1. Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency
by Maria Pia Cicalese, Francesca Ferrua, Laura Castagnaro, Roberta Pajno, Federica Barzaghi, Stefania Giannelli, Francesca Dionisio, Immacolata Brigida, Marco Bonopane, Miriam Casiraghi, Antonella Tabucchi, Filippo Carlucci, Eyal Grunebaum, Mehdi Adeli, Robbert G. Bredius, Jennifer M. Puck, Polina Stepensky, Ilhan Tezcan, Katie Rolfe, Erika De Boever, Rickey R. Reinhardt, Jonathan Appleby, Fabio Ciceri, Maria Grazia Roncarolo, and Alessandro Aiuti
Blood
Volume 128(1):45-54
July 7, 2016
©2016 by American Society of Hematology

2. GT resulted in 100% survival, with few patients requiring intervention.
GT resulted in 100% survival, with few patients requiring intervention. No deaths have occurred in this patient population. Intervention-free survival was defined as survival without post-GT SCT or PEG-ADA use for a continuous period of ≥3 months. Three patients resumed PEG-ADA therapy following GT; 2 of those patients later received a matched-sibling SCT (previously unavailable before GT). Intervention-free survival represents a sensitivity analysis of the overall survival rate.
Maria Pia Cicalese et al. Blood 2016;128:45-54
©2016 by American Society of Hematology

3. Transduced cells persist long-term and proliferate.
Transduced cells persist long-term and proliferate. All values shown are medians; black dotted lines represent minimum and maximum values. The number of patients contributing to each data point is indicated on the graph. Day 0 indicates baseline (pre-GT) values. (A) CD34+ cells were purified from bone marrow aspirate. (B-K) CD15+ cells (B), CD3+ cells (C-D), CD19+ cells (E-F), CD16+CD56+ cells (G-H), CD3+CD4+ cells (I), CD3+CD8+ cells (J), and CD4+CD45RA+ cells (K) were purified from peripheral venous blood. (A-C,E,G) Genotype was determined by qRT-PCR. (D,F,H-K) Absolute cell counts are also shown; 10 was set as the minimum value for graphs using a logarithmic scale. The shaded blue and purple regions represent median and fifth percentile values, respectively, in normal children. The top edges correspond to levels in children ages 2 to 5 years; bottom edges correspond to levels in children ages 10 to 16 years. Values for children ages 5 to 10 typically fall within the shaded areas.26 The green and orange shaded areas represent median and 10th percentile values, respectively, in normal children. Top edges correspond to levels in children ages 2 to 6 years; bottom edges correspond to levels in children ages 12 to 18 years. Values for children ages 6 to 12 years fall within the shaded areas.27
Maria Pia Cicalese et al. Blood 2016;128:45-54
©2016 by American Society of Hematology

4. GT supports ADA activity and lymphocyte function.
GT supports ADA activity and lymphocyte function. All values shown are medians; black dotted lines represent minimum and maximum values. The number of patients contributing to each data point is indicated on the graph. (A) Lymphocyte ADA levels were measured in peripheral venous blood. ADA activity of ≥210 nmol/h per mg (blue line) represents 10% of normal and was considered as a threshold for adequate activity in subjects with ADA-SCID following treatment.21 (B) RBC dAXP levels were measured in peripheral venous blood. The blue line denotes dAXP levels found in successfully allogeneic transplanted patients (≤100 nmol/mL).10,17 (C-D) Proliferative capacity was assessed following challenge with (C) anti-CD3 antibody and (D) phytohemagglutinin (PHA). Blue lines indicate normal response in healthy children.28 (E) TREC abundance in whole blood was determined by qRT-PCR.
Maria Pia Cicalese et al. Blood 2016;128:45-54
©2016 by American Society of Hematology

5. The rate of severe infections declined after GT
The rate of severe infections declined after GT. Severe infections were defined as infections leading to, or prolonging, hospitalization.
The rate of severe infections declined after GT. Severe infections were defined as infections leading to, or prolonging, hospitalization. The number of patients contributing to each data point and the number of severe infections reported are indicated on the graph. Severe infections in the 3 months immediately following GT were not included in the analysis. Severe infections after the reintroduction of long-term PEG-ADA treatment (patients 2, 8, and 17) were excluded from the analysis.
Maria Pia Cicalese et al. Blood 2016;128:45-54
©2016 by American Society of Hematology