Reduced-toxicity myeloablative conditioning regimen using fludarabine and full doses of intravenous busulfan in pediatric patients not eligible for standard myeloablative conditioning regimens: Results of a multicenter prospective phase 2 trial.
Fanny RiallandAudrey GrainMyriam LabopinGerard MichelVirginie GandemerCatherine PaillardCécile PochonLaurence ClementEolia BrissotCharlotte JubertAnne SirventPierre-Simon RohrlichDominique PlantazJean-Hugues DalleFlorent MalardPublished in: Bone marrow transplantation (2022)
Data regarding the safety and efficacy of reduced-toxicity conditioning regimen (RTC) prior to allogeneic stem cell transplantation (allo-SCT) to treat hematological malignancies in pediatric patients are limited. This prospective multicenter, phase 2 trial investigated a RTC regimen based on the combination of intravenous busulfan (3.2 mg/kg/d x 4 days), fludarabine (30 mg/m 2 /d x 5 days) and antithymocyte globulin (Thymoglobulin®, Genzyme; 5 mg/kg total dose) with the aim of delivering high dose myeloablation that would allow optimal disease control while minimizing toxicity, in a subgroup of children at very high risk of non-relapse mortality (NRM). The primary endpoint was NRM at 1 year after allo-SCT. A total of 48 high risk patients were included (median age, 13 years; range, 3-24). At 1 year, the cumulative incidence of recurrence/disease progression and NRM were 33% and 8%, respectively. With a median follow-up of 23 months, the Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) at 1 year were 69% and 58%, respectively. We conclude that the RTC regimen used in this prospective trial is safe, with a < 10% NRM rate noted among high-risk children and adolescents, paving the way for larger phase 3 trials incorporating novel agents pre- and post-allo-SCT.(ClinicalTrials.gov Identifier: NCT01572181).
Keyphrases
- stem cell transplantation
- high dose
- free survival
- low dose
- oxidative stress
- end stage renal disease
- newly diagnosed
- ejection fraction
- risk factors
- phase iii
- clinical trial
- chronic kidney disease
- young adults
- cardiovascular events
- prognostic factors
- cross sectional
- type diabetes
- study protocol
- electronic health record
- cardiovascular disease
- machine learning
- atomic force microscopy
- deep learning
- big data
- patient reported
- high resolution
- artificial intelligence
- high speed