No abstract

Summary We analysed the impact of age and gender on biology and outcome of 2084 patients diagnosed with non‐Hodgkin lymphoma (NHL) between October 1986 and December 2002 and treated according to the Berlin‐Frankfurt‐Münster (BFM) multicentre protocols NHL‐BFM‐86, ‐90 and ‐95. Median age at diagnosis was 8·0 years for 97 precursor B‐lymphoblastic lymphoma (pB‐LBL) patients, 8·8 years for 335 T‐lymphoblastic lymphoma (T‐LBL) patients, 8·4 years for 1004 Burkitt's lymphoma/leukaemia (BL/B‐AL) patients, 11·4 years for 173 diffuse large B‐cell lymphoma (centroblastic subtype) (DLBCL‐CB) patients, 13·2 years for 40 primary mediastinal large B‐cell lymphoma (PMLBL) patients and 10·8 years for 215 anaplastic large‐cell lymphoma (ALCL) patients (P < 0·00001). The male:female ratio was 0·9:1 for pB‐LBL and PMLBL, 1·7:1 for DLBCL‐CB, 1·8:1 for ALCL, 2·5:1 for T‐LBL and 4·5:1 for BL/B‐AL (P < 0·00001). The probability of event‐free survival at 5 years (5‐year pEFS) was 85 ± 1% for all 2084 patients [median follow‐up 5·7 (0·1–15·9) years], and was significantly superior for male T‐LBL and DLBCL‐CB patients. Comparing age‐groups 0–4, 5–9, 10–14 and 15–18 years, pEFS was inferior for the youngest patients only in the pB‐LBL‐ and ALCL‐groups. T‐LBL and DLBCL‐CB adolescent females had worse outcome than younger girls while age had no impact on pEFS for boys. We conclude that the distribution of age and gender differed between NHL‐subtypes. The impact of gender on outcome differed between NHL subgroups. The prognostic impact of age differed not only by NHL‐subtype but also according to gender in some subtypes.

This therapy strategy provided patients of all NHL subtypes with an equally high chance to survive event-free, except patients with PTCL. With reduced systemic failure, local tumor control may become more important.

A total of 1111 children with acute myeloblastic leukaemia (AML) were treated in four consecutive Berlin-Frankfurt-Mü nster (BFM) studies from 1978 to 1998. The first cooperative trial AML-BFM 78 established intensive chemotherapy with seven drugs, CNS irradiation and 2-year maintenance, achieving a long-term survival (overall survival (OS)) of 40%. Induction intensification in AML-BFM 83 resulted in significant improvement of disease-free survival (DFS). The risk of haemorrhage, especially in children with hyperleukocytosis, proved the high relevance of supportive care. In AML-BFM 87, the benefit of CNS irradiation in preventing CNS/systemic relapses was demonstrated. In AML-BFM 93, the introduction of idarubicin during first induction followed by intensification with HAM increased the 5-year EFS, DFS and OS to 5072, 6173 and 5772%, respectively. Stem cell transplantation (SCT), as applied in high-risk patients with a matched related donor, did not significantly improve the outcome compared to chemotherapy alone. In spite of treatment intensification, the therapyrelated death rate decreased from trial to trial, mainly during induction. The future aim is to reduce long-term sequelae, especially cardiotoxicity, by administration of less cardiotoxic drugs, and toxicity of SCT by risk-adapted indications. The AML-BFM studies performed in three European countries with 470 cooperating centres have significantly improved the outcome in AML children; nevertheless, increasing experience with these intensive treatment regimens is of fundamental importance to reduce fatal complications.

Clinical characteristics, treatment response and outcome were evaluated in children with Down's syndrome (DS) and acute lymphoblastic leukemia (ALL) as compared to other children with ALL (NDS). Sixty-one DS and 4049 NDS patients, receiving intensive antileukemic treatment during four consecutive trials (ALL-BFM 81, 83, 86 and 90) of the Berlin-Frankfurt-Mü nster Group (BFM), were retrospectively analyzed. DS and NDS children did not differ with respect to sex, leukocyte count, CNS leukemia and cytogenetic translocations. The DS cohort was slightly older (P = 0.04), presented predominantly with the common while lacking the T immunophenotype (P = 0.005), had a lower frequency of hyperdiploidy (P = 0.004) and tended to have a better initial steroid response (P = 0.057). Therapy-associated morbidity especially during high-dose methotrexate and a subsequent need for treatment modification occurred in 43% of all DS patients. Event-free survival (EFS) was slightly worse in children with DS (58 ± 8% vs 70 ± 1%, P = 0.14), mainly due to rather late bone marrow recurrences. However, EFS in DS patients was comparable to the NDS group once they either received treatment with no major modifications (65 ± 9% vs 70 ± 1%, P = 0.66) or were Ͻ6 years of age, irrespectively of therapy modifications (73 ± 9% vs 74 ± 1%, P = 0.7). Cox regression analysis revealed that DS was an adverse prognostic factor for patients having completed therapy (P = 0.0107), but was not prognostic at diagnosis (P = 0.103). Age у6 years, suboptimal treatment and infectious problems contributed to the slight inferior EFS in children with ALL and Down's syndrome. Therefore, most of these patients can be successfully treated if receiving intensive antileukemic treatment with no major modifications, but they require more sophisticated management of toxicity.