning but not RIC versus NMA conditioning had a significant impact on CIR, EFS, and OS.

Conclusion: Presumed higher anti-leukemic activity of RIC versus NMA conditioning did not translate into better outcomes after alloHSCT, but better remission status prior to conditioning did. Effective pathway inhibitor-based salvage therapies combined with NMA conditioning might thus represent the most attractive contemporary approach for alloHSCT for patients with CLL.

Keywords: Allogeneic hematopoietic stem cell transplantation; Nonmyeloablative/reduced intensity conditioning; Relapsed/refractory chronic lymphocytic leukemia.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / administration & dosage
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / mortality*
  • Hematopoietic Stem Cell Transplantation / mortality*
  • Humans
  • Incidence
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Prognosis
  • Remission Induction
  • Retrospective Studies
  • Survival Rate
  • Transplantation Conditioning / mortality*
  • Transplantation, Homologous
  • Young Adult

Substances

  • Cyclophosphamide
  • Busulfan
  • Melphalan