Dp108 | 20gy/11.5-13.5gy Total Marrow and Lymphnode Irradiation-based Conditioning Regimen for Hematopoietic Stem Cell Transplantation With T Cell Adoptive Immunotherapy in Active Disease Acute Leukemia Patients
Year: 2025
Type: article
Abstract: A novel HLA-haploidentical hematopoietic stem cell transplantation (HSCT) approach that combines an irradiation based (13.5Gy/11.5Gy total marrow and lymphoid irradiation, TMLI) conditioning regimen (CR) with donor regulatory and conventional T cell adoptive immunotherapy (Treg-Tcon) in the absence of post-transplant immune suppression provides low rates of relapse (10%) in acute leukemia patients (updated, Pierini et al. Blood Advances 2021). Patients with active disease at transplant are still an unmet clinical need because of the higher risk of relapse. Following the experience by City of Hope Cancer Center (Wong JYC et al, Front Oncol. 2022), since June 2020 we increased the dose of TMLI (using 20 Gy in the marrow) to treat 10 patients with active disease acute leukemia. Skeletal bones received 20 Gy, lymph node chains and spleen 11.5-13.5 Gy, while off-target organs were protected by such high doses (brain was targeted by 13.5 Gy in Acute Lymphoblastic Leukemia, ALL, patients). TMLI 20Gy/11.5-13.5Gy (combined with chemotherapy) was followed by Treg-Tcon immunotherapy to favor GvL effect. Patients’ median age was 48 (38-63). Six patients were affected by acute myeloid leukemia, 4 by ALL; 8 patients had more than 5% bone marrow blast, 2 patients had extramedullary disease. Three patients received HLA-matched and 7 HLA-haploidentical Treg-Tcon HSCT. The exposure of off-target organs to radiation was as it follows: bladder 10.4±1.03Gy, esophagus 13.88±0.56Gy, heart 8.47±0.39Gy, small bowel 7.67±0.43, large bowel 8.94±0.65, kidneys 6.65±0.23Gy, lens 3.38±0.19Gy, lungs 10.43±0.23Gy, oral cavity 7.17±0.45Gy, parotids 11.41±1.01Gy, rectum 7.21±0.68Gy, thyroid 10.14±1.03Gy. All patients engrafted. Oral mucositis was grade III in 1 patient, grade II or less in 9 patients. Grade >= 2 aGvHD occurred in 1 patient and resolved with steroids and Ruxolitinib. No case of veno-occlusive disease, moderate/severe chronic GvHD and non-relapse mortality was observed. One patient relapsed and died 16 moths after HSCT, 9 out of 10 patients are alive and disease-free at a median follow up of 39 months (32-58). This study showed that 20Gy/11.5-13.5Gy TMLI is followed by acceptable toxicity that appears comparable to the one observed in 13.5Gy/11.5Gy setting. In this small group of patients, disease control appears to be promising and prompted us to develop a novel clinical trial to assess efficacy of 20Gy/11.5-13.5Gy TMLI that is presently ongoing (Clinicaltrials.gov NCT06845592).
Authors: F. Zorutti, S. Saldi, L. Ruggeri, V. Viglione, C. Fulcheri, R. Sembenico, M. Mariannelli, C. Zucchetti, S. Hui, F. Camilli, T. Zei, R. Iacucci Ostini, E.K. Jardini, E. Hoxha, A. Stein, G. Ingrosso, A. Velardi, M.F. Martelli, M.P. Martelli, A. Carotti, C. Aristei, A. Pierini
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093122587
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