Severe congenital neutropenia [Kostmann Syndrome]

Severe congenital neutropenia [SCN], Kostmann syndrome is a heterogenous disorder of myelopoiesis characterized by severe chronic neutropenia, absolute neutrophil count [ANC] persistently below 0.50 x 109/L, with maturation airest of neutrophil precursors in the bone marrow; and associated with serious recurrent b…eteriiinfections from early infancy. Sepsis mortality is reduced by an advent of granulocyte colony stimulating factor [G-CSF] therapy. More than 90% of patients respond to G-CSF therapy. However, hematopoietic stem cell transplantation has shown promise in the treatment of non-responders. About 60-80% of SCN cases are associated with constitutive mutations in one copy of the gene encoding neutrophil elastase ELA2. Myelodysplastic syndrome and acute myeloid leukemia [MDS/AML] have been reported. The hazard of MDS/AML increases significantly overtime. Approximately 10% of patients with severe congenital neutropenia develop AML. This is not thought to be the direct result of G-CSF therapy but related to the underlying disease itself

Síndromes mielodisplásticos en pediatría / Pediatric myelodysplastic syndromes

Los síndromes mielodisplásticos (SMD) son desórdenes clónales de las células madres hematopoyéticas caracterizados por hematopoyesis inefectiva, citopenia periférica y riesgo variable de transformación a leucemia mieloide aguda (LMA). Los SMD son relativamente raros en niños, representando aproximadamente el 3 por ciento de las neoplasias hematológicas pediátricas. Se han descrito numerosos subtipos de SMD en niños, no existiendo actualmente una clasificación de consenso. Existen desórdenes genéticos que predisponen al desarrollo de SMD en niños, como el síndrome de Down, la neurofibromatosis tipo I y síndrome de falla medular hereditarios; por otro lado, la exposición a agentes quimioterapéuticos y radiaciones ionizantes, aumenta el riesgo de desarrollar SMD tanto en niños como en adultos. Los SMD infantiles usualmente tienen un curso clínico agresivo y son de difícil manejo, siendo el trasplante de médula ósea alogénico el único tratamiento curativo conocido actualmente.

Multiple constitutional aetiological factors in bone marrow failure syndrome (BMFS) patients from north India.

BACKGROUND AND OBJECTIVES: A large number of patients diagnosed with bone marrow failure syndromes (BMFS), comprising aplastic anaemia (AA) and myelodysplastic syndromes (MDS), remain aetiologically uncharacterized worldover, especially in resource constrained set up. We carried out this study to identify a few constitutional causes in BMFS patients attending a tertiary care hospital in north India. METHODS: Peripheral blood lymphocyte cultures were performed (with and without clastogens) in a cohort of 135 consecutive BMFS patients, in order to detect Fanconi anaemia (FA), Down's syndrome (+21), trisomy 8 (+8) and monosomy 7 (-7). RESULTS: Constitutional factors were detected in 17 (12.6%) patients. FA defect was observed in 24.07 percent (13/54), 16.66 percent (1/6) and 2.85 percent (1/35) paediatric aplastic anaemia, paediatric MDS and adult MDS patients respectively. Down's syndrome was detected in 5.00 percent (2/40) adult aplastic anaemia patients. None of the patients revealed trisomy 8 or monosomy 7. INTERPRETATION AND CONCLUSION: Presence of an underlying factor determines appropriate management, prognostication, family screening and genetic counselling of BMFS patients. Special tests required to confirm or exclude constitutional aetiological factors are not available to majority of the patients in our country. Diepoxybutane (DEB) test yielded better results than mitomycin C (MMC) test in our experience.

A Case of Treatment-Related Myelodysplastic syndrome and Acute Myelogenous Leukemia Following High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Non-Hodgkin's Lymphoma

Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy. We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma. The patient was admitted with bulky abdominal masses of B cell lineage non-Hodgkin's lymphoma. After 2 cycles of systemic chemotherapy of the Vanderbilt regimen, the patient underwent ASCT with high dose chemotherapy of the BEAC regimen. She also received radiation of 48 Gy for the residual periportal lymphadenopathy. The initial cytogenetic analysis of the infused mononuclear cells revealed a normal karyotype. Twenty two months after the ASCT, pancytopenia was noted and her bone marrow aspirate showed dysplastic hemopoiesis with myeloblasts up to 12% of nonerythroid nucleated cells. The patient was diagnosed as t-MDS (refractory anemia with an excess of blasts). Cytogenetic analysis showed complex chromosomal abnormalities including 11q23 rearrangement, which is frequently found in topoisomerase II inhibitor-related hematologic malignancies. Four months later, it was noted that the t-MDS had evolved into an overt t-AML. Cytogenetic analysis showed an evolving pattern with more complex abnormalities. The patient was treated with combination che-motherapy, but her leukemic cells were resistant to the therapy.

Childhood myelodysplasia.

The clinical data and hematological features of 29 children, under the age of 12 years, with primary myelodysplasia are presented. The diagnosis was made using the FAB (French-American-British) Cooperative Group criteria. There were 24 males and 5 females aged 4 months to 12 years (median 2.5 years) with marked male preponderance. Childhood myelodysplasia constituted 16% of all hematological malignancies and 36.7% of acute myeloid leukemias. The median duration of symptoms prior to diagnosis was 3 months. There were 15 cases of refractory anemia, one of refractory anemia with excess blasts, 3 of refractory anemia with excess blasts in transformation and 10 cases of chronic myelomonocytic leukemia. Five patients evolved to acute myeloid and 4 to acute lymphatic leukemia. The median duration of preleukemic phase in these patients was 7 months (range 4-29 months). The overall mean survival was short (5-9 months) in all the subgroups. Besides supportive therapy in most patients, two patients were treated with etoposide, one with alfa interferon 2b and one with high dose methylprednisolone. Our results show that myelodysplasia is not infrequent in children. The disease has an aggressive clinical course and may evolve into acute leukemia.

Síndrome de 5q- anemia refractaria, trombocitosis e hipolobulación de megacariocitos / 5q- syndrome: refractory anemia, thrombocytosis and hypolubulation of megakaryocytes

Se describe el caso de una mujer de raza blanca, de 30 años de edad, con anemia crónica de 3 años de evolución, refractaria a tratamiento médico y a esplenectomía. Los estudios citogenéticos demostraron una anomalía única, la delección parcial del brazo largo del cromosoma No. 5, defecto denominado "Síndrome del 5q-" descrito en aproximadamente 15 pacientes en la literatura mundial. Este síndrome aparentemente adquirido se caracteriza por anemia refractaria, moderada leucopenia, trombosistosis e hipolobulación de los megacariocitos. La anemia es resistente a los tratamientos conocidos y no evoluciona a leucemia aguda. La mayor parte de los pacientes fallecen por las complicaciones de la hemosiderosis producida por la gran cantidad de transfusiones que requieren para mantener una hemoglobina adecuada. La terapia quelante de hierro con desferroxamina, utilizando minibombas de infusión continua, es, hasta el momento, la única forma de prevenir la muerte por falla cardíaca en los pacientes dependientes de transfusiones. Este es el primer caso del "Síndrome del 5q-" informado en la literatura médica colombiana