Characteristics of the WAS-GT patients involved in this research study
Pt1, WAS Pt1-9, MPB CD34+cells, ’
PEDIATRIC HD, BLOOD, ADVERSE EVENT, PEDIATRIC HD
Our research complies with all relevant ethical regulations and it was approved by the San Raffaele Scientific Institute’s Ethics Committee at IRCCS Ospedale San Raffaele. Pediatric HD samples were analyzed after parents signed informed consent approved by the San Raffaele Scientific Institute’s Ethics Committee (TIGET09) according to CARE guidelines and in compliance with the Declaration of Helsinki principles. The sample size was determined by the number of individuals for whom exceeding BM and PB material was available in occasion of procedures performed for clinical reasons. The cohorts of pediatric HD were composed of: 7 individuals for BM evaluation (median age: 10.5 y) and 13 subjects with 1–6 years of age (median age: 4 y) and 23 subjects with 6–18 years of age (median age: 12) for PB counts. Given the rarity of BM samples from pediatric healthy individuals, sex or gender was not considered in the study design for the collection of our cohorts of PedHD for both BM samples and PB samples.Blood samples from WAS Pt1-9 were analyzed after parents signed informed consent approved by the San Raffaele Scientific Institute’s Ethics Committee (TIGET06) at IRCCS Ospedale San Raffaele according to CARE guidelines and in compliance with the Declaration of Helsinki principles. WAS patients 1 to 9 were enrolled in an open-label, non-randomized, phase 1/2 clinical studyBlood samples from WAS Pt10-14 were analyzed after parents signed informed consent approved by the San Raffaele Scientific Institute’s Ethics Committee (TIGET06) at IRCCS Ospedale San Raffaele according to CARE guidelines and in compliance with the Declaration of Helsinki principles. Patients 10 to 14 were treated under early access program (compassionate use program or hospital exemption). Detailed patients’ characteristics are reported in Table In order to analyze the groups of BM-GT vs. MPB-GT patients with the same range of age, we included in this study all the pediatric GT patients treated since 2010 up to 2018, with the exception of one patient who shows an undetectable CD90 marker expression, likely due to modification in the protein conformation (currently under investigation). In particular, the ranges of age at treatment were from 1.9 and 5.9 years (median age:1.9) for the BM-GT group and from 1.4 to 14.4 years (median age: 10.3) for MPB-GT patients. The data cutoff was chosen to evaluate all the available patients up to 2 year-follow up. The choice of the source was based on the evaluation of different clinical factors including age and weight of the patient, estimated yield of CD34+ cells (according to the content of bone marrow CD34+ cells evaluated by previous bone marrow aspiration, performed at screening) and feasibility of the procedure. Moreover, a mixture of MPB and BM CD34+cells was foreseen if required to obtain a sufficient cells dose. In particular, Pt1 required administration of cell drug product from both cell sources for reaching optimal cell dose. For Pt#2-7 (BM-GT) and for Pt#8-9 (MPB-GT) the source was chosen due to the age of the patients. Indeed, BM harvest was the preferred choice for younger pediatric subjects at the time of the procedure. With the introduction of the Plerixafor in the mobilization protocol, the improvement of the clinical management of the leukapheresis procedure as well as the CD34+cell yield obtained in patients Pt#8-9, the remaining patients treated in the expanded access program (Pt#10-14) were treated with MPB CD34+cells. All the described patients are alive, clinically well and no adverse event related to the product has been observed to date. All available healthy donors’ and patients’ samples are reported in the manuscript. For clinical data, source data include all the documents related to the patient during the trial or patient’s treatment under expanded access (infused CD34+ cell dose, VCN and percentage of transduction of the infused cell dose, blood cell counts, requirement for platelet transfusion, VCN in PB and BM subpopulation, VCN and percentage of transduction on BM CFC); these data were collected at IRCCS Ospedale San Raffaele (Milan, Italy) and entered in the respective case report form and monitored according to the clinical trial/expanded access protocol and local guidelines. All the other exploratory research data (flow cytometry and integration site analyses) were collected at San Raffaele Telethon Institute for Gene Therapy and they were analyzed and stored in a dedicated database. 6 out of 14 patients (Pt1 to Pt7) included in this research study were already present in our previous published work