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| CASE REPORT |
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| Year : 2013 | Volume
: 2
| Issue : 4 | Page : 278-281 |
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Acute megakaryocytic leukemia in a newborn with down syndrome
Ravi Ambey, Ajay Gaur, Neha Agarwal
Department of Pediatrics, Gajraraja Medical College and Kamlaraja Hospital, Gwalior, Madhya Pradesh, India
| Date of Web Publication | 26-Nov-2013 |
Correspondence Address:
Ravi Ambey
Department of Pediatrics, Gajraraja Medical College and Kamlaraja Hospital, Gwalior, Madhya Pradesh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2277-8632.122169
Patient with Down's syndrome (DS) are found to have an increased risk of developing various hematological disorders. There is 46- to 83-fold increased risk of acute myeloid leukemia (AML) and 10- to 27-fold increased risk of acute lymphoid leukemia (ALL). One of the most characteristics feature of Down syndrome associated AML (DS-AML) is that vast majority of case (c.70%) of AML in DS are megakaryoblastic i.e. M7 as per FAB classification (DS- AMKL). Virtually, all cases of DS-AMKL occur within the first 5 years of life. The median age of presentation of AMKL is 1.8 years. We report a case of AMKL in a newborn with Down's syndrome. Keywords: Acute myeloid leukemia, acute megakaryocytic leukemia, down′s syndrome
How to cite this article:
Ambey R, Gaur A, Agarwal N. Acute megakaryocytic leukemia in a newborn with down syndrome. J NTR Univ Health Sci 2013;2:278-81 |
| Introduction | |  |
Down syndrome due to trisomy 21 is the commonest chromosomal abnormality in human. The spectrum of hematological abnormalities in newborn and child with DS include a variety of benign and malignant abnormalities. The overall incidence of leukemia in DS is estimated to be 10- to 30-fold more. There is 46- to 83-fold increased risk of AML and 10- to 27-fold increased risk of ALL. One of the most characteristics features of DS-associated AML is that the vast majority of cases of AML in DS (c.70%) are megakaryoblastic. The median age at presentation of AMKL is 1.8 years, and virtually all case of DS-AMKL occurs within the first 5 years of life. Children with DS-AMKL have a superior outcome when compared with children with sporadic AML. We report a case of AMKL in a newborn with Down syndrome.
| Case Report | | |
A 22-days-old male newborn was referred to our Neonatal Intensive Care Unit (NICU) for hyperleukocytosis in peripheral blood smear. The baby was a product of non-consanguineous marriage and unbooked and uneventful pregnancy of a 26-year-old mother, delivered at hospital through a normal vaginal delivery. As per mother, for the initial 14 days of life baby was doing well, thereafter mother noticed swelling over the face and abdomen of the baby followed by dyspnea within a course of 7 days. Newborn was taken to a primary care physician. He recommended a peripheral blood smear, which was suggestive of hyperleukocytosis. On admission in NICU, the newborn was showing phenotype of Down's syndrome, which was later confirmed by karyotyping [Figure 1], [Figure 2] and [Figure 3]. On examination, he was having abdominal distension with subcutaneous nodules, hepatosplenomegaly with liver 8 cm below the costal margin and spleen 6 cm below the costal margin, respiratory distress, and icterus [Figure 4],[Figure 5]. Blood count revealed hemoglobin 9 gm%, leukocytosis (83.0 × 1000 cells per mm 3 with a predominant of blast cell (60%), and thrombocytopenia (91.0 × 1000 cells per mm 3 . Peripheral smear was showing megakaryoblasts and nucleated RBC. Bone marrow aspirate was showing dysplastic megakaryocyte, abundant megakaryoblasts, and areas of myelofibrosis. Biochemical analysis showing deranged liver function with serum bilirubin 8.2 mg/dl, direct bilirubin 5.9 mg/dl, SGPT 470 u/l, alkaline phosphatase 380 u/l. Urine examination and screening test for infections were found to be negative. Blood culture did not show any growth at 48 hours and sterile at 7 days. On 27 th day of life, repeat investigations showing serum bilirubin 18.6 mg/dl, direct bilirubin 16.5 mg/dl, SGPT 890 u/l, alkaline phosphatase 560 u/l, hemoglobin 8 gm%, total leukocyte count 68.0 × 1000 cells per mm 3 , platelet count 58 × 1000 mm 3 . Cytochemistry was found negative for myeloperoxidase (MPO) and sudan black. Immunophenotyping revealed markers positive for CD34 and CD41 antigen, suggestive of AML M7 type. He was given supportive treatment with intravenous fluids, antibiotics. Chemotherapy was started with low dose cytarabine. But, the condition of newborn kept on deteriorating and began to bleed profusely from the gastrointestinal tract. Coagulation profile was showing thrombocytopenia with raised prothrombin time, suggestive of disseminated intravascular coagulation and resulted in circulatory collapse. Blood products combined with fluids, ionotropes, and vasopressor agents were administered, but the infant could not be revived and expired at 32 days of life. | Figure 1: Facial dysmorphism of the newborn with down syndrome with AMKL
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 | Figure 3: Karyotyping depicting trisomy 21 in the newborn with down syndrome with AMKL
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 | Figure 4: Hepatosplenomegaly in the newborn with down syndrome with AMKL
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 | Figure 5: Nodular skin infi ltrates (leukemia cutis) in the newborn with down syndrome with AMKL
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| Discussion | | |
Down's syndrome, the most common chromosomal abnormality in a live newborn, is caused by an extra complete or partial copy of chromosome 21. It is found to be associated with characteristic dysmorphic facies and various congenital anomalies involving cardiovascular, gastrointestinal, endocrinal, and hematological system. Hematological abnormalities can be non-fatal blood count abnormalities like polycythemia, leukcopenia, neutropenia, thrombocytopenia or fatal conditions like leukemia and transient myeloproliferative disorder (TMD). [1],[2]
Congenital leukemia is an exceedingly uncommon disease in the newborn. Its incidence is between 4.3 and 8.6 per million live births. [3] Congenital leukemia, diagnosed between birth to 6 weeks of age, are found to be associated with syndromes like trisomy 21, Turner's syndrome, mosaic trisomy 9, mosaic monosomy 7 etc. [4] Although cases are now been reported where these leukemia are not associated with any syndrome. [5] Among the syndromic causes, Down's syndrome is found to have increased incidence of both AML and ALL. However, the incidence of AML is more during first 3 years of life. DS-AML in newborn usually presents with nodular skin infiltrates (bluish, fibroma-like tumors, leukemia cutis), hepatosplenomegaly, lethargy, poor feeding, pallor, purpura/petechiae, respiratory distress. [4] Most Down's syndrome AML are of AML-M7 (DS-AMKL) type. AML-M7 is defined under FAB classification by more than 20% blasts of megakaryocytic lineage in bone marrow aspirates as determined by morphology and immunocytochemistry. [6] In DS-AMKL peripheral blood smear, bone marrow aspirate morphology and cytochemical profile is similar to those seen in TMD. Transient myeloproliferative disorder is a clonal disorder characterized by circulating peripheral blasts cells and dysplastic features, most marked in red cells and megakaryocyte lineage. Though the frequency of TMD is estimated to be around 10%, the true incidence of TMD is unknown as it can occur in asymptomatic neonates, and the blood count and blood film are not routinely performed on newborn with DS. TMD usually manifests during the first few days of life, with normal hematocrit and platelet counts. Median age of presentation is 3-7 days of life, and all cases present within two months. [7] While hematogenic and cytogenic differences have been cited, none of them absolutely differentiates between the DS-AMKL and TMD. [8] Electron microscopy reveals positive peroxidase reaction localized exclusively on the nuclear membrane and the endoplasmic reticulum. Reported survival in TMD is good. [9] However, this is not the case, especially in babies with severe liver disease associated with fibrosis; here, the response to chemotherapy is poor, and overall there is a poor prognosis. Reported mortality in TMD is 20%. Although TMD resolves in the majority of DS infants, 20-30% subsequently go on to develop full-blown AMKL, usually within the first 4 years of life. [7] Recent studies have identified a genetic mutation "GATA1 mutation" associated in many patients of Down's syndrome with TMD or leukemia. GATA1 gene encodes a transcription factor critical for normal erythroid and megakaryocytic development. This mutation indeed was found beneficial to these patients as it is responsible for greater sensitivity for specific chemotherapeutic drug cytosine arabinoside, which contributes to greater survival rate. [10] Children with Down's syndrome are found to have an excellent response to chemotherapy. The results of treatment are found to be equal to or better than those of other groups of children with AML as long as adequate doses of chemotherapy are given and extra vigilance paid to infectious complications. [11] Children with DS-AMKL have a superior outcome when compared with children with sporadic AML. Recent results show long-term survival for the majority of DS-AMKL children, the probability of survival range from 74-91%. [7]
| References | | |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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