Reduced-intensity conditioning for hematopoietic cell transplant for HLH and primary immune deficiencies

Blood. 2018 Sep 27;132(13):1438-1451. doi: 10.1182/blood-2018-01-828277. Epub 2018 Jul 11.


Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning for disorders associated with excessive inflammation such as hemophagocytic lymphohistiocytosis (HLH) is associated with early mortality. A multicenter prospective phase 2 trial of reduced-intensity conditioning with melphalan, fludarabine, and intermediate-timing alemtuzumab was conducted for HLA matched or single HLA locus mismatched related or unrelated donor HCT in a largely pediatric cohort. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine with methylprednisolone. The primary end point was 1-year overall survival (OS). Thirty-four patients with HLH and 12 with other primary immune deficiencies were transplanted. With a median follow-up of 20 months, the 1-year OS for transplanted patients was 80.4% (90% confidence interval [CI], 68.6%-88.2%). Five additional deaths by 16 months yielded an 18-month OS probability of 66.7% (90% CI, 52.9%-77.3%). Two patients experienced primary graft failure, and 18 patients either experienced a secondary graft failure or required a second intervention (mostly donor lymphocyte infusion [DLI]). At 1 year, the proportion of patients alive with sustained engraftment without DLI or second HCT was 39.1% (95% CI, 25.2%-54.6%), and that of being alive and engrafted (with or without DLI) was 60.9% (95% CI, 45.4 %-74.9%). The day 100 incidence of grade II to IV acute GVHD was 17.4% (95% CI, 8.1%-29.7%), and 1-year incidence of chronic GVHD was 26.7% (95% CI, 14.6%-40.4%). Although the trial demonstrated low early mortality, the majority of surviving patients required DLI or second HCT. These results demonstrate a need for future approaches that maintain low early mortality with improved sustained engraftment. The trial was registered at Clinical (NCT 01998633).

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Alemtuzumab / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Lymphohistiocytosis, Hemophagocytic / therapy*
  • Male
  • Melphalan / therapeutic use
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Treatment Outcome
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Young Adult


  • Antineoplastic Agents
  • Alemtuzumab
  • Vidarabine
  • fludarabine
  • Melphalan