Myeloablative chemotherapy with autologous bone marrow rescue in children and adolescents with recurrent malignant astrocytoma: outcome compared with conventional chemotherapy: a report from the Children's Oncology Group.
OBJECTIVE
Children and adolescents with malignant astrocytomas recurring after initial treatment have a dismal prognosis, with only rare patients surviving 1-year beyond recurrence. The purpose of this study was to attempt to improve their survival.


METHODS
Twenty-seven children and adolescents with malignant astrocytomas [17 glioblastoma multiforme and 10 anaplastic astrocytoma (AA)] following initial tumor progression, received myeloablative chemotherapy followed by autologous marrow rescue with one of three thiotepa and etoposide-based chemotherapy regimens, administered alone (n = 11) or combined with carmustine (n = 5) or carboplatin (n = 11). Time to progression and death following myeloablative chemotherapy for these patients was compared non-randomly with outcome of a contemporaneously treated cohort of similar patients who received only conventional chemotherapy following initial tumor progression. The two cohorts were compared for age, histology, prior therapies, extent of surgical resection at progression, and time from initial diagnosis to progression.


RESULTS
Five of 27 children (two with glioblastoma multiforme and three with AA) survive event-free from 8.3 to 13.3 years (median of 11.1 years) following myeloablative chemotherapy. Of 56 children with recurrent malignant astrocytoma who received conventional chemotherapy following initial progression, no patient survives. Differences in distributions of survival were not significant when stratified by surgical debulking (P = 0.39). However, for patients who were surgically debulked, the survival distributions are significantly different (P = 0.017).


CONCLUSIONS
Myeloablative chemotherapy with autologous marrow rescue can produce durable remissions in children and young adults with recurrent malignant gliomas, in the setting of minimal residual tumor burden achieved surgically.
Finlay
Jonathan L
JL
The Children's Center for Cancer & Blood Diseases, Department of Pediatrics, Children's Hospital, Los Angeles, California 90027, USA. jfinlay@chla.usc.edu
Dhall
Girish
G
Boyett
James M
JM
Dunkel
Ira J
IJ
Gardner
Sharon L
SL
Goldman
Stewart
S
Yates
Allan J
AJ
Rosenblum
Marc K
MK
Stanley
Philip
P
Zimmerman
Robert A
RA
Wallace
Dana
D
Pollack
Ian F
IF
Packer
Roger J
RJ
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016026:Bone Marrow Transplantation; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018450:Disease Progression; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000628:therapy*; D011379:Prognosis; D016879:Salvage Therapy; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous
D019653:Myeloablative Agonists; D005047:Etoposide; D013852:Thiotepa; D016190:Carboplatin; D002330:Carmustine