No abstract available.
Aged ; Cytidine Deaminase/*genetics/metabolism ; Dasatinib/therapeutic use ; Disease Progression ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl/genetics/metabolism ; Humans ; Imatinib Mesylate/*therapeutic use ; In Situ Hybridization, Fluorescence ; Karyotype ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy ; Male ; Microfilament Proteins/*genetics/metabolism ; Oncogene Proteins/*genetics/metabolism ; Protein Kinase Inhibitors/*therapeutic use

INTRODUCTIONThe prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major molecular response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that early and deeper cytogenetic and molecular responses predict a better long-term outcome. This study aimed to analyse the relationship between early molecular response and clinical outcome in a real-life setting.

METHODSThis retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia.

RESULTSA total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients.

CONCLUSIONOur data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients.

Academic Medical Centers ; Adult ; Antineoplastic Agents ; therapeutic use ; Cytogenetics ; Disease-Free Survival ; Female ; Follow-Up Studies ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; drug therapy ; genetics ; Malaysia ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Universities

No abstract available.
Bone Marrow/pathology ; Chromosomes, Human, Pair 12 ; Chromosomes, Human, Pair 9 ; Core Binding Factor Alpha 2 Subunit/*genetics ; DNA/metabolism ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/*genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic

No abstract available.
Aged, 80 and over ; Base Sequence ; Bone Marrow/pathology ; DNA/chemistry/metabolism ; Female ; Fusion Proteins, bcr-abl/*genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/*genetics ; Multiplex Polymerase Chain Reaction ; Protein Isoforms/genetics ; Sequence Analysis, DNA

No abstract available.
Aged ; Base Sequence ; Bone Marrow/metabolism/pathology ; DNA Mutational Analysis ; Female ; Fusion Proteins, bcr-abl/*genetics ; Gene Duplication ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid, Acute/diagnosis/*genetics ; Multiplex Polymerase Chain Reaction ; Mutation ; Nuclear Proteins/*genetics ; Philadelphia Chromosome ; fms-Like Tyrosine Kinase 3/*genetics

OBJECTIVETo study the signal patterns of dual color dual fusion fluorescence in situ hybridization (DCDF-FISH) for detection of genetic abnormality in adult acute lymphoblastic leukemia (ALL) patients and their diagnostic value and clinical application.

METHODSThe clinical data of 68 ALL patients confirmed in our hospital were analyzed retrospectively; The bone marrow samples were detected by DCDF-FISH, flow cytometry, conventional cytogenetics (CCG), reverse transcriptase polymerase chain reaction (RT-PCR), and the correlation of these results was compared. And the reaction of patients to treatment was dynamically observed by DCDF-FISH.

RESULTSSixteen signal patterns were found in DCDF-FISH, including 14 kinds of atypical signal patterns (signal patterns of 1R2G, 2R3G, 2R4G and 3R3G as abnormal signal patterns without BCR/ABL fusion gene. Signal patterns of 1R1G1F, 1R1G3F, 1R1G4F, 1R2G1F, 1R2G2F, 1R2G3F, 1RnG2F (n ≥ 3), 2R2G1F, 1G4F, 1R4F corresponded to t (9;22) karyotype). Ph(+) ALL patients accounted for 17. All cases with Ph chromosome or BCR/ABL positive were B-ALL or My(+)-B-ALL. The Ph chromosome was detected in 12 cases (positive rate was 18%) by CCG. The positive rate was 25% (17/68) by DCDF-FISH and RT-PCR. The DCDF-FISH fluorescence pattern change before and after chemotherapy of the patients showed that the quantity and form of the signal pattern was changed after chemotherapy, and the common characteristics was the Ph chromosome in patients.

CONCLUSIONThe DCDF-FISH is a sensitive and reliable method for the detection of BCR/ABL rearrangement. Analyzing the dynamical change of DCDF-FISH signal patterns has been comfirmed to have a important guiding significance in the diagnosis, and anlysis of response to therapy, drug resistance and the prognosis of ALL patients.

Bone Marrow ; metabolism ; Flow Cytometry ; Fusion Proteins, bcr-abl ; genetics ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo explore the differences of clinical characteristics and outcome between p190 and p210 transcripts in adult Ph chromosome positive acute lymphoblastic leukemia patients in the new era with tyrosine kinase inhibitor (TKI) treatment, so as to provide an insight for improving the prognostic stratification and individualized treatment of the Ph(+) ALL patients.

METHODSThe clinical data of 65 patients were analysed retrospectively, these patients were diagnosed as Ph(+) ALL and treated with conventional chemotherapy plus TKI treatment with or without hematopoietic stem cell transplantation (HSCT) from January 2005 to December 2014 in our hospital, then the differences of clinical features and prognosis were compared between the p190 (n = 41) and the p210 group (n = 24).

RESULTSThe p190 group had lower platelet count than the p210 group (46.3 × 10(9)/L vs 65 × 10(9)/L) (P = 0.084); the leukemic blast cells in bone marrow at diagnosis was slightly higher in p190 group than that in p210 group (88.4% vs 76.8%) (P = 0.096); the other clinical features, such as sex, age, white blood cells, hemoglobin, leukemic blast cells in peripheral blood, and BCR-ABL/ABL expression level were not significantly different between these two groups. As to the response to treatment, the complete remission rate (CR) after induction therapy was 80% (32/40) and 87% (20/23) respectively in the p190 and p210 group, no significant difference was seen (P = 0.732). The time from induction to the first complete remission (CR1) was not significantly different either (28 days vs 29 days) (P = 0.922). The recurrence rate was 61% (20/33) in the p190 group and 43% (9/21) in the p210 group, but the difference was not significantly different (P = 0.202). However, the duration of remission in p190 group was shorter than that in p210 group, whether from the time of initial diagnosis to relapse (212 days vs 274 days) (P = 0.077) or from the time of CR1 to relapse (146 days vs 242 days) (P = 0.084). For the prognosis, the p190 group presented with a shorter 5 year-survival rate (P = 0.016) as well as event-free survival rate (P = 0.085).

CONCLUSIONThe p190 group tends to have lower peripheral blood platelet count and higher percentage of leukemic blasts in bone marrow at diagnosis; while the CR rate and the time from induction to CR1 are not significantly different; however, the p190 group is more likely to relapse at a relatively early stage, and the 5 year-survival rate and event-free survival rate are lower in p190 group than that in p210 group, indicating that the patients carrying p190 transcript are probably necessary to receive more intensive therapy such as HSCT as early as possible after achieving CR1, which can promisingly improve the overall prognosis of the Ph(+) ALL patients.

Acute Disease ; Disease-Free Survival ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Hematopoietic Stem Cell Transplantation ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; metabolism ; Prognosis ; Protein Kinase Inhibitors ; therapeutic use ; Recurrence ; Remission Induction ; Retrospective Studies ; Survival Rate

No abstract available.
Aged ; Antineoplastic Agents/therapeutic use ; Bone Marrow/pathology ; Fusion Proteins, bcr-abl/genetics/metabolism ; Humans ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications/*diagnosis/drug therapy ; Leukocyte Count ; Male ; Multiple Myeloma/complications/*diagnosis/drug therapy ; Platelet Count ; Polymerase Chain Reaction ; Thrombocytosis/etiology

No abstract available.
Aged ; Base Sequence ; Bone Marrow/metabolism/pathology ; Chromosome Aberrations ; DNA/chemistry/genetics/metabolism ; Fusion Proteins, bcr-abl/*genetics ; Humans ; Immunophenotyping ; In Situ Hybridization, Fluorescence ; Male ; Myelodysplastic Syndromes/diagnosis/*genetics ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA

No abstract available.
Antineoplastic Agents/therapeutic use ; Base Sequence ; DNA/chemistry/genetics/metabolism ; DNA Mutational Analysis ; Fusion Proteins, bcr-abl/*genetics ; Genotype ; Humans ; Imatinib Mesylate/therapeutic use ; Karyotyping ; Male ; Multiplex Polymerase Chain Reaction ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/drug therapy/*genetics