Pre-analytical parameters associated with unsuccessful karyotyping in myeloid neoplasm: a study of 421 samples

Cytogenetics is essential in myeloid neoplasms (MN) and pre-analytical variables are important for karyotyping. We assessed the relationship between pre-analytical variables (time from collection to sample processing, material type, sample cellularity, and diagnosis) and failures of karyotyping. Bone marrow (BM, n=352) and peripheral blood (PB, n=69) samples were analyzed from acute myeloid leukemia (n=113), myelodysplastic syndromes (n=73), myelodysplastic syndromes/myeloproliferative neoplasms (n=17), myeloproliferative neoplasms (n=137), and other with conclusive diagnosis (n=6), and reactive disorders/no conclusive diagnosis (n=75). The rate of unsuccessful karyotyping was 18.5% and was associated with the use of PB and a low number of nucleated cells (≤7×103/µL) in the sample. High and low cellularity in BM and high and low cellularity in PB samples showed no metaphases in 3.9, 39.7, 41.9, and 84.6% of cases, respectively. Collecting a good BM sample is the key for the success of karyotyping in MN and avoids the use of expensive molecular techniques.

Cytotoxic and pro-apoptotic action of MjTX-I, a phospholipase A2 isolated from Bothrops moojeni snake venom, towards leukemic cells

A leucemia mieloide crônica (LMC) é uma neoplasia mieloproliferativa BCR-ABL1 + marcada por aumento da mieloproliferação e presença de células leucêmicas resistentes à apoptose. A terapia de primeira linha atual para a LMC é a administração de inibidores da tirosina quinase, mesilato de imatinibe, dasatinibe ou nilotinibe. Embora eficaz no tratamento da LMC, alguns pacientes se tornaram resistentes a essa terapia, levando à progressão da doença e à morte. Assim, a descoberta de novos compostos para melhorar a terapia da LMC ainda é um desafio. Aqui, os destinatários se MjTX-I, uma fosfolipase A 2 isolado a partir de Bothrops moojeni de veneno de cobra, afecta a viabilidade de Bcr-Abl de mesilato de imatinib-resistente + linhas celulares. Métodos: Examinamos o efeito citotóxico e pró-apoptótico de MjTX-I em células K562-S e K562-R Bcr-Abl + e na linha de células HEK-293 não tumorais e células mononucleares de sangue periférico, usando o 3- (4, Brometo de 5-dimetiltiazol-2-il) -2,5-difeniltetrazólio e os métodos de solução fluorescente hipotônica, associados à detecção de ativação de caspases 3, 8 e 9 e clivagem de poli (ADP-ribose) polimerase (PARP). Também analisamos o potencial MjTX-I para modular a expressão de genes relacionados à apoptose em células K562-S e K562-R. Resultados: O MjTX-I diminuiu a viabilidade das células K562-S e K562-R em 60 a 65%, sem afetar a viabilidade das células não tumorais, ou seja, exerceu citotoxicidade seletiva para as linhagens celulares Bcr-Abl + . Em linhas de células leucêmicas, a toxina induziu apoptose, caspases 3, 8 e 9 ativadas, PARP clivada, expressão negativa do gene anti-apoptótico BCL-2 e expressão aumentada do gene pró-apoptótico BAD. Conclusão: O efeito antitumoral de MjTX-I está associado ao seu potencial para induzir apoptose e citotoxicidade em linhagens celulares positivas para Bcr-Abl sensíveis e resistentes ao mesilato de imatinibe, indicando que MjTX-I é um candidato promissor a fármaco para atualizar a terapia de LMC.(AU)

Leucemia mieloide asociada a tumor de ovario en ausencia de tratamiento antineoplásico previo / Acute myeloid leukemia associated with ovarian tumor in the abscence of prior antineoplastic treatment

Se presenta caso de adolescente admitida al Hospital Mario Catarino Rivas con historia de ebre, cefalea y aparición espontánea de hematomas en muslos de 4 días de evolución, acompañado de masa abdominal palpable de 10 cm, con hemograma que reportaba trom- bocitopenia y anemia. Al realizar Aspirado de médula ósea e inmunofenotipo reportaron Leucemia mieloide Aguda (LMA) estadio M7. La tomagrafía de abdomen reportó extensa tumoración retro peritoneal por lo que se reali- zó laparotomía exploradora donde se encon- tró tumor gigante de ovario derecho con metástasis a ganglios paraaórticos. La biopsia reportó un tumor mixto ovárico de células germinales. La aparición de leucemia mieloide aguda de forma simultánea a tumor de ovario sin antece- dente de haber recibido tratamiento quimiote- rapéutico previo es un hallazgo inusual, y no se encontraron descripciones al respecto en la literatura consultada..(AU)

Tratamiento de la leucemia promielocítica aguda con acido transretinoico en dosis de 25 miligramos por metro cuadrado / Treatment of acute promyelocytic leukemia with acid trans dose of 25 milligrams per square meter

Se realizó un estudio observacional, descriptivo, de serie de casos, en el Hospital Esdcuela Dr. Roberto Calderón G. (HEDRCG) durante el periodo de 2002 al 2007, con el objetivo de determinar la respuesta a la administración de acido transretinoico en dosis de 25 mg/m cudrado de superficie corporal en los pacientes con diagnóstico de leucemia promielocitica aguda. Ingresados en el servicio de Heamto- ontología del Hospital en estudio. El universo lo constituyeron todos los pacientes diagnósticados con leucemia promielocitica aguda en el HEDRCG registrados en el servicio de estadísticas del Hospital. La muestra la conformaron 14 pacientes diagnósticados con leucemia promielocitica aguda en el HEDRCG durante el periodo de estudio que fueron seleccionados según criterios de inclusión y de exclusíon. No podemos dejar de mencionar que aunque nuestra muestra es poica, los estudios internacionales tampoco reportan en gran cantidad de pacientes, en la mayor parte los estudios no pasan de 25 pacientes estudiados. El 92 por ciento tenían manifestaciones de sangrado al ingreso al Hospital y la localización más frecuente fue la piel y mucosa...

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.

Leucemia mieloide crónica en crisis: blástica bases moleculares y diagnóstico / Chronic myelogenous leukemia in blastic crisis: molecular basis and diagnostic

La leucemia mieloide crónica es una enfermedad con comportamiento bifásico o trifásico, 90 por ciento de los pacientes debuta en fase crónica, 50 por ciento asintomáticos al diagnóstico. Un porcentaje con enfermedad crónica desarrollan en tiempo variable una enfermedad más agresiva definida por un período intermedio y crisis blástica. Se diagnostica al encontrar más del 20 por ciento de blastos en médula ósea, 30 por ciento en sangre periférica o enfermedad extramedular. El pronóstico es pobre, al lograr respuesta completa, con una mediana de sobrevida de 3-12 meses, independiente del fenotipo. El 50 por ciento de los pacientes tendrán una mieloide, 25 por ciento linfoide y 25 por ciento fenotipo indiferenciado. Un grupo de expertos clínicos de Bogotá, Colombia, revisaron la mejor evidencia sobre diagnóstico y tratamiento. La información se obtuvo de búsquedas estructuradas y varios registros de experimentos clínicos en curso. Presentamos conclusiones y recomendaciones para la toma de decisiones basadas en la mejor evidencia.

Myeloid leukaemia treatment and survival--the South Australian experience, 1977 to 2002.

OBJECTIVE: To evaluate trends in survival and treatment for myeloid leukaemia in South Australia during 1977-2002, using population-based survival data plus data on survival and treatment of patients at three teaching hospitals. METHODS: Population data were analysed using relative survival methods and hospital registry data using disease-specific survival. Univariate and multivariable analyses were undertaken. Multiple logistic regression analysis was used to investigate factors associated with first-line chemotherapy. RESULTS: South Australia recorded 1,572 new cases of acute myeloid leukaemia (AML) in 1977-2002, together with 536 cases of chronic myeloid leukaemia (CML). Of these cases, 42.6% were recorded in teaching hospital registries. The five-year survival for AML at the teaching hospitals of 14.5% was similar to the corresponding 12.0% for South Australia as a whole. The five-year survival for CML at these hospitals was higher, however, at 48.1% compared with 37.5% for all South Australian cases. Younger patients had higher survivals, both for AML and CML. An increase in survival was evident for more recently diagnosed cases for both leukaemia types, after adjusting for age. This increase in survival was accompanied by an increase over time in the proportion of patients at teaching hospitals having a primary course of chemotherapy. Cytarabine in combination with other agents was the most common induction therapy for AML. While hydroxyurea was the most common first-line treatment of CML, there were changes in clinical policies towards higher-dose treatments, plus trials of new agents and combination therapies. CONCLUSIONS: Secular gains in survival have occurred from AML and CML in association with an increased use of chemotherapy.

Comparison of clinical manifestations and age and sex distribution in childhood acute lymphoblastic leukemia and acute myelocytic leukemia

Acute leukemia is the most common childhood malignancy and acute lymphoblastic leukemia [ALL] has been reported five times more common than acute myelocytic leukemia [AML] among children. The present study addresses the clinical manifestations and age and sex distribution in childhood ALL and AML. This is a descriptive-analytic study performed on 70 ALL and 70 AML patients who have been hospitalized at Children Medical Center. Initial data were obtained through patients' files and analyzed by SPSS software and chi-square test. The mean age of patients with ALL was 5.1 years compared to 8 years in AML patients. Most of ALL patients aged under 5 years whereas AML patients aged >/= 10 years [p<0.0001]. In both groups, disease was more common in boys than girls. Palor was the most frequent sign in both groups. Lymphadenopathy, hepatosplenomegaly and bone pain in ALL, and fever and bleeding in AML patients were more prevalent than other manifestations. Leukemia must be considered in children with palor and nonspecific signs. Although age distribution and some other clinical manifestations are differed between ALL and AML patients, these two entities could not be easily differentiated according to the age, sex and clinical manifestations. Indeed, definite diagnosis must be achieved with bone marrow aspiration or biopsy, fluocytometery and specific staining

Usefulness of cytogenetics in leukemias.

Present study consists of cytogenetic evaluation in 141 cases referred to our centre for various leukemias. This includes 110 cases of CML, 10 of ALL, 16 of AML (M3), 2 of AML(M2), 2 of MDS and 1 of CMML. The conventional cytogenetic study was carried out in all the cases using G Banding technique. Of the 141 patients studied, 17 patients showed secondary chromosomal alterations along with primary chromosomal alterations. In two patients of CML with secondary chromosomal alteration t(4:9:22), molecular cytogenetic technique (FISH) has been carried out which has confirmed the primary observations revealed by the conventional cytogenetic technique. Other secondary alterations were numerous and would have been missed if only FISH or PCR technique would have been used for diagnosis. We observed from our study that advanced molecular techniques like FISH and PCR cannot replace the conventional cytogenetic study but are useful as supportive and confirmative diagnostic tools.

we underestimating the leukemogenic risk of hydroxyurea

Hydroxyurea is an established drug that has been used for the treatment of myeloproliferative disorders and some solid tumors for some time. In recent years it has also been found to be effective in the treatment of sickle cell disease. Short term side effects are not serious, and are manageable. The major concern is the potential leukemogenesis with long term use. The risk of leukemogenesis is not defined with its use in benign hematological conditions. We report a case of acute myeloid leukemia with no preceding myelodysplastic syndrome, occurring after 2 years of hydroxyurea therapy in a patient with sickle cell disease

Infiltraçäo conjuntival como primeira mansifestaçäo de leucemia mielóide aguda - relato de um caso / Conjunctival infiltration as first clinical manifestation of acute myelogenous leukemia - a case report

Os autores descrevem o caso de paciente portadora de leucemia mielóide aguda que apresentou como primeira manifestaçäo da doença, infiltraçäo leucêmica conjuntival. Säo feitas consideraçöes a respeito das manifestaçöes sistêmicas e oftalmológicas e atualizaçäo desta doença.

Role of immunophenotyping in the diagnosis of acute leukemia

This study was aimed to compare the diagnosis of acute leukemia based on morphology and cytochemistry with the diagnosis based on immunophenotyping. The study was carried out in the Hematology department of Dr. Ziauddin Hospital, Karachi from September, 1996 to August, 1998. Of 100 cases of acute leukemia of 2 to 50 years of age, inducted from various hospitals and laboratories of Karachi, our results showed that among 43 cases classified as Acute Lymphoblastic Leukemia [ALL] on morphology and cytochemistry, 35 [81%] were ALL, 4 [9%] turned out to be Acute Myeloid Leukemia [AML] and 4 [9%] were bi-phenotypic on immunophenotyping. Similarly, among 46 cases classified as AML on morphology and cytochemistry, 38 [83%] were AML, 5 [11%] turned out to be ALL, 2 [4%] were bi-phenotypic, while 1[2%] was still unclassified on immunophenotyping. Finally, out of 11 unclassified cases, 6 [55%] were ALL, 4 [36%] were AML and 1 [9%] remained unclassified. Therefore, more than 80% of the cases of acute leukemia were classified according to their respective lineages by morphology and cytochemistry. Immunophenotyping provided correct diagnosis in 99% of cases establishing its efficacy in correct diagnosis of those cases of acute leukemia, which are difficult to be diagnosed on morphology and cytochemistry

Leucemias agudas na infância / Acute leukemias in childhood

Os autores destacam a elevada incidência das leucemias agudas na infância e estudam sua classificaçäo e fatores de risco envolvidos. Atualizam os conhecimentos a respeito das formas linfóide e mielóide e finalizam com rápida mençäo à leucemia mielóide crônica