Targeted Marrow Irradiation Intensification of Reduced-Intensity Fludarabine/Busulfan Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation

Reduced-intensity conditioning (RIC) regimens frequently provide insufficient disease control in patients with high-risk hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated intensification of fludarabine/busulfan (Flu/Bu) RIC with targeted marr...

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Veröffentlicht in:Transplantation and cellular therapy 2022-07, Vol.28 (7), p.370.e1-370.e10
Hauptverfasser: Ali, Naveed, Sharma, Ashish Arunkumar, de Rezende, Ana Carolina Pires, Otegbeye, Folashade, Latif, Bilal Muhammad, Kerbauy, Mariana Nassif, Cooper, Brenda W., Sanchez, Gabriela, Metheny, Leland, Bal, Saswat K., Sakuraba, Roberto, Tomlinson, Benjamin K., Boughan, Kirsten M., Kerbauy, Lucila, Malek, Ehsan, Ribeiro, Andreza Feitosa, Gallogly, Molly, Mansur, David, Pereira, Gisele, Weltman, Eduardo, Sekaly, Rafick-Pierre, de Lima, Marcos, Caimi, Paolo F., Hamerschlak, Nelson
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Sprache:eng
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Zusammenfassung:Reduced-intensity conditioning (RIC) regimens frequently provide insufficient disease control in patients with high-risk hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated intensification of fludarabine/busulfan (Flu/Bu) RIC with targeted marrow irradiation (TMI) in a dose escalation with expansion phase I clinical trial. TMI doses were delivered at 1.5 Gy in twice daily fractions on days -10 through -7 (dose levels: 3 Gy, 4.5 Gy, and 6 Gy), Flu (30 mg/m2 for 5 days) and Bu (area under the curve, 4800 µM*minute for 2 days). Eligible patients were age ≥18 years with high-risk hematologic malignancy and compromised organ function ineligible for myeloablative transplantation (n = 26). The median patient age was 64 years (range, 25 to 76 years). Nineteen patients (73%) had active or measurable residual disease at transplantation. One-year disease-free survival and overall survival were 55% (95% confidence interval [CI], 34% to 76%) and 65% (95% CI, 46% to 85%), respectively. Day +100 and 1 year transplantation-related mortality were 4% (95% CI, 0.6% to 27%) and 8.5% (95% CI, 2% to 32%), respectively. The 1-year cumulative incidence of relapse was 43% (95% CI, 27% to 69%). Rates of grade II-IV and III-IV acute GVHD rates were 57% (95% CI, 39% to 84%) and 22% (95% CI, 9% to 53%), respectively. Whole blood immune profiling demonstrated enrichment of central/transitional memory-like T cells with higher TMI doses, which correlated with improved survival compared with control samples from patients undergoing allogeneic HSCT. Intensification of a Flu/Bu RIC regimen with TMI is feasible with a low incidence of transplantation-related mortality in medically frail patients with advanced malignancies. The recommended phase 2 TMI dose is 6 Gy.
ISSN:2666-6367
2666-6367
DOI:10.1016/j.jtct.2022.04.001