Infusion of leukocytes from HLA haplo-identical familial donors as an adjuvant in the HLH-2004 protocol to treat the virus-associated adult hemophagocytic lymphohistiocytosis: a retrospective study of 26 patients

Ann Hematol. 2018 Feb;97(2):319-326. doi: 10.1007/s00277-017-3174-8. Epub 2017 Nov 12.

Abstract

Adult hemophagocytic lymphohistiocytosis (HLH) is a fatal disease with poor survival and a limited role of drug therapies. To help to recognize virus and enhance survival, we infused leukocytes derived from human leukocyte antigen (HLA) haplo-identical familial donors to patients. We retrospectively investigated 26 adult virus-associated hemophagocytic syndrome (VAHS) patients' medical records from 2006-2017. Eleven of the 26 patients accepted relatives' derived leukocytes infusions in addition to drug therapies recommended in the HLH-2004 protocol. The leukocyte doses ranged from 0.75 to 3.30×108 per kilogram of body weight. The other 15 patients accepted immunosuppressive and supportive therapies referred to in the HLH-2004 protocol. We compared the treatment outcomes of the two groups of patients. Patients in the cell infusion group had a lower viral load (P = 0.023) and better laboratory results and prolonged overall survival (60.44 vs. 20.18 weeks, P = 0.047). A factor that might relate to overall survival is platelet count (P = 0.032), except for the leukocyte infusions (P = 0.012). For patients without acceptable donors, infusions of leukocytes from HLA haplo-identical familial donors could be a feasible treatment to prolong overall survival as an adjuvant to drug therapies.

Keywords: Conventional therapy; Hemophagocytic lymphohistiocytosis; Leukocytes infusion; Overall survival.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adolescent
  • Adult
  • Antiviral Agents / therapeutic use*
  • Cyclosporine / therapeutic use
  • Dexamethasone / therapeutic use
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / mortality
  • Epstein-Barr Virus Infections / therapy*
  • Epstein-Barr Virus Infections / virology
  • Family
  • Female
  • Ganciclovir / therapeutic use
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Haplotypes
  • Herpesvirus 4, Human / drug effects
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 4, Human / pathogenicity
  • Histocompatibility Testing
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / therapeutic use*
  • Leukocyte Transfusion*
  • Leukocytes / cytology
  • Leukocytes / immunology
  • Lymphohistiocytosis, Hemophagocytic / immunology
  • Lymphohistiocytosis, Hemophagocytic / mortality
  • Lymphohistiocytosis, Hemophagocytic / therapy*
  • Lymphohistiocytosis, Hemophagocytic / virology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Analysis
  • Tissue Donors
  • Treatment Outcome
  • Viral Load / drug effects

Substances

  • Adjuvants, Immunologic
  • Antiviral Agents
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • entecavir
  • Guanine
  • Dexamethasone
  • Cyclosporine
  • Ganciclovir