Impact of Conditioning Regimen in Allogeneic Hematopoetic Stem Cell Transplantation for Children with Acute Myelogenous Leukemia beyond First Complete Remission: A Pediatric Blood and Marrow Transplant Consortium (PBMTC) Study

Abstract

Total body irradiation (TBI)-based conditioning regimens for pediatric patients with acute myelogenous leukemia (AML) beyond first complete remission (CR1) are controversial. Because the long-term morbidity of busulfan (Bu)-based regimens appears to be lower, determining efficacy is critical. We retrospectively evaluated 151 pediatric patients with AML beyond CR1, comparing outcomes in 90 patients who received a TBI-based conditioning regimen and 61 patients who received a Bu-based conditioning regimen. There were no differences between the 2 groups with respect to age, sex, duration of CR1, time from most recent remission to transplantation, or donor source. The probability of relapse at 2 years also did not differ between the 2 groups (26% and 27%, respectively; P=.93). No significant difference in event-free survival (EFS) (P=.29) or overall survival (OS) (P=.11) was noted between the 2 groups. These findings were supported by a multivariate analysis in which TBI was not associated with improved EFS (hazard ratio [HR]=1.17; 95% confidence interval [CI]=0.66-2.10; P=.58) or OS (HR=1.42; 95% CI=0.76-2.64; P=.27). Shorter CR1 and receiving an HLA-mismatched transplant adversely affected EFS and OS in this cohort. Our study provides no evidence of an advantage to using TBI in children with AML beyond CR1. A prospective, randomized study is needed to confirm these results.

Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR: TBI+CY versus BU+CY: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

“…25 After stratification by acute leukemia type, they concluded in favor of TBI-based one with lower rate of relapse and best TRM. But, as with Sisler et al, 22 they have some concern regarding TBI in children and the same interrogations regarding the possible benefit of IV-BU. In another slightly older metaanalysis comparing the use of Bu-Cy vs TBI-Cy regimen in patients with either acute or chronic leukemia, TBI regimen seemed to be superior to Bu-Cy regimen with significant results for OS, TRM and relapse.…”

“…In the Sisler et al retrospective international multi-center study published in 2009 that analyzed 241 pediatric patients transplanted for AML in CR2 or more, the authors reported no differences for both OS and of relapseincidence between Bu-based and TBI-based conditioning regimen in pediatric patients transplanted for AML beyond CR1. 22 In multivariate analysis, conditioning regimen did not independently influence rates of OS, EFS, relapse or TRM. Nevertheless, the authors claimed their preference for Bu-Cy-based conditioning regimen because of possible expected lower rate of severe and late complications after BU than after TBI as described in different papers.…”

“…26,31,32 On the other hand, Bu seemed to be responsible of more early toxicity with more venoocclusive disease, hemorrhagic cystitis and interstitial pneumonia than TBI and to be responsible of more irreversible alopecia. 22,25,33 We may postulate that the availability of IV-Bu associated to dose adjustment either to body weight or to individual pharmacokinetics study improve the results for both relapse incidence and-may be-early and late toxicities. Even though fractioned TBI seems to give superior results regarding relapse and OS rates while limiting adverse effects on the other tissues comparing to single-dose TBI, the huge concerns regarding secondary malignancies and growth, hormonal and metabolic disorders still remain crucial, particularly in pediatric population with expected long-time survival.…”

The Outcome of Allogeneic Hematopoietic Cell Transplantation for Children with FMS-Like Tyrosine Kinase 3 Internal Tandem Duplication–Positive Acute Myelogenous Leukemia

“…Prior studies have shown no advantage of using a TBI-based preparative regimen on the outcome of children with AML in second CR [12]. These results should be interpreted with caution because the use of TBI was based on local institutional protocols in each center.…”

“…Based on these findings, children with FLT3/ITD are generally referred for allogeneic HSCT in CR1 with the best available donor. Published reports on the outcome of children with high-risk AML after allogeneic HSCT do not address the impact of FLT3/ITD on the posttransplantation outcome [1,11,12]. We sought to examine the outcome for all children with FLT3/ITDepositive AML who underwent allogeneic HSCT.…”