Do specific mutations associated with clonal hematopoiesis in peripheral blood stem cells (PBSC) increase the risk of therapy-related myeloid neoplasia in patients with Hodgkin's lymphoma after transplantation? Yan et al. investigated this question in the study presented.

Therapy-related myeloid neoplasia (t-MN) can be a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for the treatment of Hodgkin's lymphoma (HL). Previous studies have reported an association between clonal hematopoiesis (CH) in the infused PBSC product and the subsequent risk of t-MN after aPBSCT in patients with other diseases. The study by Yan et al. aimed to investigate possible associations between CH and t-MN in HL patients treated with aPBSCT.

To decipher these relationships, the research team retrospectively sequenced the DNA of PBSC products from a total of 321 patients with Hodgkin's lymphoma between the ages of 18 and 71 (median age 34 years).

Their analyses revealed clonal hematopoiesis in 46 patients (14.3%) and identified the most common mutations (DNMT3A (n = 25), PPM1D (n = 7), TET2 (n = 7), and TP53 (n = 5)). CH in the PBSC product was found to be an independent predictor of t-MN.

This information suggests that depending on the gene in which the mutation occurs, the risk of patients developing t-MN - and consequently dying from it - increases. In particular, the TP53 mutation led to t-MN in all patients studied. TP53 and PPM1D mutations were associated with a 7.3-fold increased risk of t-MN and a 4.2-fold increased risk of treatment-related mortality. In contrast, DNMT3A mutations did not lead to t-MN in this study.

These results provide important insights into the long-term effects of aPBSCT. They may help to optimize future treatment protocols for patients. Yan et al. emphasize the need for further research to validate and extend the results, especially with regard to identifying factors that may influence prognosis after transplantation.

Yan C et al. Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms After Autologous Transplant for Hodgkin Lymphoma. J Clin Oncol. 2024 Apr 18:JCO2302547.