Transplant Conditioning Regimens and Outcomes After Allogeneic Hematopoietic Cell Transplantation (HCT) In Children and Adolescents with Acute Lymphoblastic Leukemia (ALL)

Abstract

3506 Recurrent disease is the most important cause of treatment failure after HCT. Total body irradiation (TBI)-containing conditioning regimens are associated with fewer relapses and longer leukemia-free survival (LFS) in children and adolescents with ALL. While TBI <13 Gy + cyclophosphamide (Cy) is considered standard, attempts to lower relapse rates have led to addition of a second chemotherapeutic agent (etoposide) or higher dose TBI (≥13 Gy) with or without addition of etoposide. TBI dosing (<13 Gy vs. ≥13 Gy) or the addition of etoposide to TBI + Cy regimen has not been examined in children. We report on 765 patients aged <18 years, who received either an HLA-matched sibling (n=160) or an unrelated donor (URD, n=605) HCT between 1998 and 2007. Seventy percent of patients were in 2nd complete remission (CR), 20% were in 3rd CR, and the remaining 10%, in relapse at HCT. The median age of the study population is 9 years and the median follow-up of surviving patients is 4 years. Transplant outcomes were examined in four treatment groups: 1) TBI <13 Gy + Cy (n=304), 2) TBI <13 Gy + Cy + etoposide (n=108), 3) TBI ≥13 Gy + Cy (n=327), and 4) TBI ≥13 Gy + Cy + etoposide (n=26). Ninety-six percent of patients in the TBI <13 Gy group received 12 Gy and 4%, 10 Gy. Irradiation doses in the TBI ≥13 Gy group were 13.2 Gy (24%), 13.5 Gy (41%) and 14 Gy (35%). Patient and disease characteristics (performance score, disease status, NCI-risk score, duration of first remission and cytogenetic risk) were similar among the treatment groups. The 3-year probabilities (95% confidence interval) of treatment-related mortality (TRM), relapse, and LFS in the four treatment groups are shown in the Table below. Neither higher dose TBI (≥13 Gy) nor the addition of etoposide regardless of TBI dose was associated with lower risks of leukemia recurrence or longer LFS after HCT. In the absence of an advantage for leukemia control, further intensification of the conditioning regimen TBI <13 Gy + Cy is not recommended. TRM Relapse LFS 1) TBI dose <13 Gy + Cy 25 (21–31)% 30 (24–35)% 45 (39–51)% 2) TBI dose <13 Gy + Cy + etoposide 29 (21–38)% 26 (18–34)% 45 (35–54)% 3) TBI dose ≥13 Gy + Cy 23 (19–28)% 33 (28–39)% 43 (38–49)% 4) TBI dose ≥13 Gy + Cy + etoposide 35 (17–52)% 31 (15–69)% 35 (17–52)% Disclosures: No relevant conflicts of interest to declare.

Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Treatment of Pediatric Acute Lymphoblastic Leukemia: Update of the 2005 Evidence-Based Review

“…Myeloablative Related versus Unrelated SCT for Relapsed ALL Tracey et al [56] examined the impact of conditioning regimen and donor source on outcomes in children and adolescents with ALL in $CR2 (90%) or active relapse (10%). TBI dosing (\13 Gy versus $13 Gy) or the addition of etoposide to a TBI 1 Cy regimen was examined in 765 children who received either an HLA-matched sibling (n 5 160) or unrelated donor (n 5 605) SCT.…”