Cytogenetic profile of Indian patients with de novo myelodysplastic syndromes.

Background & objectives: Myelodysplastic syndrome (MDS) is a clonal haematopoietic stem cell disorder characterized by ineffective haematopoiesis and leukaemia progression. Cytogenetic analysis has proven to be a mandatory part of the diagnosis of MDS as well as a major indicator for predicting clinical course and outcome. Studies on cytogenetics of MDS are reported mostly from the West and only a few are available from Asian countries. We report herein cytogenetic studies on 40 Indian patients with primary MDS to find out the occurrence and type of chromosome abnormalities and recurring defects. Methods: Cytogenetic analysis was done using GTG banding and karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN). Results: Of the 40 patients, 19 patients (47.5%) showed clonal karyotypic abnormalities with distribution as follows: 3 of 15 (20%) of refractory anaemia (RA), 4 of 7 (57%) of refractory anaemia with excess blasts-1 (RAEB-1), 4 of 6 (67%) of refractory anaemia with excess blasts 2 (RAEB-2), 2 of 3 (67%) of refractory anaemia with ring sideroblasts (RARS), 2 of 4 (50%) of refractory cytopenia with multilineage dysplasia (RCMD), none (0%) RCMD-ringed sideroblasts (RCMD-RS) and 4 patients with 5q syndrome. The frequent abnormalities observed in our study were -7, 5q-and trisomy 8. Interpretation & conclusions: Two rare chromosomal abnormalities (6q-, 3q-) were found with unknown prognostic significance. Hence, cytogenetic analysis may be incorporated in the routine diagnosis of MDS since there are racial differences in clinical pictures and the molecular events.

Two Cases of Trisomy 19 as a Sole Chromosomal Abnormality in Myeloid Disorders / 대한진단검사의학회지

Trisomy 19 is frequently encountered in cases of chronic myeloid leukemia (CML) as a secondary abnormality: however, trisomy 19 rarely occurs as a sole chromosomal abnormality and, to date, it has only been reported in 48 hematopoietic malignancies, 1 case of adenocarcinoma and 1 case of astrocytic tumor. Here, we report two additional cases of trisomy 19 as a sole karyotypic aberration in myeloid malignancies. One of these cases involved a 6-month-old male who was diagnosed with acute myeloid leukemia minimally differentiated. His karyotype was 47,XY,+19[20]. He expired 5 days after diagnosis. Another case occurred in an 80-yr-old female who had refractory anemia with excess blasts. Her karyotype was 47,XX,+19[16]/46,XX[4]. Four months later, her peripheral blood smears suggested that the disease had progressed, but she refused further evaluation. Based on a review of the existing literature and the results of this report, trisomy 19 not only as a secondary abnormality but also as a sole karyotypic aberration is strongly associated with myeloid disorder; however, it is not preferentially found in specific FAB subgroups of myelodysplasic syndrome or acute myeloid leukemia.

Refractory anemia after epoetin therapy in patients with chronic renal failure

Anemia is the most frequent complication of chronic renal failure. Epoetin therapy reveals to be an effective therapy; however, development of anti-erythropoietin antibodies has been reported. The present study was conducted to determine the etiology of refractory anemia after Epoetin therapy in patients with chronic renal failure. All adult patients [530 patients] who had been prescribed regular hemodialysis and rHUEPO for at least three months were followed in seven hemodialysis units in Tehran. During a 6- month period, Venofer-Eprex dose and hemoglobin was recorded monthly. Having ruled out hemolysis and iron deficiently state in severe anemic patients, bone marrow examination was ordered. Of 530 patients, 58% were men with median age of 59 years. About%80 of patients had received baseline dose of at least 4000 units Eprex per week, prescribed subcutaneously after hemodialysis. Approximately, 21% were not anemic, while 19% did suffer from severe anemia [Hb<8]. There were statistically significant associations between severity of anemia and age [p<0.001], longer Epoetin therapy [p<0.001], co-treatment with Venofer [p<0.011] and lack of underlying disease [p<0.04]. Bone marrow aspiration was performed for 30 patients and the most frequent findings were anemia due to chronic disease, bone marrow dysplasia, amd megaloblastic anemia. In case of poor response to Epoetin therapy, discontinuing the drug is strongly recommended. Bone marrow examination is an appropriate tool to find the cause of refractoriness to Epoetin therapy in hemodialysis patients

Sindromes mielodisplásicos / Myelodisplastic syndromes

Estudiamos retrospectivamente a 18 pacientes con sindrome mielodisplásico (SMD) en un periodo de 7 años (enero de 1984 a diciembre de 1990) en el Hospital Nacional Cayetano Heredia. Diez fueron mujeres y ocho varones, la edad promedio fue de 61.1 años. El 61 por ciento presento pancitopenia; todos presentaron anemia, 83 por ciento trombocitopenia y el 65 por ciento neutropenia. Las medulas oseas fueron hiper o normocelulares; 95 por ciento de los pacientes presento diseritropoyesis y el 89 por ciento presento dismegacariopoyesis micromegacariocitos. De acuerdo a la clasificación FAB 44 por ciento presento anemia refractaria con sideroblastos en anillo (ARSA), 16.7 por ciento anemia refractaria con exeso de blastos (AREB), 22.2 por ciento con anemia refractaria con exesos de blastos en transformación (AREBt) y un 5.5 por ciento fue diagnosticado con leucemia mielomonocítica crónica (LMMC). Cinco pacientes (27.8 por ciento) se transformaron a otra variedad; cuatro de estos (22.2 por ciento) se transformaron a LMA. Un paciente con localización de precursores anormal en la biopsia de hueso evoluciono a LMA. Las complicaciones mas frecuentes fueron las infecciones (45.8 por ciento), un 16.6 por ciento tuvieron hemorragia en el SNC. El tiempo medio de sobrevida desde el diagnóstico fue 9.2 meses

Mielodisplasias: experiencia clínica en 35 pacientes / Myelodysplasia: an analysis of 35 patients

Myelodysplasia, characterized by varied reductions of peripheral blood elements with normal or hypercellular bone marrow, is reltively frequent among older patients and may evolve to acute leukemia. We reviewed findings in 35 patients whon, according to the FAB classification were distributed as follows: simple refractory anemia (RA) 34%, sideroblastic refractory anemia (SRA) 14%, refractory anemia with excess blast forms (RAEB) 31%, chromic myelomonocytic leukemia (CMML) 12% and refractory anemia eith excess blast forms in transformation (RAEBT 9%). Cytogenetic studies performed in 16 patients were abnormal in 5(31%), al among patients with poor prognosis forms of the disorder. All patients had anemia; thrombopenia and neutropenia were more frequent in subtypes RAEB, CMML and RAEBT). Mean survival rate was 30 months, significantly greater in RA and SRA comapred to the other groups. Infections and development of acute leukemia were the causes of death

El medulograma y la biopsia de médula ósea en las leucemias agudas: síndromes mieloproliferativos crónicos y otras enfermedades hematológicas / Medullogram and bone marrow biopsy in acute leukemias, chronic myeloproliferative syndromes and other hematologic diseases

Se le realizaron medulograma y biopsia de médula ósea a 62 pacientes con las siguientes enfermedades agudas (17), mielofibrosis aguda (1), síndromes mieloproliferativos (33) y anemias refractarias (11). La biopsia de médula ósea permitió confirmar el diagnóstico en todos los casos y lo estableció en algunos en los que la muestra de la punción medular fue blanca. Además, mostró diferentes patrones histológicos y de infiltración medular que ayudaron a estadificar las enfermedades y a predecir el pronóstico

Evidencia del origen pre-mieloide de las anemias dishemopoyeticas: leucemia aguda linfoblastica de linfocitos B. posterior a un sindrome mielodisplásico indiferenciado (tipo I de la clasificación FAB) / Evidence of the pre-myeloid origin of dyshemopoyetic anemias: B-lymphocytes lymphoblastic acute leukemia after undifferentiated myelodysplasic syndrome (type I of the FAB classification)

Se presenta el caso de un escolar de 12 años de edad, quien, con motivo de pancitopenia fue sometido a estudios hematológicos que permitieron establecer el diagnóstico de anemia dishemopoyética indiferenciada (anemia refractaria indiferenciada o tipo I de la clasificación FAB). El paciente fue tratado con andrógenos con lo que no se obtuvo respuesta satisfactoria. Cinco semanas después, aparecieron en la sangre periférica células leucémicas. La caracterización inmunológica de las células malignas en médula ósea mostró que se trataba de linfoblastos de estirpe B, en tanto que el 90% de ellas exhibieron inmunoglobulinas de superficie. El paciente fue tratado entonces con quimioterapia combinada empleando adriamicina, sulfato de vincristina y prednisona. Después de administrar 7 ciclos de este esquema anti-leucémico el enfermo falleció por sangrado en sistema nervioso central. Nunca logró la remisión de la enfermedad a lo largo de 2 meses de tratamiento anti-leucémico. Se discute la ocurrencia de esta neoplasia linfoide en el sindrome mielodisplásico, observación que apoya la idea de que los síndromes mielodisplásicos son alteraciones de la célula totipotencial, pre-linfoide y pre-mieloide

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