Transient neonatal myeloproliferative disorder in the absence of Down syndrome

Transient neonatal leukemia or transient neonatal myeloproliferative disorder is commonly associated with Down syndrome. It usually resolves spontaneously in 4-5 months. However, 25 % of patients will subsequently develop acute megakaryoblastic leukemia or myelodysplastic syndrome. It has seldom been described without constitutional anomalies and is even less frequent in twins. We present three phenotypically normal patients with this disorder. One of them was diagnosed because he presented blueberry muffin syndrome. Diagnosis was guided by pathological examination of the skin lesions. The other two patients were monochorionic triplets. Their bichorionic sister presented no hematological disorders. Constitutional chromosomal abnormalities were ruled out in all three patients. They received support treatment only without chemotherapy. The clinical course was favorable with disappearance of marrow and peripheral blastosis in 4-5 months. Follow-up of 18 and 19 months has not revealed any hematological disorders. Caution must be exercised before initiating chemotherapy in these patients. We discuss the differential diagnosis with congenital leukemia and the prognostic and therapeutic implications that this entails.     

Transient myeloproliferative disorder and acute nonlymphoblastic leukemia in Down syndrome

Two infants with Down syndrome had transient myeloproliferative disorder (TMD) during the neonatal period and subsequently acute nonlymphoblastic leukemia (ANLL). Histochemically, the blast cells in TMD were indistinguishable from those in ANLL. Only the constitutional chromosome (trisomy 21) was found in TMD, whereas new cytogenetic abnormalities emerged in ANLL. A mixed growth pattern in stem cell cultures during TMD suggested the existence of an abnormal clone that might be responsible for the evolution into ANLL at a later date. Serial cytogenetic studies and culture studies of peripheral blood cells may help to understand the pathophysiology and risk of ANLL in patients with TMD.     

Transient myeloproliferative disorder in neonates with and without Down syndrome: a tale of 2 syndromes

Transient myeloproliferative disorder (TMD) in newborns with Down syndrome (DS) has been well described. We report 4 newborns, 2 with DS and 2 without DS, who developed TMD. One newborn with DS developed multiorgan failure and died despite treatment with low-dose cytarabine. In 3 newborns, the TMD resolved spontaneously. Two of these patients, 1 with and 1 without DS developed leukemia on subsequent follow-up and were treated successfully. We reviewed the clinical and laboratory data on 14 non-DS infants with TMD reported in the literature. According to limited data, these patients are more likely to develop leukemia than DS patients, however their outcome is better.     

Transient myeloproliferative disorder. In a neonate with Down syndrome. Immunophenotypic studies

This report describes the results of bone marrow leukocyte immunophenotypic studies, DNA index measurement, and chromosome analysis in a newborn with Down syndrome and transient myeloproliferative disorder. The infant's initial leukocytosis with immature cells in the peripheral blood and thrombocytopenia resolved without treatment by 6 months of age, and he was well at 2 years of age. The lack of specific reactivity between the patient's morphologically immature cells and multiple monoclonal antibodies directed against lymphoid and myeloid leukemia cells may be characteristic of this disorder. Other cases should be examined for immunophenotype to correlate the results with chromosomal analysis and to provide a basis for comparison in those who subsequently develop true acute leukemia.     

Transient myeloproliferative disorder and eosinophilic pericardial effusion in a down syndrome neonate

Transient myeloproliferative disorder seen in neonates with Down syndrome is often thought to have a benign course. The authors describe the clinical and laboratory profile of a neonate with Down phenotype and transient myeloproliferative disorder with pericardial effusion as co-morbidity. Pericardial fluid analysis showed eosinophils. Pericardial effusion resolved with prednisolone therapy. Regression in hepatosplenomegaly with clearance of blasts was seen by third week of illness. The clinical course suggested a benign infiltration of the pericardium. Presence of eosinophils supports the differentiating capability of the blast cells in transient myeloproliferative disorders.     

Acute nonlymphocytic leukemia after transient myeloproliferative disorder in a patient with Down syndrome

An infant with Down syndrome (DS) and RH isoimmunization developed transient myeloproliferative disorder (TMD) during the neonatal period. At 16 months she presented with acute nonlymphocytic leukemia (ANLL). Cytogenetic studies during TMD showed trisomy 21 only but new abnormalities emerged during ANLL. She is now in complete remission 5 years after diagnosis. Patients with TMD have either trisomy 21 or mosaic 21 in blood and bone marrow but in phenotypically normal children this cell line disappears with resolution of the TMD. A review of the literature indicates that there are no clinical, hematological, or cytogenetic differences between DS children with TMD who subsequently develop acute leukemia and those who do not. However, the leukemia in the former group may differ in presentation, type, and possibly survival time from other DS children who develop leukemia de novo.     

Down’s syndrome with transient myeloproliferative syndrome

Two cases of Down’s syndrome with high leukocyte count are being reported. Both patients had spontaneous remission without cytotoxic therapy.     

Risk factors for early death in transient myeloproliferative disorder without phenotypic features of Down syndrome: a case report and literature review

Not only in newborns with Down syndrome, but newborns without phenotypic features of Down syndrome also develop transient myeloproliferative disorder (TMD). In these cases, trisomy 21 and related chromosomal abnormalities are either constitutionally mosaic or limited to blood cells. Risk factors for early death of these patients are unknown so far. We here report a fatal case of TMD without phenotypic features of Down syndrome and review literature to identify risk factors associated with early death. Not only are gestational age and white blood cell count risk factors for early death in TMD with Down syndrome, but they also appear to be risk factors in TMD without Down syndrome.     

Transient myeloproliferative disorder in Down's syndrome: three cases with megakaryocytic markers.

In this paper we describe three infants with Down's syndrome and transient myeloproliferative disorder. The blast cells of all three displayed positive megakaryocytic markers. One patient developed acute megakaryoblastic leukemia in his second year, with blasts identical to those of the initial episode. The other two cases remain well at 12 and 15 months of age.     

Transient myeloproliferative disorder in chromosomally normal newborn infant

Transient myeloproliferative disorder is a condition clinically resembling congenital acute myelogenous leukemia. As in acute leukemias the blast cell population in this disorder may have either normal or abnormal chromosomal complement. Transient myeloproliferative disorder is well recognized in neonates with a complete or mosaic trisomy 21 (Down's syndrome). We report a phenotypically and cytogenetically normal infant with this syndrome in whom only blast cells showed trisomy 21. We postulate that the pathogenesis of the transient myeloproliferative disorder in both Down's syndrome infants and those with a normal chromosomal complement is related to abnormal prenatal production of placental regulatory hemopoietic factors caused by chromosomal defect(s) confined to placental tissues.