Early Transplantation After Pretransplant Reduction of <i>TP53</i> ‐Altered Clones and Prolonged Dose‐Adjusted Azacitidine Maintenance: A Three‐Case Series

ABSTRACT TP53 ‐altered myeloid neoplasms are associated with an extremely high risk of relapse even after allogeneic hematopoietic cell transplantation (allo‐HCT), and the optimal pretransplant and posttransplant strategies remain undefined. We report the cases of three patients with TP53 ‐altered myeloid neoplasms who achieved durable complete remission after a sequential strategy consisting of limited pretransplant therapy, prompt allo‐HCT after reduction of the TP53 ‐positive clone, and early dose‐adjusted azacitidine (Aza) maintenance. At presentation, Cases 1 and 2 had TP53 abnormalities detectable by both fluorescence in situ hybridization (FISH) and sequencing, whereas Case 3 had a TP53 single‐nucleotide variant and an Intron 1 structural variant detectable only by molecular testing. Pretransplant treatment was intentionally limited to 2–3 cycles: three cycles of Aza in Case 1, intensive induction chemotherapy followed by one cycle of Aza in Case 2, and two cycles of venetoclax plus Aza in Case 3. In all cases, serial molecular monitoring demonstrated a reduction of TP53 ‐altered clones before transplantation, followed by complete disappearance after allo‐HCT. Aza maintenance was initiated approximately 1.5–2 months after transplantation at 30–35 mg/m 2 for 5 days and was subsequently escalated according to tolerability. Maintenance was continued for 53, 37, and 27 cycles, respectively. All three patients remain in complete remission more than 4 years after transplantation. These cases highlight two clinically relevant points. First, in TP53 ‐altered myeloid neoplasms, pretransplant therapy may be best viewed as a bridge to transplantation, and transplantation should be considered promptly once the TP53 ‐positive clone has decreased, rather than prolonging non‐curative therapy. Second, posttransplant Aza maintenance may be more beneficial when initiated early, individualized according to tolerability and disease status, and continued as long as feasible. In addition, for patients with FISH‐detectable TP53 abnormalities, serial FISH may provide a practical adjunct for pretransplant decision‐making in routine practice. Trial Registration : The authors have confirmed clinical trial registration is not needed for this submission