Busulfan, melphalan, and thiotepa with or without total marrow irradiation with hematopoietic stem cell rescue for poor-risk Ewing-Sarcoma-Family tumors.
BACKGROUND
Survival following metastatic or recurrent Ewing sarcoma family tumors (ESFT) remains <25%. Myeloablative therapy with hematopoietic stem cell transplantation (HSCT) may improve survival for poor-risk ESFT. We describe the toxicity and efficacy of a myeloablative chemotherapy regimen, followed by a second myeloablative radiotherapy regimen as consolidation treatment for poor-risk ESFT.


METHODS
Sixteen patients with poor-risk ESFT were treated with myeloablative therapy followed by HSCT. All patients received busulfan, melphalan, and thiotepa (BuMelTT) as chemotherapy conditioning. Nine patients received total marrow irradiation (TMI) as a second myeloablative therapy, also followed by HSCT. Seven patients were excluded from TMI because of inadequate peripheral blood stem cell harvest, extensive prior radiation therapy, early disease progression, orpatient refusal. The disease status prior to my eloablative therapy was first complete response (CR1) in three patients, CR2 in nine, second partial response (PR2) in one, CR3 in one, and progressive disease (PD) in two.


RESULTS
One patient died of regimen-related toxicity, one from late pulmonary toxicity, and one following allogeneic transplantation for myelodysplasia. Eight developed recurrent disease (median time to progression 6.8 months). Six survive without relapse from 27 to 66 months following BuMelTT (median follow-up 42 months), all of whom received both BuMelTT and TMI patients (3-year event-free survival 36%).


CONCLUSIONS
Dual myeloablative therapy with BuMelTT and TMI was a feasible and promising treatment approach for patients with poor-risk ESFT. Inability to collect sufficient PBSC and extensive previous radiation therapy limit the ability to deliver TMI as a second HSCT conditioning regimen.
Hawkins
D
D
Fred Hutchinson Cancer Research Center, Seattle, WA, USA. dhawki@chmc.org
Barnett
T
T
Bensinger
W
W
Gooley
T
T
Sanders
J
J
D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects; D016465:Bone Marrow Purging / Q000379:methods*; D002066:Busulfan / Q000008:administration & dosage*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018572:Disease-Free Survival; D005240:Feasibility Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage*; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012074:Remission Induction; D012512:Sarcoma, Ewing / Q000556:secondary / Q000628:therapy*; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage*; D016896:Treatment Outcome; D016312:Treatment Refusal
D018906:Antineoplastic Agents, Alkylating; D013852:Thiotepa; D002066:Busulfan; D008558:Melphalan