Hematopoietic Stem Cell Transplantation for Progressive Combined Immunodeficiency and Lymphoproliferation in Patients With Activated Phosphatidylinositol–3–OH Kinase δ Syndrome Type 1

Abstract

To examine clinical features, laboratory findings, treatment, and outcomes of patients with activated phosphatidylinositol-OH-3 kinase δ syndrome type 1 (APDS1) and evaluate hematopoietic stem cell transplant (HSCT) as a potential treatment option.This study included 23 patients with confirmed PIK3CD mutations. Nine of these patients underwent HSCT.This was a retrospective study to characterize clinical characteristics, laboratory findings, treatment, and outcomes of patients with APDS1. Patients were identified by patient registry, physician referral, or having been previously reported in literature. Data were obtained by review of medical records and physician questionnaires.Common clinical features of patients with APDS1 included recurrent infections, lymphoproliferation, and enteropathy, with a median age at symptoms onset of 11 years old. The majority (65%) of patients received immunoglobulin replacement, and some additionally had prophylactic antimicrobial agents. Eleven transplantations were performed for recurrent infections or treatment refractory disease among 9 total patients. Fludarabine-based reduced-intensity conditioning regimens were used in all transplants (90–180 mg/m2), and 55% used human leukocyte antigen–mismatched donors. All but 1 patient ultimately achieved engraftment, but 36.4% had initial graft failure and required retransplantation, boosts of peripheral blood stem cells, or growth hormone administration for delayed T lymphocyte recovery. More than 90% of transplanted patients had an adverse complication, most commonly mild graft-versus-host disease. Despite this, most symptoms were improved post-HSCT, and no patients required ongoing immunoglobulin replacement by day 100 post-HSCT. The 30-year overall survival was 86.1%, and event-free survival was 39.6%.HSCT should be considered in patients with APDS1 and recurrent infections and/or treatment refractory lymphoproliferation. Clinical symptoms improved posttransplantation, although adverse complications and graft failure were frequent.Patients with APDS1 are at increased risk for recurrent infections, bronchiectasis, lymphoproliferation, chronic viral infections, and lymphoma. This article highlights the role that HSCT may play in the future management of patients with APDS1. Although not without its own risks, early HSCT can improve clinical symptoms and reduce the lifetime risk for potentially fatal complications in this disease. Investigators in this study closely examine HSCT regimens for APDS1 patients among various international medical centers, which serves as the first critical step toward improving event-free and overall survival for these patients.