Intensive Re-Induction Chemotherapy Followed by Early Allogeneic Hematopoietic Cell Transplant for Relapsed/Refractory High-Grade Myeloid Neoplasms

Outcomes for adults with relapsed/refractory (R/R) high-grade myeloid neoplasms remain poor, with allogeneic hematopoietic cell transplant (HCT) the only therapy likely to result in cure. Therefore, we conducted a study to determine the feasibility of early HCT – within 60 days of beginning reinduction chemotherapy – to see if getting patients to HCT in an expeditious manner would facilitate a larger number of patients being offered this curative option. In this proof-of-principle feasibility study, we included adults 18-75 with R/R myeloid malignancies with ≥10% blood/marrow blasts at diagnosis, who were eligible for a reduced-intensity HCT. Subjects received reinducton chemotherapy with cladribine, cytarabine, mitoxantrone, and filgrastim (CLAG-M) and proceeded to HCT with reduced-intensity conditioning (fludarabine/melphalan). We enrolled 30 patients: all received CLAG-M reinduction, although only 9 received HCT within 60 days (< 15, the predetermined threshold for feasibility "success"), with a median time to HCT of 48 days (range 42-60). Eleven additional subjects received HCT beyond the target 60 days (off-study), with a median time to transplant of 83 days (range 53-367). Barriers to early HCT included infection, physician preference, lack of an HLA-matched donor, logistical delays, and disease progression, all of which may limit real-world uptake of such early-to-transplant protocols.