Folates are essential enzyme cofactors involved in one-carbon metabolism There were fewer marrow and CNS relapses in the high-dose versus Capizzi arms 42 and 22 vs 68 and 32he said This impressive improvement has been largely attributed to novel prognostic factors Although therapeutic progress in ALL during the past 4 decades has been closely associated with more widespread use of intravenous methotrexate and in progressively larger doses MTX was shown to promote the conversion of mercaptopurine to one of its active metabolites—thioguanine nucleotides [ 3132 ]—of which high concentration in leukemic cells was associated with increased EFS in leukemia patients [ 33 ]
Towards this goal, we have determined a range of in vitro parameters associated with MTX resistance in a large cohort of pediatric ALL patients and subsequently assessed their relation with treatment outcome as well as with clinical characteristics. Therefore, it methotrexate acute lymphoblastic leukemia imperative to characterize the extent of resistance to this important chemotherapeutic as well as the mechanisms underlying this phenomenon.
Due to logistic challenges and leukemic blast number limitations, none of the MTX-related parameters could be measured in all the patients in our cohort.
Table S1. Febrile neutropenia occurred in fewer patients treated with high-dose methotrexate vs Capizzi methotrexate 5. Patients in the Capizzi arm were offered the high-dose treatment at protocol close, Larsen noted. The aim of the current study was therefore to determine which parameters of MTX resistance are related to the long-term clinical outcome in childhood ALL patients treated with combination chemotherapy.
Therefore, the number of cases included in the statistical analysis varied considerably for the different parameters and the number of patients used for each measurement as listed in the various tables. No statistically significant differences were observed between the two arms in acute neurotoxicity, osteonecrosis, or other clinically relevant toxicities.
Its use has a strong pharmacologic rationale: MTX was shown to promote the conversion of mercaptopurine to one of its active metabolites—thioguanine nucleotides [ 3132 ]—of which high concentration in leukemic cells was associated with increased EFS in leukemia patients [ 33 ], .
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Despite its extensive use, high-dose intravenous methotrexate has not been proved conclusively to be more effective than less toxic, less labor intensive, and less costly methods of methotrexate administration. Fewer treatment failures occurred in the high-dose methotrexate arm; 68 marrow failures were reported in the Capizzi methotrexate arm vs 42 in the high-dose methotrexate arm; a total of 68 and 32 central nervous system failures occurred in the two arms, respectively. Although therapeutic progress in ALL during the past 4 decades has been closely associated with more widespread use of intravenous methotrexate and in progressively larger doses, little data exist to clearly support the use of high-dose intravenous methotrexate over a regimen of prolonged administration of low-dose methotrexate.
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At the same time, high concentration of long-chain but not total MTX polyglutamates was associated with inhibition of de novo purine synthesis [ 15 ]. Although therapeutic progress in ALL during the past 4 decades has been closely associated with more widespread use of intravenous methotrexate and in progressively larger doses, little data exist to clearly support the use of high-dose intravenous methotrexate over a regimen of prolonged administration of low-dose methotrexate.
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