ESTRO 2024 - Abstract Book

S1175

Clinical - Haematology

ESTRO 2024

1 Santa Maria della Misericordia Hospital, Section of Radiation Oncology, Perugia, Italy. 2 Santa Maria della Misericordia Hospital, Medical Physics, Perugia, Italy. 3 Santa Maria della Misericordia Hospital, Department of Medicin Division of Hematology and Clinical Immunology, Perugia, Italy. 4 University of Perugia, Department of Medicin Division of Hematology and Clinical Immunology, Perugia, Italy. 5 University of Perugia, Department of Medicine and Surgery Section of Radiation Oncology, Perugia, Italy

Purpose/Objective:

In high-risk patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) with refractory leukemia or minimal residual disease (MRD), the risk of relapse is significantly increased. To mitigate this risk, one potential strategy is the irradiation intensification, particularly at sites of disease, such as the bone marrow. Therefore, patients with active or minimal residual disease in which the standard 13.5 Gy to the bone marrow were hypothesized to be not useful, we designed a conditioning regimen to deliver a higher dose to the bone marrow. Here the toxicity profiles and survival outcomes are reported.

Material/Methods:

The conditioning regimen consisted in TMLI which was delivered in 5 days in 2 daily fractions by Helical Tomotherapy. Using a simultaneous integrated boost (SIB) procedure, target volumes were the skeletal bones for TMI (total dose 20 Gy) and the major lymph node chains and the spleen for TLI (total dose 11.5 Gy). Patients with ALL also received 13.5 Gy to the brain. Following radiation therapy, chemotherapy was administered, including Thiotepa (2.5 or 3.75 mg/kg per day for 2 days), Fludarabine (30 mg/m2 per day for 5 days), Cyclophosphamide (15 mg/kg per day for 2 days). Haploidentical grafts consisted of 2 x106/kg Tregs, 1x106/kg Tcons and a “megadose” (~circa10x106/kg) of purified CD34+cells. No post-transplant immunosuppression was given.

Results:

From May 2020 to May 2023,10 pts (7AML, 3 ALL; 7 male and 3 female; median age 51 years) were recruited. Four patients underwent transplantation with detectable MRD, 6 with active disease. All patients received haploidentical HSCT. Dosimetric results are presented in the Table. All patients achieved full donor – type engraftment after transplantation. The majority of conditioning regimen-related adverse events occurring within 30 days after transplantation were graded as 1 to 2 according to the Common Terminology Criteria for Adverse Events (version 5.0). Oral and intestinal mucositis were generally mild and fully resolved in all patients No patient developed cytokine release syndrome after Treg and/or Tcon infusion. No cases of veno-occlusive disease (VOD) occurred. Only one case of transplantation-associated microangiopathy was observed. Acute GvHD occurred in 2 patient (20%), one Grade III and the other Grade IV; in the former patient dasth was caused by GvHD. No patients developed moderate or severe chronic GvHD. At a median follow-up of 22 months (range, 13-38 months), nine out of the ten patients (90%) remain alive. Importantly, no disease relapse occurred in any of these patients.