Infection Rates and Rapid Immune Cell Reconstitution Following Familial Haploidentical (FHI) CD34 Enriched Peripheral Blood (PB) Stem Cell Transplantation (HISCT) with PB Mononuclear Cell Addback in Patients with High-Risk Sickle Cell Disease (SCD)

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

2022

DOI

10.1002/pbc.29735

Journal Title

Pediatric Blood and Cancer

Department

Public Health

Second Department

Pediatrics

Abstract

Background:We previously reported the results of a phase II multicenter transplant trial using haploidentical parental donors for children and adolescents with high-risk Sickle Cell Disease (SCD) achieving excellent survival with exceptionally low rates of graft-versus-host disease (GVHD) and resolution of SCD symptoms. Objective: To investigate the rates of infections and immune reconstitution in 20 patients with high risk sickle cell disease who have undergone haploidentical transplantation. Methods: Comprehensive assessment of immune reconstitution included lymphocyte subsets, plasma cytokines, complement levels, and activation markers were obtained. Incidence of viral, bacterial and fungal infections were recorded. Results: Myeloid engraftment was robust (100%) at a median of 9 days. NK cell levels were rapidly restored by 30 days. By 60 days, CD19 B cells were normal. CD8 and CD4 T cells levels were normal by 279 and 365 days, respectively. Activated CD4 and CD8 T cells were elevated 100-365 days post-transplant while naïve cells renewal was below baseline. Tregs were elevated 100-270 days post-transplant, returning to baseline levels at one year. At one year, C3 and C4 levels were above baseline and CH50 levels were similar to baseline. The incidence of viral reactivation was CMV = 5, EBV = 5, HHV6 = 3, and Adenovirus = 2. Three fungal infections occurred (Candida = 2, Aspergillus fumigatus = 1). There were 10 bacterial infections-, Enterobacter cloacae = 4, Bacillus = 2, Staph coag neg = 2, Elizabethkingia menignoseptica = 1, and Strep slavarius = 1. The cumulative incidence of grades 2 to 4 acute GVHD and late acute GVHD was 6.2% and moderate and/or severe chronic GVHD was 6.7%. The probability of 1-year EFS or overall survival was 90% (95% CI, 64.1%-97.3%) and of 2-year EFS or overall survival was 84% (95% CI, 57.0%-94.4%), and no patient had residual SCD symptoms. Conclusion: These results suggest that haploidentical transplantation utilizing CD34 enrichment and PB MNC addback resulted in rapid and 100% engraftment with excellent OS and EFS. The fixed T cell addback was protective against significant viral infections but reactivations did occur. There were no primary deaths attributable to infection. The 50% incidence of bacterial infections is significant and should warrant future studies. Extended bacterial prophylaxis may be warranted for this population.

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