Winick N, Buchanan G R, Murphy S B, Yu A, Boyett J
Southwestern Medical School, University of Texas Southwestern Medical Center, Dallas.
Med Pediatr Oncol. 1988;16(5):327-32. doi: 10.1002/mpo.2950160507.
2-Deoxycoformycin (DCF) was added to an intensive Pediatric Oncology Group protocol (#8303) for children with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma in first relapse. Twenty-seven patients received one or more courses of DCF at 15 mg/m2/day as a 3-day continuous infusion immediately after achieving a second remission with a four-drug reinduction regimen. Renal and neuromuscular toxicities were frequent and occasionally severe despite the provision of a source of adenosine deaminase by means of a packed red cell transfusion 1 day following the infusion of DCF. Hepatic toxicity, manifested by transaminase elevations, accompanied 62% of the courses. The median duration of the second complete remission was 4 months (range 2-16+ months), with only two of the 27 patients still in remission at 13+ and 16+ months. Plasma concentrations of deoxyadenosine (dAdo) and the ratio of red cell deoxyadenosine triphosphate to adenosine triphosphate (dATP:ATP) were measured prior to the DCF infusion and on day 4. A dATP:ATP ratio of 1.0 or greater was seen in two patients with acute renal failure. There was no apparent correlation between toxicity or response and the plasma dAdo concentrations. DCF administered according to this dose and schedule was excessively toxic and did not appreciably prolong the duration of the second complete remission in children with T-cell lymphoblastic malignancies.
2-脱氧助间型霉素(DCF)被纳入儿童肿瘤学组的一项强化方案(#8303),用于治疗首次复发的T细胞急性淋巴细胞白血病或T细胞淋巴母细胞淋巴瘤患儿。27例患者在采用四药再诱导方案实现第二次缓解后,立即接受一个或多个疗程的DCF治疗,剂量为15mg/m²/天,持续输注3天。尽管在输注DCF后1天通过输注浓缩红细胞提供了腺苷脱氨酶来源,但肾毒性和神经肌肉毒性仍很常见,偶尔还很严重。62%的疗程出现转氨酶升高所表现的肝毒性。第二次完全缓解的中位持续时间为4个月(范围2 - 16 +个月),27例患者中只有2例在13 +和16 +个月时仍处于缓解状态。在输注DCF前及第4天测量血浆脱氧腺苷(dAdo)浓度以及红细胞三磷酸脱氧腺苷与三磷酸腺苷的比值(dATP:ATP)。两名急性肾衰竭患者的dATP:ATP比值达到或超过1.0。毒性或反应与血浆dAdo浓度之间无明显相关性。按照此剂量和疗程给予DCF毒性过大,并未显著延长T细胞淋巴母细胞恶性肿瘤患儿第二次完全缓解的持续时间。