Early and delayed consolidation chemotherapy significantly improves the outcome of children with intermediate risk acute lymphoblastic leukemia. Final results of the prospective randomized PETHEMA ALL-89 TRIAL.

BACKGROUND AND OBJECTIVES: To evaluate the impact of early and delayed consolidation chemotherapy on the outcome of children with acute lymphoblastic leukemia (ALL) stratified according to risk groups. DESIGN AND METHODS: From 1989 to 1994, 195 children (< or = 15 years old) diagnosed as having ALL (ALL-L3 excluded) in 15 Spanish hospitals entered the prospective, randomized PETHEMA ALL-89 trial. Patients were stratified into low-risk (LR), intermediate-risk (IR) and high-risk (HR) groups according to their initial features and the rate of response to induction therapy. LR-ALL patients were randomized to receive or not early consolidation chemotherapy (C-1). After receiving C-1, IR patients were randomized to receive or not delayed consolidation chemotherapy (C-2). HR patients received C-1 and C-2 chemotherapy. Standard maintenance chemotherapy was administered to all patients for 2 years. High doses of intravenous methotrexate and 12 triple intrathecal doses were given as prophylaxis against central nervous system (CNS) disease. RESULTS: The mean (and standard deviation) age was 6 (4) years and 120 patients were males. Fourteen patients had early pre-B-ALL, 149 common or pre-B-ALL, and 32 T-ALL. Complete remission (CR) was attained in 189 patients (97%), 11 of whom (6%) had a slow response. Risk group stratification after CR was: LR 89, IR 50 and HR 56 patients (including a subset of 26 patients at very high risk). Ten-year event-free survival (EFS) and overall survival (OS) probabilities for the whole series were 58% (95% CI: 52-64%) and 69% (61-77), respectively, with a median follow-up of 8.7 years. Dividing the patients according to risk group, the 10-year EFS and OS probabilities in the LR group were 71% (63-79) and 86% (80-92), respectively; in the IR group 69% (57-81) and 76% (64-88), respectively, and in the HR group 30% (18-42) and 44% (32-57), respectively. For LR patients receiving C-1, EFS and OS were 79% (57-92) and 90% (82-98), respectively, versus 62% (48-76) and 66% (51-81) in patients not receiving C-1 (p= 0.06). For IR patients, EFS and OS were significantly improved in those receiving early and delayed consolidation (EFS 87% (74-88) vs. 52% (41-70), and OS 92% (87-97) vs. 61% (51-71)(p=0.036). Prognostic factors for EFS identified in multivariable analyses were: age >10 years in the LR group (OR 3.5, 95% CI 1.3-9.5, p=0.01), and treatment with C-2 in IR patients (OR 5.0, 95% CI 1.4-17.8, p=0.01). The CNS relapse rate was 4% for all the series (including the HR subset). Tolerance to treatment was good. INTERPRETATION AND CONCLUSIONS: In this study, early consolidation seemed to improve the prognosis of children with LR-ALL, but differences in EFS were not significant. Delayed consolidation had a favorable influence on the outcome of IR-ALL. CNS preventive treatment without cranial irradiation was effective in all the groups of ALL patients.

[Hodgkin's disease. Our 9-year experience with the 1980 protocol]. / Enfermedad de Hodgkin. Nuestra experiencia de neuve años con el protocolo de 1980.

The purpose of this work was to evaluate the therapeutic results attained with our 1980 protocol for Hodgkin's disease. The usefulness of staging laparotomy was also analysed. Along a 9-year period, 94 patients were diagnosed (stages IA and IIA: 26 cases, IB, IIB and IIIA: 24 cases, and IIIB and IV: 44 cases). The complete remission (CR) rate, as a whole, was 85%; there were 14 relapses, of whom a new CR was attained in 9 instances. The overall actuarial survival is 64% at 47 months. The appearance of 3 cases of acute non-lymphoblastic leukaemia is noteworthy. Laparotomy induced changes of the patient's staging in 49% of cases (rise in 43% and descent in 6%). In account of this, laparotomy seems an adequate procedure in staging, although the criteria for selecting the patients who will undergo this, procedure should be perhaps restrictive.

[Non-Hodgkin's lymphoma in childhood. Review of 33 cases]. / Linfoma no Hodgkin infantil. Revisión de 33 casos.

A retrospective study was performed of 33 cases of non Hodgkin's lymphoma in children diagnosed in our hospital. The mean age was 10 years and there were 24 males and 9 females. The distribution, according to Rappaport's diagnostic classification, was: 11 undifferentiated lymphomas, 9 lymphoblastic lymphomas, 6 diffuse histiocytic lymphomas, and 7 cases of other types. Of the 33 patients, 23 had bulky disease (over 5 cm. in diameter). The mean serum LDH and uric acid values were, respectively, 537 (68-2021) and 6.0 (2.7-19). According to Murphy's staging system, the distribution of the cases was as follows: I (1), II (4), III (12), IV (16). Since this study spreads for a long period, several protocols have been used in the treatment of the group, but most patients received the LSA2-L2 regimen. Complete remission (CR) was achieved in 26 cases (78%), this being 100% of the lymphoblastic lymphomas. After a mean follow-up of 45 months, the actuarial survival is 48.1%, and the disease-free survival of patients attaining CR is 60.4%. The prognostic factors analysed, such as histologic type, stage, and serum LDH showed no statistical significance, probably due to the low number of cases studied.