A Case of Neuroendocrine Carcinoma and Childhood Myelodysplastic Syndrome in Hyper-IgM Syndrome

Congenital immunodeficiency is one or combined immune defect in immunoglobulin, leukocyte, and complement. These patients have increased susceptibility to respiratory infection. Hence, their infection must be taken care of, tried to gene therapy and stem cell transplantation. We present here a case of hyper-IgM syndrome in an 11-year-old male patient who complained of abdominal distension and abdominal pain. Multiple abdominal masses were detected by abdominal computed tomography (CT) and he was diagnosed with neuroendocrine carcinoma by mass biopsy. There was no evidence of metastasis of cancer cells to the bone marrow, but a dysgranulopoietic feature was noted and he was diagnosed with childhood myelodysplastic syndrome. This is the first report that neuroendocrine carcinoma is associated with childhood myelodysplastic syndrome in hyper-IgM syndrome.

Treatment with IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF) Regimen in Children with Myelodysplastic Syndrome and Relapsed/Refractory Acute Myelogenous Leukemia / 대한소아혈액종양학회지

PURPOSE: The prognosis of refractory or relapsed acute myelogenous leukemia (AML) is poor and effective reinduction regimens are rare. Myelodysplastic syndrome (MDS) is a heterogenous group of clonal disorders of hematopoiesis and the outcome for children with MDS is poor, and the optimal treatment of MDS has not been defined. This study was undertaken to investigate the therapeutic results of IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF) in children with MDS and relapsed or refractory AML. METHODS: Eleven children with refractory or relapsed AML and ten with MDS were treated with the IDA-FLAG regimen, a combination therapy of idaraubicin (day 1~3, 12 mg/m2/day), fludarabine (day 1~5, 30 mg/m2/day), cytarabine (day 1~5, 2 g/m2/day) and G-CSF (day 0~5, 400 g/m2/day & day 12 up to ANC > 1,000/L, 5 g/kg/day). RESULTS: In AML group, they received a total 15 courses of IDA-FLAG. Complete remission (CR) was achieved in 4/11 (36.4%) with median remission duration of 3 (2~6) months. In MDS group, they received 13 courses of IDA-FLAG and 8 courses of FLAG (IDA-FLAG without idarubicin). CR was achieved in 6/8 (75.0%) with median remission duration of 4 (2~13) months. All the patients experienced grade 4 hematologic toxicities. The median duration of neutropenia (<500/ mm3) and thrombocytopenia (<30,000/mm3) was 23 days (20~46 days) and 23.5 days (16~44 days) in AML, meanwhile those were 18 days (14~30 days) and 16 days (13~32 days) in MDS, respectively. Infectious complications were the main non-hematological toxicity. Two patients died of sepsis and intracerebral hemorrhage on day 7 and 27, respectively. CONCLUSION: IDA-FLAG may be an efficient reinduction therapy for resistant and intensively pretreated AML and an effective regimen for poor prognostic MDS with acceptable toxicity, even though remission duration seems to be relatively short. Therefore, an intensified post-remission therapy seems necessary.

A Case of Juvenile Myelomonocytic Leukemia in a Six Months Old Infant / 대한혈액학회지

Myelodysplastic syndrome (MDS) in childhood is a rare hematologic malignancy and its classification has been the subject of some controversy. Cases of pediatric MDS are subdivided into those with features of adult-type MDS and those with myeloproliferative features occasionally observed in infancy and early childhood. There appears to be an international consensus to rename the disease juvenile myelomonocytic leukemia (JMML), which includes all leukemias of childhood previously classed as chronic myelomonocytic leukemia (CMML), juvenile chronic myelogenous leukemia (JCML), and infantile monosomy 7 syndrome. We experienced a 6-month-old female infant with JMML who developed extensive extramedullary hematopoiesis. The patient developed abdominal distention, hepatosplenome-galy, anemia, thrombocytopenia, and leukocytosis with significant monocytosis and was found to have a high hemoglobin F level of 30%. Her bone marrow biopsy section and aspirate smears revealed normocellularity with no increment of blast cells and no dysplastic changes. Cytogenetic analysis revealed a normal 46, XX karyotype. Her liver, spleen, lymph nodes, and appendix were found to be heavily infiltrated by partially differentiated myelomonocytic cells. These findings supported the diagnosis of JMML with extensive extramedullary hematopoiesis.

A Clinical Study on Myelodysplastic Syndrome in Childhood / 대한소아혈액종양학회지

PURPOSE: This study was undertaken to investigate the clinical characteristics and prognostic predictors of myelodysplastic syndrome (MDS) in childhood. Method: The characteristics and laboratory findings of 20 patients seen at Asan Medical Center for the past 10 years from September 1989 to August 1998 were reviewed retrospectively with regard to the new International Prognostic Scoring System (IPSS) proposed by International MDS Risk Analysis Workshop. RESULTS: 1) In 20 children with MDS we studied, there was no age or sex predilection unique to the subgroups of MDS. 2) 19 cases (95%) out of the 20 had pallor at the time of diagnosis. Other major clinical findings were bleeding tendency in 11 (55%), fever in 8 (40%), hepatosplenomegaly in 8 (40%), and lymphadenopathy in 3 (15%). 3) The hemoglobin level was less than 10 g/dL in all cases and absolute neutrophil count (ANC) was decreased in 11 cases, thrombocytopenia in 15 cases. Pancytopenia was noted in 8 cases (40%). 4) Of the 20 cases, 9 had refractory anemia (RA), 3 refractory anemia with excess blasts (RAEB), 3 refractory anemia with excess blasts in transformation (RAEBIT), and 5 juvenile chronic myelogenous leukemia (JCML). 5) All RA patients were Intermediate (INT)-1 risk group, and all RAEB children were INT-2 risk group. The 3 cases of RAEBIT fell into INT-1, INT-2, and high risk group. Three cases of JCML were INT-1 group, and 2 cases INT-2 group. 6) Seven cases out of 13 INT-1 group had mean survival of 20.2 month (6~57 month), but only 1 out of 6 INT-2 survived. One case of high risk group succumbed to disease 50 months after diagnosis. CONCLUSION: These results showed that there was no age or sex predilection for the specific subgroup of childhood MDS. All the FAB subtypes of the childhood MDS except RA subgroup had poor survival. In this study, we found the IPSS seemed to be a prognostic predictor in childhood MDS but more cases are needed to confirm the validity of IPSS.