ABSTRACT
Clonal hematopoiesis (CH) describes somatic mutations in hematopoietic stem and progenitor cells resulting in clonal expansion in individuals with no overt hematologic disease. Since CH increases in an age-related manner, understanding its role in hematopoietic cell transplantation (HCT) has become increasingly relevant to an aging transplant population. Multiple factors distinguish post-transplant hematopoiesis from unperturbed, steady-state hematopoiesis, including the influence of immunosuppressants, cytotoxic reagents, and marked proliferative stress, all of which may enhance or diminish the opportunity for clonal expansion. We reviewed the available clinical evidence on the consequences of CH at time of transplant in patients undergoing autologous HCT, and the impact of donor and recipient CH on allogeneic HCT outcomes. In the absence of evidence-based guidelines, we share our suggestions for managing donors and recipients found to have CH. Large-scale studies are needed to guide an evidence-based, uniform approach for the management of CH in the setting of HCT.
Subject(s)
Clonal Hematopoiesis , Hematopoiesis , Hematopoietic Stem Cell Transplantation , Clinical Decision-Making , Disease Management , Disease Progression , Graft vs Host Disease/etiology , Hematologic Diseases/diagnosis , Hematologic Diseases/etiology , Hematologic Diseases/mortality , Hematologic Diseases/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Humans , Prognosis , Tissue Donors , Transplantation, Autologous , Transplantation, Homologous , Treatment OutcomeABSTRACT
Young children and allogeneic hematopoietic cell transplantation (HCT) recipients respond poorly to polysaccharide antigens, rendering them susceptible to severe infections because of encapsulated bacteria. This study evaluated the responses of 127 HCT patients, median age 23.0 years, vaccinated with PNCRM7 and Haemophilus influenzae (HIB) conjugate, 2 conjugate vaccines highly immunogenic in healthy children. Median time to vaccination was 1.1 years after HCT. Sixty-two percent of patients responded to PNCRM7 (45 of 51 children, 34 of 76 adults, P < .001). Overall response to HIB was 86%, including 77% of PNCRM7 nonresponders. Although PNCRM7 response was adversely affected by older age (P < .001), individuals > or =50 years old responded significantly better if vaccinated following acquisition of specific minimal milestones of immune competence, CD4 >200/microL, IgG >500 mg/dL, PHA within 60% lower limit of normal (11 of 19 versus 0 of 8, P < .006). A similar trend was observed in patients with limited chronic graft-versus-host disease (cGVHD). In all patients, higher levels of circulating CD4(+)CD45RA cells correlated with improved PNCRM7 response. These data demonstrate that PNCRM7 is immunogenic in allogeneic HCT patients, including older adults, but suggest that vaccination at fixed intervals after HCT, irrespective of immune competence, may limit its effectiveness. Prospective, multicenter trials assessing the best strategy to administer this vaccine and its impact on pneumococcal infections following transplantation are warranted.
