Analysis of treatment in childhood leukaemia. I. Predisposition to methotrexate-induced neutropenia after craniospinal irradiation. Report to the Medical Research Council of the Working Party on Leukaemia in Childhood.
The degree of drug-induced neutropenia resulting from a controlled trial (UKALL I) of treatment in acute lymphoblastic leukaemia was analysed. The main agent associated with severe neutropenia was methotrexate, and methotrexate-induced neutropenia was significantly greater in patients who had received craniospinal irradiation. The synergistic toxic effect of irradiation followed by methotrexate treatment seems to have contributed to three of the five deaths which occurred in complete remission in this trial; all deaths in remission occurred in patients who had received central nervous system prophylaxis. Analysis of patients who subsequently relapsed compared with those still in remission after 18 months of treatment indicated that the former, on average, had slightly lower neutrophil counts. This suggests that the children who relapsed did not receive any less aggressive treatment than those who remained in remission.
D000380:Agranulocytosis / Q000139:chemically induced*; D002490:Central Nervous System / Q000528:radiation effects*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D007278:Injections, Spinal; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000532:radiotherapy; D008214:Lymphocytes; D015122:Mercaptopurine / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D009503:Neutropenia / Q000139:chemically induced*; D011239:Prednisolone / Q000627:therapeutic use; D011830:Radiation Effects; D011879:Radiotherapy Dosage; D012075:Remission, Spontaneous; D013997:Time Factors; D014750:Vincristine / Q000627:therapeutic use
D003561:Cytarabine; D014750:Vincristine; D011239:Prednisolone; D015122:Mercaptopurine; D008727:Methotrexate