Down's syndrome in childhood acute lymphoblastic leukemia:: clinical characteristics and treatment outcome in four consecutive BFM trials

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-B FM 81, 83, 86 and 90) of the Berlin-Frankfurt-Munster 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 <6 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 greater than or equal to 6 years, suboptimal treatment and infectious problems contributed to the slight inferior EFS in children with ALL and Dawn'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.