Work

High Dose Chemotherapy (HDT) with Busulfan, Melphalan and Topotecan Followed by Autologous Hematopoietic Stem Cell Transplantation (ASCT) in Pediatric Patients (pts) with High Risk Solid Tumors

Year: 2012

Type: article

Abstract: The prognosis of pts with high risk solid tumors remains poor despite advances in multimodal and high dose radiation and chemotherapy. HDT followed by ASCT appears to provide survival benefit to a select group of pts. We hypothesize that patients with chemo-sensitive solid tumors with poor risk features at diagnosis or with recurrent metastatic disease will have lower morbidity and improved survival with a conditioning regimen using a novel combination of busulfan, melphalan and topotecan (B-M-T) followed by ASCT. In this pilot study pts received topotecan continuous infusion in combination with busulfan (pharmacokinetics (PK) based dose adjustment) and melphalan. The primary outcome of interest was the toxicity of combined HDT with B-M-T. Secondary objectives were to evaluate engraftment, survival and PK of busulfan and topotecan. Twenty-two patients aged 2.2-27 years (median 8.8 yrs) were treated on the B-M-T protocol at City of Hope from 5/2007 to 4/2011. Diagnoses included Ewing sarcoma (n = 8), neuroblastoma (n = 7), Wilms (n = 3), rhadbomyosarcoma (n = 3) and medulloblastoma (n = 1). Seven pts were in complete remission, while 15 demonstrated a partial response at the time of transplant. The conditioning was tolerated well with no treatment related mortality (TRM) within 100 days and no grade 4 toxicities. All pts developed grade 1-3 mucositis, while 13 reported diarrhea (7 pts grade 3) and 21 developed liver toxicity (transaminitis and/or bilirubin elevation); 2 pts with grade 3. Four pts had grade 3 lung toxicities and 1 pt grade 3 colitis. All pts engrafted: ANC >500 achieved on day 8-17 (median 10); platelets >25,000 on day 11-58 (median 18); platelets >50,000 on day 14-119 (median 23). Overall 1-yr survival is 95% (1 pt died 306 days post transplant); 3 year survival is 72%. All deaths were related to a disease recurrence: two pts with Ewing sarcoma, 2 with rhabdomyosarcoma, and one each with neuroblastoma, Wilms and medullodlastoma. These data suggest that the B-M-T preparative regimen followed by an ASCT was tolerated well without unexpected or severe toxicities; pts had prompt engraftment and 0% TRM. The survival data are encouraging compared to historical data. This novel conditioning regimen with a favorable toxicity profile can be used in the future as a platform for gene therapy, immune-based cellular therapies or to intensify local control with prompt administration of intensity modulated radiation therapy (IMRT) such as helical-tomotherapy.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2011.12.135