Abstract | BACKGROUND: PROCEDURE: Twenty-seven patients were enrolled on ASCT1221 from 2013 to 2015. Pre- and post-HCT (starting Day +30) mutant allele burden was measured in all and pre-HCT therapy was administered according to physician discretion. RESULTS: Fifteen patients were randomized (six to Bu-Cy-Mel and nine to Bu-Flu) after meeting diagnostic criteria for JMML. Pre-HCT low-dose chemotherapy did not appear to reduce pre-HCT disease burden. Two patients, however, received aggressive chemotherapy pre-HCT and achieved low disease-burden state; both are long-term survivors. All four patients with detectable mutant allele burden at Day +30 post-HCT eventually progressed compared to two of nine patients with unmeasurable allele burden (P = 0.04). The 18-month event-free survival of the entire cohort was 47% (95% CI, 21-69%), and was 83% (95% CI, 27-97%) and 22% (95% CI, 03-51%) for Bu-Cy-Mel and Bu-Flu, respectively (P = 0.04). ASCT1221 was terminated early due to concerns that the Bu-Flu arm had inferior outcomes. CONCLUSIONS: The regimen of Bu-Flu is inadequate to provide disease control in patients with JMML who present to HCT with large burdens of disease. Advances in molecular testing may allow better characterization of biologic risk, pre-HCT responses to chemotherapy, and post-HCT management.
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Authors | Christopher C Dvorak, Prakash Satwani, Elliot Stieglitz, Mitchell S Cairo, Ha Dang, Qinglin Pei, Yun Gao, Donna Wall, Tali Mazor, Adam B Olshen, Joel S Parker, Samir Kahwash, Betsy Hirsch, Susana Raimondi, Neil Patel, Micah Skeens, Todd Cooper, Parinda A Mehta, Stephan A Grupp, Mignon L Loh |
Journal | Pediatric blood & cancer
(Pediatr Blood Cancer)
Vol. 65
Issue 7
Pg. e27034
(07 2018)
ISSN: 1545-5017 [Electronic] United States |
PMID | 29528181
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
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Copyright | © 2018 Wiley Periodicals, Inc. |
Chemical References |
- Myeloablative Agonists
- Vidarabine
- Busulfan
- fludarabine
|
Topics |
- Busulfan
(administration & dosage)
- Child
- Child, Preschool
- Female
- Follow-Up Studies
- Graft Rejection
(drug therapy, etiology)
- Graft vs Host Disease
(drug therapy, etiology)
- Hematopoietic Stem Cell Transplantation
(adverse effects)
- Humans
- Infant
- Infant, Newborn
- Leukemia, Myelomonocytic, Juvenile
(complications, therapy)
- Male
- Myeloablative Agonists
(administration & dosage)
- Prognosis
- Transplantation Conditioning
- Vidarabine
(administration & dosage, analogs & derivatives)
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