ABSTRACT
The distinction between myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) often relies on an arbitrary marrow blast cutoff of 30% in pediatrics and 20% in adults. There is little data about the treatment of children with extramedullary myeloid malignancy that has features of both, MDS and AML. Herein, we report for the first time 2 patients MDS/AML (1 with Shwachman-Diamond syndrome and 1 with idiopathic MDS and monosomy 7) who presented with extramedullary complications, received treatment with azacitidine, achieved complete remission and subsequently underwent hematopoietic stem cell transplantation.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Adolescent , Child, Preschool , Chromosome Deletion , Chromosomes, Human, Pair 7 , Humans , Leukemia, Myeloid, Acute/genetics , Male , Myelodysplastic Syndromes/genetics , Shwachman-Diamond Syndrome/complicationsABSTRACT
Bone marrow angiogenesis is increased in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), but has not been studied in inherited or acquired marrow failure syndromes. Shwachman-Diamond syndrome (SDS) carries a high risk of MDS/AML and is characterised by marrow stromal dysfunction. Compared with controls, SDS patients without MDS/AML had higher marrow microvessel density. Stromal VEGF gene expression, stromal vascular endothelial growth factor (VEGF) secretion and VEGF levels in serum and marrow mononuclear cells were normal. Future studies should investigate the mechanism for increased angiogenesis in SDS, and whether SDS marrow, with its increased angiogenesis, promotes progression of malignant clones.
Subject(s)
Abnormalities, Multiple/genetics , Bone Marrow/blood supply , Hematologic Diseases/genetics , Abnormalities, Multiple/pathology , Acute Disease , Adolescent , Anemia, Aplastic/genetics , Anemia, Aplastic/pathology , Bone Marrow/pathology , Bone Marrow Cells/pathology , Child , Child, Preschool , Female , Gene Expression/genetics , Hematologic Diseases/pathology , Humans , Infant , Leukemia, Myeloid/genetics , Leukemia, Myeloid/pathology , Male , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/pathology , Neovascularization, Pathologic/genetics , Syndrome , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Myelodysplastic syndrome (MDS) in childhood is a rare hematological condition that is often associated with cytogenetic abnormalities, the most common being monosomy 7/del(7q). The clinical course of MDS can vary from stable disease to rapid progression into acute leukemia. Rarely, spontaneous remission of MDS has been observed. The authors report the first case of a transient MDS associated with a clonal marrow cytogenetic abnormality consisting of isochromosome 7q in a previously well child. Without intervention, the bone marrow cytogenetics reverted to normal and there was complete hematologic recovery. This case illustrates the importance of close follow-up in a child presenting with MDS, to detect spontaneous recovery or evolution of the disease.
Subject(s)
Chromosomes, Human, Pair 7 , Isochromosomes , Myelodysplastic Syndromes/genetics , Neoplasm Regression, Spontaneous , Bone Marrow/pathology , Bone Marrow Examination , Cell Transformation, Neoplastic/genetics , Clone Cells/pathology , Female , Humans , Infant , Myelodysplastic Syndromes/diagnosisABSTRACT
The most common myeloid malignancy seen in children with neurofibromatosis type 1 (NF-1) is juvenile myelomonocytic leukemia (JMML), a myeloproliferative disease. The vast majority of these children have inherited the neurocutaneous disease from an affected mother; boys are more often affected than girls. We present the rare finding of a 7-year-old girl with NF-1 who developed JMML. She inherited her NF-1 from the father. At the time of her initial presentation, clonogenic assays of bone marrow mononuclear cells did not show the spontaneous growth of granulocyte-macrophage colony-forming units or hypersensitivity to granulocyte-macrophage colony-stimulating factor that is characteristic of this disorder. After 1 month, repeat evaluations of the patient's clinical and laboratory test results became fully consistent with those for a diagnosis of JMML. This illustrates the stepwise evolution of this myeloproliferative disorder in NF-1 and the importance of close follow-up and reassessment of these patients. Our case is only the second report of JMML in a girl who inherited NF-1 from her father.
