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2056 Prospective Phase II Study of HSCT Using Targeted Busulfan, Fludarabine, Etoposide Conditioning for Pediatric ALL

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphoid Leukemias, ALL, Clinical Research, Combination therapy, pediatric, Diseases, Therapies, Lymphoid Malignancies, Study Population, Human
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Kyung Taek Hong, MD1*, Hyun Jin Park, MD2*, Bo Kyung Kim, MD3*, Hong Yul An, MD2*, Jung Yoon Choi, MD2* and Hyoung Jin Kang, MD, PhD4

1Department of Pediatrics, Seoul National University Cancer Research Institute, Seoul National University College of medicine, Seoul, South Korea
2Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul, Korea, Republic of (South)
3Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul, Korea, Republic of (South)
4Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul National University Children’s Hospital, Seoul, South Korea

Background: Hematopoietic stem cell transplantation (HSCT) is one of the important treatment options for very high-risk pediatric acute lymphoblastic leukemia (ALL). Conditioning including total body irradiation is commonly used, but irradiation-free chemo-conditioning has also been tried in consideration of long-term toxicity. Here, we report the results of phase II, prospective study of HSCT using targeted busulfan, fludarabine, and etoposide conditioning regimen.

Methods: Patients were enrolled from 2014 Feb to 2021 Aug. Patients eligible for this study had ALL aged < 21 years old who needs HSCT and had matched siblings or unrelated donors. The primary endpoint was 1-year event-free survival (EFS). Engraftment rate was the second endpoint. We estimated the sample size on a 20% increase in 1-year EFS rate (to 80%) than historical data, with a type I error of 5% and power of 80%. The conditioning regimen included targeted busulfan (age > 1 year, 120 mg/m2; age < 1 year, 80 mg/m2) which was administered once daily as the first dose on day 8, and a targeted dose of busulfan was used according to the therapeutic drug monitoring results on days 7 to 5, fludarabine (40mg/m2 once daily i.v. on days 8 to 3), and etoposide (20 mg/kg once daily i.v. on days 4 to 2).

Results: A total of 36 patients met the eligible criteria. The median age at HSCT was 8.1 years old (range, 1.0-18.9) and 20 were male (61.1%). The median follow-up time was 4.3 years (range 0.8-8.0). All patients received mobilized peripheral blood stem cells, and 14 patients (38.9%) from matched sibling donors, and the others from matched unrelated donors (10/10 17 patients; 9/10, 5 patients). The indications for HSCT were recurrence (11/36, 30.6%), induction failure (5/36, 13.9%), and very-high risk features (20/36, 55.6%) including Philadelphia chromosome, MLL rearrangement, hyperleukocytosis, and hypodiploidy. The infused total nuclear cell counts and CD34 positive cell counts were 13.5 x 108/recipient body weight (range, 4.8-39.0) and 7.5 x 106/recipient body weight (range, 1.1-18.1), respectively. All patients achieved neutrophil (median 10 days) and platelet engraftment (median 13 days). The cumulative incidences of acute graft-versus-host disease (GVHD) grade II to IV, grade III to IV, moderate to severe chronic GVHD, relapse, and non-relapse mortality were 36.1%, 2.8%, 8.4%, 33.6%, and 3.1%, respectively. The 1-year EFS and overall survival (OS) rate were 80.5% (95% confidence interval [CI] 67.9-93.4) and 94.3% (95% CI 86.7-100). The 3-year EFS and OS rates were 63.3% (95% CI 46.4-80.2) and 84.8% (95% CI 92.5-97.1), respectively. The donor type, age, and complete remission status were not significantly associated with the EFS or OS rates. Among 10 patients who relapsed after HSCT, 7 patients are alive following a second HSCT (5 patients) and salvage chemotherapy with another tyrosine kinase inhibitor (2 patients).

Conclusions: Our study shows a favorable outcome of irradiation-free, chemo-conditioning regimen using targeted busulfan, fludarabine, and etoposide in very-high risk childhood and adolescent ALL. Our study met 80% of the 1-year EFS rate, which was the primary endpoint. The 3-year OS rates, which are more than 20% higher than the EFS rates, show that many patients can be successfully treated even after recurrence. However, efforts are needed to improve long-term EFS using various modern innovative treatments.

Disclosures: Kang: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

*signifies non-member of ASH