In this How I Treat podcast episode, Laura Michaelis, MD interviews Sung-Yun Pai, MD about their recently published article in Blood journal "How I treat Wiskott-Alrich syndrome". They highlight recent updates in treatment, including new risk-benefit calculations due to safer treatments and longer follow-ups. Challenges include late diagnosis, lack of well-matched donors, and limited gene therapy availability. They emphasize the importance of early referral to specialized centers and the need for discussions about curative intent therapies, including transplant and gene therapy. The conversation also covers the complexities of gene therapy, such as the need for better conditioning agents and the challenges of achieving full correction in all cell types.

In this week's episode we'll learn about targeting the tissue factor pathway inhibitor with a monoclonal antibody to rebalance HEMOSTASIS in hemophilia A and B. In the phase 3 BASIS trial, the monoclonal antibody marstacimab reduced bleeding events, and was generally well tolerated, with no unanticipated side effects. After that: matched-donor allogeneic CD19 CAR-T for adult B-ALL. Given after allogeneic transplantation, CAR-donor lymphocyte infusion after lymphodepleting chemotherapy was associated with favorable efficacy and a tolerable safety profile. Finally: a new prognostic index for mycosis fungoides and Sézary syndrome. Comprised of four prognostic factors, the “CLIPI” could enable more personalized treatment of cutaneous lymphomas, identifying patients who may benefit from intensified treatment.

Featured Articles

• Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial
• Matched donor allogeneic CAR-T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletion
• A new prognostic index (CLIPI) for advanced cutaneous lymphoma enables precise patient risk stratification

In this week's episode, we’ll learn more about relationships between Epstein-Barr virus genomic variants and human diseases, including hematological malignancies; the presence and timing of somatic GATA1 mutations and their relationship to a Down syndrome-specific form of leukemia; and new definitions for high-risk multiple myeloma that emphasize the presence of two or more high-risk cytogenetic abnormalities.

Featured Articles:

• Association of Epstein-Barr virus genomic alterations with human pathologies
• Clinical significance of preleukemic somatic GATA1 mutations in children with Down syndrome
• Biallelic antigen escape is a mechanism of resistance to anti-CD38 antibodies in multiple myeloma