Faculty, Staff and Student Publications

Publication Date

12-1-2024

Journal

Bone Marrow Transplant

Abstract

Refractory aggressive lymphomas can be treated with allo-SCT, pursuing a graft-vs-lymphoma effect. While reduced intensity conditioning is safe, tumors often progress rapidly, indicating the need for more active conditioning regimens. The preclinical synergy we saw between gemcitabine (Gem), clofarabine (Clo) and busulfan (Bu) against lymphoma cell lines led us to study Gem/Clo/Bu clinically. Eligibility: age 12-65, refractory aggressive B-NHL, T-NHL or Hodgkin, with a matched donor. Infusional Gem was dose-escalated on days (d) -6 and -4 (475-975 mg/m2/day), followed by Clo (40 mg/m2/day) and Bu (target AUC, 4000 μMol min/day) (d -6 to -3). CD20+ tumors received rituximab. GVHD prophylaxis included ATG (MUD), tacrolimus and MMF. We compared their outcomes to matched-pair concurrent controls receiving Flu/Mel + matched allo-SCT. We enrolled 64 patients, median age 46 (17-63), 31 B-NHL/22 T-NHL/11 Hodgkin, 36 MSD/28 MUD (all PBPC), median 4 (2-10) prior therapies; 18 prior auto-SCT, 42 active diseases at allo-SCT (12 PD). Toxicities (mucositis and transaminitis) were manageable. Gem/Clo/Bu was myeloablative yielding early full donor chimerism. Grades II-IV/III-IV acute GVHD rates of 37% and 18%; chronic GVHD of 33% (13% severe); NRM at D100/1 year was 7% and 18%. ORR/CR rates: 78%/71% (B-NHL), 93%/93% (T-NHL), 67%/67% (Hodgkin). At a median follow-up of 60 (12-110) months, EFS/OS rates: 36%/47%. Gem/Clo/Bu patients had better median EFS (12 vs. 3 months, P = 0.001) and OS (25 vs. 7 months, P = 0.003) than 113 Flu/Mel matched-pair controls. The new myeloablative regimen Gem/Clo/Bu has limited toxicity and high activity in allo-SCT for aggressive lymphomas, yielding better outcomes than concurrent matched-pair controls receiving Flu/Mel.

Keywords

Humans, Gemcitabine, Middle Aged, Adult, Deoxycytidine, Busulfan, Male, Female, Adolescent, Clofarabine, Aged, Young Adult, Lymphoma, Transplantation Conditioning, Antineoplastic Combined Chemotherapy Protocols, Transplantation, Homologous, Child, Hematopoietic Stem Cell Transplantation, B-cell lymphoma, T-cell lymphoma, Hodgkin lymphoma, Haematopoietic stem cells

DOI

10.1038/s41409-024-02394-0

PMID

39341929

PMCID

PMC11611727

PubMedCentral® Posted Date

9-28-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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