Acute lymphoblastic leukemia in patients with Down syndrome with a previous history of acute myeloid leukemia

Abstract

Patients with Down syndrome (DS) are predisposed to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in early and later childhood, respectively, but rarely experience both. We herein discuss four patients with DS with ALL and a history of AML who were treated with various chemotherapies, one of whom later received a bone marrow transplantation. Three patients survived and remain in remission. One patient died of fulminant hepatitis during therapy. No common cytogenetic abnormalities in AML and ALL besides constitutional +21 were identified, indicating that the two leukemia types were independent events. However, the underlying pathomechanism of these conditions awaits clarification.

Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with Down syndrome: A case report and retrospective review of Children's Oncology Group acute myeloid leukemia trials

“…When we reviewed the literature for cases of ALL following AML in patients with Down syndrome, eight cases were reported, published in three manuscripts . A case report by Hellebostad et al from Norway and a case series of four patients by Tomizawa et al in Japan were published with detailed patient demographics and clinical findings (Table ) .…”

“…When we reviewed the literature for cases of ALL following AML in patients with Down syndrome, eight cases were reported, published in three manuscripts . A case report by Hellebostad et al from Norway and a case series of four patients by Tomizawa et al in Japan were published with detailed patient demographics and clinical findings (Table ) . A clinical trial from the Nordic Society of Paediatric Haematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and AML‐BFM study group in 2006 focusing on reduced total dose of etoposide in their Down syndrome cohort by Uffmann et al reported three cases of ALL 1.6‐2.1 years following AML therapy, of which two patients died .…”

“…There was a female predominance in the published cases and presence of transient abnormal myelopoiesis preceding AML diagnosis was reported in half of the patients. GATA1 mutation information was largely unavailable but was tested and present in the one patient in the Japanese cohort . There were no common genetic alterations between any of the published cases other than Inv(9)(p11q13) in the Japan case series .…”

“…GATA1 mutation information was largely unavailable but was tested and present in the one patient in the Japanese cohort . There were no common genetic alterations between any of the published cases other than Inv(9)(p11q13) in the Japan case series . The range of patient ages at diagnosis was 6‐15 years, presenting 1.6‐14 years following AML diagnosis.…”

“…Although the risk of developing AML and ALL is significantly increased in children with Down syndrome, the development of both malignancies in the same patient is very rare. To date, there have been only eight published cases describing ALL developing in survivors of AML with Down syndrome …”