Faculty Collaboration Database

Reduced-intensity conditioning for hematopoietic cell transplant for HLH and primary immune deficiencies. Blood 2018 Sep 27;132(13):1438-1451

Date

07/13/2018

Pubmed ID

29997222

Pubmed Central ID

PMC6161764

DOI

10.1182/blood-2018-01-828277

Scopus ID

2-s2.0-85053908983 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

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 Trials.gov (NCT 01998633).

Author List

Allen CE, Marsh R, Dawson P, Bollard CM, Shenoy S, Roehrs P, Hanna R, Burroughs L, Kean L, Talano JA, Schultz KR, Pai SY, Baker KS, Andolina JR, Stenger EO, Connelly J, Ramirez A, Bryant C, Eapen M, Pulsipher MA

Authors

Mary Eapen MBBS, DCh, MRCPI, MS Professor in the Medicine department at Medical College of Wisconsin
Julie-An M. Talano MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Alemtuzumab
Antineoplastic Agents
Child
Child, Preschool
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Infant
Lymphohistiocytosis, Hemophagocytic
Male
Melphalan
Survival Analysis
Transplantation Conditioning
Treatment Outcome
Vidarabine
Young Adult