Comparison of Allogeneic Transplant Outcomes Using Conditioning with Different Dose of Busulfan for Children with Acute Myeloid Leukemia

Background. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for patients with acute myeloid leukemia (AML). The conditioning regimen administered for this patient based on busulfan combined with cyclophosphamide (BuCy), fludarabine (BuFlu) or some other agents....

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Published in:Blood 2019-11, Vol.134 (Supplement_1), p.4510-4510
Main Authors: Paina, Olesia V, Rakhmanova, Zhemal Zarifovna, Kozhokar, Polina Valerievna, Frolova, Anastasia S, Ekushov, Kirill Alexandrovich, Tsvetkova, Luibov, Bykova, Tatiana A, Markova, Inna V, Bondarenko, Sergey N., Barkhatov, Ildar M, Alyanski, Aleksandr, Babenko, Elena, Moiseev, Ivan S, Popova, Marina O, Semenova, Elena Vladimirovna, Zubarovskaya, Ludmila S, Zander, Axel, Afanasyev, Boris
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Language:English
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Summary:Background. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for patients with acute myeloid leukemia (AML). The conditioning regimen administered for this patient based on busulfan combined with cyclophosphamide (BuCy), fludarabine (BuFlu) or some other agents. Comparisons of myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) have demonstrated a various results between relapse and toxicity in a few reports. We supposed, that dose intensity of busulfan across regimens may affect treatment outcomes. The goal of this retrospective study was to evaluate the impact dose of busulfan to overall survival (OS), transplant-related mortality (TRM), relapse-free survival (RFS), toxicity, the incidence of primary graft failure and acute graft-versus-host disease (GVHD) in transplantation in children and adolescents with AML. Material and methods. We analyzed 110 AML pediatric patients with the median age 9 y.o. (range 1-19), who underwent first allo-HSCT with busulfan based (per os and IV) conditioning in R.M. Gorbacheva Memorial Institute from 2002 to 2018. Patients were divided into 3 groups: Bu1 - patients, who received busulfan at the dose 8-10 mg/kg, n=34 (31%), in Bu2 - dose of busulfan was 12 mg/kg, n= 35 (32%), in Bu3 - dose of busulfan was >12 mg/kg, n= 41 (37%). In Bu1 busulfan was combined with Flu in 31 pts (91%) and Cy in 3 (9%); in Bu2 - with Flu in 12 (34%) , Cy in 7 (20%) and other agents in 16 (46%); in Bu3 - with Cy in 32 (78%), with Flu in 7 (17%) and other agents in 2 pts (5%) (p < 0.001). Patients in Bu2 received more Cy based GVHD prophylaxis regimens (69% vs 44% in Bu1, vs 29% in Bu3, p = 0.003) and more HAPLO grafts (51% vs 29% in Bu1, vs 15% in Bu3, p = 0.003). The complete remission at the HSCT was observed in 79 % in Bu1, 49% in Bu2, 61% in Bu3 p=0,02. Probabilities of OS, RFS, TRM were estimated by using the Kaplan-Meier method. Incidence of toxicity, acute GVHD and primary graft failure - by using Mann - Whitney U-test. Results. Transplant engraftment was achieved in 95 (86%) of patients. Graft failure occurs in the 5 patients of Bu1 group (15%), in the 6 pts of Bu2 (17%) and in the 4 pts of Bu3 (10%), p=0,7. Median follow-up was 2 years for Bu1 and Bu3, 1 year for Bu2. OS was similar (Bu1=59% vs Bu2=60% vs Bu3=51%), p=0,7. OS of pts with CR before HSCT was 70% in Bu1, 82% in Bu2, 60% in Bu3, p=0,3 and 14%, 39%, 38% for pts with progression disease (PD), respectively, p=0,5. RF
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2019-128155