Pretransplant active disease status and HLA class II mismatching are associated with increased incidence and severity of cytokine release syndrome after haploidentical transplantation with posttransplant cyclophosphamide

Cancer Med. 2020 Jan;9(1):52-61. doi: 10.1002/cam4.2607. Epub 2019 Nov 8.

Abstract

Cytokine release syndrome (CRS) represents a life-threatening side effect after haploidentical stem cell transplantation (Haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). Factors predictive of CRS development is still a matter of debate. We retrospectively analyzed 102 consecutive patients receiving a bone marrow (BM) (n = 42) or peripheral blood stem cells (PBSC) (n = 60) Haplo-SCT with PT-Cy. The two cohorts were similar in main patients' characteristics besides disease type (P = .02). Cumulative incidence of grades 1, 2, and ≥3 CRS was 80%, 52%, and 15% at a median of 2, 4, and 7 days, respectively. Moderate/High-grade fever (39°-41°), grade 1 and grade ≥3 CRS occurred more frequently after PBSC relative to BM grafts (68% vs 33%, P = .0005; 87% vs 71%, P = .009; 20% vs 7%, P = .07). Only patients experiencing grade ≥3 CRS had a worse outcome in terms of 1-year overall survival (OS) and nonrelapse mortality (NRM): 39% vs 80% (P = .002) and 40% vs 8% (P = .005), respectively. By univariate analysis the only factors associated with the increased risk of ≥3 CRS were pretransplant disease status (8% for complete remission, 11% for partial remission, and 38% for active disease, P = .002), HLA-DRB1 mismatching (57% vs 14%, P = .007), and PBSC graft (P = .07). By multivariable analysis, only pretransplant disease status (hazard ratio, HR: 6.84, P = .005) and HLA-DRB1 mismatching (HR: 17.19, P = .003) remained independent predictors of grade ≥3 CRS. Only grade ≥3 CRS is clinically relevant for the final outcome of patients receiving Haplo-SCT with PT-Cy, is more frequent after a PBSC graft and is associated with pretransplant active disease and HLA-DRB1 mismatching.

Keywords: HLA mismatch; cytokine release syndrome; disease burden; haploidentical stem cell transplant with posttransplant cyclophosphamide.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow Transplantation / adverse effects*
  • Bone Marrow Transplantation / methods
  • Cyclophosphamide / administration & dosage
  • Cytokine Release Syndrome / diagnosis
  • Cytokine Release Syndrome / epidemiology*
  • Cytokine Release Syndrome / immunology
  • Female
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • HLA-DRB1 Chains / analysis
  • HLA-DRB1 Chains / immunology*
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy*
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation / adverse effects*
  • Peripheral Blood Stem Cell Transplantation / methods
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Transplantation Conditioning / methods
  • Transplantation, Haploidentical / adverse effects
  • Transplantation, Haploidentical / methods
  • Young Adult

Substances

  • HLA-DRB1 Chains
  • Immunosuppressive Agents
  • Cyclophosphamide