Optimizing Posttransplant Cyclophosphamide to Improve Immune Reconstitution

Johannes Schetelig, MD, MSc, of director of medical research at DKMS; as well as a professor at Technical University Dresden, discusses potential strategies to overcome the elevated infection risks associated with allogeneic transplant with posttransplant cyclophosphamide (PTCy) at the European Hematology Association Annual Congress. Although PTCy is highly effective at suppressing graft-vs-host disease (GVHD), its associated delays in immune recovery present an ongoing clinical challenge. Schetelig suggests that immune reconstitution could be optimized by reducing the cumulative dose of cyclophosphamide or exploring pharmacological interventions. This is a field with ongoing research, with multiple contributing factors under investigation, ranging from the patient’s microbiome to specific prophylactic regimens.

A key challenge with PTCy is its distinct vulnerability profile regarding infections. Schetelig highlights data from a large retrospective study demonstrating that patients receiving PTCy are significantly more susceptible to community-acquired respiratory viral infections compared with patients who receive alternative types of GVHD prophylaxis. To counteract this vulnerability, providers should aggressively advocate for patient compliance with vaccinations and maintain a heightened clinical awareness of these long-term risks.

Crucially, findings from the large randomized controlled trial that Schetelig presented indicate that this excessive infection risk is not just an early posttransplant concern; the danger remains significantly elevated well beyond the 1-year landmark. Because patients continue to face threats 6, 12, or even 18 months after transplantation, prolonged protective measures are vital. Schetelig notes that while escalating standard anti-infective prophylaxis such as administering more antivirals, antifungals, and antibiotics may benefit certain high-risk individuals, it is not the overall solution. Instead, the medical community must focus on advanced strategies designed to accelerate true immune system recovery and implement better environmental protection policies to safely minimize pathogen exposure during the extended posttransplant recovery window.