Clonal Myeloproliferative Disorders in Patients with Down Syndrome—Treatment and Outcome Results from an Institution in Argentina

Abstract

Children with Down syndrome (DS) are at an increased risk of developing clonal myeloproliferative disorders. The balance between treatment intensity and treatment-related toxicity has not yet been defined. We analyzed this population to identify risk factors and optimal treatment. This single-center retrospective study included 78 DS patients <16 years-old with Transient Abnormal Myelopoiesis (TAM, n = 25), Acute Myeloblastic Leukemia (DS-AML, n = 41) of which 35 had classical Myeloid Leukemia associated with DS (ML-DS) with megakaryoblastic immunophenotype (AMKL) and 6 sporadic DS-AML (non-AMKL). Patients with DS-AML were treated according to four BFM-based protocols. Classical ML-DS vs. non-DS-AMKL were compared and the outcome of ML-DS was analyzed according to treatment intensity. Only four patients with TAM required cytoreduction with a 5-year Event-Free Survival probability (EFSp) of 74.4 (±9.1)%. DS-AML treatment-related deaths were due to infections, with a 5-year EFSp of 60.6 (±8.2)%. Megakaryoblastic immunophenotype was the strongest good-prognostic factor in univariate and multivariate analysis (p = 0.000). When compared ML-DS with non-DS-AMKL, a better outcome was associated with a lower relapse rate (p = 0.0002). Analysis of administered treatment was done on 32/33 ML-DS patients who achieved CR according to receiving or not high-dose ARA-C block (HDARA-C), and no difference in 5-year EFSp was observed (p = 0.172). TAM rarely required treatment and when severe manifestations occurred, early intervention was effective. DS-AML good outcome was associated with AMKL with a low relapse-rate. Even if treatment-related mortality is still high, our data do not support the omission of HDARA-C in ML-DS since we observed a trend to detect a higher relapse rate in the arm without HDARA-C.

Down syndrome child with multiple heart diseases: A case report

“…In some cases, cardiac catheterization and acute pulmonary vascular dilation tests may be necessary to determine the level of PVD[ 21 ]. A pulmonary artery pressure of ≥ 25 mmHg under right cardiac catheterization in a static state is diagnostic for PH.…”

“…A pulmonary artery pressure of ≥ 25 mmHg under right cardiac catheterization in a static state is diagnostic for PH. Severe PH patients who cannot undergo surgery can lower their pulmonary artery pressure by taking oral diuretics and vasodilators, and partially benefit from targeted therapies[ 21 ].…”

Low‐dose cytarabine and hypomethylating agents for Down syndrome with acute myeloid leukemia

“…4,5 ML-DS originates from transient abnormal myelopoiesis (TAM) and harbors somatic GATA1 mutations. 1,6,7 In most cases, TAM resolves spontaneously within a few months, but in 10%-20% of cases, it is followed by the development of ML-DS, 8,9 likely due to the acquisition of additional mutations in JAK/STAT and RAS pathways, 1,10,11 while mutations like NPM1, DNMT3A, and FLT3 are uncommon. ML-DS exhibits heightened chemosensitivity [12][13][14] ; however, reducedintensity chemotherapy shows a 90% 5-year event-free survival.…”