Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: A Pediatric Blood and Marrow Transplant Consortium study

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.

Section: Discussionmentioning

confidence: 99%

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

Kalaycio

Bolwell

Rybicki

et al. 2010

“…16 In ALL patients, TBI is widely used as it has not been shown that TBI could be replaced by chemotherapy. [17][18][19] Since the late 1970s, both TBI therapy and supportive care have greatly improved, and this may result in less frequent late effects among the more recently treated survivors.…”

Section: Discussionmentioning

confidence: 99%

Adverse health events and late mortality after pediatric allogeneic hematopoietic SCT—two decades of longitudinal follow-up

Wilhelmsson

Vatanen

Borgström

et al. 2015

Treatment-related late toxicities after pediatric allogeneic hematopoietic SCT (allo-HSCT) are increasingly important as long-term survival has become an expected outcome for many transplanted children and adolescents. In a retrospective cohort study, we assessed long-term health outcomes in 204 allo-HSCT survivors transplanted in childhood or adolescence (o 20 years) between 1978 through 2000 after a median follow-up time of 12 (range 4-28) years. Data on conditioning regimen, adverse health events (AE) and growth and hormonal substitutions (hormone replacement therapies (HRTs)) were obtained from medical records. AEs were graded retrospectively according to Common Terminology Criteria for Adverse Events v3.0. Late deaths (⩾48 months after allo-HSCT) were evaluated separately. Multivariate analysis demonstrated that chronic GVHD (P o0.000) and longer follow-up time (P o0.05) correlated with AEs, whereas CY-based conditioning was inversely correlated (P o 0.002). TBI and longer follow-up duration predicted more severe AEs (P o 0.001 and P o 0.001, respectively). HRTs were more frequent after TBI. Diabetes type II, dyslipidemia and hypertension were detected in 9, 7 and 7% of the survivors, respectively. Late deaths (n = 22) were most frequently due to pulmonary failure (n = 7), followed by secondary malignancy (n = 5). The occurrence of AEs after pediatric allo-HSCT is high and likely to increase during extended follow-up, particularly in patients who have received TBI.

“…These findings seem to confirm the significant anti-leukemic efficacy of TREO-prep-reg, which appears to be comparable with that of standard-prep-reg in childhood hematological malignancies. 43,46,49,50 The significant anti-leukemic effect of TREO-based conditioning regimens along with their low toxicity, makes them also an attractive alternative to RIC regimens, especially for patients with high-risk hematological malignancies, in whom relapse remains the most common obstacle to a successful outcome of RIC. 4,[35][36][37] However, as a prodrug nonenzymatically activated to alkylating mono-and diepoxides, TREO demonstrates gonadotoxicity and mutagenicity, and thus monitoring and evaluation of its long-term effects, including secondary MDS in children demonstrating mixed chimerism, will be of special importance in children conditioned for HSCT with high-dose TREO.…”

Section: Discussionmentioning

confidence: 99%

Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT pediatric diseases working party

Wachowiak

Sykora²,

Cornish

et al. 2011

This retrospective analysis evaluated 51 children (0.7-17 years; median eight) with high-risk or advanced hematological malignancies, including 18 (35%) patients undergoing second/third hematopoietic SCT (allo-HSCT), not eligible for standard myeloablative regimens and transplanted from matched sibling (MSD) (n ¼ 24) or matched unrelated (MUD) (n ¼ 27) donors. Preparative regimens were based on treosulfan (TREO) i.v., a structural analog of BU, given at total dose of 30 g/m 2 (n ¼ 21) or 36-42 g/ m 2 (n ¼ 30) in combination with, fludarabine, cyclophosphamide, melphalan and/or VP-16 according to diagnosis, and risk factors. Deaths due to early regimenrelated toxicity (RRT) did not occur. Nonrelapse mortality was 8% at 1 year and 16% after 4 years. Myeloid engraftment was achieved in 94%, complete donor chimerism in 90% of patients. A 4-year incidence of relapse was 24%, and was significantly lower after MUD-HSCT (8%) than after MSD-HSCT (39%), but similar in children undergoing first (28%) or second/third HSCT (17%). A 4-year disease-free survival was 61%, but it was significantly better in myeloid (73%), than in lymphoid malignancies (41%). Thus, children with high-risk and advanced hematological malignancies and high-risk of life-threatening RRT can be transplanted effectively and safely using TREO-based regimens. Particularly favorable results were achieved in myeloid malignancies and in children undergoing second HSCT.