Novel multiagent chemotherapy for bone marrow relapse of pediatric acute lymphoblastic leukemia.
BACKGROUND
Despite improvements in the treatment of pediatric acute lymphoblastic leukemia, approximately one in five patients will develop recurrent disease. The majority of these patients do not survive. This limited institution study sought to improve event-free survival (EFS) by intensification of chemotherapy.


METHODS
Twenty-one patients with either an isolated marrow (n = 16) or a combined marrow and central nervous system relapse (n = 5) received treatment according to Children's Hospital of Philadelphia protocol CHP-540. Six patients had an initial remission of <36 months, and five patients had relapsed within 1 year of completion of phase III therapy. Induction and reinduction therapy consisted of idarubicin, vincristine, dexamethasone, asparaginase, and triple intrathecal chemotherapy. Consolidation and reconsolidation therapy employed high-dose cytarabine, etoposide, and asparaginase given in a sequential manner. Maintenance therapy included courses of high- or low-dose cytarabine followed by sequential etoposide and asparaginase pulse, moderate-dose methotrexate with delayed leukovorin rescue, and vincristine/dexamethasone pulses. Therapy continued for 2 years from the start of interim maintenance in the 16 patients who did not receive a bone marrow transplant (BMT). Two patients underwent an HLA-identical sibling BMT specified by protocol. Four received a nonprotocol-prescribed alternative donor BMT.


RESULTS
The complete remission induction rate was 95%. With a median follow-up from date of relapse of 49 months in survivors, the actuarial EFS based on intent to treat is 75%. There were three toxic deaths in patients in CR and two deaths from relapse.


CONCLUSIONS
This regimen is toxic but effective and deserves study in a larger setting.
Leahey
A M
AM
Department of Pediatrics, Division of Oncology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia 19104, USA.
Bunin
N J
NJ
Belasco
J B
JB
Meek
R
R
Scher
C
C
Lange
B J
BJ
D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D001853:Bone Marrow / Q000187:drug effects*; D016026:Bone Marrow Transplantation; D016543:Central Nervous System Neoplasms / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D001215:Asparaginase; D015255:Idarubicin