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Recurrent childhood lymphocytic leukemia. Clinical and cytokinetic studies of cytosine arabinoside and methotrexate for maintenance of second hematologic remission
Author(s) -
Rivera Gaston,
Murphy Sharon B.,
Aur Rhomes J. A.,
Verzosa Manuel S.,
Dahl Gary V.,
Mauer Alvin M.
Publication year - 1978
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(197812)42:6<2521::aid-cncr2820420603>3.0.co;2-4
Subject(s) - medicine , methotrexate , vincristine , cytosine , cytarabine , prednisone , leukemia , acute lymphocytic leukemia , maintenance therapy , chemotherapy , gastroenterology , lymphoblast , bone marrow , drug , immunology , pharmacology , cyclophosphamide , lymphoblastic leukemia , dna , biology , genetics , cell culture
Fifty‐six children with acute lymphocytic leukemic (ALL) who had initial marrow relapses during continuation chemotherapy were retreated with vincristine and prednisone. By one month, 36 of 56 (64%) were again in hematologic remission. Twelve of the remaining 20 achieved marrow remissions with additional therapy. Thus, 48 of 56 patients (85%) achieved second marrow remissions. Continuation therapy consisted of weekly cytosine arabinoside (Ara‐C), 150 mg/m 2 , and methotrexate (MTX), 40 mg/m 2 . Patients were randomly selected to receive the drugs simultaneously or sequentially (48 hours apart) to evaluate the theoretical advantage of scheduling Ara‐C before MTX. In 13 children, drug‐induced changes in DNA‐synthetic activity were documented before reinduction of remission by determining tritiated thymidine and deoxyuridine labeling indices, autoradiographically, in marrow samples obtained at 0, 4, 24, 48 and 72 hours after a dose of Ara‐C and MTX. Neither clinical nor cytokinetic results supported the sequential schedule. The duration of second remissions among 25 patients treated with simultaneous Ara‐C and MTX (median = 56 days) did not differ significantly from that of 22 sequentially treated patients (median = 65 days). Moreover, there was no convincing cytokinetic evidence for partial synchronization of the mitotic cycle of leukemia blasts following Ara‐C administration. Instead, the labeling indices showed extensive variability from patient to patient, and, in the simultaneously treated group, the drug‐induced suppression of lymphoblast labeling was unexpectedly brief, possibly due to relative drug resistance. We conclude that, while reinduction of a second remission in ALL is comparatively easy, effective maintenance treatment for these remissions remains a difficult therapeutic problem. Combinations of Ara‐C and MTX, under the conditions of this study, failed to interfere effectively with leukemic cell replication as evidenced by both cytokinetic studies and end results. Cancer 42:2521–2528, 1978.