Ribera J M, Ortega J J, Oriol A, Fontanillas M, Hernández-Rivas J M, Brunet S, García-Conde J, Maldonado J, Zuazu J, Gardella S, Besalduch J, León P, Macià J, Domingo-Albós A, Feliu E, San Miguel J F
Hematology Department, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
Haematologica. 1998 Mar;83(3):222-30.
Intensive induction and post-remission therapies have improved the prognosis in adult acute lymphoblastic leukemia (ALL). However, different from children, the impact of late intensification therapy in the overall results of treatment has not been consistently evaluated. The objective of this study was to analyze the results of a multicenter prospective protocol, PETHEMA ALL-89, in which, after intensive induction and consolidation therapy, randomization to receive delayed intensification treatment was performed.
One hundred and eight adults (age > or = 15 years) diagnosed with ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with a five-drug induction therapy, followed by four cycles of early post-remission treatment during four months, and maintenance therapy for two years. Patients in remission at the end of the first year were randomized to receive one six-week cycle of late intensification therapy. Uni- and multivariate analyses of early response to treatment, complete remission (CR), leukemia-free survival (LFS) and overall survival (OS) were performed.
The median (range) age of the series was 28 (15-74) years and leukocyte count 26 x 10(9)/L (1-600). ALL L1/L2 was present in 38/70 patients, early pre-B in 13, common in 53, pre-B in 12 and T in 30 cases. The CR rate was 86%, and refractory disease 9%. Median LFS was 34 months, with a 5-yr probability of 41% (95% CI, 29-53), whereas median OS was 51 months and 5-year probability 47% (34-59%). There were no differences in either LFS and OS between patients who did or did not receive delayed intensification therapy. Prognostic factors for CR attainment were advanced age and slow response to therapy. These two features were, in addition to high leukocyte counts, the parameters with negative influence in both LFS and OS.
The results of PETHEMA ALL-89 are similar to those referred in other chemotherapy-based protocols in adult ALL. Delayed intensification has not improved the length of remission and survival. Efforts to improve the prognosis of adult ALL patients must be mainly focused in early intensification treatment.
强化诱导缓解及缓解后治疗已改善了成人急性淋巴细胞白血病（ALL）的预后。然而，与儿童不同，延迟强化治疗对总体治疗结果的影响尚未得到一致评估。本研究的目的是分析一项多中心前瞻性方案PETHEMA ALL - 89的结果，该方案在强化诱导和巩固治疗后，进行随机分组以接受延迟强化治疗。
1989年至1994年期间，来自22家西班牙医院的108例确诊为ALL（排除ALL L3）的成人患者（年龄≥15岁）接受了五药诱导治疗，随后在四个月内进行四个周期的早期缓解后治疗，并进行两年的维持治疗。第一年结束时处于缓解期的患者被随机分组接受一个为期六周的延迟强化治疗周期。对治疗的早期反应、完全缓解（CR）、无白血病生存（LFS）和总生存（OS）进行单因素和多因素分析。
该系列患者的中位（范围）年龄为28（15 - 74）岁，白细胞计数为26×10⁹/L（1 - 600）。70例患者中ALL L1/L2型38例，早期前B型13例，普通型53例，前B型12例，T型30例。CR率为86%，难治性疾病为9%。中位LFS为34个月，5年概率为41%（95%CI，29 - 53），而中位OS为51个月，5年概率为47%（34 - 59%）。接受或未接受延迟强化治疗的患者在LFS和OS方面均无差异。达到CR的预后因素为高龄和对治疗反应缓慢。除白细胞计数高外，这两个特征对LFS和OS均有负面影响。
PETHEMA ALL - 89的结果与其他基于化疗的成人ALL方案中报道的结果相似。延迟强化并未改善缓解期长度和生存期。改善成人ALL患者预后的努力必须主要集中在早期强化治疗上。
