Circulating Blasts and Associated Hematologic Disorders in Neonates with Down Syndrome

Gregory L. Jackson; Dorothy M. Sendelbach; Brooke Rambally; M. Denise Manning; William D. Engle

doi:10.1055/s-0031-1285103

American Journal of Perinatology, Table of Contents

Am J Perinatol 2012; 29(04): 259-266
DOI: 10.1055/s-0031-1285103

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Circulating Blasts and Associated Hematologic Disorders in Neonates with Down Syndrome

Gregory L. Jackson

¹Department of Pediatrics, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

,

Dorothy M. Sendelbach

¹Department of Pediatrics, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

,

Brooke Rambally

²University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina

,

M. Denise Manning

¹Department of Pediatrics, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

,

William D. Engle

²University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina

› Author Affiliations

Abstract

We analyzed complete blood count (CBC) data obtained from neonates with Down syndrome (DS) in a primarily Hispanic population over a 10-year period to determine the incidence of hematologic abnormalities and the relationship of abnormalities to the presence of circulating blasts (CB). Hematologic values obtained during the first 10 days were analyzed. Definitions were: CB, ≥ 1% blasts manually counted on peripheral smear; elevated white blood cell count (WBC), >30,000 cells/mm³; thrombocytopenia, platelet count < 150,000/mm³; polycythemia, hematocrit >65%. Two hundred thirty-two neonates (88% Hispanic) with DS had 692 CBCs available for analysis. The presence of CB (11.6%) and the incidence of thrombocytopenia (60.2%) were significantly higher in DS neonates than in the reference group. Elevated WBC (33.3%) and thrombocytopenia (84.6%) were more common in DS neonates with CB versus those with no CB. No relationship between thrombocytopenia and polycythemia was observed. Unlike previous reports, we did not observe a male predominance in those DS neonates with CB. Thrombocytopenia occurred frequently in DS neonates and was significantly more likely in those with CB than in those with no CB. CBC screening should be performed routinely in DS neonates.

Keywords

myeloproliferative disorder - megakaryoblasts - thrombocytopenia - transient leukemia - polycythemia

Full Text

References

References
1 Brink DS. Transient leukemia (transient myeloproliferative disorder, transient abnormal myelopoiesis) of Down syndrome. Adv Anat Pathol 2006; 13: 256-262
2 Zipursky A, Brown EJ, Christensen H, Doyle J. Transient myeloproliferative disorder (transient leukemia) and hematologic manifestations of Down syndrome. Clin Lab Med 1999; 19: 157-167 ; vii
3 Bajwa RPS, Skinner R, Windebank KP, Reid MM. Demographic study of leukaemia presenting within the first 3 months of life in the Northern Health Region of England. J Clin Pathol 2004; 57: 186-188
4 Massey GV. Transient leukemia in newborns with Down syndrome. Pediatr Blood Cancer 2005; 44: 29-32
5 Massey GV, Zipursky A, Chang MN , et al. Children's Oncology Group (COG). A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481. Blood 2006; 107: 4606-4613
6 Al-Kasim F, Doyle JJ, Massey GV, Weinstein HJ, Zipursky A. Pediatric Oncology Group. Incidence and treatment of potentially lethal diseases in transient leukemia of Down syndrome: Pediatric Oncology Group Study. J Pediatr Hematol Oncol 2002; 24: 9-13
7 Hitzler JK, Zipursky A. Origins of leukaemia in children with Down syndrome. Nat Rev Cancer 2005; 5: 11-20
8 Henry E, Walker D, Wiedmeier SE, Christensen RD. Hematological abnormalities during the first week of life among neonates with Down syndrome: data from a multihospital healthcare system. Am J Med Genet A 2007; 143: 42-50
9 Webb D, Roberts I, Vyas P. Haematology of Down syndrome. Arch Dis Child Fetal Neonatal Ed 2007; 92: F503-F507
10 Smrcek JM, Baschat AA, Germer U, Gloeckner-Hofmann K, Gembruch U. Fetal hydrops and hepatosplenomegaly in the second half of pregnancy: a sign of myeloproliferative disorder in fetuses with trisomy 21. Ultrasound Obstet Gynecol 2001; 17: 403-409
11 Homans AC, Verissimo AM, Vlacha V. Transient abnormal myelopoiesis of infancy associated with trisomy 21. Am J Pediatr Hematol Oncol 1993; 15: 392-399
12 Taub JW, Mundschau G, Ge Y , et al. Prenatal origin of GATA1 mutations may be an initiating step in the development of megakaryocytic leukemia in Down syndrome. Blood 2004; 104: 1588-1589
13 Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A. GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood 2003; 101: 4301-4304
14 Pine SR, Guo Q, Yin C, Jayabose S, Druschel CM, Sandoval C. Incidence and clinical implications of GATA1 mutations in newborns with Down syndrome. Blood 2007; 110: 2128-2131
15 Awasthi A, Das R, Varma N , et al. Hematological disorders in Down syndrome: ten-year experience at a Tertiary Care Centre in North India. Pediatr Hematol Oncol 2005; 22: 507-512
16 Zipursky A, Brown E, Christensen H, Sutherland R, Doyle J. Leukemia and/or myeloproliferative syndrome in neonates with Down syndrome. Semin Perinatol 1997; 21: 97-101
17 Nakagawa T, Nishida H, Arai T, Yamada T, Fukuda M, Sakamoto S. Hyperviscosity syndrome with transient abnormal myelopoiesis in Down syndrome. J Pediatr 1988; 112: 58-61
18 Jackson GL, Engle WD, Sendelbach DM , et al. Are complete blood cell counts useful in the evaluation of asymptomatic neonates exposed to suspected chorioamnionitis?. Pediatrics 2004; 113: 1173-1180
19 Widness JA, Pueschel SM, Pezzullo JC, Clemons GK. Elevated erythropoietin levels in cord blood of newborns with Down's syndrome. Biol Neonate 1994; 66: 50-55
20 Dixon N, Kishnani PS, Zimmerman S. Clinical manifestations of hematologic and oncologic disorders in patients with Down syndrome. Am J Med Genet C Semin Med Genet 2006; 142C: 149-157
21 American Academy of Pediatrics. Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics 2001; 107: 442-449
22 Pui CH. Two tales of infant leukemia. Blood 2006; 107: 4576-4577
23 Hord JD, Gay JC, Whitlock JA. Thrombocytopenia in neonates with trisomy 21. Arch Pediatr Adolesc Med 1995; 149: 824-825
24 Hayashi Y, Hanada R, Yamamoto K , et al. Transient megakaryoblastic proliferation in a newborn infant with Down's syndrome. Cancer Genet Cytogenet 1987; 28: 373-374
25 Suda J, Eguchi M, Ozawa T , et al. Platelet peroxidase-positive blast cells in transient myeloproliferative disorder with Down's syndrome. Br J Haematol 1988; 68: 181-187
26 Bunin N, Nowell PC, Belasco J , et al. Chromosome 7 abnormalities in children with Down syndrome and preleukemia. Cancer Genet Cytogenet 1991; 54: 119-126
27 Zipursky A, Peeters M, Poon A. Megakaryoblastic leukemia and Down's syndrome—a review. Prog Clin Biol Res 1987; 246: 33-56
28 Matsubara K, Nigami H, Yura K, Inoue T, Isome K, Fukaya T. Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome. J Perinatol 2010; 30: 98-102
29 Wechsler J, Greene M, McDevitt MA , et al. Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet 2002; 32: 148-152
30 Groet J, McElwaine S, Spinelli M , et al. Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder. Lancet 2003; 361: 1617-1620
31 Mundschau G, Gurbuxani S, Gamis AS, Greene ME, Arceci RJ, Crispino JD. Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis. Blood 2003; 101: 4298-4300
32 Ahmed M, Sternberg A, Hall G , et al. Natural history of GATA1 mutations in Down syndrome. Blood 2004; 103: 2480-2489
33 Hayashi Y, Eguchi M, Sugita K , et al. Cytogenetic findings and clinical features in acute leukemia and transient myeloproliferative disorder in Down's syndrome. Blood 1988; 72: 15-23