Patients with down syndrome are at increased risk of acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia M7 (AML-M7).
This patient's quad screen in consistent with a diagnosis of down syndrome (trisomy 21). In addition to an increased risk of duodenal atresia, congenital heart disease, and Alzheimer's disease, patients with trisomy 21 are also at an increased risk of childhood acute lymphoblastic leukemia and acute myelogenous leukemia M7 (AML-M7). ALL typically presents before 15 years of age, and an increased number of lymphoblasts are seen in the peripheral blood and bone marrow (Illustrations A and B). It tends to be responsive to therapy, with a current 5-year survival rate of 85%.
Goto et al. performed a case series to assess the efficacy and toxicities associated with hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia and Down syndrome. They find that there is significant morbidity and mortality in those patients with Down syndrome, and therapy-related mortality accounted for five out of seven deceased patients in their case series.
Mezei et al. examine the epidemiology of childhood leukemia in
the presence and absence of Down syndrome. The authors note that Down syndrome is a known substantial risk factor for childhood leukemia and further describe environmental factors which could also contribute. They state that, while ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia, other possible factors include infections, exposure to pesticides, and extremely low frequency magnetic fields.
Illustrations A and B demonstrate a peripheral blood smear and bone marrow biopsy, respectively, with an increased number of lymphoblasts consistent with ALL. Illustration C shows the characteristic smudge cells seen in CLL. Illustration D demonstrates the characteristic filamentous, hair-like projections on B cells seen in hairy cell leukemia. Illustration E depicts the characteristic Auer rods present in APML-M3.
Answer 1: Chronic lymphocytic leukemia is not associated with Down syndrome. It typically presents >60 years of age and has characteristic smudge cells seen in the peripheral blood smear (Illustration C).
Answer 2: Hairy cell leukemia is not associated with Down syndrome. It is usually seen in adults, and B cells have the characteristic filamentous, hair-like projections on peripheral blood smear (Illustration D).
Answer 3: Acute promyelocytic leukemia is not associated with Down syndrome. It is usually seen in adults and displays the characteristic auer rod on peripheral smear (Illustration E).
Answer 5: Chronic myelogenous leukemia is not associated with Down syndrome. It is seen between 30-60 years of age and contains the Philadelphia chromosome t(9;22).
Goto H, Kaneko T, Shioda Y, Kajiwara M, Sakashita K, Kitoh T, Hayakawa A, Miki M, Kato K, Ogawa A, Hashii Y, Inukai T, Kato C, Sakamaki H, Yabe H, Suzuki R, Kato K. Hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia and Down syndrome. Pediatr Blood Cancer. 2015 Jan;62(1):148-52. doi: 10.1002/pbc.25245. Epub 2014 Sep 27. PubMed PMID: 25262825.
PMID:25262825 (Link to Abstract)
Mezei G, Sudan M, Izraeli S, Kheifets L. Epidemiology of childhood leukemia in the presence and absence of Down syndrome. Cancer Epidemiol. 2014 Oct;38(5):479-89. doi: 10.1016/j.canep.2014.07.006. Epub 2014 Aug 10. PubMed PMID: .
PMID:25113940 (Link to Abstract)