Downs Syndrome Patients with Acute Lymphoblastic Leukemia; an Intermediate Outcome with a High Infectious Morbidity.

Unlike AML, children with Down syndrome and Acute Lymphoblastic Leukemia (DS-ALL) have been reported to achieve significantly lower rates of remission, with higher mortality and a poorer overall survival. To further study this, we conducted a retrospective review for all DS children who were diagnosed and treated for ALL at our institution from 1997 to 2006. 12 (1.8%) out of 645 children (age 0–14 years) diagnosed with ALL had DS. The median age at diagnosis was 55 months (range 23 – 108 months) and eight were male. The most frequent signs and symptoms were fever (n=11; 91.6%), bleeding tendency (n=8; 75%) and organomegaly (n=9; 83.3%). The median WBC count at diagnosis was 4.99×10⁹/L (range 0.58–500×10⁹/L). The median platelet count and hemoglobin were 255×10⁹/L and 80.5g/L, respectively. None of the patients had CNS disease at diagnosis. Leukemia cell cytogenetics revealed only the additional chromosome 21 for all patients, except in one patient who had 48XY,+X,+21. All cases had a precursor B-cell phenotype, and a DNA index of 1.0. Patients received treatment according to the protocol utilized for intermediate risk ALL at our institution. A good early response to induction therapy by a day-14 bone marrow (BM) evaluation was seen in all patients, and complete remission (CR) was achieved by day 28 of induction for the 11 who completed induction chemotherapy. One patient died toward the end of induction due to severe sepsis. Infection was the most commonly encountered morbidity throughout the course of therapy. Six episodes of febrile neutropenia, two documented bacteremias and one disseminated invasive Aspergillosis were reported during the induction phase. In the post-induction period, 21 episodes of febrile neutropenia were reported, in addition to six documented bacteremias and two patients developed fungal infections, one with fungemia and the other with a nail bed infection. Four patients relapsed at a median time of 13 months from diagnosis. Relapses occurred in the BM for two, as isolated CNS in one, and as combined BM and CNS relapse in one. Seven patients continue in first CR. The overall survival and the relapse free survival at 3 years were 53.7% and 60% respectively.

Conclusion: Although DS ALL children do not present with poor-risk features (infancy, T-cell phenotype, adverse cytogenetics, CNS involvement) they tend to have an intermediate treatment outcome even if treated on relatively intensive protocols. Delays in appropriate therapy due to infectious morbidity could contribute to this sub-optimal outcome.