Clinical Comparation of Two Kinds of Chemotherapy Regimens in the Treatment of Patients with MDS-RAEB/AML-MRC / 中国实验血液学杂志

OBJECTIVE@#To investigate the influence of conventional CAG regimen and decitabine + decreased dose CAG (D+dCAG) regimen on the clinical efficacy and safety of patients with MDS-RAEB/AML-MRC.@*METHODS@#The clinical data of 67 patients with MDS-RAEB/AML-MRC hospitalized in our hospital from March 2012 to July 2017 were analyzed retrospectively. According to chemotherapecctic regimens, 76 patients were divided into 2 groups: 37 patients treated with conventional CAG regimen were enrolled in control group, 30 patients treated with decitabine + decreased dose CAG regimen were enrolled in D+dCAG group. The complete remission (CR) rate, overall remission rate (ORR), OS and PFS time and incidence of adverse reactions in 2 groups were compared.@*RESULTS@#The CR in D+dCAG group was significantly higher than that in control group (P＜0.05). ORR was not significanly different between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate between 2 groups (P＞0.05). There was no significant difference in the cumulative OS rate and PFS rate in nonimplantation between 2 groups (P＞0.05). The incidence of adverse reactions of hematological system, pulmonary infection, skin and soft tissue infection, agranulocytosic fever and mycotic infection was not significanly different between 2 groups (P＞0.05). The duration of granulocyte deficiency and platelet count less than 20×10/L were not significanly different between 2 groups (P＞0.05).@*CONCLUSION@#Compared with conventional CAG regimen, decitabine + decreased dose CAG regimen in the treatment of patients with MDS-RAEB/AML-MRC can efficiently improve the remission effects and showed the well overall safety, but can not increase the survival rate.

Comparation of Clinical Efficacy between Two Regimens of Preexcitation Chemotherapy for MDS-RAEB Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safely of DAC and CAG/HAG preexcitation chemotherapy regimens for the treatment of patients with MDS-RAEB (refractory anemia with excess blasts, RAEB).@*METHODS@#The clinical data of 86 MDS-RAEB patients were analyzed retrospectively from February 2014 to February 2018. According to therapeutic regimem, the 86 patients were divided into 2 groups: group A (41 patients) with DAC preexcitation chemotherapy regimen, and group B (45 patients) with CAG/HAG preexcitation chemotherapy regimen; and the disease control effect, effective treatment course, median survival time and incidence of adverse reactions were compared between these 2 groups.@*RESULTS@#The CR rate and ORR rate were not significantly different between these 2 groups (P＞0.05). The mCR rate in group A was significantly higher than that in group B (P＜0.05). The numbers of cases obtained therapeutic efficacy at 2 rd and 3 rd conrse in group A significantly more than those in group B (P＜0.05), but the number of cases obtained efficacy at 1 st course in group B was significantly higher than that in group A (P＜0.05). The median OS time was not significanly different between 2 groups (P＞0.05). The duration of neutrophils deficiency in group A was significantly shorter than that in group B (P＜0.05). The transfusion volume of red blood cells and platelets in group A was significantly less than that of group B (P＜0.05). The incidence of neutropenia, anemia and thrombocytopenia of III-IV grade at different treatment courses of group A were significantly lower than that in group B (P＜0.05). The incidence of infection of III-IV grade in group A at 3rd treatment course was significantly lower than that in group B (P＜0.05).@*CONCLUSION@#Preexcitation chemotherapy regimens of DAC and CAG/HAG for the treatment of MDS-RAEB possess the same effects for disease control; application of DAC regimen can efficiently reduce the risk of adverse reaction, but CAG/HAG regimen can be helpful to accelerate the effective process of treatment.

Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02)×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65)×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days) and had platelet counts of >20×109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

Clinical and cytogenetic study of chromosome 1 abnormality in myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the incidence of chromosome 1 abnormality in myelodysplastic syndrome（MDS）to couple its association with clinical presentation and prognosis.</p><p><b>METHODS</b>R- band karyotype analyses were performed in 672 cases of MDS between 2010 and 2013. Clinical data of those with abnormal chromosome l were collected and then analyzed factors affecting the prognosis.</p><p><b>RESULTS</b>Of 672 cases of patients with MDS, chromosome 1 aberration［der（1）, dup（1）, －1 were most frequent］ were found in 41（6.1%）cases. 1q trisomy was found in 18/41（43.9%）cases, and the most common patterns were duplication of the long arm as well as unbalanced translocation with other chromosomes. Of 41 patients with chromosomal 1 abnormality, 32 cases were accompanied with other chromosomal aberration, usually involving 3 or more abnormal chromosomal karyotypes, e.g., chromosome 8, 7 abnormalities. According to IPSS-R scoring system, 19 patients were diagnosed with very high risk, 10 patients high risk, 10 patients intermediate risk and 2 patients low risk MDS. 9 patients transformed into acute leukemia with median transforming time of 7.18（0.56-54.28）months. Median survival of 36 cases after 2010 was 17.48（95% CI 14.38-20.58）months. There were significant differences on median survival between RAEB and non-RAEB groups（χ²=10.398, P=0.001）, and between with more than 3 chromosome abnormalities and with less than 3 groups（χ²=3.939, P=0.047）. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.</p><p><b>CONCLUSION</b>Chromosome 1 aberration was not rare in MDS. 1q trisomy was the most common abnormal karyotype in China, which often accompanied with other chromosomal abnormalities. The prognosis of MDS patients with chromosome 1 abnormality was poor, especially worse in those diagnosed with RAEB-1, RAEB-2 and with more than 3 chromosome abnormality. For patients whose percentage of bone marrow blasts less than 5%, the prognosis of patients with 1q trisomy was better than those without 1q trisomy. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.</p>

Identification of genes underlying different methylation profiles in refractory anemia with excess blast and refractory cytopenia with multilineage dysplasia in myelodysplastic syndrome / 대한혈액학회지

BACKGROUND: Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD). METHODS: Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD. RESULTS: Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB. CONCLUSION: DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.

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.

Bullous Pemphigoid in an Elderly Patient with Myelodysplastic Syndrome and Refractory Anemia Coupled with Excess of Blast

Bullous pemphigoid (BP) has a recognized association with solid organ tumors, but is relatively rare in hematological malignancies. We report a 67-year-old male who developed BP after being diagnosed with myelodysplastic syndrome and refractory anemia with excess of blast (RAEB). Skin biopsy elucidated sub-epidermal bulla using direct immunofluorescence, revealing linear C3 and IgG deposits along the basement membrane. His BP was recalcitrant to the conventional treatment and only responded to a combination of high dose oral prednisolone and azathioprine. The relative refractory nature of his condition and concurrent RAEB supports a paraneoplastic nature.

Cyclosporine A in combination with thalidomide for the treatment of patients with myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficiency and side-effects of the combination of cyclosporine A (CsA) and thalidomide in patients with myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>A total of thirty-seven patients with MDS-RCMD or-RAEB-I were treated with CsA in combination with thalidomide. The initial CsA dose of 3 mg×kg(-1)×d(-1) was administered, all patients had their CsA blood concentration concurrently monitored until it reached and maintained between 100 and 200 µg/L. The initial dose of thalidomide was 50 mg/d, with increasing dose of 50 mg every week until the maximum of 200 mg/d. The hematological response was assessed according to the modified criteria of the International Working Group, and adverse events were graded with the Common Toxicity Criteria (v3.0) of the National Cancer Institute. The response duration and overall survival of the patients were also observed.</p><p><b>RESULTS</b>19/37 cases (51.4%) achieved hematologic improvement (HI)-erythroid response (HI-E), 9/29 cases (31.0%) HI-platelet response (HI-P) and 7/33 cases (21.2%) HI-neutrophil response (HI-N). 15 of 32 transfusion-dependent patients (46.9%) achieved transfusion independence. The median response duration of HI-E, HI-P and HI-N were 88 (4 - 88) weeks, 78 (8 - 84(+)) weeks and 78 (10 - 84(+)) weeks respectively. The median overall survival was 52 months on a 29 (4 - 103) months median follow-up. Some patients developed grades I-II hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rashes or numbness, and all were tolerable and reversible. No grade III or severer adverse events were observed.</p><p><b>CONCLUSION</b>CsA in combination with thalidomide appears to be effective mainly in inducing HI-E and relatively well-tolerated for the treatment of patients with MDS.</p>

Primary myelodysplastic syndrome in Jordan: a single-centre experience

Study of the disease patterns and clinical evaluation of myelodysplastic syndrome [MDS]. A retrospective analysis was carried out on 85 patients, with MDS who were followed up over a period of 23 years at Jordan University Hospital, Amman, Jordan. Cases were analyzed according to the French, American and British Classification. Of the 85 patients, 42 [49.4%] were females and 43 [50%] males; mean age was 59 +/- 19 years [range 18-88]. Most subtypes found in patients were refractory anemia [RA] in 27 [31.8%] and RA with excess blasts [RAEB] in 28 [32.9%]. Adverse prognostic indicators were RAEB subtype and requirement for blood transfusion. Our findings showed that MDSs appeared at a younger age and tended to be of the aggressive subtype. Chronic myelomonocytic leukemia subtype seemed to appear dominantly in men

Serum proteomics in patients with RAEB myelodysplastic syndromes / 南方医科大学学报

<p><b>OBJECTIVE</b>To screen the molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling.</p><p><b>METHODS</b>The serum protein were isolated from patients with RAEB, acute myeloid leukemia or normal subjects by 2-dimensional electrophoresis (2-DE), and the electrophoresis gels were obtained to identify the differentially reacting protein spots. The replica gels of the differentially reacting proteins were analyzed to locate the matching protein spots, which were identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching.</p><p><b>RESULTS</b>Seven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified by MALDI-TOF-MS to have significantly differential expression in RAEB, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and an albumin-like protein.</p><p><b>CONCLUSION</b>2-DE-based serum proteome profiling helps identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased expression in the serum in RAEB subtype MDS, suggesting its possible role in advanced MDS.</p>

Clinical characteristics and prognosis according to the classification of myelodysplastic syndrome / 대한내과학회지

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal hematologic stem cell disorders characterized clinically and morphologically by ineffective hematopoiesis. A consensus-defined French-American-British (FAB) classification and International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. So we investigate clinical characteristics and prognosis of MDS, according to French-American-British (FAB) classification and International Prognostic Scoring System (IPSS). METHODS: A retrospective analysis of 50 patients who were diagnosed as myelodysplastic syndrome at Ajou University Hospital was performed from November, 1994 to April, 2003. The patients with secondary MDS were excluded. All patients were classified according to the FAB classification and calculated prognostic scores for IPSS. Patients were evaluated for clinical features and for blood and bone marrow findings at the time of diagnosis, and were followed up for survival and leukemic progression. Survival curves were based on the Kaplan-Meier method. All reported p values less than or equal to 0.05 were regarded as stastistically significant. RESULTS: The peak age was in the fifth decade and the male to female ratio was 1.5:1. RA (36%) was observed most frequently. Thereafter, RAEB-t (26%), RAEB (24%), RARS (12%) and CMML (2%) were observed, respectively. The initial symptoms on admission were fever (24%), dizziness and headache (16%), general weakness (16%), hemorrhage (14%), dyspnea (12%), abdominal pain (4%) and vomiting (4%). Cytogenetic studies were performed in 34 patients with MDS. They were classified as good, intermediate, poor group by chromosome score of IPSS. The median survival was 16.4 months for the good group, 15 months for the intermediate, 10.3 months for the poor. The median survival according to FAB classified groups were RA (33.8 mo), RARS (12.5 mo), RAEB (16.4 mo), RAEB-t (6.7 mo) and CMML (1.3 mo). Survival according to IPSS scoring system were 67.2 months for low, 27.1 months for intermediate-1, 10.3 months for intermediate-2 and 6.0 months for high groups. These data were statistically significant (p<0.05). CONCLUSIONS: In our experiencies, FAB and IPSS classification would be good predictors in clinical outcomes. But, because of the heterogeneity of MDS, large multicenter studies will be needed to define the issue of a new classification for these disorders.

Avaliacão da importância da coloracão de Perls na rotina de mielogramas de pacientes com anemia associada a uma ou mais citopenias em sangue periférico / Evaluation of the importance of Perls stain in the routine testing of myelograms of patients with anemia associated with one or more peripheral blood cytopenias

As síndromes mielodisplásicas (SMD) são um grupo heterogêneo de doencas malignas das células-tronco hematopoéticas, classificadas segundo a Organizacão Mundial da Saúde (OMS) em: anemia refratária, anemia refratária com sideroblastos em anel, citopenia refratária com displasia de multilinhagens, anemia refratária com excesso de blastos, síndrome mielodisplásica inclassificável e sindrome mielodisplásica associada com anormalidade isolada do cromossomo 5q(del). Na anemia refratária com sideroblastos em anel observam-se hiperplasia e displasia eritróide com presenca de 15 por cento ou mais de sideroblastos em anel. Utilizamos neste estudo a coloracão de Perls em esfregacos de medula óssea de pacientes com idade superior a 40 anos e que apresentavam uma ou mais citopenias no sangue periférico associada a anemia. Por tratar-se de técnica de manejo fácil e ágil sugerimos seu emprego em esfregacos de aspirado de medula óssea de pacientes que apresentem os achados laboratoriais acima, pois, dentre os casos analisados 18,7 por cento apresentavam mais que 10 grânulos sideróticos circundando a terca parte ou mais do núcleo do precursor eritróide (sideroblasto em anel), sugerindo ao hematologista um possível diagnóstico de Síndrome Mielodisplásica com Sideroblastos em Anel (SMD-ARSA). Importante relatar que a grande maioria destes casos com aumento de sideroblastos em anel não foi encaminhada ao nosso servico, com suspeita de SMD, e em somente um caso foi solicitada a realizacão da coloracão de Perls.

Myelodysplastic syndrome with erythroid hypoplasia: a rare and distinct clincopathological entity--a report of two cases.

Erythroid hypoplasia in myelodysplastic syndrome (MDS) happens to be a rare association and is being recognized as a distinct clinico pathological entity. We report here two such cases diagnosed as Refractory anaemia (RA) and Refractory anaemia with excess blast (RAEB) who had marked suppression of the erythroid cell lines. Both patients presented with severe transfusion dependent anaemia. Recognition of these cases is important as alternative modalities of treatment such as immunosuppressives may be considered for these patients.

Clasificaciones y sistemas pronósticos en síndromes mielodisplásicos / Classification and prognostic systems in myelodysplastic syndromes

Myelodysplastic syndrome (MDS) comprises a group of heterogeneous hematological disorders with risk of leukaemic evolution (LE), characterized by varied degrees of peripheral cytopenias related to a progressive bone marrow (BM) failure. Due to the heterogeneity of this pathology and the difficulty to make decisions regarding therapy, different classification and prognostic systems have been developed. The French-AmericanBritish cooperative group defined the first criterion for a systematic classification in 1982 that recognized morphologic entities: refractory anemia (RA), RA with ringed sideroblasts (RARS), RA with excess of blast (RAEB), RAEB in transformation (RAEBt) and chronic myelomonocytic leukemia (CMML). Although the FAB is the classification with major agreement, it has some prognostic failures. Therefore, since 1985 different instruments-scoring systems for prognosis were developed taking into account diverse clinical parameters including the cytogenetic analysis in 1993. In order to standardize prognostic features in MDS the International Scoring System (IPSS) was generated in 1997. This score defined risk groups for survival and LE on the basis of percentage of BM myeloblasts, cytogenetic abnormalities and number of cytopenias. Finally in 1999, the World Health Organization proposed a new classification system based on morphology and cytogenetic findings making another intent to sort out the heterogeneity of this pathology

Los síndromes mielodisplásicos comprenden un grupo heterogéneo de trastornos ematológicos caracterizados por grados variables de citopenias periféricas relacionadas con una falla medular progresiva con riesgo de evolución leucémica. Dada la heterogeneidad de la patología y la dificultad de aplicar una terapéutica eficaz, se han publicado diversos sistemas de clasificación y pronóstico. El primer criterio de clasificación sistemática fue definido en 1982 por el Grupo Cooperativo FrancoAmericano-Británico (FAB) reconociendo entidades morfológicas: anemia refractaria (AR), AR con sideroblastos anillados (ARSA), AR con exceso de blastos (AREB), AREB en transformación (AREBt), y leucemia mielomonocítica crónica (LMMC). Aunque es la clasificación de mayor reconocimiento internacional, posee ciertas falencias pronósticas. Consecuentemente, desde 1985 se registran diferentes sistemas de predicción que toman en cuenta ciertas variables clínicas e incorporan, en 1993, el estudio citogenético. Finalmente, en 1997 se genera el Sistema Pronóstico Internacional (IPSS), el cual discrimina grupos de riesgo para supervivencia y evolución leucémica teniendo en cuenta el porcentaje de blastos en médula ósea, el cariotipo y las citopenias periféricas. El último abordaje sugerido por la Organización Mundial de la Salud, en 1999, propone un nuevo sistema de clasificación basado en hallazgos morfológicos y citogenéticos para entender esta compleja patología.

Cyclosporine A based therapy for myelodysplastic syndrome / 中国实验血液学杂志

To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of 10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than 10% (RAEB-1) were analyzed. Five patients had hypocellular bone marrows and 11 patients had normocellular or hypercellular marrows. The dose of CsA was 2.5-5.5 mg/(kg.d) for 2 weeks to 2 years (mean 8 months). Two out of 16 patients were treated with CsA alone, 14 patients were treated with CsA, recombinant human erythropoietin, androgens, 1, 25 dihydroxy vitamin D(3) or two or three of them combination with CsA. Treatment responses were classified according to the International Working Group (IWG) criteria as complete remission (CR), partial remission (PR), hematological improvement (HI) and no response (NR). Patients who obtained CR, PR or HI were defined as responders. The results showed that HI was observed in 12 patients, PR in 2 patients and NR in 2 patients. Total response rate was 87.5%. Response rates shown in neutrophil lineage, platelet and erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time required to obtain some hematologic improvement after initiation of CsA therapy was 2 weeks, 1 month and 1 month, respectively. Of 13 patients being transfusion-dependent before treatment, 3 patients did not need transfusion any more and 5 showed the reduced transfusion requirements after CsA therapy. In 10 patients with RA, 9 responded to CsA. Of 6 patients with RAEB, 1 patient had no response and died of RAEB-t and 5 patients had transient responses. One of the latter transformed to CMML and two relapsed. The total response rate decreased to 50% in the patients with CsA therapy lasting more than 3 months at the end of following-up. The adverse effects included hirsutism, hyperplastic gingiva, reversible hepatic and renal dysfunction. In conclusion, the usefulness of CsA based therapy for MDS-RA and RAEB-1 with any marrow cellularity is useful, the CsA dose of 3-5 mg/(kg.d) is safe and efficacious.

Correlation between survivin mRNA expression and homoharringtonine induced apoptosis of malignant hematopoietic cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The inhibitor of apoptosis (IAP) gene family is involved in the suppression of apoptotic cell death as well as an increasing number of seemingly unrelated cellular functions. It is not known, however, whether IAP expression in malignant hematopoietic cells is affected by chemotherapeutic agents such as homoharringtonine (HHT). In this study, we investigated mRNA expression levels of IAPs, especially survivin, in various hematopoietic cell lines in relation with apoptosis induced by HHT.</p><p><b>METHODS</b>Semiquantitative reverse transcriptase polymerase chain reaction was used to determine survivin mRNA levels. Cell apoptosis was examined by flow cytometry. Cell viability and proliferation assay was evaluated by MTT. The experiments were performed on the malignant hematopoietic cell lines MUTZ-1, K562, Jurkat, RMPI and HL60, with or without survivin antisense-oligodeoxynucleotides (AS-ODN) and HHT.</p><p><b>RESULTS</b>The expression levels of survivin mRNA were variable in the cell lines and negatively correlated to HHT induced cell apoptosis. Survivin AS-ODN significantly decreased mRNA level of survivin, but not those of bax and bcl-2. Survivin also inhibited MUTZ-1 cell growth and induced apoptosis in a dose dependent manner. AS-ODN and HHT showed synergistic effect on MUTZ-1 cell growth.</p><p><b>CONCLUSION</b>The apoptotic effect of HHT on the hematopoietic cell lines is associated with decreased level of survivin expression. Survivin could be a new marker for drug sensitivity and a new target for cancer treatment.</p>

Low dose all-trans retinoic acid and androgen therapy for patients with myelodysplastic syndrome / 中国实验血液学杂志

To explore therapeutic efficacy of androgens and low dose all-trans retinoic acid (ATRA) for myelodysplastic syndrome (MDS) patients, 55 patients of MDS were observed, including 41 cases of refractory anemia (RA), 11 cases of refractory anemia with excess of blasts (RAEB), 2 cases of refractory anemia with excess of blasts in transformation (RAEB-t) and 1 case of chronic myeloic-monocytic leukemia (CMML). These patients received danazol (600 mg/day) or stanazol (6 mg/day) and ATRA (10 mg/day) for at least 3 months. The results showed that according to MDS international working group response criteria, at the end of three months,complete remission (CR) was seen in 1 patient, partial remission (PR) was found in 2 patients. Hematologic improvement: major response (MaR) were seen in 15 patients, minor response (MiR) were seen in 4 patients. The total response rate was 35.8%. In conclusion, danazol or stanazol in combination with low dose ATRA are partialy effective in therapy for patients with low-risk myelodysplastic syndrome.

RAEB-t in young adults--a rare entity.

Refractory anemia with excess blasts in transformation (RAEB-t) in young adults is a rare entity. RAEB-t presenting with megaloblastic erythropoiesis should be differentiated from nutritional B12 and folic acid deficiency and from acute erythroleukemia. We report two cases in the present article.

Expression of Fas, FasL and Bcl-2 and apoptosis of bone marrow CD34+ cells in patients with myelodysplastic syndrome / 中国实验血液学杂志

In order to observe the expression of Fas, FasL and Bcl-2 and apoptosis of bone marrow CD34(+) cells in patients with myelodysplastic syndrome (MDS), and to explore the relation between the expression of these antigens and apoptosis, the expression of Fas, FasL and Bcl-2 and apoptosis of bone marrow CD34(+) cell were evaluated by flow cytometry in 26 patients with MDS including 9 cases of refactory anemia (RA), 1 case of RA with ringed sideroblasts (RAS), 9 cases of RA with excess blasts (RAEB) and 7 cases of RAEB in transformation (RAEB-t), 10 patients with acute myeloid leukemia (AML) and 6 control patients with normal bone marrow. The results showed that the expression of Fas and FasL of CD34(+) cells significantly increased in all types of MDS patients compared with control group (P < 0.01). The expression of Bcl-2 on CD34(+) cells in RAEB and RAEB-t patients was much higher as compared with that in control group (P < 0.01), but there was no significant difference between RA/RAS patients and control group (P > 0.05). The expression rates of Fas on CD34(+) cells were almost identical in all kinds of MDS, but there was significant difference on the expression of Bcl-2 (RA/RAS < RAEB < RAEB-t). Apoptosis of CD34(+) cells significantly increased in RA/RAS and RAEB patients compared with control group (P < 0.01), but there was no difference between RAEB-t and control group. Moreover, apoptosis of CD34(+) cells in control much higher than that in AML group (P < 0.01). There was no correlation between the expression of Fas or FasL and apoptosis on CD34(+) cell of MDS patients. Nevertheless, there was a negative correlation between the expression of Bcl-2 and apoptosis. It is concluded that apoptosis of CD34(+) cells was affected by a lot of factors in MDS, in which Bcl-2 is an important factor of depressing apoptosis. During the progress from MDS to AML, apoptosis changes from overgoing to deficiency in CD34(+) cell.

Comparison of FAB and WHO Classifications and Validation of WHO Classifications in 218 Korean Patients with Myelodysplastic Syndrome / 대한진단검사의학회지

BACKGROUND: World Health Organization (WHO) proposed a new classification of myelodysplastic syndrome (MDS) in 1999, based on significant modifications of the original FAB proposals. The aim of the present study was to validate the new classification with respect to prognostic importance. METHODS: Two hundred and eighteen patients were diagnosed with MDS according to the FAB criteria between August 1989 and June 2001 in the Asan Medical Center. They were studied retrospectively to evaluate morphological, clinical and cytogenetic data for diagnosis and clinical outcomes with long-term follow up, and reclassified with a new WHO classification. RESULTS: According to the original FAB classification, 218 patients were classified as RA 78, RARS 17, RAEB 76, RAEB-t 38 and CMML 9. They were reclassified to the WHO classification to RA 24, RARS 6, RCMD 51, RCMD-RS 11, RAEB-1 42, RAEB-2 51, del(5q) syndrome 1 and unclassifiable 2. Twenty-one cases of RAEB-t and 9 cases of CMML were reclassified to acute myeloid leukemia and myelodysplastic syndrome/myeloproliferative disease (MDS/MPD). Among the reclassified groups in the WHO classification, there is a significant difference in prognosis between RA and RCMD (median survival, not reached vs. 28.4 months, P=0.020), and in leukemic transformation between RAEB-1 and RAEB-2 (5% vs. 37%, P=0.001). CONCLUSIONS: These data provide the proper evidence, especially of prognosis and leukemic transformation for the WHO classifications. We recommended using the WHO classification rather than the FAB classification of the diagnosis of MDS.