[Clinical and cytogenetic features and their influencing factors of core binding factor acute myeloid leukemia].

OBJECTIVE: To discuss the clinical and cytogenetic features of core binding factor (CBF) acute myeloid leukemia (AML) patients and the main factors that influence the prognosis. METHOD: Totally 130 CBF AML patients were followed up and their clinical features, immunophenotype, chromosome karyotype, treatment regimen, overall survival (OS), and relapse-free survival (RFS) were analyzed. RESULTS: The overall complete remission (CR) rate was 96.1%, among which the CR rate after the first treatment course was 77.2%. The overall median OS was 51.64 (0.26-132.5) months, while the median RFS did not reach 1.18-96.62 months. The 3-year OS was 50% and the 5-year OS was 41%; the 3-year RFS was 59% and the 5-year RFS was 54%. Patients who were over 45 years and those with chromosome karyotype of 9q- tended to have poorer prognosis. During the consolidating chemotherapy, patients who had received two or more courses of intermediate-dose Ara-C therapy had better prognosis and longer survival. AML patients with inv (16) /t (16; 16) had a significantly higher OS than those with t (8; 21) (P = 0.046), while the RFS showed an opposite finding (P = 0.038). CONCLUSIONS: Age, chromosomal karyotype, and consolidating chemotherapy are the main factors that influence the survival and prognosis of CBF AML patients. Two or more courses of intermediate-dose Ara-C during consolidating chemotherapy can obviously prolong the OS and RFS of CBF AML patients. AML patients with a chromosomal karyotype of inv (16) /t (16; 16) have longer OS and better prognosis than those with t (8; 21).

[A new prognostic stratification for patients with acute myeloid leukemia].

OBJECTIVE: To evaluate the impact of the percentage of residual blasts in bone marrow at the end of induction chemotherapy (T1) or during myelosuppression phase (T2) on prognosis of de novo acute myeloid leukemia (AML) (non M(3)) in 105 cases. To refine AML risk-stratification by combining the percentage of residual blast cells (T1 or/and T2) with cytogenetic data based the South West Oncology Group (SWOG) criteria. METHODS: The data of 105 de novo AML (non M(3)) patients hospitalized between January 1st 1999 and February 1st 2008 were retrospectively reviewed. Results were analyzed with SPSS15.0 software. RESULTS: (1) Patients were divided into two subgroups by a cutoff of 5% residual bone marrow blasts at T1 or T2 time point. Patients with percentage of residual bone marrow blast cells < 5% had better complete remission (CR) rate, relapse-free survival (RFS) and overall survival (OS) than the patients with percentage > or = 5% at T1 or T2. The percentage of residual bone marrow blast cells at T1 was correlated with that at T2. (2) The prognosis of patients with intermediate karyotypes with percentage < 5% at T1 or T2 was similar to that of the patients with favorable karyotypes. The patients with intermediate karyotypes and percentage of residual bone marrow blasts > or = 5% at T1 or T2 are defined as a subgroup with prognosis similar to that of patients with unfavorable karyotypes. (3) COX regression analysis showed that the percentage of residual bone marrow blasts at T1 or T2 is an independent prognostic factor of AML. The percentage of residual bone marrow blasts at T1 may be more helpful in prognostication than that at T2. CONCLUSION: AML patients with percentage of residual bone marrow blasts < 5% after induction chemotherapy (T1 or T2) have better CR rate, RFS, OS than the patients with percentage > or = 5% at the same time point. Combination of cytogenetics and percentage of residual bone marrow blasts at T1 or T2 is helpful to divide patients with intermediate karyotypes into two subgroups with different prognosis. Thus, a better decision of treatment strategy can be designed.

[Clinical study on fluoroquinolone prophylaxis in neutropenia patients with acute leukemia].

OBJECTIVE: To investigate the clinical benefits and the impacts on distribution and antibiotic resistance of pathogenic bacterium associated with fluoroquinolone prophylaxis during neutropenia in patients with acute leukemia. METHODS: A total of 309 infection episodes occurred in patients with acute leukemia were retrospectively analyzed. The patients admitted in ward A (group A, n = 149) received oral ofloxacin as antibacterial prophylaxis during the neutropenia phase; no antibacterial prophylaxis was administered to the patients in ward B (group B, n = 160). The influences of prophylactic ofloxacin were determined by comparative evaluation on the clinical characteristics and the microbiological profile in both groups' patients. RESULTS: Almost all enrolled patients experienced severe neutropenia. The median durations of ANC (absolute neutrophil count, ANC) < 0.2 x 10(9)/L were 11 (range 0 - 43) days. The median persistence time of fever was 8(range 1 - 46) days. Prophylaxis of ofloxacin decreased the proportion of normal flora (P = 0.00). The frequency of Escherichia coli was higher in group A than group B (23.9%, 12.5%, respectively, P = 0.00). Exposure to ofloxacin didn't affect the distributions of other pathogenic bacteria. No difference in the rate of ESBL (+) Escherichia coli was discovered between ofloxacin and no ofloxacin prophylaxis groups (31.9%, 35.4%, respectively, P = 0.61). Commonly used antibiotics had similar activity against the major strains isolated from two groups. Patients who received antibacterial prophylaxis showed a lower incidence (10.7%) of upper respiratory infections/tonsillitis and a relative higher incidence (14.4%) of gastrointestinal tract infections than those without intervention measure. The prophylactic use of ofloxacin couldn't cut down the risk of septicemia. Ofloxacin prophylaxis did not display negative effect on initial clinical response (65.8% in group A, 60.6% in group B, respectively, P = 0.35) and final efficacy (96.0% in group A, 91.9% in group A, P = 0.14) to the same empirical antimicrobial treatment schemes. CONCLUSION: The fluoroquinolone prophylaxis induces diminishing proportion of normal flora and increasing frequency of Escherichia coli in severely neutropenic patients with acute leukemia, may not influence the distribution of other bacteria. The susceptibility of main pathogens may not be affected by antibiotic prophylaxis. The fluoroquinolone don't decrease the incidence of septicemia and infection in gastrointestinal tract. Our data suggest that more prudent use of antibiotic prophylaxis may be reasonable even in patients at high-risk for developing infection.

[An analysis of cytogenetic characteristics and prognosis of 189 t (8; 21) acute myeloid leukemia patients].

OBJECTIVE: To investigate the cytogenetic and prognostic significance of acute myeloid leukemia (AML) with t (8; 21). METHODS: 189 patients with t (8; 21) AML were categorized according to their additional karyotypic aberration and their clinical outcomes analysed. RESULTS: Among them, 63 patients (33.3%) were t (8; 21) without other additional aberrations, 126 cases (66.7%) were t (8; 21) with other additional aberrations. -Y was found in 46.7% (63/135) of the male and -X was found in 25.9% (14/54) of female patients. In additional aberrations, loss of the sex chromosome were found in 77 cases (61.1%), Del (9q) was found in 16 cases (12.7%), +4 was found in 5 cases (4.0%); 7q- was found in 6 cases (4.8%); Tetraploidy (4N) was found in 2 cases (1.6%); Variant translocation was found in 7 cases (5.6%). The 189 patients had a high remission rate (87.0%) and a relatively long median survival (21.6 months). +4 and 4N were an unfavorable prognostic factors. Fluorescence in situ hybridization technique is a more sensitive and accurate method to detect t (8; 21), especially in variant translocation, complex variant translocation and masked translocation. CONCLUSION: t (8; 21) AML is also frequently associated with additional chromosome aberrations, these aberration had influence on prognosis.

[Clinical study of zoledronic acid in the treatment of cancer-induced hypercalcemia].

OBJECTIVE: To investigate the effect and safety of zoledronic acid (Zoledex) in patients with cancer-induced hypercalcemia. METHODS: Seventeen patients with cancer-induced hypercalcemia (corrected blood calcium > 2.70 mmol/L) were treated intravenously by 4 mg zoledex within 15 minutes on the first day. The corrected blood calcium was observed every 4 days in the following 28 days. RESULTS: The response rate was 94.1% (16/17). The mean corrected blood calcium became normal after the first dose of zoledex (P < 0.01). The lowest value was found on the fourteenth day after treatment. The main side effects consisted of fever (29.4%, 5/17), hypocalcemic tetany (11.8%, 2/17) and arythmia (5.9%, 1/17). CONCLUSION: Zoledex is effective and safe in the treatment of patient with cancer-induced hypercalcemia.

[Clinical trial on ibandronate in patients with tumor-associated hypercalcemia].

OBJECTIVE: Ibandronate, a third generation bisphosphonate, inhibits bone resorption in human and animal studies. This study is to evaluate the efficacy and safety of ibandronate as a single agent in patients with tumor-associated hypercalcemia. METHODS: An open, multicenter, non-controlled clinical trial was conducted in 22 patients. The patients received 2 mg ibandronate intravenously if the corrected calcium was less than 3.0 mmol/L but more than 2.7 mmol/L; they received 4 mg ibandronate iv if corrected calcium was more than 3.0 mmol/L. RESULTS: There was 100% efficacy in these two dose groups but the calcium correcting effect was more pronounced in the 4-mg dose group than the 2-mg dose group. The most common adverse reactions were fever and skin itching with an incidence of 4.5%. CONCLUSION: Ibandronate is active in patients with tumor-associated hypercalcemia and the adverse effects are well tolerated.

[Analysis of effectiveness and prognostic factors for (m)HAD regimen as induction therapy in acute monocytic leukaemia].

OBJECTIVE: To analyze the treatment outcome and impact of cytogenetic abnormalities on the response and survival of acute monocytic leukaemia (AMOL) patients received (m)HAD regimen as induction chemotherapy. METHODS: Seventy-nine AMOL patients were treated with (m)HAD regimen as induction therapy (HHT 2 mg/m(2), d 1-7; Ara-C 100 mg/m(2), d 1-7 and increasing to 1.5 g×m(-2)×(12 h)(-1), d 5-7 in some patients; DNR 40 mg/m(2), d 1-3). The treatment outcome and prognostic factors were analyzed. RESULTS: (1) The complete remission (CR) rate was 79.7% (63/79), partial remission (PR) rate was 6.3% (5/79), overall rate was 86.0%. (2) The chromosome karyotypes were analyzed in 75 patients, of whom 43 with normal karyotypes (NCR) and 30 abnormal karyotypes (ACR). For the cytogenetic prognostic groups, 49 patients were intermediate, 18 poor and 6 unknown. The CR, 1-year and 3-year overal survival (OS) rates in NCR group were significantly higher than those in ACR group (P < 0.05); but there was no significantly statistical difference in disease free survival (DFS) between the two groups (P > 0.05). The CR, 1-year OS, 3-year OS and 1-year DFS and 3-year DFS rates in intermediate prognostic group were significantly higher than those in poor prognostic group (85.7% vs 61.1%, 75.9% vs 51.3%, 65.4% vs 25.6%, 82.2% vs 66.7%, and 77.9% vs 26.7%, respectively) (P < 0.05). (3) Chromosome karyotype and the number of consolidation therapy courses had more important influence on survival in COX analysis. CONCLUSION: (m)HAD regimen as induction chemotherapy for AMOL patients achieves a high CR rate. It has an important influence on survival for the patients to received adequate consolidation therapy. The frequency of cytogenetic abnormalities in AMOL is similar to that in other AMLs. The prognosis of AMOL patients with chromosome karyotype in intermediate prognostic group is significantly better than that in poor prognostic group.

[Clinical features and prognosis of acute myeloid leukemia-M(4).].

OBJECTIVE: To investigate factors that affect survival and prognosis of acute myeloid leukemia (AML)-M(4). METHODS: Seventy AML-M(4) patients were divided into three groups, neither eosinophilia nor inv(16)\[Eos(-)\], eosinophilia with inv (16)\[Eos(+) inv(16)(+)\], and eosinophilia with no inv(16)\[Eos(+) inv(16)(-)\]. Clinical features, immunophenotype, chromosome karyotype, overall survival (OS) and relapse-free survival (RFS) were analyzed. RESULTS: The total complete remssion (CR) rate was 85.7%, CR rate after the first course of induction therapy was 71.4%. The median OS was 20 (1.2 - 162.4) months, and median RFS 78.0 (1.2 - 129.5) months. The 3 and 5 year OS rates were 42% and 42%, and 3 and 5 year RFS rates were 59% and 54%, respectively. The CR rate, CR after the first course of induction therapy and the median OS for the Eos(-) group were 76.9%, 61.5% and 11.2 (1.2 - 162.4) months; for the Eos(+) group were 96.8%, 89.6% and did not reach; for the Eos(+)inv16(+) group were 100%, 94.4% and did not reach; and for the Eos(+) inv(16)(-) group were 91.7%,69.2% and 14.3 months respectively. The statistical assay showed significant difference between Eos(+)inv(16)(-) and Eos(+)inv(16)(+) groups in OS. The Eos(+) patients present with early onset and low count of platelets. CONCLUSION: Eosinophilia emerged as a favorable prognostic factor, and the concomitant presence of both eosinophilia and inv(16) is associated with a significantly favorlable prognosis.

[Study on the clinical characteristics of adult biphenotypic acute leukaemia].

OBJECTIVE: To analyze the clinical and biological characteristics and prognosis of adult biphenotypic acute leukaemia (BAL). METHODS: Immunophenotypes were analyzed using multicolor flow cytometry, karyotype analysis by short-term culture R-banding technique. The chemotherapy regimens were accordingly for acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) or for both ALL and AML. Patients with Ph (+) or bcr-abl (+) were treated with Imatinib. RESULTS: (1) The incidence of BAL in acute leukaemias was 6.7%, with a male predominance and 52.3% of BAL patients had WBC > or = 30 x 10(9)/L and 16.9% WBC > or = 100 x 10(9)/L. (2) Percentages of coexpression of myeloid and B lymphoid antigens were 81.5%, of myeloid and T lymphoid antigens 10.8%, of myeloid, B- and T lymphoid antigens 4.6%, and of B and T lymphoid antigens 3.1%. (3) Normal and abnormal karyotypes accounted for 41.5% and 58.5%, respectively in 53 BAL patients with karyotype analysis. The rate of Ph (+) or bcr-abl (+) was 32.1%. (4) 31 (56.4%) of 65 patients achieved complete remission (CR), but CR rate was only 35.3% for Ph (+) or bcr-abl (+) cases. CONCLUSION: (1) High white blood cell count and coexpression of myeloid/B lymphoid antigens are common in BAL. (2) Abnormal karyotypes and Ph (+) or bcr-abl( +) often happen. (3) The treatment outcome of BAL is poor.

[Long term outcome of acute myeloid leukemia with t(8;21)].

OBJECTIVE: To investigate the influence factors on survival and outcome of acute myeloid leukemia (AML) patients with t(8;21). METHODS: Eighty seven AML patients with t(8;21) after long-term follow-up were enrolled in the analysis of clinical feature, immunophenotype, chromosome karyotype, treatment regimen, as well as the overall survival (OS) and relapse-free survival (RFS). RESULTS: The overall complete remission (CR) rate was 95.3%. CR rate after first course therapy was 69.8%, after first course therapy containing medium dose Ara-C was 86.2%, and after first course of therapy containing standard-dose Ara-C was 60.3%. The median OS duration was 16.4 months, median RFS 11.7 months, 3 year OS rate 42%, 5 year OS rate 39%, 3 year RFS rate 55% and 5 year RFS rate 55%. Male gender chromosome 9q(-) had statistical significance for shorter OS and poor outcome, 2 courses of post-remission therapy with intermediate dose Ara-C, induction therapy with intermediate-dose Ara-C and post-remission with 4 courses consolidation therapy had statistically longer OS and RFS. CONCLUSION: Sex, chromosome karyotype, induction and consolidation therapy were important influence factors on OS and RFS. Application of intermediate dose Ara-C to induction and consolidation therapy leads to a higher CR rate, prolong OS and RFS.

[Analysis of chemotherapeutic results and prognostic factors of adult acute lymphoblastic leukemia].

OBJECTIVE: To explore the clinical characteristics of adult acute lymphoblastic leukemia (ALL), compare the efficacy of different induction regimens and analyze the prognostic factors. METHODS: Data of 149 adult ALL patients hospitalized in our institute between June 1998 and December 2005 were retrospectively reviewed. The results were analyzed with the SPSS11.5 software. RESULTS: 1) Out of 133 patients available immunophenotype data, 118 (88.7%) were B-ALL and 15 (11.3%) T-ALL. Cytogenetic analysis was performed in 105 patients, 40 cases (38.1%) of them had a normal karyotype and 65 (61.9%) chromosome aberrations. 2) 149 patients completed the VDCP, VDLP or VDCLP induction therapies (at least 4 weeks treatment for each), 140 (93.7%) of them achieved complete remission (CR) with the first course CR rates of 80.8%, 92.3% and 81.4% , respectively (P=0.618). CR rates in patients after the induction regimens with or without asparaginase were 95.5% versus 92.1% (P=0.566). With a median follow-up of 14.5 (1-75) months, the median disease free survival (DFS) was 12 (1-74) months and median overall survival (OS) 17.5 (1-97) months. DFS of the three regimen groups at 3 and 5 years were 18.5% and 14.8%, 24.7% and 9.9%, 39.5% and 39.5%, respectively (P=0.0066). 3) COX regression analysis showed that the age (over 40 years), white blood cell (WBC) count ( > 40 x 10(9)/L) , t(9;22) (q34;q11)-positive and less than 4 courses consolidation chemotherapy were the unfavorable prognostic factors. CONCLUSIONS: Most adult ALL patients are B-ALL and karyotype have more changed. More than 90% patients can achieve CR with induction regimens consisting of 4 or 5 drugs. Induction regimens containing L-asparaginase may not affect the CR rate, but can improve DFS and OS. Age and WBC at diagnosis, presence of t(9;22) (q34;q11) and the courses of post-remission treatment are important prognostic factors.

[Effectiveness analysis of HA based triple-drug regimen as induction chemotherapy in the treatment of acute myeloid leukemia and its relationship with karyotype].

OBJECTIVE: To analyze the complete remission (CR) rate, disease free survival (DFS) and overall survival (OS) of de novo acute myeloid leukemia (AML) patients treated with HA based three drugs induction chemotherapy and to explore the impact of cytogenetic abnormalities on the prognosis. METHODS: Two hundred and forty-three untreated de novo AML patients were treated with HA based three drugs induction therapy. CR rate, DFS and OS were calculated. One hundred and eighty-four patients who had karyotype results were divided into four or three groups according to SWOG or MRC criteria respectively. Differences in CR rate, DFS and OS among different groups were evaluated. RESULTS: The CR rate of all the 243 cases was 77.4%. The median DFS of the 188 CR patients was 28.5 (ranged from 1.0 to 153.0) months, DFS rates at 3 and 5 years were 45.4% and 40.2% respectively. The median OS of the 243 patients was 18.4 (range from 0.5 to 154.0) months. OS rates at 3 and 5 years were 36.9% and 31.4% respectively. According to SWOG criteria, CR rate, median DFS and OS were 97.8%, 87.4 months and 89.0 months for the favorable group; 81.9%, 17.6 months and 22.3 months for the intermediate group; 61.5%, 9 months and 11.5 months for the adverse group; and 79.3%, 29.0 months, 19.9 months for the unknown group, respectively. The differences among the four groups were statistically significant (P < 0.001). According to MRC criteria, CR rate, median DFS and OS were 96.1%, 79.9 months, 72.2 months for the favorable group; 80%, 17.6 months, 19.7 months for the intermediate group; and 43.8%, 16.5 months, 12 months for the adverse group, respectively. The differences among the three groups were statistically significant excepting for DFS between intermediate and adverse groups. CONCLUSIONS: HA based triple-drug induction regimens are highly effective in obtaining higher CR rate and longer survival time. Cytogenetics is the important prognostic factor for AML patients and SWOG karyotype subtyping criteria is more appropriate than that of MRC, the differences among the three groups being statistically significant.

[Dendritic cells (DC) induced from acute myeloid leukemia (AML) cells with cytokine cocktails].

OBJECTIVES: To explore the feasibility of DC being in vitro induced from AML cells with cytokine cocktails and their biological properties. METHODS: AML cells were cultured in either presence or absence of cytokine cocktails. DC were studied for morphology, and cytochemical and immunofluorescent staining. Functions of DC were examined by MLC, FITC-conjugated dextran uptake test, and LDH release assay. RT-PCR and FISH were used to analyze the specific fusion genes of culture-derived DC. RESULTS: Classical DC morphological changes occurred in all 15 cultured AML cells. DC-associated surface molecules such as CD(1a), CD(80), CD(86), CD(106), CD(83) and HLA-DR were upregulated (P < 0.05). The allostimulatory abilities of culture-derived DC were significantly higher than those of AML cells uncultured or cultured in the absence of cytokines (P < 0.05). Culture-derived DC only in the presence of GM-CSF + IL-4 have phagocytotic activities. CTL assay was performed in 5 of the 15 samples. At effector/target ratio of 20:1, auto-T lymphocytes primed with the culture-derived DC exhibited no more killing activity to auto-AML cells than those stimulated by IL-2 or uncultured AML cells. Culture-derived DC presenced the native AML-specific aberrant karyotype and related fusion gene. CONCLUSIONS: Cytokine cocktails could in vitro induce AML cells into DC with classical morphology, immunophenotype and function. DC maturity induced by different cytokine cocktails could be variable. Culture-derived DC were originated from the native AML cells. AML cells could make the auto-T lymphocyte anergy.

[Analysis of the factors associated with prognosis in patients with Ph chromosome positive adult acute lymphoblastic leukemia].

OBJECTIVE: To investigate factors associated with survival of patients with Ph chromosome positive adult acute lymphoblastic leukemia (aALL) in a period of 11 years. METHODS: All the clinical parameters of 31 Ph positive patients were statistically analyzed by SPSS software. RESULT: Ph(+) patients account for 15.3% (31/203) of all the aALL patients. Clinically, these patients manifested older in age, higher white blood cell counts with high blast fractions and lower platelet counts (PC). Phenotypically 82.6% of them were common ALL, 39.1% coexpressed myeloid antigens, and 56.5% expressed CD34 antigen. 65.4% of them (17/26) achieved complete remission (CR) and the median remission and survival durations were 4 months and 8 months, respectively. Patients with Ph(+) and additional chromosomal aberrations accounted for 42% of all the Ph(+) patients, including monosomy 7, +Ph, del(9)(p11-12) and add/t(16)(p13), and they had lower PC as compared with those with sole Ph(+) (P = 0.012) and variant Ph translocation (P = 0.01). CD34 positive patients had a shorter remission and survival duration than CD34 negative ones (0 vs 9 months for median remission time, P = 0.024; and 6 vs 12 months for median survival time, P = 0.034). There was no evidence to support the correlation between myeloid antigen expression and survival time in these patients. CONCLUSION: Ph(+) aALL is associated with adverse prognosis and CD34 expression is a poorer prognostic factor in Ph(+) aALL patients. There is no significant clinical difference between Ph(+) aALL with or without additional chromosomal aberrations.