Myelodysplastic and myeloproliferative disorders of childhood

Abstract

Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions. RCC is often hypoplastic and may respond to immunosuppressive therapy. In case of immunosuppressive therapy failure, hypercellular RCC, or RCC with monosomy 7, hematopoietic stem cell transplantation (HSCT) using reduced-intensity conditioning regimens is indicated. Almost all patients with refractory anemia with excess blasts are candidates for HSCT; children age 12 years or older have a higher risk of treatmentrelated death, and the conditioning regimens should be adjusted accordingly. Unraveling the genetics of JMML has demonstrated that JMML in patients with germ line PTPN11 and CBL mutations often regresses spontaneously, and therapy is seldom indicated. Conversely, patients with JMML and neurofibromatosis type 1, somatic PTPN11, KRAS, and most of those with NRAS mutations have a rapidly progressive disease, and early HSCT is indicated. The risk of relapse after HSCT is high, and prophylaxis for graft-versus-host disease and monitoring should be adapted to this risk. Learning Objectives• To recognize the challenges in making a diagnosis of MDS in children • To know the different therapeutic strategies in low-grade and advanced MDS • To understand the genetics of JMML and how it may be used for treatment stratification Myelodysplastic and myeloproliferative disorders are rare in children and have different morphologic features, cytogenetic findings, prognostic factors, and therapeutic aims than in adults. Therefore, there is a need for a pediatric approach to the classification of these disorders 1 as integrated in the 2008 version of the World Health Organization classification 2 that recognizes the specific features of diseases in children vs those in adults (Table 1).The diseases are divided into low-grade myelodysplastic syndrome (MDS), advanced MDS, and juvenile myelomonocytic leukemia (JMML). The myeloid leukemia of Down syndrome represents a specific entity that should not be included in series of MDSs and will not be discussed in this review. There is an increasing recognition that more children have an underlying genetic predisposition for the development of MDS or JMML. For a more thorough overview, the reader is referred to several reviews published recently. 3-7Low-grade MDS MDS with less than 2% blasts in peripheral blood (PB) or less than 5% blasts in the bone marrow (BM) are classified as refractory cytopenia of childhood (RCC) or low-grade MDS.1,2 The majority of the children wit...

Cutaneous involvement in an 8-year-old boy with Ras-associated autoimmune leucoproliferative disorder (RALD)

“…RALD and JMML are more common in boys in childhood, but the prognosis of the two diseases is entirely different. While most patients with JMML die within a year of diagnosis without treatment, the prognosis is uncertain in patients with RALD, and no treatment is required . Even though most patients with RALD have a good prognosis, a child who progressed to JMML 10 years after the diagnosis has been reported …”

“…While most patients with JMML die within a year of diagnosis without treatment, the prognosis is uncertain in patients with RALD, and no treatment is required. 8 Even though most patients with RALD have a good prognosis, a child who progressed to JMML 10 years after the diagnosis has been reported. 9 Our patient continues to have persistence of recurrent migratory skin lesions, and remains asymptomatic after 1 year of follow-up, as with the other cases published in the literature.…”

Leukemoid reactions and chronic chronic myeloproliferative diseases in children: similarity and differences

“…Виконання ТГСК при ЮММЛ асоційоване з 10-20% ризиком трансплантаційної смертно сті і у 30-40% -рецидивом захворювання [31,42]. Для підготовки пацієнтів з ЮММЛ до ало ТГСК можливе застосування низьких доз хіміотерапії (ХТ) -6 меркаптопурин ± 13 цис ретиноєва кислота [19], цитозин арабі нозид ± 13 цис ретиноєва кислота [9].…”

Efficacy allogeneic hematopoietic stem cell transplantation with different conditioning regimens in pediatric myelodysplastic syndrome

“…Прогностические шкалы МДС для взрослых (IPSS, IPSS-R, WPSS, WPSS-R) при МДС у детей не имеют явного прогно-стического значения [3], ввиду особенностей патофи-зиологии, связанной с различиями в частоте мутации генов, участвующих в патогенезе. Среди них редкая встречаемость, по сравнению со взрослыми пациента-ми, мутаций, связанных с РНК-сплайсингом (SF3B1, SRSF2, U2AF1, ZRSR2), ТЕТ2-мутации [4,5]. Все дети с МДС/МПЗ, за исключением пациентов с синдромом Дауна, имеют крайне неблагоприятный прогноз.…”