Incidence and impact of community respiratory viral infections in post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis and haploidentical stem cell transplantation

Br J Haematol. 2021 Jul;194(1):145-157. doi: 10.1111/bjh.17563. Epub 2021 Jun 14.

Abstract

Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA-haploidentical HCT recipients who receive post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin-based GVHD prophylaxis (SibCNI, N = 1605) or PTCy (SibCy, N = 403), and related haploidentical transplants receiving PTCy (HaploCy, N = 757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment-related mortality [hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13-4⋅07; P = 0⋅002] and inferior 2-year overall survival (HR 1⋅65, 99% CI 1⋅11-2⋅43; P = 0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long-term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long-term outcomes in such patients.

Keywords: Allogeneic transplant; Post Transplant Cyclophosphamide; Respiratory viral infection.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Community-Acquired Infections / epidemiology
  • Community-Acquired Infections / etiology*
  • Cyclophosphamide / adverse effects*
  • Cyclophosphamide / therapeutic use
  • Female
  • Graft vs Host Disease / prevention & control*
  • HLA Antigens / immunology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Incidence
  • Kaplan-Meier Estimate
  • Leukemia / therapy
  • Living Donors
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / therapy
  • Proportional Hazards Models
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / etiology*
  • Retrospective Studies
  • Siblings
  • Transplantation, Haploidentical*
  • Virus Diseases / epidemiology
  • Virus Diseases / etiology*
  • Young Adult

Substances

  • HLA Antigens
  • Immunosuppressive Agents
  • Cyclophosphamide