de Diego-Floreschapa J, López-Hernández M, Borbolla-Escoboza J R, Trueba-Christy E, Carrillo-Rosales T, González-Avante M
Servicio de Hematología, Centro Médico Nacional 20 de Noviembre, México, D.F.
Gac Med Mex. 1999 May-Jun;135(3):253-8.
This paper reports the long-term, disease-free survival of children with high-risk (HR) acute lymphoblastic leukemia (ALL) treated with two different chemotherapy regimens. HR was defined in children with ALL, younger than 2 or older than 10 years, with or without initial extrahematopoietic disease, with a leukocyte count higher than 25 x 10(9)L, or with L3 FAB type. The first group, LAL1, included 67 patients; they received induction with vincristine (VCR) and prednisone (PDN), early consolidation with 3 cycles of 6-mercaptopurine (6MP), citarabine (ARA) and VCR: central nervous system (CNS) prophylaxis (PFX) consisted of both chemotherapy in induction, consolidation and maintenance, radiotherapy (RT) in consolidation. Maintenance was given with 6MP, methotrexate (MTX), VCR adriamycin (ADR), ARA, cyclophosphamide (CFA) and PDN. The second group, LAL2, with 45 patients, received induction with VCR, PDN, CFA, epirrubicin (EPI), L-Asparaginase (L-ASP); early and late consolidation with 6MP, ARA, VCR, carmustine (BCNU), CFA, EPI, MTX and teniposide 8VM26): CNS PFX consisted of both chemotherapy in induction, consolidation and maintenance, RT in consolidation, maintenance with 6MP, MTX, EPI, CFA, ARA VM26 and BCNU. At the time of diagnosis, both groups were comparable. Disease-free survival probability, for LAL1 group was 0.41 at 14 years and for LAL2 group 0.34 at 8 years (p = 0.45). In the LAL1 group there were three failures and 20 relapses, and in the LAL2 group, there were two failures and 22 relapses. CNS relapses were one and seven in LAL1 and LAL2 groups respectively (p = 0.04). In the LAL2, group relapses were more frequent in patients with dose reduction or difered dose due to marrow toxicity (p = 0.02). We believe that the increase in CNS relapse in the LAL2 group was caused by the late administration of CNS PFX. We also believe that although intensive chemotherapy can increase long-term survival, dose adjustments due to marrow toxicity have a negative effect on long-term, relapse-free survival.
本文报告了采用两种不同化疗方案治疗的高危（HR）急性淋巴细胞白血病（ALL）患儿的长期无病生存率。HR定义为年龄小于2岁或大于10岁、有或无初始造血外疾病、白细胞计数高于25×10⁹/L或FAB分型为L3型的ALL患儿。第一组，LAL1，包括67例患者；他们接受长春新碱（VCR）和泼尼松（PDN）诱导治疗，6-巯基嘌呤（6MP）、阿糖胞苷（ARA）和VCR进行3个周期的早期巩固治疗：中枢神经系统（CNS）预防（PFX）包括诱导、巩固和维持期的化疗，巩固期的放疗（RT）。维持治疗采用6MP、甲氨蝶呤（MTX）、VCR、阿霉素（ADR）、ARA、环磷酰胺（CFA）和PDN。第二组，LAL2，有45例患者，接受VCR、PDN、CFA、表柔比星（EPI）、L-天冬酰胺酶（L-ASP）诱导治疗；6MP、ARA、VCR、卡莫司汀（BCNU）、CFA、EPI、MTX和替尼泊苷8VM26进行早期和晚期巩固治疗：CNS PFX包括诱导、巩固和维持期的化疗，巩固期的RT，维持治疗采用6MP、MTX、EPI、CFA、ARA VM26和BCNU。在诊断时，两组具有可比性。LAL1组14年时的无病生存概率为0.41，LAL2组8年时为0.34（p = 0.45）。LAL1组有3例治疗失败和20例复发，LAL2组有2例治疗失败和22例复发。LAL1组和LAL2组的CNS复发分别为1例和7例（p = 0.04）。在LAL2组中，因骨髓毒性而剂量减少或剂量不同的患者复发更频繁（p = 0.02）。我们认为LAL2组CNS复发增加是由于CNS PFX给药延迟所致。我们还认为，尽管强化化疗可提高长期生存率，但因骨髓毒性进行剂量调整对长期无复发生存率有负面影响。
