Intermediate-dose methotrexate versus cranial irradiation in childhood acute lymphoblastic leukemia: a ten-year follow-up.
The cure rate of childhood acute lymphoblastic leukemia (ALL) has improved dramatically. Still there is a paucity of long-term data. With the improving cure rate, the quality of life and avoidance of second cancers have become important concerns. We evaluated 596 children and adolescents with ALL on Cancer and Leukemia Group B 7611 (CALGB 7611) who were randomized between 1976 and 1979 to receive intermediate-dose methotrexate (IDM) plus intrathecal methotrexate (IT MTX) or cranial radiation (CRT) plus IT MTX. After 10 additional years of follow-up, the pattern and significance of the results reported in 1983 are confirmed. IDM offered better hematologic protection (P < 0.0006), better testicular protection (P = 0.002), but CRT offered better central nervous system (CNS) protection (P < 0.0001). The retrieval rate for the 231 patients who relapsed while on therapy or within 6 months of elective cessation of therapy is 20 +/- 5%. For the 33 patients who relapsed more than 6 months after cessation of therapy, the retrieval rate is 49 +/- 10%. For all patients, the 12-year event-free survival was 37 +/- 3.6% and the overall survival was 49 +/- 3.5%. There were two cases of second malignancies reported in 3,502 person-years of survival. Both occurred following salvage therapy. There was no evidence of an excessive number of second primaries over the general population of children. There were no reported instances of clinical cardiopathy. After a median follow-up of 11 years, there have been no reports of cardiopathy and no evidence of an increased risk of second cancers in children treated on CALGB 7611. While the overall outcome is not what would be expected with modern therapy, one can conclude that CRT offered better CNS protection, but IDM offered better systemic and testicular protection. A small risk of second cancers or cardiac dys-function may be acceptable with therapies which produce long-term documented survival benefits.
Freeman
A I
AI
Department of Hematology/Oncology, Children's Mercy Hospital, Kansas City, Missouri, USA.
Boyett
J M
JM
Glicksman
A S
AS
Brecher
M L
ML
Leventhal
B G
BG
Sinks
L F
LF
Holland
J F
JF
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy*; D011241:Prednisone / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D014750:Vincristine; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate