Pediatric Hematology and Oncology, 29:386–388, 2012Copyright C© Informa Healthcare USA, Inc.ISSN: 0888-0018 print / 1521-0669 onlineDOI: 10.3109/08880018.2012.680683

ORIGINAL ARTICLEPericardial Temponade in Down Syndrome

Transient Leukemia-Associated PericardialTamponade in a Neonate with Down Syndrome

Gokhan Buyukkale, MD,1 Merih Cetinkaya,1 Arzu Akcay,2 Muge Payaslı,1

Kazım Oztarhan,3 Ayse Sibel Ozbek,1 and Sultan Kavuncuoglu1

1Division of Neonatology, Department of Pediatrics, Kanuni Sultan Suleyman Training andResearch Hospital, Istanbul, Turkey; 2Department of Pediatric Hematology, Kanuni SultanSuleyman Training and Research Hospital, Istanbul, Turkey; 3Department of PediatricCardiology, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey

Approximately 10% of neonates with Down syndrome may develop a form of megakaryoblas-tic leukemia that usually disappear spontaneously during the first months of the life. Although itseems to have a benign course, it may also be lethal and severe in some cases, especially in theform of hydrops and/or cardiopulmonary failure. Herein, we report a male infant with Down syn-drome who was admitted with respiratory distress due to severe pericardial effusion leading topericardial tamponade in the first 2 weeks of life. Pericardiosentesis and pericardial tube replace-ment in combination with steroid therapy was performed. He responded well to these therapiesand his leukemia resolved on the fourth month of life. This case suggests that severe pericardialeffusion and pericardial tamponade may be life-threatening complications of transient leukemiaof Down syndrome and also it may be managed successfully with appropriate treatments.

Keywords acute leukemias, myeloproliferative disorder, neonatology

INTRODUCTION

Dysmegakaryopoiesisand dyserythropoiesis characterized by an increase ofmegakaryocyte-erythrocyte progenitors in the liver develop in fetuses with Downsyndrome (DS) during the second trimester of gestation and subsequently leadto transient neutrophilia, thrombocytopenia, and polycytemia in neonates [1].In addition to these common abnormalities, 3%–10% of infants with DS developtransient leukemia (DS-TL) or transient myeloproliferative disease (TMD) that ischaracterized by clonal proliferation of blast cells, which show megakaryocyticfeatures in the blood and/or bone marrow [1]. Hyperleukocytosis, abnormal plateletcount, and anemia are usually detected in these infants and it shows regressionwithin 3 months [1]. Approximately, 20% of infants with DS-TL develop acute myeloidleukemia (AML). DS promotes the occurrence of somatic GATA1 mutation inducingan altered hematopoiesis in fetus that characterizes DS-TL. GATA1-mutated cellsshow regression in 80% of DS-TL cases, whereas additional genetic events lead

Received 14 February 2012; accepted 23 March 2012.Address correspondence to Gokhan Buyukkale, Division of Neonatology, Department ofPediatrics, Kanuni Sultan Suleyman Training and Research Hospital, Turgut Ozal Bulvarı No:1,Halkalı/Kucukcekmece/Istanbul, Turkey. E-mail: gbuyukkale@hotmail.com

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Transient Leukemia-Associated Down Syndrome

to AML development in the remaining 20% cases [1]. Isolated fetal and neonatalpericardial/pleural effusion were reported in infants with DS-TL [2–6].

We present a neonate with DS-TL and associated pericardial tamponade who re-quired pericardiosentesis and pericardial tube placement in combination with steroidtherapy.

CASE REPORT

A male infant with clinical stigmata of DS was born at 40 weeks of gestation whowas admitted with respiratory distress on the 13th day of life. Physical examinationrevealed tachycardia, tachypnea, dyspnea, and hepatomegaly. The complete bloodcount showed leukocytosis and thrombocytopenia with hemoglobin of 15.6 g/dL,platelet count 122,000/mm3, and white blood cell count 57,900/mm3. The periph-eral blood smear revealed 24% neutrophils, 9% lymphocytes, 6% monocytes, and 61%blast cells. Bone marrow aspiration yielded 54% blasts. The karyotype of the infant wasfound to be 47,XY,-21 (DS). A chest radiograph showed an enlarged heart and an in-creased cardiothoracic index with clear lung fields. As the echocardiography (ECHO)demonstrated severe pericardial effusion with cardiac tamponade, pericardiocentesiswas performed and a pericardial drainage tube was placed. After the procedure, peri-cardial effusion decreased and his clinical condition improved. After the removal ofpericardial drainage tube, reaccumulation of pericardial fluid necessitated the insti-tution of oral prednisolone therapy. Prednisolone therapy was discontinued within aweek as the pericardial effusion regressed completely. Follow-up ECHO was normal.The leukocytosis and blasts disappeared on the fourth month of follow-up. However,the efficacy of prednisolone treatment on the regression of effusion remained incon-clusive. He did not require any further therapy for DS-TL and he is now in a stablecondition at the age of 6 months.

DISCUSSION

DS-TL is characterized by a clonal proliferation of medullary or circulating blasts ininfants with DS that usually shows spontaneous regression [7]. Although it may be de-tected randomly with laboratory tests, the symptoms may include abdominal disten-sion, bleeding, respiratory distress, congestive heart failure, and infections [4].

Laboratory findings of DS-TL typically include leukocytosis, with normal numbersof neutrophils and lymphocytes, and variable number of blasts. Thrombocytopeniais also common, whereas anemia is uncommon [8, 9]. DS-TL is characterized by in-creased numbers of blasts in the peripheral blood, variable anemia, and thrombocy-topenia with a partial infiltration of blasts in bone marrow aspirates [1, 8].

Although DS-TL is a benign and self-limited process, some fetal complications maybe associated with it. Pericardial effusion was seen as a part of generalized edema andhydrops fetalis. To our knowledge, only three neonates with DS who were admittedwith pericardial tamponade were reported [2, 5, 6]. Pericardial effusion, an importantmorbidity in infants with DS-TL, may either be isolated or it may also be associatedwith hydrops and hypothyroidism [6, 8].

DS-TL is generally accepted as leukemia and clonal cytogenetic abnormalities weredetermined in DS-TL [8]. Also, 20%–30% of infants with DS-TL might develop acuteleukemia usually within 3 years [2, 7, 8].

As most cases of DS-TL do not show progression to leukemia, chemotherapy is notadvocated typically [2, 7]. Recent studies recommend initiating chemotherapy with cy-tosine arabinoside in DS-TL infants with organomegaly, evidence of liver dysfunctionwith reduced hepatic functional reserve, and presence of liver fibrosis [10]. As there

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was no evidence of these risk factors, we did not implement cytosine arabinoside ther-apy.

This case suggests that pericardial effusion in DS-TL might be so severe to lead peri-cardial tamponade in neonates. However, appropriate supportive treatment might behelpful for preventing lethal conditions associated with DS-TL.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for thecontent and writing of the article.

REFERENCES

[1] Bruwier A, Chantrain CF. Hematological disorders and leukemia in children with Down syndrome.Eur J Pediatr. 2011 (Epub ahead of print).

[2] Al-Kasim F, Doyle JJ, Massey GV, et al. Incidence and treatment of potentially lethal diseases intransient leukemia of Down syndrome: Pediatric Oncology Study Group. J Pediatr Hematol Oncol.2002;24:9–13.

[3] Azancot A, Diehl R, Dorgeret S, et al. Isolated pericardial effusion in the human fetus: a report ofthree cases. Prenat Diagn. 2003;23:193–197.

[4] Massey GV, Zipursky A, Chang MN, et al. A prospective study of the natural history of transientleukemia (TL) in neonates with Down syndrome (DS): a Children’s Oncology Group (COG) studyPOG-9481. Blood. 2006;107:4606–4613.

[5] Shenoy RD, Bhat KG, Kamath N, Kumble Y. Transient myeloproliferative disorder and eosinophilicpericardial effusion in a down syndrome neonate. Pediatr Hematol Oncol. 2008;25:123–129.

[6] Hirashima C, Egushi Y, Kohmura Y, et al. Isolated pericardial effusion and abnormal myelopoiesisin a fetus with Down’s syndrome. J Obstet Gynaecol Res. 2000;26:303–306.

[7] Brink DS. Transient leukemia (transient myeloproliferative disorder, transient abnormalmyelopoiesis) of Down syndrome. Adv Anat Pathol. 2006;13:256–262.

[8] Zipursky A, Brown E, Christensen H, et al. Leukemia and/or myeloproliferative syndrome in infantswith Down syndrome. Sem Perinat. 1997;21:97–101.

[9] Smrcek JM, Baschat AA, Germer U, et al. Fetal hydrops and hepatosplenomegaly in the second halfof pregnancy: a sign of myeloproliferative disorder in fetuses with trisomy 21. Ultrasound Obstet Gy-necol. 2001;17:403–409.

[10] Hirabayashi K, Shiohara M, Takahashi D, et al. Retrospective analysis of risk factors for developmentof liver dysfunction in transient leukemia of Down syndrome. Leuk Lymphoma. 2011;52:1523–1527.

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