BU- vs TBI-based conditioning for adult patients with ALL

Abstract

Evidence suggests an advantage for TBI over BU as a component of conditioning regimens for allogeneic hematopoietic cell transplant in patients with ALL. We have employed both TBI and BU for conditioning in ALL and reviewed our experience to compare outcomes. From July 1989 to June 2008, we identified 86-adult ALL patients treated with either a TBI-or BU-based regimen and transplanted with either a well-matched sibling or unrelated donor. Data including demographics, immunophenotype, disease status and cytogenetic risk were examined by Cox proportional hazards analysis. Patients treated with TBI were older (median age 40 vs 33 years; P ¼ 0.018), had a higher-risk cytogenetic profile (P ¼ 0.010), were more often transplanted using an unrelated donor (P ¼ 0.038) and were treated more recently (Po0.001). There was a significant improvement in EFS (P ¼ 0.046), and a trend to improved OS (P ¼ 0.08) in patients treated with TBI compared with those treated with BU. However, the advantage for TBI could not be confirmed by multivariable analysis where only disease status retained statistical significance.

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

“…[46][47][48][49][50] Although TBI-based regimens are widely used in HSCT, excellent outcomes of BU-based regimens were also reported by several single institution trials. We observed a superiority of BU/CY-based regimen over TBI/CY-based regimen on 1-year PFS in this co-infusion approach.…”

Haploidentical versus Matched-Sibling Transplant in Adults with Philadelphia-Negative High-Risk Acute Lymphoblastic Leukemia: A Biologically Phase III Randomized Study

“…Furthermore, in our sibling donor cohort, the use of TBI did not result in superior outcomes as compared with non-TBI regimen (see Results). Although some studies demonstrated superior outcome using TBI as compared with BUCY after matched donor HSCT (31,32), other reports did not find significant difference between TBI or non-TBI regimen for patients transplanted in CR (33,34). Due to inconvenient TBI facilities and worry about the fertility, the uniform protocol (non-TBI) with our T-cell-replete modality was implemented in our haploidentical study population.…”

Pharmacokinetically-targeted BU and fludarabine as conditioning before allogeneic hematopoietic cell transplantation for adults with ALL in first remission

“…BU is a potent inducer of apoptosis in ALL cells 6 and has been evaluated in myeloablative doses with CY in order to avoid TBIrelated toxicity in ALL patients. [7][8][9] In pediatric patients, BU was inferior to TBI; however, pharmacokinetic dose adjustment was not done and, because of a higher clearance of BU in children, subtherapeutic BU exposures may have accounted for the outcome. In addition, poor results with BU may be explained by erratic oral absorption that results in as much as a 10-fold range of systemic exposures, with excess toxicity at high exposure and lack of efficacy at low exposure.…”