小児急性リンパ球性白血病の治療研究

寛解維持療法における6-MercaptopurineとMethotrexateの大量間歇投与法の有効性：CCLSG-S811 (Phase III Study)

抄録

From 1981 to 1983, 131 previously untreated patients with childhood acute lymphoblastic leukemia were stratified in the standard risk group and were entered on this protocol S811. Of 119 eligible patients, 115 (96.6%) attained complete remission by the treatment with prednisone (PRD) and vincristine (VCR) or vindesine (VDS). There was no significant difference between VCR and VDS. After preventive central nervous system (CNS) therapy uniformly including 18Gy cranial irradiation and three doses of intrathecal methotrexate (MTX), the patients were randomized to receive a maintenance chemotherapy of Regimen A or Regimen B. The Regimen A consisted of MTX 225mg/m² i.v. push alternating at two week-interval VCR 2.0mg/m²×1, PRD 120mg/m²/d×5 and 6-mercaptopurine (6MP) 175mg/m²/d×5. The Regimen B consisted of daily 6MP 50mg/m² and MTX 20mg/m² p.o. weekly combined with pulses of VCR and PRD every four weeks. As a late intensification therapy (LIT), five courses of high-dose (2,000mg/m² i.v.) MTX with leukovorin rescue were administered to all the patients in continuous complete remission (CCR) for more than two years. Sixty and 55 patients were registered in Regimen A and B, respectively. The CCR rates in regimen A and B were 79.2%±5.4% (mean±SE) and 69.5%±6.4% at 3 years, 74.5±6.0% and 51.6%±8.0% (p<0.05) at 4 years, and 74.5%±6.0% and 45.1±9.3% at 5 years (p<0.01), respectively. CNS and testicular relapses appeared to be increased in the Regimen B after 3 years duration of CCR. The LIT with high-dose MTX showed no important effect on the duration of CCR. We conclude that the intermittent pulses of 6MP and MTX may be more effective than the continuous administration of these drugs for a maintenance chemotherapy.