High-dose chemotherapy and autologous hematopoietic progenitor cell rescue in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors: the impact of prior radiotherapy on outcome.
BACKGROUND
The role of myeloablative chemotherapy in children with recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors (MB/ST-PNET) is controversial, in particular in patients who develop recurrent disease after craniospinal radiotherapy.


METHODS
In this retrospective analysis, the authors investigated the outcome of children with recurrent MB/ST-PNET who were referred for myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue at Childrens Hospital Los Angeles.


RESULTS
Thirty-three children were referred for myeloablative chemotherapy: Fourteen of those children were never transplanted because of pre-transplant adverse events, and 19, including 6 without and 13 with previous irradiation, underwent transplant. Conditioning regimens included a backbone of thiotepa, which was given either in a single cycle or in multiple sequential cycles. The 3-year post-transplant event-free survival rate in unirradiated versus previously irradiated children was 83% +/- 15% versus 20% +/- 12%, respectively (P = .04). One child who had never been exposed to radiotherapy died of toxicity; the other children received post-transplant radiotherapy and remained disease free. Nine previously irradiated children experienced 4 toxic deaths and 6 tumor recurrences (1 patient had both): An interval of <1 year between initial radiotherapy and myeloablative chemotherapy predicted a greater risk of toxic death (P = .02), whereas a history of meningeal metastases at diagnosis and a poor response to the initial rescue therapy predicted a greater risk of post-transplant recurrence (P = .03 and P = .08, respectively).


CONCLUSIONS
Myeloablative doses of thiotepa-based chemotherapy and radiotherapy were able to cure most children who had radiotherapy-naive, chemoresponsive recurrences. Children who developed recurrences after craniospinal radiotherapy had poorer outcomes; however, cure was possible in those who had good prognostic features at presentation, chemoresponsive recurrences, and a long interval between initial radiotherapy and myeloablative chemotherapy.
Butturini
Anna M
AM
Division of Hematology/Oncology, Childrens Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, California, USA. abutturini@chla.usc.edu
Jacob
Mary
M
Aguajo
Jennifer
J
Vander-Walde
Noam A
NA
Villablanca
Judy
J
Jubran
Rima
R
Erdreich-Epstein
Anat
A
Marachelian
Araz
A
Dhall
Girish
G
Finlay
Jonathan L
JL
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000628:therapy*; D009364:Neoplasm Recurrence, Local; D018242:Neuroectodermal Tumors, Primitive / Q000628:therapy*; D015173:Supratentorial Neoplasms / Q000628:therapy*; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage*
D013852:Thiotepa