A randomized phase III study of pretransplant conditioning for AML/MDS with fludarabine and once daily IV busulfan ± clofarabine in allogeneic stem cell transplantation
| Autor: | Borje S. Andersson, Peter F. Thall, Junsheng Ma, Benigno C. Valdez, Roland Bassett, Julianne Chen, Sairah Ahmed, Amin Alousi, Qaiser Bashir, Stefan Ciurea, Alison Gulbis, Rita Cool, Jitesh Kawedia, Chitra Hosing, Partow Kebriaei, Steve Kornblau, Alan Myers, Betul Oran, Katayoun Rezvani, Nina Shah, Elizabeth Shpall, Simrit Parmar, Uday R. Popat, Yago Nieto, Richard E. Champlin |
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| Rok vydání: | 2022 |
| Předmět: |
Myeloid
Transplantation Conditioning Clinical Sciences Oncology and Carcinogenesis Immunology Graft vs Host Disease Acute Clinical Research Neoplasms Humans Busulfan Cancer Transplantation Leukemia Hematopoietic Stem Cell Transplantation Evaluation of treatments and therapeutic interventions Bayes Theorem Neoplasms Second Primary Hematology Leukemia Myeloid Acute Second Primary Neoplasm Recurrence Local 6.1 Pharmaceuticals Neoplasm Recurrence Local Vidarabine Clofarabine |
| Zdroj: | Bone marrow transplantation, vol 57, iss 8 |
| ISSN: | 1476-5365 |
| Popis: | Pretransplant conditioning with Fludarabine (Flu)-Busulfan (Bu) is safe, but clofarabine (Clo) has improved antileukemic activity. Hypothesis: Flu+Clo-Bu (FCB) yields superior progression-free survival (PFS) after allogeneic transplantation. We randomized 250 AML/MDS patients aged 3–70, Karnofsky Score ≥80, with matched donors, to FCB (n = 120) or Flu-Bu (n = 130), stratifying complete remission (CR) vs. No CR, (NCR). HCT-CI scores varied, from 0 to 10. All evaluable patients engrafted. Median follow-up was 66 months (interquartile range: 58–80). Three-year relapse incidence (RI), 25% with FCB, vs. 39% with Flu-Bu (p = 0.018), offset by higher non-relapse mortality, 22.6% (95%CI: 16–30.2%) vs. 12.3% (95%CI: 6.5–19%). Three-year PFS was 52% (95%CI: 44–62%) (FCB), vs. 48% (95%CI: 41–58%) (Flu-Bu). FCB benefited CR patients less, NCR patients age ≤ 60 had 3-year 34% RI (95%CI: 19–49%) (FCB) vs. 56% (95%CI: 38–70%) after Flu-Bu (p = 0.037). NCR patients >60 years had 3-year RI 10.0% (FCB), vs. 56.0%, after Flu-Bu (p = 0.003). Bayesian regression analysis including treatment-covariate interactions showed FCB superiority in NCR patients with low HCT-CI (0–2). Serious adverse event profiles were similar for the regimens. Conditioning with FCB did not improve PFS overall, but improved disease control in NCR patients, mandating confirmatory trials. Remission status and HCT-CI should be considered when using FCB. |
| Databáze: | OpenAIRE |
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