2873 - Ring Gantry Linear Accelerator Based Total Lymphoid Irradiation (TLI) Based Myeloablative Conditioning Regimen in Hematopoietic Stem Cell Transplant (HSCT) in Thalassemia: A Single Institute Experience

Purpose/Objective(s): Hematopoietic stem cell transplantation (HSCT) is curative in transfusion dependent thalassaemia (TDT). Graft rejection remains a major obstacle in haploidentical HSCT in thalassaemia. Total lymphoid irradiation (TLI) based conditioning regimen may reduce the rejection risk by effective lymphoablation and improve outcome. We present the feasibility, tolerability and efficacy of TLI based conditioning regimen for HSCT in ring gantry linear accelerator.

Materials/Methods: This is a single centre retrospective study of children who underwent hematopoietic stem cell transplantation (HSCT) using a uniform conditioning with single fraction TLI, Antithymocyte globulin, Cyclophosphamide, Fludarabine, Treosulfan and Thiotepa. All children received TCRaß and CD45RA-depleted stem cell grafts from haploidentical family donors. Total lymphoid irradiation (TLI) was administered at a dose of 5 Gy in a single fraction on day -10. Treatment planning was performed using the Eclipse planning system (v15.6.3) with the Photon Optimizer (PO) algorithm. For the cranial region, three full VMAT arcs were employed using the Halcyon (HAL) platform. In the dorsal and lumbar regions, two to three full arcs (179°–0°–180°) were used to achieve adequate target coverage with optimal dose conformity. All patients received treatment in the Halcyon-E ring gantry accelerator equipped with an effective multi leaf collimator width of 5 mm, 6MV unflatten beam and 2 revolution per minute gantry rotational speed with a dose rate of 800 MU/min. treatment plans were done with median three full arcs per isocentre. The following prescription targets are applicable: D98% = 95%; V110% < 3–5 %; V120% < 1%.

Results: Nine children were treated with a median age of 5 years (range: 3–7 years), male-to-female ratio of 4:5 and median follow-up of 4 months (range: 2–5 months), the mean planning target volume (PTV) was 1445.7 cc (range: 1200–1651.2 cc). The mean PTV dose delivered was 512.8 cGy (range: 509.1–518.3 cGy). Organ-at-risk (OAR) constraints were achieved in accordance with standard dose guidelines. There was no graft rejection or transplant-related mortality. No Grade III or IV toxicities were observed. Most frequently reported adverse effects were nausea, vomiting, and mild mucositis. All children engrafted with full donor chimerism at Day 30 and 60 post transplant. Long-term toxicity outcomes are currently under follow-up.

Conclusion: TLI-based conditioning demonstrates a favorable tolerability, limited treatment related toxicity and should be included in haploidentical HSCT to ensure engraftment will full donor chimerism in children with TDT Thalassaemia.