Transient myeloproliferative disorder associated with trisomy 21, a wide range syndrome: Report of two cases with trisomy 21 mosaicism

Abstract

Transient myeloproliferative disorder (TMD) is an uncommon syndrome strongly associated with abnormalities of chromosome 21. Blast transient proliferation appears most frequently at neonatal age and usually resolves spontaneously in two or three months. Two patients, a girl and a boy, with neonatal onset of TMD are reported. They both presented trisomy 21 mosaicism according to bone marrow cytogenetic analysis. Patient 1, on one end of the spectrum, showed a "classic" benign course with rapid resolution and favorable outcome. Patient 2, on the other hand, had two blast outbursts both followed by spontaneous remissions. He failed to thrive and never reached a good general condition, dying at 5 months of age from a respiratory infectious complication. The necropsy showed generalized extramedullary hemopoiesis without evidence of bone marrow blast infiltration or myelofibrosis. TMD has some clinical and laboratory features that make it unique and distinguishable from true congenital leukemia with which it may be initially mistaken. It usually has a benign course followed by a favorable outcome. As trisomy 21 mosaicism may not have overt phenotypic stigmata, it is possible that many cases of TMD in these children may have a silent, non-detected course. We also conclude that a favorable outcome is not always to be expected in TMD.

Proinflammatory Cytokinemia Associated with Transient Myeloproliferative Disorder in Down Syndrome

“…These twin patients also demonstrated that TMD can begin in utero, since patient 3 showed hydrops fetalis at 29 weeks. Several reports have described stillborns with TMD, and in other reports, TMD was diagnosed as early as at 27 weeks of gestation [7,9,13,14]. Proinflammatory cytokinemia in TMD may exist in utero, possibly beginning early in gestation.…”

“…Declines in the excess of proinflammatory cytokines on day 46 in this patient could be explained by steroid therapy and exchange transfusion, but these were clinically ineffective. As illustrated by patient 2, liver failure is frequent in fatal cases of TMD, although the pathophysiological basis remains unclear [3,[7][8][9][10][11][12]. We suspect that chronic hepatocellular damage was caused by large excesses of proinflammatory cytokines such as IL-1ß, IL-6, and TNF-·, resulting in liver fibrosis and failure.…”

“…For unclear reasons, blasts disappear spontaneously during the first several months [1][2][3]. However, several reports have focused on fatal TMD cases characterized by cardiopulmonary distress, liver failure, and DIC [7][8][9][10][11][12]. A recent Pediatric Oncology Group study [3] suggested that about 20% of the TMD cases are potentially fatal, without identifying distinctive pathophysiological mechanisms in these cases.…”

“…TMD blasts are morphologically, cytochemically, and immunophenotypically indistinguishable from megakaryoblasts in AMKL, although the clinical courses of the two conditions are quite different. TMD blasts are derived from a common erythroid and megakaryoblastic progenitor [4,5] and show pluripotency for differentiation into neutrophils, macrophages, and megakaryocytes [6,7]. In most cases TMD resolves spontaneously within a few months after birth for unclear reasons.…”

“…Other reports have described fatal Shimada et al TMD = Transient myeloproliferative disorder; PDA = patent ductus arteriosus; PFO = patent foramen ovale; ASD = atrial septal defect; GIA = gastrointestinal tract atresia; RD = respiratory distress; H = hepatomegaly; S = splenomegaly; J = jaundice; PE = pleural effusion; PCE = pericardial effusion; AS = ascites; DIC = disseminated intravascular coagulation; MDS = myelodysplastic syndrome. infantile cases, as well as stillborns with evidence of TMD [7][8][9][10][11][12]. Indeed, TMD may originate during intrauterine life, since several cases have been diagnosed on the basis of hydrops fetalis as early as the 27th week of gestation [13,14].…”