Encouraging Leukemia-Free Survival Rates in 72 Pediatric Acute Lymphoblastic Leukemia (ALL) in CR Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Using a TBI-Free Conditioning Regimen

Background: TBI-based preparative regimen has been widely recommended for pediatric ALL. These assumptions are based on older registry studies. Because of the significantly high rates of serious late effect using TBI in pediatric patients it is of utmost importance to find alternative regimens. Chemotherapy regimens are developed to minimize the toxicities of irradiation-based regimens.

Methods: Since the year 1994, 111 pediatric patients (78 male&33female: 72 in CR and 39 not in CR) with ALL underwent HSCT in our center using a TBI-free conditioning. Here, we describe the outcomes of HSCT of the 72 patients in CR: 30 patients were in first CR, 28 second CR, and 14 ≥third CR. Only very high-risk patients underwent HSCT in the first CR. Patients were treated and classified according to BFM protocols. The conditioning regimen was included of Busulfan (IV or Oral) and Cyclophosphamide with or without ATG. For GVHD prophylaxis, patients received cyclosporine with or without methotrexate.

Outcomes: Patients underwent transplantation from sibling donors (n=58), other related donors (n=10), unrelated donor (n=4). Source of grafts were peripheral blood (n=60), bone marrow (n=7) and cord blood (n=5). The probability of neutrophil engraftment (at day60) was 94+-3% (med.time to of 14days) and of platelets-engraftment was 90+-10% (med.time 22days). The estimated 5-year leukemic free survival (LFS) was 73%+-6% (82+-7% in CR1, 71+-10% in CR2 and 38+-25% in CR>=2). Relapse rates were 8+-5% in CR1, 22+-9% in CR2 and 20+-17% in CR>=2. Acute GvHD grade 2-4 occurred in 49+-5% patients and 15+-5% patients have experienced chronic extended GvHD.

Conclusion: A TBI-free (Bu/Cy) preparative regimens can be used in pediatric ALL with encouraging LFS rates, similar to what is reported in literature using TBI. Well-designed randomized trials are needed to better clarify the difference between radiation and TBI-free conditioning regimens in pediatric ALL, including late effects.