Objective To study the clinical outcome of patients with fns-like tyrosine kinase-3internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia (AML) treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to explore the potential prognostic factors to patients' survival including transplant types or disease status.Methods A total of 314 AML patients in our center from October 2006 to October 2012 were retrospectively analyzed,among whom,54 patients were defined with FLT3-ITD positive.Survival rates and treatment-related mortality were further analyzed.Results For all 54 FLT3-ITD positive patients,the 3-year overall survival (3-OS) rate was 56％ and 3-year leukemia-free survival (3-LFS) rate was 47％.The outcome of haplo-identical HSCT was similar as that of sibling donors(3-OS rate:60％ vs 54％ ; 3-LFS rate:54％ vs 45％,respectively).There were 47 patients who received transplantation in first complete remission(CR1).The other 7 patients were of disease relapse or in CR2 before transplantation.Not surprisingly,patients in CR1 had better prognosis than those in nonCR1.Conclusions Allo-HSCT is an effective treatment for AML patients with FLT3-ITD positive mutation.The survival outcome of haplo-identical HSCT was comparable with that of sibling donors.Relapse of AML was the dominant factor related to the mortality of FLT3-ITD positive AML patients after allo-HSCT.

Objective To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome ( MDS) and erythroid hyperplasia.Methods MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study.The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia ( MDS-E ).The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University.Clinical characteristics , karyotype , and the prognostic significance of erythroid hyperplasia were evaluated.Results A total of 48 MDS-E patients (47.1%) presented a variety of cytogenetic abnormalities.The most frequently involved chromosomes were chromosome 8 (39.5%of all abnormal karyotypes ), chromosome 7 (22.9%), followed by chromosome 5 ( 18.8%) , chromosome 1 ( 16.7%) and chromosome 20 ( 16.7%) .Hemoglobin ( Hb) level affected the prognosis by survival analysis.The overall survival ( OS) of MDS-E patients with Hb equal or more than 70 g/L was longer than that of patients less than 70 g/L ( P<0.001).Allogeneic hematopoietic stem cell transplantation (HSCT) significantly improved the OS compared with best supportive care (P<0.001) and chemotherapy (P<0.001).The extent of erythroid hyperplasia in bone marrow did not impact on prognosis ( P=0.187 ).Conclusions Compared with previous reports of MDS patients, MDS-E patients have higher level of erythroid hyperplasia , more common erythroid dyshematopoiesis , more frequent 8 and 1 chromosome abnormalities .The degree of erythroid hyperplasia is not correlated with prognosis.Allogeneic hematopoietic stem cell transplantation improves the prognosis.

Objective To investigate the effect of fasudil on vascular endothelial function in patients with coronary slow flow( CSF) . Methods Eighty?two patients with CSF and normal coronary angiography were selected and randomly divided into conventional treatment group and fasudil group, 41 cases in each group. Patients in conventional treatment group were given conventional treatment( aspirin,nitrates and atorvasta?tin) ,while patients in the fasudil group were given fasudil on the basis of conventional treatment. The angina pectoris,TIMI,endothelial?dependent flow?mediated vasodilation( FMD) ,the levels of plasma nitric oxide( NO) , endothelin?1( ET?1) and Rho kinase( ROCKI) of the brachial artery were observed in the two groups before and after two weeks of treatment. Results The total effective rate of fasudil group was 87. 80%,higher than that of conventional treatment group of 65. 85%,the difference was significant(χ2=68. 176,P<0. 05) . TIMI,FMD im?proved in the fasudil group after treatment compared with before treatment, the difference was significant ( t =4. 37,4. 43;P<0. 05);plasma NO level increased compared with before treatment(t=5. 63,P<0. 01),while ROCKI,ET?1 level decreased(t=6. 19,5. 66;P<0. 01). Plasma NO,ET?1,ROCKI and FMD,TIMI of conven?tional treatment had no significantly changes before and after treatment(P<0. 05). The post?treatment of NO, FMD,TIMI levels in fasudil group were significantly increased compared with conventional group ( ( 36. 17 ±7. 64) μmol/L vs. (24. 99±8. 96) μmol/L,(9. 96±1. 76)% vs. (5. 86±1. 45)%,17. 53±5. 81 vs. 29. 71 ±7. 83;t=4. 06,4. 18,5. 41;P<0. 05),while ROCKI,ET?1 levels in fasudil group were significantly decreased compared with conventional group((19. 57±1. 33) μg/L vs. (34. 38±1. 51) μg/L,(14. 36±6. 05) ng/L vs. (20. 95±6. 57) ng/L;t=3. 87,4. 36,P<0. 01). Conclusion Fasudil can significantly improve the vascular en?dothelial function in patients with CSF.

Objective To investigate the frequency of c-kit mutation and prognosis in t (8;21) acute myeloid leukemia (AML) patients with trisomy 4. Methods A total of 145 de novo t(8;21) AML patients from February 2005 to January 2013 were analyzed retrospectively. Detection of exons 8 and 17 mutation of c-kit by PCR and cytogenetic analysis by R-banding technologies were performed on bone marrow samples of all patients at diagnosis. Clinical data were collected and analyzed statistically. Results Among 145 t (8;21) AML patients, 12 cases (8.3 %) were trisomy 4, 91.7 % (11/12) of them were identified with c-kit mutation, which was significantly higher than that without trisomy 4 [26.3 % (35/133), P< 0.01]. The follow-up data showed that the patients with trisomy 4 were correlated with the lower overall survival (OS) rate (15 % vs 56 %, P< 0.01) and disease-free survival (DFS) rate (0 vs 51 %, P< 0.01) when compared with patients without trisomy 4. Furthermore, the subgroup of patients with both trisomy 4 and c-kit mutation had a worse OS and DFS (P< 0.05). Conclusions Trisomy 4 is associated with high frequency of c-kit mutation and demonstrates poor prognosis in t(8;21) AML patients. Trisomy 4 or it combined with c-kit gene mutation is the main influencing factor on the survival of the patients with t(8;21) AML.

Objective The management of medical projects of the National Key Research and Development Program of China is difficult.Thus this article aims to analyze the common problems and summarize the preparatory work before the project initiation.Methods Comprehensively adopted the methodologies of literature analysis,survey investigation to analyze the common problems before the project initiation,and then particularly summarize the preparatory works for biomedical research,especially for clinical research,from the perspective of investigators.Results Proposed several aspects that should take into consideration before the initiation of the projects..clarify the organizational management framework,play the role of kick-off meeting,organize tailored training on financial management,prepare research protocol and related documents,seek Institutional Review Board approval and conduct clinical research registration,normalize document managment,formulate project management plan,and prepare research facilities timely.Conclusions Investigators should develop a detailed project management plan before initiation of the project,preparation work should focus on personnel,financial resources,facilities,research progress,quality,data,etc.

Objective: To investigate the characteristics of the essential thrombocythemia (ET) cases transformed to the acute myeloid leukemia (AML) and the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of this disease. Methods: The clinical and laboratory characteristics of 3 ET cases before and after transformation and after allo-HSCT were retrospectively analyzed, meanwhile the related literatures were reviewed and discussed. Results: Case 1 was a male patient of 44 years old, whose PLT was 500×10⁹/L when firstly diagnosed ET. After 3 years the disease progressed into myelodysplastic syndrome (MDS) while WT1 expression increased from 77 (first visit) to 13 171 copies/10 000 ABL copies, at the same time chromosome changed dramatically. During the period of decitabine treatment the disease processed into AML. Case 2 was a male of 58 years old whose PLT was 2 100×10⁹/L when firstly diagnosed ET. The disease progressed to AML after 9 years, whose WT1 expression increased from 130 (first visit) to 3 222 copies/10 000 ABL copies, and he relapsed shortly after intensive chemotherapy. Case 3 was a male of 60 years old whose PLT was 900×10⁹/L when firstly diagnosed ET. The disease progressed to AML after 5 years, whose WT1 increased from 56 (first visit) to3 696 copies/10 000 ABL copies. Moreover leukemia spread to central nervous system (CNS) during chemotherapy. Before allo-HSCT, cases 1 did not achieve remission; case 2 relapsed after a short time of remission and case 3 transferred to CNS leukemia. All of the 3 cases underwent allo-HSCT successfully, and they all achieved completely remission, whose chromosome and gene mutation recovered negative. At the same time, CNS leukemia of case 3 disappeared. The median WT1 decreased to 50 copies/10 000 ABL copies. There was no severe complication during the median time of 5 months after allo-HSCT. Conclusions The patients transformed to AML had poor prognosis, allo-HSCT was the only method that can cure the disease now.

OBJECTIVETo report clinical and laboratory features of 4 cases of myeloid neoplasm with t (5;12) (q33;p13).

METHODSCytogenetic examination of bone marrow cells obtained from patients was performed by 24 h culture method. R banding technical was used for karyotype analysis. PDGFRβ gene rearrangement was detected by FISH using dual color break apart PDGFRβ probe. ETV6-PDGFRβ fusion genes were detected by multiple-reverse transcription polymerase chain reaction (RT-PCR). Direct sequencing analysis was performed on the PCR products in case 1. Immunophenotype analysis was carried out by flow cytometry. Four cases were treated with imatinib (IM) and followed up.

RESULTSThe diagnoses included 3 MPN and 1 AML-M2. The t (5;12) (q33;p13) was a primary abnormality in 3 cases of MPN and a secondary abnormality in 1 case of AML-M2. PDGFRβ gene rearrangement and ETV6-PDGFRβ fusion genes were detected by FISH and multiple-RT-PCR in 4 cases, respectively. The immunophenotypical analysis of leukemia cells showed positive for CD13, CD33 and CD34. Two cases obtained MMR after the treatment of IM, one case complete hematologic and complete cytogenetic response. ETV6-PDGFRβ was negative detected by multiple-RT-PCR after the treatment of IM, but relapsed and died soon in case 4.

CONCLUSIONSThe t (5;12) myeloid neoplasm was a subtype with unique features. The t (5;12) maybe a primary chromosome abnormality in MPN and a secondary in AML. MPN with t (5;12) could benefit from IM, but not for AML. Dual-FISH was a reliable tool for detecting PDGFRβ rearrangement.

Chromosome Banding ; Gene Rearrangement ; Hematologic Neoplasms ; genetics ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Karyotyping ; Myeloproliferative Disorders ; genetics ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-ets ; genetics ; Receptor, Platelet-Derived Growth Factor beta ; genetics ; Remission Induction ; Repressor Proteins ; genetics ; Translocation, Genetic

No abstract available.
Base Sequence ; Cell Cycle Proteins/*genetics ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 22 ; Female ; Gene Rearrangement ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Karyotype ; Leukemia, Myeloid, Acute/*diagnosis/metabolism ; Male ; Myeloid-Lymphoid Leukemia Protein/*genetics ; Oncogene Proteins, Fusion/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Septins/*genetics ; Sequence Analysis, DNA ; Translocation, Genetic ; Young Adult

OBJECTIVETo clarify the clinical, cytogenetical and molecular characteristics and prognosis of Ph(+) ALL patients with ABL kinase domain mutations (ABL-KDMs), and to evaluate the therapeutic value of allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with tyrosine kinase inhibitor (TKI) in these patients.

METHODSRetrospective analysis of clinical features, molecular genetic characteristics, mutation distribution and prognosis of newly diagnosed Ph(+) ALL patients with ABL-KDMs from February 2010 to August 2014 were performed, and the efficacy of treatment regimen of allo-HSCT combined with different TKIs was compared.

RESULTSOf 88 Ph(+) ALL patients during maintenance treatment stage for ABL-KDMs monitoring, mutation was detected in 42 patients with median time of 8 months from diagnosis to mutation occurrence. The median age of mutation group was 40-year-old, older than that of non-mutation group (32.5-year-old) (P=0.023). The incidence of complex chromosome abnormality of mutation group was higher than that of non-mutation group (P=0.043), with alternations in chromosome 7, 5 and +Ph more frequently observed. There were 21 types of mutation at 18 locations detected, with T315I mutation ranking the top followed by E255K/V, Y253H/F and E459K. Mutation group featured no significant difference in complete remission (CR) rate in contrast to nonmutation group, but was remarkably lower in major molecular remission (MMR) rate than non-mutation group. The 2 year and 5 year overall survival rate of mutation group was 45.4% and 35.0% respectively, much shorter than that of non-mutation group (67.8% and 63.3%), (P=0.047). The median survival of patients with T315I and E255K/V was 19 and 10 months, significantly shorter than that of patients with other mutations. Among the 42 patients with mutations, 14 underwent allo-HSCT, and the median survival was 29 months, longer than that of patients received chemotherapy alone (17 months) (P=0.024). Fourteen allo-HSCT patients were given nilotinib or dasatinib at the time of mutation occurrence, and there was no significant difference in the overall survival in contrast to patients who continue to take imatinib.

CONCLUSIONSABL kinase domain mutations are closely related to the older age and high genomic instability in the newly diagnosed Ph(+) ALL patients. Mutation types showed diversity and complexity, which remarkably affected patients' prognosis and survival. T315I and E255K mutations account for more than half of all cases, characterized by a less favorable prognosis. Currently, allo-HSCT is the only method that has the potential of elongating life expectancy, but the utility of second-generation TKI during relapse does not necessarily have an edge on survival over imatinib.

Chromosome Aberrations ; Dasatinib ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Imatinib Mesylate ; therapeutic use ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Prognosis ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins c-abl ; genetics ; Pyrimidines ; therapeutic use ; Remission Induction ; Retrospective Studies ; Survival Rate

OBJECTIVETo evaluate the value of a panel fluorescence in situ hybridization (FISH) in the detection of common chromosome abnormalities in myelodysplastic syndrome (MDS).

METHODSTwenty cases of MDS patients, whose karyotypes were unknown by the FISH examiner beforehand, were analyzed with a panel FISH using YAC248F5 (5q31), YAC938G5 (7q32), CEP8 and YAC 912C3 (20q12) probes to detect the frequently occurring chromosome abnormalities (-5/5q, -/7q-, +8, 20q-) in MDS. Then the results were compared to those of conventional cytogenetics (CC).

RESULTSAmong 20 cases, 13 cases were found to carry common chromosome abnormalities by panel FISH (trisomy 8, five cases; -5/5q-, one case; 20q-, five cases; 5q- accompanying 20q-, one case; complex abnormalities, one case). However, on CC examination, only five cases were found to have common chromosomal abnormalities (20q-, four cases; 5q- accompanying 20q-, one case). In addition, trisomy 21, marker chromosome and complex abnormalities comprising -5, -7 and marker chromosomes were seen in one case each, the rest were normal.

CONCLUSIONPanel FISH is a useful tool of molecular cytogenetics in the detection of common chromosome abnormalities in MDS.

Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Chromosomes, Human, Pair 20 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics