Impact of type of reduced-intensity conditioning regimen on the outcomes of allogeneic haematopoietic cell transplantation in classical Hodgkin lymphoma

Br J Haematol. 2020 Aug;190(4):573-582. doi: 10.1111/bjh.16664. Epub 2020 Apr 21.

Abstract

Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0·01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0·54), relapse/progression (P = 0·02) or progression-free survival (PFS) (P = 0·14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0·28; 95% CI = 0·10-0·73; P = 0·009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2·46; 95% CI = 0·1.32-4·61; P = 0·005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0·64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).

Keywords: allogeneic hematopoietic cell transplant; classical Hodgkin lymphoma; reduced-intensity conditioning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Cause of Death
  • Comorbidity
  • Cyclophosphamide
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Middle Aged
  • Myeloablative Agonists / administration & dosage*
  • Myeloablative Agonists / adverse effects
  • Progression-Free Survival
  • Recurrence
  • Siblings
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Unrelated Donors
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Young Adult

Substances

  • Myeloablative Agonists
  • Cyclophosphamide
  • Vidarabine
  • Busulfan
  • Melphalan