Intensive Reinduction Chemotherapy Followed by Early Allogeneic Hematopoietic Cell Transplantation for Relapsed/Refractory High-Grade Myeloid Neoplasms

• Published in: Transplantation and cellular therapy Vol. 30; no. 7; pp. 727.e1 - 727.e8
• Main Authors: Kopmar, Noam E., Othus, Megan, Quach, Kim, Rasmussen, Allegra, Schonhoff, Kelda, Becker, Pamela S., Walter, Roland B., Halpern, Anna B., Salit, Rachel, Cassaday, Ryan D., Shustov, Andrei, Stewart, F. Marc, Oehler, Vivian G., Scott, Bart L., Sandmaier, Brenda M., Lee, Stephanie J., Estey, Elihu H., Percival, Mary-Elizabeth M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2024
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cladribine - administration & dosage; Cladribine - therapeutic use; Cytarabine - administration & dosage; Cytarabine - therapeutic use; Feasibility Studies; Female; Hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation - methods; High-grade myeloid neoplasms; Humans; Male; Middle Aged; Mitoxantrone - administration & dosage; Mitoxantrone - therapeutic use; Recurrence; Transplantation Conditioning - methods; Transplantation, Homologous; Young Adult; High-grade myeloid neoplasms; Hematopoietic cell transplantation
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2024.05.002

•Hematopoietic cell transplantation (HCT) remains the sole curative option for adults with relapsed/refractory (R/R) high-grade myeloid neoplasms.•Early HCT for R/R disease remains an area of interest in the field, and we conducted a proof-of-principle feasibility study to address this question.•Although this feasibility study did not meet its primary endpoint, important lessons can be derived from this study and applied to future practice surrounding early HCT. Outcomes for adults with relapsed/refractory (R/R) high-grade myeloid neoplasms remain poor, with allogeneic hematopoietic cell transplantation (HCT) the sole therapy likely to result in cure. We conducted the present study to determine the feasibility of early HCT—within 60 days of beginning reinduction chemotherapy—to see whether getting patients to HCT in an expeditious manner would expand the number of patients being offered this curative option. In this proof-of-principle feasibility study, we included adults age 18 to 75 years with R/R myeloid malignancies with ≥10% blood/marrow blasts at diagnosis who were eligible for a reduced-intensity HCT. Subjects received reinduction chemotherapy with cladribine, cytarabine, mitoxantrone, and filgrastim (CLAG-M) and proceeded to HCT with reduced-intensity conditioning (fludarabine/ melphalan). We enrolled 30 subjects, all of whom received CLAG-M reinduction, although only 9 underwent HCT within 60 days (<15, the predetermined threshold for feasibility “success”), with a median time to HCT of 48 days (range, 42 to 60 days). Eleven additional subjects received HCT beyond the target 60 days (off-study), with a median time to transplantation of 83 days (range, 53 to 367 days). Barriers to early HCT included infection, physician preference, lack of an HLA-matched donor, logistical delays, and disease progression, all of which may limit the real-world uptake of such early-to-transplantation protocols.