Hematopoietic Cell Transplantation for Wiskott-Aldrich Syndrome - Impact of Age, Donor, and Infection: A Pidtc Report

Résumé fourni par la source

Intro/Objectives Hematopoietic cell transplantation (HCT) can cure patients with Wiskott-Aldrich Syndrome (WAS). The optimal HCT regimen and donor chimerism required for disease correction is not fully defined. In the largest WAS HCT cohort to date, we report host factors that impact overall (OS) and event free survival (EFS), and the association of HCT regimen with donor chimerism, platelet recovery, and autoimmunity. Methods Patients from 37 centers (n=308) were enrolled on PIDTC protocol 6904, a multicenter natural history study of patients with WAS who underwent HCT in North America from 1990-2018 Results The median age at HCT was 1.2 (0.2-21.7) years. Patients with class I WAS variants, predicted to have milder phenotype (n=47), had similar clinical severity WAS scores and OS as those with class II variants (n=212). Most patients received myeloablative busulfan (Bu)-based conditioning (n=215), predominantly Bu/Cy (n=199). Reduced intensity (RIC) recipients (n=71) received mostly Bu-based (n=47) or Flu/Mel ± thiotepa (n=20) regimens. With median follow-up of 5.3 years, the 5-year OS and EFS were 87% and 80%, respectively, with inferior outcomes in patients who underwent HCT prior to 1999. Age ≥5 years, donor type, history of severe pre-HCT infections (life-threatening and/or opportunistic infections), race/ethnicity, and WAS score 4 were associated with decreased OS and/or EFS on univariable analysis; however, only age ≥5 years, donor type, and severe infections pre-HCT remained significant on multivariable analysis ( Figure 1 ). Non-Bu RIC regimens had a higher risk of mixed T and myeloid donor chimerism compared to Bu regimens ( Figure 2 ). Low (<50%) donor myeloid chimerism was associated with lower platelet counts compared to patients who achieved >95% donor chimerism and there was no difference in platelet counts based on WAS class variants ( Figure 3 ). Pre-HCT autoimmunity (27%) was not associated with OS/EFS. The incidence of post-HCT autoimmunity (16%) was higher in recipients of matched unrelated or mismatched related grafts (p=0.01) compared to other donors. Early mixed chimerism did not correlate with a higher 3-year incidence of post-HCT autoimmunity. Conclusions Similar to our earlier report, HCT for WAS has excellent OS. We now report encouraging EFS and establish age ≥5 years, donor type, and pre-HCT severe infections as factors that reduce OS/EFS, supporting early HCT. Bu regimens achieved higher myeloid donor chimerism, critical for platelet reconstitution post-HCT. Patients with class I variants with low clinical score (historically XLT), have often not been referred for early HCT, due to risk of toxicity and failure to correct platelets. WAS variant class did not correlate with post-HCT survival and platelet recovery was uniformly excellent in all patients. This data supports reevaluating candidacy and timing of HCT for patients with mild clinical WAS phenotypes.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.