The Genetic and Prognostic Characteristics of AML-MRC Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the genetic and prognostic characteristics of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) patients.@*METHODS@#There were 230 non-M3 AML patients treated in Ningbo First Hospital enrolled, among which 58 patients were newly diagnosed AML-MRC, the patients were followed up and SPSS 25.0 was used to statistically analyze.@*RESULTS@#There were 49 patients performed genetic testing, 29 patients (59.2%) showed chromosomal abnormalities, including 7q- 8 cases (16.3%), 5q- 6 cases (12.2%), 5 cases (10.2%) of 17p abnormalities, 13 cases (26.5%) of highly abnormal complex karyotypes (CK) (≥5 unrelated chromosomal abnormalities), CK contained chromosomal abnormalities such as +8, 5q-, and 12 cases (24.5%) of monosomal karyotypes (MK). Genetic testing was performed in 37 patients, and 24 (64.9%) patients showed genetic mutations, among which ASXL1 mutation was the most common (8 cases, 21.6%), followed by TET2 mutation in 6 cases (16.2%). Kaplan-Meier analysis showed that AML-MRC patients with high CK (P=0.012), 5q- abnormalities (P=0.038), and TP53 mutations (P=0.008) had poor overall survival.@*CONCLUSION@#AML-MRC has unique genetic characteristics, and high CK, 5q- and TP53 mutations are poor prognostic factors.

Segmental hypoplasia of the spinal cord and syringomyelia in a calf / Hipoplasia segmentar de medula espinhal e siringomielia em um bezerro

ABSTRACT: Congenital malformations are functional and structural changes in organ systems, tissues, or organs that may develop during the embryonic or fetal phase. Spinal cord malformations, such as segmental hypoplasia of the spinal cord (SHSC) and syringomyelia, are rare in bovines. A Girolando calf from Valença, Rio de Janeiro, was admitted to the Veterinary Hospital of Universidade Federal Rural do Rio de Janeiro because of motor incoordination. Clinical evaluation revealed a 5-cm depression area in the spine at the dorsal line of the thoracic region. Neurological examination revealed reduced proprioception, pelvic limb extension with increased nociceptive activity, and reduced anal reflex. In radiographic examination, the body of the T11 vertebra had a trapezoidal wedge shape with ventral hemivertebra, probable agenesis or hypoplasia of the T11-T12 spinous processes, and fusion of the T9-T10 spinous processes. Myelography revealed extradural spinal compression caused by vertebral malformations. Necropsy showed no spinous processes (T11-T12), cranial stenosis in the medullary canal (T11-T13), and 1-3-mm pores in the white matter of the thoracic spinal cord (T8-T11). Microscopy revealed cystic dilatations in the white matter (T9-T11), cystic areas of varying sizes (T8-T9), and moderate reduction in the gray matter around the central canal of the medulla (T11-T13). Here, we reported the clinical and pathological findings of SHSC and syringomyelia in a Girolando calf. The features should be differentiated from other spinal cord syndromes. Congenital malformations are of economic importance, and their etiology and diagnosis are fundamental to disease control and progenitor-selection programs.

RESUMO: Malformações congênitas são alterações funcionais e estruturais dos sistemas, tecidos ou órgãos que podem ocorrer na fase embrionária ou fetal. Malformações na medula espinhal, como hipoplasia segmentar da medula espinhal (HSME) e siringomielia, possuem raras descrições em bovinos. Uma bezerra Girolando, proveniente do Município de Valença, RJ, foi atendida no Hospital Veterinário da Universidade Federal Rural do Rio de Janeiro (UFRRJ), com quadro de incoordenação motora. À avaliação clínica, na coluna vertebral, à linha dorsal da região torácica havia uma área com depressão de 5 cm. Ao exame neurológico foi observado propriocepção reduzida, extensão de membros pélvicos com aumento da atividade nociceptiva e redução de reflexo anal. Ao exame radiográfico, o corpo vertebral T11 apresentou forma trapezoidal em cunha com hemivértebra ventral, provável agenesia ou hipoplasia dos processos espinhosos T11-T12 e fusão dos processos espinhosos T9-T10. À mielografia indicou compressão medular extradural provocada pelas malformações vertebrais. À necropsia não foram observados os processos espinhosos T11-T12, o canal medular apresentou estenose cranial (T11-T13) e, na medula espinhal torácica (T8-T11) foram observados poros de 1-3 mm na substância branca. À microscopia, os segmentos T9-T11 apresentaram dilatações císticas na substância branca e os segmentos T8-T9, formações de áreas císticas de tamanhos variados; nos segmentos T11-T13 denotou-se moderada redução da substância cinzenta ao redor do canal central da medula. O presente trabalho tem o objetivo de apresentar os achados clínicos e patológicos desta bezerra Girolando com HSME e siringomielia, que devem ser diferenciadas de outras síndromes da medula espinhal. As malformações congênitas possuem importância econômica e sua etiologia e diagnóstico são fundamentais para a condução de programas de controle de doenças e seleção de progenitores.

The Effects of Intradetrusor BoNT-A Injections on Vesicoureteral Reflux in Children With Myelodysplasia / 대한배뇨장애요실금학회지

PURPOSE: We retrospectively evaluated the efficacy of botulinum neurotoxin A (BoNT-A) on vesicoureteral reflux (VUR), continence status, and urodynamic parameters in children with myelodysplasia who were not responsive to standard conservative therapy.METHODS: The study included 31 children (13 boys, 18 girls) with a mean age of 9.2±2.3 years (range, 5–14 years) with myelodysplasia, retrospectively. All children were fully compatible with clean intermittent catheterization (CIC) and did not respond to the maximum tolerable anticholinergic dose. All children received an intradetrusor injection of 10 U/kg (maximum, 300 U) of BoNT-A into an infection-free bladder. All patients had VUR (22 unilateral, 9 bilateral) preoperatively. The grade of reflux was mild (grades 1, 2), intermediate (grade 3), and severe (grades 4, 5) in 25, 7, and 8 ureters, respectively.RESULTS: The mean maximum bladder capacity increased from 152.9±76.9 mL to 243.7±103 mL (P<0.001), and the maximum detrusor pressure decreased from 57±29.4 cm H₂O to 29.6±13.9 cm H₂O (P<0.001). After BoNT-A treatment, 16 refluxing ureters (40%) completely resolved, 17 (42.5%) improved, 5 (12.5%) remained unchanged, and 2 (5%) became worse. Of the 31 children with urinary leakage between CICs, 22 (71%) became completely dry, 6 (19%) improved, and 3 (10%) experienced partial improvement.CONCLUSIONS: In children with myelodysplasia, we were able to increase bladder capacity, enhance continence, and prevent VUR by using intradetrusor BoNT-A injections. Although our results are promising, a larger group of long-term prospective studies are warranted to investigate this method of treatment.

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.

Mielodisplasia na peritonite infecciosa felina: 16 casos (2000-2017) / Myelodysplasia in feline infectious peritonitis: 16 cases (2000-2017)

Apesar da prevalência da peritonite infecciosa felina (PIF) ser alta em praticamente o mundo todo, estudos anatomopatológicos recentes acerca dessa doença são escassos. Não obstante, as características microscópicas da medula óssea de gatos com PIF estão ausentes da literatura consultada. O objetivo deste artigo é descrever alterações medulares ósseas vistas em casos espontâneos de PIF. As medulas ósseas colhidas sistematicamente da região diafisária dos fêmures de 16 gatos necropsiados no Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Santa Maria (UFSM), Rio Grande do Sul, entre janeiro de 2000 e junho de 2017, e que tiveram diagnóstico definitivo de PIF, foram avaliadas fenotípica (histopatologia - hematoxilina e eosina e histoquímica - reação de Perls) e imunofenotipicamente (utilizando marcadores mieloides (anti-MAC387) e de linfócitos (anti-CD79αcy e anti-CD3). Os resultados permitem afirmar que, independentemente da apresentação clinicopatológica da doença ocorrem as seguintes alterações: 1) hiperplasia mieloide; 2) hipoplasia eritroide, 3) displasia megacariocítica (dismegacariocitopoiese) e 4) plasmocitose medular. Exclusivamente nos casos de PIF seca há hemossiderose medular óssea e hepática. Essas alterações permitem estabelecer que gatos com PIF desenvolvem mielodisplasia, uma lesão mieloproliferativa muito semelhante àquela relatada em humanos infectados pelo HIV. Sugere-se que a partir dos achados aqui descritos, a mielodisplasia seja considerada a principal responsável pelas alterações hematológicas observadas na PIF, especialmente pela anemia e trombocitopenia arregenerativas frequentemente desenvolvidas pelos pacientes com essa doença.(AU)

Although the prevalence of feline infectious peritonitis (FIP) is high worldwide, recent anatomopathological studies about this disease are scarce. Information on the microscopic characteristics of the bone marrow in FIP-affected cats are absent in the available literature. Based on this, the purpose of this article is to describe bone marrow lesions seen in spontaneous cases of FIP. The bone marrow collected systematically from the femoral diaphysis of 16 cats necropsied in the Laboratory of Veterinary Pathology (LPV) of the Federal University (UFSM) of Southern Brazil, between January 2000 and June 2017, with a definitive diagnosis of FIP, were evaluated phenotypically (histopathology - hematoxylin and eosin and histochemistry - Perls stain) and immunophenotypically (immunohistochemistry using myeloid - Anti-MAC387, and lymphocytic - Anti-CD79 αcy and Anti-CD3 markers). Regardless the following was observed the clinicopathological form of the disease ("dry" - noneffusive or "wet" - effusive): 1) myeloid hyperplasia; 2) erythroid hipoplasia; 3) megakaryocytic dysplasia (dismegakaryocytopoiesis); and 4) medullary plasmacytosis. Exclusively in cases of "dry FIP" was bone marrow and hepatic hemosiderosis. These lesions allowed establishing that cats with FIP develop myelodysplasia, a myeloproliferative lesion very similar to that reported in HIV-infected humans. It is suggested that, based on the findings described here, myelodysplasia is considered to be the main cause of hematological abnormalities observed in FIP, especially for non-regenerative anemia and thrombocytopenia, frequently developed by patients.(AU)

Transformación leucémica en paciente con linfoma folicular e hiperleucocitosis al diagnóstico / Leukemic transformation in a patient with follicular lymphoma and hyperleukocytosis at diagnosis

La fase leucémica como presentación de un linfoma folicular es rara y debe ser considerada factor de mal pronóstico. Por otra parte, la asociación entre linfoma folicular y síndrome mielodisplásico no se ha descrito. Se presenta el caso de una paciente en la que se detectó marcada leucocitosis y a la que se diagnosticó un linfoma folicular. Recibió quimioterapia con R-CHOP y FCR cuando recayó. Meses después, se realizó un aspirado medular en el cual se observaron cambios compatibles con mielodisplasia, únicamente recibió terapia de soporte y finalmente evolucionó a leucemia mieloide aguda. Aunque se conoce que la mielodisplasia puede ser secundaria al uso de quimioterapia, la paciente presentó además trisomía del cromosoma 11, descrita previamente en mielodisplasia y linfoma tipo Burkitt, la cual pudiera estar en relación con la evolución a leucemia mieloide aguda(AU)

Follicular lymphoma rarely presents with a leukemic phase and this should be considered a negative prognostic factor. Also, follicular lymphoma and myelodysplastic syndrome association has not been previously reported. Herein we present a patient who debuted with marked hyperleukocytosis and was diagnosed with follicular lymphoma, receiving CHOP-R and FCR after she relapsed. Several months later, secondary myelodysplastic changes were observed in her bone marrow. She received supportive therapy and finally progressed into acute myeloid leukemia. Although secondary myelodysplasia is known to be produced by chemotherapy, this patient additionally had trisomy 11, previously described in myelodysplasia and Burkitt's lymphoma, which could be linked to progression to acute myeloid leukemia(AU)

No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome

BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Detection of RUNX1-MECOM Fusion Gene and t(3;21) in a Very Elderly Patient Having Acute Myeloid Leukemia with Myelodysplasia-Related Changes

An 87-yr-old woman was diagnosed with AML with myelodysplasia-related changes (AML-MRC). The initial complete blood count showed Hb level of 5.9 g/dL, platelet counts of 27x10(9)/L, and white blood cell counts of 85.33x10(9)/L with 55% blasts. Peripheral blood samples were used in all the tests, as bone marrow examination could not be performed because of the patient's extremely advanced age and poor general health condition. Flow cytometric analysis, chromosome analysis, FISH, and reverse transcriptase-PCR (RT-PCR) results indicated AML-MRC resulting from t(3;21) with the RUNX1-MECOM fusion gene. To our knowledge, this is the second most elderly de novo AML patient associated with t(3;21) to be reported.

Anemia posgastrectomía con evolución a un síndrome mielodisplástico / Postgastrectomy anemia evolving to a myelodysplastic syndrome

Se presenta un caso en que el diagnóstico etiológico de la anemia debió ser revisado cuando aparecieron nuevas características clínicas o hematológicas y el paciente dejó de responder al tratamiento habitual. El caso clínico corresponde a un hombre de 63 años de edad, mestizo, que ingresa 5 años antes con una enfermedad cerebrovascular y se diagnostica además, una anemia ferripriva posgastrectomía por estudios de sangre periférica y medulograma, que respondió al tratamiento con fumarato ferroso intramuscular. Vuelve a ingresar posteriormente por anemia severa, a la que se asocia neutropenia, que no respondió al tratamiento con hierro y vitamina B12 intramuscular. Se repite el medulograma y es concluido como una anemia refractaria. La anemia ferripriva constituye una de las anemias que más frecuentemente se diagnostican en la práctica clínica. La gastrectomía es una de las causas invocadas y requiere tratamiento sustitutivo parenteral. La refractariedad que aparece posteriormente en este paciente mayor de 60 años debe hacer sospechar síndromes mielodisplásticos, especialmente si existen otras citopenias asociadas. Aunque el diagnóstico de una anemia esté correctamente fundamentado, el médico debe estar preparado para evaluar otras posibilidades ante cualquier cambio evolutivo, sin aferrarse al diagnótico inicial. En este caso, la refractariedad al tratamiento inicialmente exitoso y la asociación de otra citopenia, permitieron sospechar y confirmar una nueva entidad

This is a case presentation in which the etiological diagnosis of anemia must to be reviewed when appeared new clinical and hematological features and the patient don't respond anymore to the habitual treatment. The clinical case corresponds to a black man aged 63 admitted five years before due to a cerebrovascular disease as well as a post-grastrectomy iron-deficiency anemia according to study of peripheral blood and medullogram responding to treatment with i.m. ferrous fumarate. He is readmitted due to a neutropenia-associated severe anemia without response to treatment with iron and i.m. vitamin B12 medullogram is repeated concluded that it is a refractory anemia. The iron-deficiency anemia is one of the more frequent diagnosed in the clinical practice. Gastrectomy if one of major causes and it requires a parenteral substitutive treatment. The refractory character appearing later in this patient aged over 60 leads to the presence of myelodysplasia syndrome specially if there are other associated cytopenias. Although the diagnosis of a anemia be appropriately based, the physician must to be able to assess other possibilities in face any evolutionary change, and no to persist in the initial diagnosis. In this case, the refractory character to treatment successful at onset and the association of other cytopenia, allowed us to suspect and to confirm a new entity

Study of bone marrow changes in antiretroviral naive human immunodeficiency virus-infected anemic patients.

Background: Bone marrow changes are common throughout the course of HIV infection. There is scanty data addressing this issue in Indian subcontinent. The present study was aimed at characterizing the bone marrow changes in the antiretroviral naive HIV-infected Indian patients with anemia. Materials and Methods: This was a nonrandomized cross-sectional observational study undertaken over a period of 2 years. Forty-six randomly selected patients with documented anemia served as the study population. None of them was on any antiretroviral therapy or suffering from any known causes of anemia. All the patients underwent thorough evaluation, including bone marrow examination. Results: Majority of the patients had normocytic-normochromic anemia (63%), in tune with the available data. In most of the cases bone marrow was hypercellular (63.04%), although in a significant proportion it was found to be hypocellular (19.57%). Erythropoiesis was suppressed in 36.96% of patients. Dysplastic changes involving isolated cell lines ranged from 13.04% to 45.65%, dysmegakaryopoiesis being the most common, followed by dyserythropoiesis. Marrow plasmacytosis was detected in 23.91% of patients. No statistically significant correlation was detected in between immunological status (CD4 count) and marrow cellularity, myelodysplastic changes or marrow plasmacytosis. In a fair number of cases bone marrow examination aided in the diagnosis of opportunistic infections. Conclusions: Bone marrow changes are common in Indian HIV-infected anemic population, particularly in the advanced stages of the disease. HIV infection should be considered in the differential diagnosis of patients with secondary myelodysplasia or unexplained bone marrow changes.

Avaliação do método da imunofenotipagem por citometria de fluxo no diagnóstico das doenças displásicas (SMD, LMA-relacionada à mielodisplasia, LMMC e LMMJ) em adultos e crianças / Evaluation of the method of immunophenotyping by flow cytometry in the diagnosis of dysplastic disease (MDS, AML-related to myelodysplasia,CMML and JMML) in adults and children

As síndromes mielodisplásicas (SMD) se caracterizam por terem uma hematopoese displásica, citopenias e pelo risco de progressão para leucemia mielóide aguda. O diagnóstico baseia-se na clínica e nos achados citomorfológicos da medula óssea (MO) e citogenéticos. Na fase inicial ou quando a MO é hipocelular o diagnóstico é difícil e a citogenética frequentemente é normal. A imunofenotipagem (IMF) tem sido cada vez mais utilizada nos casos de SMD em adultos e pouco explorada na SMD pediátrica. Os nossos objetivos foram: estudar os casos de SMD e doenças correlatas (LMA relacioanda à SMD: LMA-rMD; leucemia mielomonocítica crônica: LMMC e leucemia mielomonocítica juvenil: LMMJ) em adultos e crianças, associando os dados clínicos e laboratoriais aos obtidos pela IMF, que utilizou um painel de anticorpos monoclonais para as várias linhagens medulares. No período compreendido entre 2000 e 2010 foram estudados 87 pacientes (64 adultos e 23 crianças) oriundos do HUPE/UERJ e IPPMG/UFRJ e 46 controles (23 adultos e 20 crianças). Todos os doentes realizaram mielograma, biópsia óssea, citogenética, citoquímica e estudo imunofenotípico. Segundo os critérios da OMS 50 adultos foram classificados como SMD, 11 como LMA-rMD e 3 LMMC. Entre as crianças 18 eram SMD, 2 LMA e 3 LMMJ. Os pacientes adultos com SMD foram divididos em alto risco (n=9; AREB-1 e AREB-2) e baixo risco (n=41; CRDU, CRDM, CRDM-SA, SMD-N e SMD-5q). As crianças com SMD em CR (n=16) e AREB (n=2). Anormalidades clonais recorrentes foram encontradas em 22 pacientes adultos e em 7 crianças. Na análise de IMF foi utilizada a metodologia da curva ROC para a determinação dos valores de ponto de corte a fim de identificar os resultados anormais dos anticorpos monoclonais nos pacientes e nos controles, permitindo determinar a sensibilidade e especificidade desses em cada linhagem. A IMF foi adequada para a análise em todos os pacientes e 3 ou mais anormalidades foram encontradas. A associação da IMF...

Myelodysplastic syndrome (MDS) is characterized by having a dysplastic hematopoiesis, cytopenias and risk of progression to acute myeloid leukemia. The diagnosis is based on clinical and cytomorphologic findings in bone marrow (BM) and cytogenetics. In the initial phase of when the BM is hypocellular, diagnosis is difficult and often with normal karyotype. The flow cytometry immunophenotyping (FCI) analysis has been broadly used in adult MDS cases but is rarely in pediatric MDS. The objectives of this work were: to study MDS cases and correlated diseases (AML with myelodysplasia-related changes; chronic myelomonocytic leukemia - CMML and juvenite myelomonocytic leukemia - JMML) and to correlate laboratorial data to FCI using a panel of monoclonal antibodies for the various marrow lineages in both adult and children. In the period between 2000 and 2010, 87 patients were studied (64 adults and 23 children) coming from HUPE/UERJ and IPPMG/UFRJ and 46 controls (26 adults and 20 children). All patients were submitted to myelogram, bone marrow biopsy, cytogenetic, cytochemistry and immunophenotypic study. According to WHO criteria 50 adults were classified MDS, 12 AML and 3 CMML. Among the children there were 18 MDS, 2 AML, and 3 JMML. MDS adult patients were subdivided into high risk (n=9; RAEB-1 and RAEB-2) and low risk (n=41; RCUD, RCMD-RS, MDS-U and MDS-5q). MDS children were classified as RCC (n=16) and RAEB (n=2). Clonal abnormalities were found in 22 (35%) adult patients and 7 (30%) children. In the analysis of FCI methodology ROC curve was used for determination of cut off abnormalities at monoclonal antibodies in patients and controls which allowed to estimate the sensitivity and specificity of each strain. The FCI was suitable for analysis in all patients and 3 or more abnormalities were found. The association of the FCI increased the sensitivity of morphological analysis in the erythroid lineage from 70 to 97% in adults and from 59 to 86% in children...

Screening for hotspot mutations in PI3K, JAK2, FLT3 and NPM1 in patients with myelodysplastic syndromes

INTRODUCTION: Myelodysplastic syndromes encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, refractory cytopenia and a tendency to progress toward acute myeloid leukemia. The accumulation of genetic alterations is closely associated with the progression of myelodysplastic syndromes toward acute myeloid leukemia. OBJECTIVE: To investigate the presence of mutations in the points most frequent for mutations (hotspot mutations) in phosphatidylinositol-3-kinase (PI3K), Janus kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1), which are involved in leukemia and other cancers, in a population of Brazilian MDS patients. METHODS: Fifty-one myelodysplastic syndromes patients were included in the study. According to French-American-British classification, the patients were distributed as follows: 31 with refractory anemia, 8 with refractory anemia with ringed sideroblasts, 7 with refractory anemia with excess blasts, 3 with refractory anemia with excess blasts in transformation and 2 with chronic myelomonocytic leukemia. Bone marrow samples were obtained and screened for the presence of hotspot mutations using analysis based on amplification with the polymerase chain reaction, sequencing, fragment size polymorphisms or restriction enzyme digestion. All patients were screened for mutations at the time of diagnosis, and 5 patients were also screened at the time of disease progression. RESULTS: These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression. CONCLUSIONS: These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression.

The value of flow cytometry for the differential diagnosis between refractory cytopenia with multiple dysplasia and aplastic anemia / 中华内科杂志

Objective To evaluate the value of flow cytometry ( FCM) for the differential diagnosis between myelodysplasia (MDS) subtype refractory cytopenia with multiple dysplasia (RCMD) and aplastic anemia (AA). Methods The flow cytometric data of bone marrow samples from 168 cases of RCMD and 77 cases of AA were analyzed retrospectively in blind, and its results were compared with gold standard to evaluate its diagnosis values. Results The specificity of abnormal of single immunophenotype in the surface of granulocytes and myeloblasts was high (range 75.3% -100% ) , but the sensitivity was very low (range 5.4%-50% ). In parallel tests, the sensitivity and specificity of the combination of CD+34 cells≥1% , myeloblasts ≥3% , abnormal expression of CD117 in granulocytes and loss of CD13 in myeloblasts or increased intensity of CD33 in granulocytes were higher than other combinations. The sensitivity and specificity of above combination were more than 62% and 92% , respectively. In the scoring method,different score was given to 8 markers according to different diagnostic value, which were CD+34 cells ≥1 % ,myeloblasts≥3% , abnormal expression of CD117 in granulocytes, loss of CD13 in myeloblasts, increased intensity of CD33 in granulocytes, loss of CD13 in granulocytes, loss of CD10 in granulocytes, and decreased SSC in granulocytes. The sensitivity and specificity were both high if we defined that the total score ≥1.5 was RCMD and the score < 1. 5 was AA. Conclusions The value of abnormal of single immunophenotype for differential diagnosis between RCMD and AA is low. Parallel tests can increase the diagnostic sensitivity obviously and not decrease the specificity. CD+34 cells≥1% , myeloblasts≥3% and abnormal expression of CO117 in granulocytes were the most important markers. The scoring method is precise to distinguish RCMD from AA.

Clinical Importance of Morphological Multilineage Dysplasia in Acute Myeloid Leukemia with Myelodysplasia Related Changes / 대한진단검사의학회지

BACKGROUND: AML with myelodysplasia related changes (AML MRC) is known to show a poor prognosis compared with de novo AML, but controversies exist about the prognostic impact of multilineage dysplasia (MLD) among MRC. We investigated the prognostic impact of MLD in AML MRC. METHODS: A total of 357 patients newly diagnosed as AML at Asan Medical Center from January 2001 to December 2005 were analyzed. They were diagnosed and classified as AML with recurrent genetic abnormalities, AML MRC, and AML not otherwise specified (AML NOS). Prognostic markers including overall survival (OS) and event free survival (EFS) were obtained through retrospective analysis of electronic medical records. RESULTS: AML MRC patients showed a lower complete remission (CR) rate (44.7% vs. 64.9%, P=0.002) and shorter OS (297 vs. 561 days, P=0.004) and EFS (229 vs. 374 days, P=0.004) than AML NOS patients. Patients with MLD among AML MRC also showed a lower CR rate (37.7%, P=0.001) and shorter OS (351 days, P=0.036) and EFS (242 days, P=0.076) than AML NOS patients. However, among AML MRC patients, there were no differences in OS, EFS and CR between patients with and without MLD. CONCLUSIONS: AML MRC patients showed a lower CR rate and shorter OS and EFS than AML NOS patients. AML MRC patients with MLD showed similar results and their prognosis was not different from those without MLD. MLD findings among AML MRC could be an independent poor prognostic factor in de novo AML.

When should Videourodynamic Study be Performed after Correcting the Defect in Patients with Myelodysplasia? / 대한비뇨기과학회지

PURPOSE: Because vesicourethral dysfunction in myelodysplasia patients is a major cause of upper urinary deterioration and urinary incontinence, urodynamic evaluation should be performed as early as possible. We attempted to establish the proper time when videourodynamic study should be performed and which patients require early interventional therapy. MATERIALS AND METHODS: Out of the 222 patients seen in the pediatric urology department, 22 patients underwent correction of myeloplasia defect from January 2001 to September 2004. Preoperatively, the patients were assessed with videourodynamic study, and the postoperative videourodynamic studies were repeated at 2 to 6 months intervals. Four urodynamic parameters (bladder volume, compliance, detrusor activity and detrusor sphincteric synergy) were identified, graded and then added to obtain the urodynamic score. RESULTS: There was no statically significant difference in all urodynamic parameters between the preoperative and postoperative 2 month videourodynamic studies, but a statistically significant difference was noted in compliance between the preoperative and postoperative 6 month videourodynamic studies. The compliance was more decreased in the patients who had received surgical correction in their older age and high detrusor activity was observed for these patients on the preoperative videourodynamic study. CONCLUSIONS: Postoperative videourodynamic study and early treatment are recommended for the patients who are at high risk for upper urinary tract deterioration. However, for the low risk patients, postoperative 2 month videourodynamic study can prevent unnecessary treatment.

Treatment of myelodysplasia syndrome

Myelodysplasia syndrome is a diseases group of which quite difficult cure and prediction. There are many treatment methods however it depends on patient’s age, level of diease, rate of blast in bone marrow. The treatment includes: chemical treatment, trasplant originative cell, support treatment. Other method is combination of various treatment methods: Use Ara-C combine with depersolon, chemical treatment combine with stimulative agent of blood and trasplant originative cell

A case of juvenile rheumatoid arthritis with myelodysplastic features / 대한내과학회지

Juvenile rheumatoid arthritis (JRA), an autoimmune disease, was characterized by chronic synovitis and associated with various extra-articular manifestations. Abnormal hematologic findings have been reported in all form of JRA, especially anemia due to chronic disease or iron deficiency. Dysplastic changes were rarely noted in the peripheral blood and bone marrow. We experienced a 15-year-old female patient with pauciarticular JRA who have pancytopenia in peripheral blood and a number of dysplastic changes in bone marrow, and present the case here with brief review of literatures.

Significance of trilineage myelodysplasia in de novo acute myeloid leukemia / 대한임상병리학회지

BACKGROUND: The findings of dysplastic features in haemopoietic cells in de novo acute myeloid leukemia(AML) is defined as AML with trilineage myelodysplasia(AML/TMDS). These cases have been reported accounting for 10-5% of de novo AML. The rate of complete remission(CR) in AML/TMDS to conventional chemotherapy is poor and relapse occur much earlier than in patients without dysplastic features. TMDS features are also observed during remission and termed this de novo AML with myelodysplastic remission marrow(AML/MRM). Recent report described that TMDS during remission was more closely related to prognosis than dysplastic features at diagnosis. We investigated the incidence of AML/TMDS and AML/MRM and evaluated the impending role of dysplasia in prognosis. METHOD: Ninety-ive patients with de novo AML from March 1994 to December 1998 were enrolled according to the FAB classifiction. To determine AML/TMDS and AML/MRM, we used Brito-abapulle's criteria and Kazuhiro's criteria. Prognosis was aalysed by the means of disease free survival(DFS) and overall survival(OS). RESULTS: Nine(9.5%) patients had AML/TMDS and it was 7.7%, 17.2%, 50% of patients with M2, M4 and M6. CR rate was 44.4% for TMDS patients compared to 76.7% for patients without TMDS(p<0.05). AML/TMDS also showed significantly shorter DFS and OS. The incidence of AML/MRM was higher in the group of AML/TMDS(44.4%) compared to AML without TMDS(8.1%) but was not related to prognosis. CONCLUSION: We concluded that the presence of TMDS in de novo AML exerts a negative effect on the ability to achieve CR and in the prognosis. But the MRM has no significance to predict poor prognosis and early relapse.

Significance of trilineage myelodysplasia in de novo acute myeloid leukemia / 대한임상병리학회지

BACKGROUND: The findings of dysplastic features in haemopoietic cells in de novo acute myeloid leukemia(AML) is defined as AML with trilineage myelodysplasia(AML/TMDS). These cases have been reported accounting for 10-5% of de novo AML. The rate of complete remission(CR) in AML/TMDS to conventional chemotherapy is poor and relapse occur much earlier than in patients without dysplastic features. TMDS features are also observed during remission and termed this de novo AML with myelodysplastic remission marrow(AML/MRM). Recent report described that TMDS during remission was more closely related to prognosis than dysplastic features at diagnosis. We investigated the incidence of AML/TMDS and AML/MRM and evaluated the impending role of dysplasia in prognosis. METHOD: Ninety-ive patients with de novo AML from March 1994 to December 1998 were enrolled according to the FAB classifiction. To determine AML/TMDS and AML/MRM, we used Brito-abapulle's criteria and Kazuhiro's criteria. Prognosis was aalysed by the means of disease free survival(DFS) and overall survival(OS). RESULTS: Nine(9.5%) patients had AML/TMDS and it was 7.7%, 17.2%, 50% of patients with M2, M4 and M6. CR rate was 44.4% for TMDS patients compared to 76.7% for patients without TMDS(p<0.05). AML/TMDS also showed significantly shorter DFS and OS. The incidence of AML/MRM was higher in the group of AML/TMDS(44.4%) compared to AML without TMDS(8.1%) but was not related to prognosis. CONCLUSION: We concluded that the presence of TMDS in de novo AML exerts a negative effect on the ability to achieve CR and in the prognosis. But the MRM has no significance to predict poor prognosis and early relapse.

Analysis of the Relationship between Deformity and Activity of Daily Living According to the Level of Neurologic Deficit in Myelodysplasia - Part Two: Lipomeningocele - / 대한정형외과학회잡지

PURPOSE: To clarify the relationship between the level of neurologic deficit and deformity of the lower extremity and also the ambulatory status. MATERIALS AND METHODS: We performed retrograde analysis on 79 patients older than 30months with lipomeningocele. All of the patients were classified according to the level of neurologic functional motor deficit. There were 52 males and 27 females patients. Average age was 6 years and 8 months. RESULTS: There was only one patient in the upper lumbar (L1-L2) motor level deficit. He was a non ambulator. Among the 26 with lower lumbar (L3-L5) deficit, 6 were household ambulators, 20 were community ambulators; 2 had hip deformities and 22 had foot deformities. Among the 48 patients with sacral (S1-S3) deficit, all were community ambulators; 3 had hip deformities and 27 had foot deformities. In 4 patients who showed normal motor function, all were community ambulators without any deformity. CONCLUSION: In lipomeningocele, patients who had a functional motor deficit above L4 level showed poor ambulatory status. However, those below L4 level showed good ambulation, and in cases with the L4-5 motor level deficit, we were able to improve the ambulatory status after correction of the deformities of the lower extremity.