[Clinical characteristics and efficacy analysis for patients over 55 years of age with acute lymphoblastic leukemia].

OBJECTIVE: We investigated the clinical characteristics and therapeutic of elderly patients (≥55) with acute lymphoblastic leukemia (ALL). METHODS: From Jenuary 2000 to July 2012, 45 elderly patients (≥55) were enrolled in the study. Patients assighed into CVDP VDP/VP induction chemotherapy based on organ function. Patients in complete remission (CR) undertake consolidation therapy, maintenance therapy or follow up. The patient who had appropriate donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT). CR, Overall survival (OS), disease free survival (DFS), relapse rate and prognosis factors were analyzed. RESULTS: 45 elderly patients (≥55) about 9.6% in all 470 cases ALL simultaneity, and B-ALL about 88.9%. 27 patients (60%) obtained CR after 1 cycle of induction chemotherapy. 33 patients (73.3%) obtained overall CR. The CR rate significantly decreased in the elderly patients more than 60 years old vs. 55-60 years old patients (86.2% vs. 50%;P=0.009). All 45 patients 2 years OS rate was 33.7%, The median OS was 12 months (95%CI,6.68-17.32). 55-60 years (P=0.014), CR (P=0.002) and consolidation therapy (P=0.001) were independent favorite prognostic factors for OS. CVDP induction chemotherapy (P=0.013) and consolidation (P=0.049) were independent favorite prognostic factors for DFS. CONCLUSION: The outcomes of elderly patients with ALL were poor, 55-60 years, CVDP induction chemotherapy, CR and consolidation therapy were independent favorite prognostic factors.

[In vitro effects of mesenchymal stem cells on secreting function of T lymphocytes and CD4⁺CD25⁺ T cells from patients with immune thrombocytopenia].

OBJECTIVE: To analyze in vitro the effect of mesenchymal stem cells (MSCs) on secreting cytokines by T lymphocytes and ratio of CD4⁺CD25⁺ T cells from patients with immune thrombocytopenia (ITP). METHODS: Human bone marrow-derived MSCs were isolated by Ficoll Hypaque and cultured for proliferating to passage cells. Allogeneic T lymphocytes of health adults and ITP patients were isolated from peripheral blood by Ficoll Hypaque and nylon cotton column, and the ratio of CD4⁺CD25⁺ T cells was detected by flow cytometry. Then the different amounts of 1 × 104, 5 × 104, 2 × 105 MSCs per well treated with mitomycin as stromal feeder layers were co-cultured with above-mentioned T lymphocytes, 5 days after cocultivation, the ratio of CD4⁺CD25⁺ T cells was detected by flow cytometry and the levels of IL-2, IFN-γ, IL-4, IL-10 were measured by enzyme- linked immune sorbent assay (ELISA). RESULTS: After co-cultured with 2 × 105 MSCs for 5 days, the ratio of CD4⁺CD25⁺ T cells and CD4⁺CD25⁺/CD4⁺ were significantly higher than of separate T lymphocytes in ITP patients [(4.56 ± 0.70)% vs (2.24 ± 0.81)%, (9.91 ± 1.18)% vs (4.08 ± 1.17)%, respectively] (P<0.05). To compare with separate T lymphocytes in ITP patients, the cytokine concentrations of IL-2 and IFN-γ from the culture supernatants significantly reduced from (280.47 ± 17.33) pg/ml to (97.21 ± 12.07) pg/ml and from (129.33 ± 16.34) pg/ml to (72.75 ± 7.81) pg/ml, respectively. In contrast, the cytokine concentrations of IL-4 and IL-10 increased from (16.34 ± 2.60) pg/ml to (37.98 ± 4.05) pg/ml and from (54.78 ± 5.62) pg/ml to (113.77 ± 5.68) pg/ml, respectively. CONCLUSION: MSCs significantly inhibited the cytokine levels of IL-2 and IFN-γ secreted by Th1 cells and promoted the releases of IL-4 and IL-10 by Th2 cells in ITP , thereby regulating the balance between Th1 and Th2 reaction, as well as up-regulating the expression of CD4⁺CD25⁺ T cells in vitro,then induced the immunologic tolerance of ITP.

Which method better evaluates the molecular response in newly diagnosed chronic phase chronic myeloid leukemia patients with imatinib treatment, BCR-ABL(IS) or log reduction from the baseline level?

The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all P<0.0001). Thirty-six patients, who were identified as MMR patients by the IS method but as non-MMR patients by the log reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤ 10%(IS) and ≥ 1 log reduction at 3 months and ≤ 1%(IS) at 6 months were significantly associated with PFS (P=0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories.

[Clinical characteristics of splenic marginal zone lymphoma with abnormal complete blood count].

The aim of this study was to investigate the clinical and laboratorial characteristics of splenic marginal zone lymphoma (SMZL) with an abnormal complete blood count (CBC). Data of 19 newly diagnosed SMZL patients with abnormal CBC were analyzed retrospectively. Seven patients were diagnosed by using splenic histology, 12 patients who did not undergo splenectomy were diagnosed on the basis of typical clinical presentation and cytologic, immunophenotypic and histologic characteristics of peripheral blood and bone marrow, according to SBLG guidelines. The results showed that leukocytosis (≥ 10.0×10(9)/L) was seen in 5 cases (26.3%); leukocytopenia (< 4.0×10(9)/L) was found in 6 cases (31.6%), hemoglobin concentration less than 120 g/L was found in 14 cases (73.7%) and thrombocytopenia was found in 11 (57.9%) patients. Fourteen (73.7%) patients had cytopenia in one or more lineage. As a specific morphologic character, villous lymphocytes were found in 10 (52.6%) patients. Similar immunophenotype was determined by histology in both bone marrow and spleen. Various histological infiltration patterns including intrasinusoidal pattern were found in bone marrow. Nine out of 16 (56.3%) patients displayed an increase of serum monoclonal immunoglobin. Autoimmune phenomena was found in 12 out of 15 (80.0%) patients. Splenectomy, as the only treatment could not achieve a ≥ 50% improvement of CBC in 4 patients, and then was judged as no response. Splenectomy followed by chemotherapy achieved partial response (PR) in 1 patient. Overall response rate of the therapeutic strategies with Rituximab was 100.0% (11/11). Furthermore, complete response was achieved in 9 out of 11 (81.8%) patients. It is concluded that SMZL with abnormal CBC has a higher incidence of cytopenia, bone marrow involvement and autoimmune phenomena. Therapeutic strategies consisting of Rituximab show a better efficacy.

[The efficacy and safety of autologous cryopreserved platelet transfusion in management of thrombocytopenia after chemotherapy in hematological malignancy].

OBJECTIVE: To investigate the efficacy and safety of autologous cryopreserved platelet transfusion in the management of thrombocytopenia after chemotherapy in hematological malignancy. METHODS: A total of 40 patients diagnosed as hematological malignancy with complete remission were equally assigned into study group and control group. During chemotherapy interval in the study group, when platelet counts exceeded 120 × 10(9)/L, autologous platelets were collected with CS3000 Cell Separator and cryopreserved at -80°C with 5% dimethylsulfoxide. When platelet counts dropped below 15 × 10(9)/L after chemotherapy, autologous platelets were thawed with 40°C water bath and transfused back to each patient. In the control group, when platelet counts dropped below 15 × 10(9)/L after chemotherapy, allogeneic fresh platelets were transfused. Median loss during the freeze-thaw-wash procedure in study group was observed, and the 1 h, 24 h corrected count increments (CCI) were calculated in the both groups. The hemostatic effects and adverse reactions were also observed. RESULTS: In the control group, 1hCCI and 24h CCI were (19.3 ± 6.1) × 10(9)/L and (12.2 ± 7.0) × 10(9)/L, respectively, with the effective rate of 80% and the transfusion reaction rate of 45%. Totally 20 collection and transfusions were finished in the study group. A total of (3.4 - 8.5) × 10(11) platelet were obtained in each collection. Platelet recovery after freezing and thawing was (73.51 ± 9.03)% (62% - 83%). 1hCCI was (17.4 ± 7.6) × 10(9)/L, 24h CCI was (10.5 ± 5.8) × 10(9)/L and the effective rate was 85%. There was no significant different between the two groups (P > 0.05). The transfusion reaction rate was 15%, which was significantly lower than that of the control group (P < 0.05). Meanwhile, adverse reactions were occurred less in the study group. CONCLUSION: This study demonstrates that autologous cryopreserved platelet transfusions can be safely administered for supporting thrombocytopenia in hematological malignancy patients undergoing chemotherapy.

[Effect of different regimens on bone disease of multiple myeloma].

OBJECTIVE: To explore the difference of effects of two regimens (bortezomib and dexamethasone, BD; and thalidomide and dexamethasone, TD) on bone disease in multiple myeloma (MM). METHODS: Forty patients with newly diagnosed and refractory or relapsed MM were treated with BD or TD regimens from Dec 2006 to Sep 2008. Bone pain score and X-ray examination were carried out before and after therapy. Serum levels of DKK-1, sRANKL, OPG and TRACP-5b were measured by ELISA before and 3 months after therapy. RESULTS: Serum TRACP-5b concentration was significantly decreased in patients received TD regimen (5.94 U/L before therapy vs 4.84 U/L 3 months after therapy, P < 0.05), and so did for serum DKK-1 concentration in patients responded to BD regimen (35.11 µg/L before vs 32.03 µg/L 3 months after therapy, P < 0.05); for serum concentration of sRANKL in patients responded to BD regimen (1.05 pmol/L before vs 0.67 pmol/L 3 months after therapy, P < 0.05); and for serum concentration of TRACP-5b in responders to BD regimen (5.57 U/L before therapy vs 4.90 U/L 3 months after therapy, P < 0.05). CONCLUSION: Bortezomib lowers levels of serum DKK-1 and RANKL in responders, thus leads to normalization of abnormal bone remodeling through the increase of bone formation and reduction of bone resorption. Thalidomide decreases bone resorption regardless of treatment response.

[The clinical characteristics of newly diagnosed acute myeloid leukemia patients with NPM1 mutation].

OBJECTIVE: To investigate the clinical characteristics of newly diagnosed acute myeloid leukemia (AML) with NPM1 mutation. METHODS: NPM1 mutation (including A, B, D mutation type) was detected in 206 patients with newly diagnosed AML by real-time quantitative RT-PCR. RESULTS: The incidence of NPM1 mutation was 15.5% in total AML patients and 32.5% in normal karyotypes AML patients. The characteristics of 174 NPM1 wild type patients v.s. that of 32 NPM1 mutation patients was as follow, median age (46 vs 35 years old, P < 0.01), WBC counts (27 × 10(9)/L vs 8 × 10(9)/L, P < 0.01), BPC (82 × 10(9)/L vs 36 × 10(9)/L, P < 0.01), proportion of AML-M(5) (31.2% vs 5.8%, P = 0.01), incidence of normal karyotypes (92.6% vs 40.8%, P < 0.01), incidence of FLT3-ITD-positive (25.0% vs 7.5%, P < 0.01), CD34-positvie (23.3% vs 69.5%, P < 0.01), cases with fusion gene (0 vs 47.1%, P < 0.01). No statistic difference was found in sex, percentage of blasts in bone marrow, complete remission rate, overall survival between the two groups. Relapse-free survival in AML patients with NPM1-mutation and FLT3-ITD-negative tended to be higher than in those with NPM1-mutation and FLT3-ITD-positive. CONCLUSION: It is necessary to detect NPM1 mutation and FLT3-ITD in newly diagnosed AML patients, especially in patients with high WBC and BPC, CD34-negative, normal karyotype, which might help to molecular classification and treatment.

[Abnormal expression of programmed cell death 5 gene in multiple myeloma patients].

The aim of this study was to investigate the gene expression of programmed cell death 5 (pdcd5) in plasma and bone marrow cells from patients with multiple myeloma (MM). Enzyme liked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) were used to examine pdcd5 gene expression in plasma and marrow cells in 45 MM patients and 20 normal controls. The results showed that serum levels of PDCD5 protein in 45 MM patients were lower significantly compared with the normal controls and 20 responsive patients after chemotherapy, their plasma levels were (16.91 +/- 0.28) ng/ml, (19.11 +/- 0.29) ng/ml and (17.94 +/- 0.154) ng/ml respectively (p < 0.05). The pdcd5 gene expression levels detected by RQ-RT-PCR in 45 MM patients were lower significantly compared with the normal controls, their pdcd5 gene expression levels were 0.64 +/- 0.47 and 1.28 +/- 1.21 respectively (p < 0.05). It is concluded that the PDCD5 protein expression levels are low in patients with MM. These findings suggest that abnormal expression of pdcd5 may be involved in the pathogenesis of MM.

Arsenic trioxide downregulates the expression of annexin II in bone marrow cells from patients with acute myelogenous leukemia.

BACKGROUND: Most patients with acute myelogenous leukemia (AML) suffer from disordered hemostasis. We have previously shown that annexin II (Ann II), a high-affinity co-receptor for plasminogen/tissue plasminogen activator, plays a central role in primary hyperfibrinolysis in patients with acute promyelocytic leukemia (APL). The expression of Ann II in cells from patients with major subtypes of AML and the effect of arsenic trioxide (As2O3) on Ann II expression in AML cells were investigated to determine whether As2O3-mediated downregulation of Ann II could restore hemostatic stability. METHODS: A total of 103 patients (48 females and 55 males; age, 19 - 58 years) were included. Plasma samples were collected before and after treatment as well as after complete remission. Ann II and plasminogen activation were measured in leukemic cells during treatment with 1 micromol/L As2O3. RESULTS: Before As2O3 treatment, Ann II mRNA expression (real-time PCR) was the highest in M3 cells (P < 0.05), higher in M5 cells than that in M1, M2, M4, and M6 cells (P < 0.001), and positively correlated with Ann II protein expression (flow cytometry) (r = 0.752, P < 0.01). Exposure for up to 120 hours to As2O3 (1 micromol/L) had no significant effect on Ann II protein in M1 and M2 leukemic cells, but decreased Ann II protein expression twofold within 48 hours of exposure in M3 cells (P < 0.05) and twofold within 96 hours in M5 cells (P < 0.05). The rate of plasmin generation was higher in APL, M5, and M4 cells than in M1, M2, and M6 cells. CONCLUSIONS: As2O3 may reduce hyperfibrinolysis in AML by downregulation of Ann II. Furthermore, As2O3 affects more than one form of AML (APL, M4 and M5), suggesting its potential role in their management.

[Candida colonization and invasive fungal infection in hospitalized patients with hematological malignancies].

OBJECTIVE: To investigate thee status of Candida colonization and the risk factors of invasive fungal infection (IFI) in hospitalized patients with hematological malignancies. METHODS: 114 patients with hematological malignancies admitted to the hematology wards from May 2004 to April 2005 underwent fungal culture of their samples of urine, feces, and saliva once a week until the end of the sixth week of hospitalization or they were discharged. Culture of blood, sputum, or sterile body fluids were carried out when the patients were suspected to have IFI. RESULTS: 165 strains of Candida spp. were isolated from 46 of the 114 patients, C. albicans accounting for 78.8% and non-albicans Candida for 21.2% respectively. Candida was found in 38 patients (33.3%) were found to have colonization of Candida, chiefly C. albicans (76.3%). The risk factors of Candida colonization included long duration of leucopenia (WBC < 0.5 x 10(9)/L for more than 10 days) and broad-spectrum antibiotic administration. Univariate analysis showed that the risk factors of IFI included Candida colonization, long duration of leucopenia, and administration of carbapenem antibiotics, and multivariate analysis showed that long duration of leucopenia (WBC < 0.5 x 10(9)/L for more than 10 days) was the only risk factor of IFI (P = 0.015). CONCLUSION: C. albicans is still the major organism isolated from the patients with hematological malignancies. Patients with hematological malignancies have a high incidence of Candida colonization. Long duration of leucopenia is the only risk factor for IFI.

[Effects of bortezomib at different doses in combination with dexamethasone in treatment of relapsed or refractory multiple myeloma: a comparative study].

OBJECTIVE: To investigate the efficacy and toxicity of bortezomib of different doses in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma (MM). METHODS: 23 patients with relapsed or refractory MM, 10 males and 13 females, aged 65 (42-86), were randomized to 2 groups: low dose group receiving intravenous 1.0 mg/m2 bortezomib (n=10) on days 1, 4, 6, and 11 (twice weekly) combined with dexamethasone 20 mg/d on days 1-4, with 3 weeks as a course of treatment, and (20 standard dose group: receiving intravenous 1.3 mg/m2 bortezomib (n=13) combined with dexamethasone. The patients were followed up for 9.5 (3-15) months. The effect was determined using modified European Group for Blood and Marrow Transplantation (EBMT) criteria. RESULTS: The complete response (CR) + partial response (PR) rate of the 1.0 mg/m2 bortezomib group was 70.0%, not significantly different from that of the 1.3 mg/m2 bortezomib group (61.5%, P > 0.05). The relief rate (CR + near CR rate) of the 1.0 mg/m2 bortezomib group was 20.0% not significantly different from that of the 1.3 mg/m2 bortezomib group (38.5%, P > 0.05). Only 1 case of adverse event over the grade 3 of National Cancer Institute Common Terminology Criteria for Adverse Events occurred in the 1.3 mg/m2 bortezomib group. Five cases of infectious fever and 2 cases of treatment-associated death occurred in the 1.3 mg/m2 bortezomib group. CONCLUSION: Bortezomib at the dose of 1.3 mg/m2 is more effective in treatment of relapsed or refractory MM than that at the dose of 1.3 mg/m2 and has more side effects.

[Effect of additional chromosome abnormalities on the outcome of newly diagnosed acute promyelocytic leukemia treated with red arsenic sulfide and all trans-retinoic acid plus anthracyclin based protocol].

OBJECTIVE: To analyze the effect of additional chromosome abnormalities on the prognosis and the clinical manifestations of acute promyelocytic leukemia (APL) and the reaction of the patients with additional chromosomes to the treatment of combination of red arsenic sulfide, all trans-retinoic acid (ATRA) and anthracyclin. METHODS: The clinical data of 158 patients with newly diagnosed APL who were treated with combination of red arsenic sulfide, ATRA, and anthracyclin were analyzed retrospectively. RESULTS: The frequency of additional chromosome abnormalities in the APL patients was 18.4%, and trisomy 8 and i17q- were the most to be seen. The disseminated intravascular coagulation rate of the patients with additional chromosome abnormality was 62.1%, significantly higher than that of the patients without additional chromosome abnormality (35.6%, P < 0.05). The complete remission rate of the patients with additional chromosome abnormality was 75.9%, not significantly lower than that of those without additional chromosome abnormality (90.7%), and the relapse rate and incidence rate of central nervous system leukemia were 13.8% and 17.2%, both higher, but not significantly, than those of the patients without additional chromosome abnormality (6.2% and 6.2% respectively) (all P > 0.05). There was no significant difference in survival rate between these 2 groups (P = 0.160). CONCLUSION: Additional chromosome abnormality does not significantly influence the prognosis of APL treated with combination of red arsenic sulfide, ATRA, and anthracyclin.

[PRAME mRNA expression in newly diagnosed acute myeloid leukemia patients and its application to monitoring minimal residual disease].

OBJECTIVE: To investigate the expression level of preferentially expressed antigen of melanoma (PRAME) mRNA in newly diagnosed acute myeloid leukemia (AML) patients and evaluate its usefulness for detecting minimal residual disease (MRD). METHODS: PRAME mRNA levels were detected in bone marrow samples from 142 newly diagnosed AML patients (72 of them didn't express any specific fusion gene) by TaqMan based real-time quantitative PCR methods, and were serially monitored in 60 bone marrow samples from 9 follow-up patients (2 of them without specific fusion gene), including 3 in continuous complete remission, 6 in hematological relapse. Bone marrow samples from 22 bone marrow donors (NBM) were served as normal controls. Samples from 7 AML1-ETO (+) M2 patients were detected for AML1-ETO mRNA simultaneously. abl was selected as control gene, PRAME and AML1-ETO mRNA levels were expressed by their copies/abl copies in percentage. RESULTS: All NBM samples expressed PRAME mRNA and the upper limit was 0.28%. For all newly diagnosed AML patients, median PRAME mRNA level was 3.97% (0.00%-714.97%), 76.8% of them was higher than 0.28%, 54.9% had over 1-log increasing and 26.1% had over 2-log increasing. For patients without specific fusion gene, median PRAME mRNA level was 0.60% (0.00%-408.72%), 56.3% of them was over 0.28%, 32.4% and 11.3% had over 1-log and 2-log increasing, respectively. There was a significant difference in PRAME mRNA levels between subtypes of AML patients (P<0.01). AML1-ETO (+) M2 patients expressed the highest levels (all P<0.01), followed by acute promyelocytic leukemia patients with S type PML-RAR alpha fusion gene. PRAME and AML1-ETO mRNA levels of follow up patients displayed similar kinetic patterns, and correlated well in 43 follow up samples (r=0.88, P<0.01). PRAME mRNA levels in 3 hematological relapsed patients increased above 0.28% 1-4 months ahead relapse, and in other 3 relapsed patients the levels never decreased to normal range even in remission. CONCLUSIONS: PRAME mRNA could be used to monitor MRD for AML patients with higher than normal levels, and it increases over or persistently higher than normal range predicts hematological relapse.

[Studies of treatment strategy and prognosis on acute myeloid leukemia with chromosome 8 and 21 translocation].

OBJECTIVE: To investigate the relationship between the biological features and the treatment efficacy and prognosis in acute myeloid leukemia subtype M2 (AML-M2) patients with chromosome 8 and 21 translocation. METHODS: By using Cox regression model and Kaplan-Meier analyses, prognostic factors in 54 cases of de novo adult AML with t(8;21) in our institute from 1990 to 2003 were retrospectively analyzed. RESULT: The complete remission (CR) rates were 81.9% for all M2 patients, 82.4% for patients with normal karyotype, 88.5% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], 100.0% for 28 patients with t(8;21) alone and 75.0% for 24 patients with additional chromosome abnormalities (P < 0.01). The actuarial 3 year overall survival(OS) was 26% for M2 patients with normal karyotype, 25% for patients with t(8;21) [P > 0.05 for normal karyotype vs t(8;21)], in whole t(8;21) group, 46.4% for patients with t(8;21) alone and 0% for patients with additional chromosome abnormalities (P < 0.01). Multivariate analysis of prognostic factors showed that chromosome abnormalities besides t(8;21) was the only factor affecting CR, disease-free survival (DFS) and OS. DFS of allogeneic hematopoietic stem cell transplantation (HSCT) and intermediate-dose cytarabine/high dose cytarabine (IDAC) groups were better than the group received routine dose cytarabine as postremission therapy (P < 0.01). CONCLUSION: AML with t(8;21) is not a single defined AML subset, and patients with additional chromosome abnormalities have a worse prognosis. HSCT and IDAC could improve the outcome. HSCT is the best choice for patients with high risks, especially with additional chromosome abnormalities.

Characteristics and prognostic factors of acute myeloid leukemia with t (8; 21) (q22; q22).

The translocation t (8; 21) (q22; q22) frequently associated with additional chromosomal aberrations is one of the most recurrent chromosomal abnormalities in AML. Clinically, this type of AML usually shows some specific characteristics and has a good response to chemotherapy with a high remission rate and a relatively long median survival. On the other hand, some reports also showed poor prognosis in AML patients with t (8; 21), and the associated bad-prognosis factors have not been strongly established to date. To investigate this issue and to further identify the related characteristics of t (8; 21) AML in China, 75 Chinese AML patients with t (8; 21) were retrospectively analyzed. They comprised 68 cases of M(2), five of M(4) and two of M(5) according to FAB classification. The results indicated that Auer rods were observed in 39 patients (52%) and marrow eosinophilia was detected in only 5 patients (6.7%). These patients showed high level of HLA-DR and CD34 expression, while CD19 was detected in only 13 patients (20.9%). Cytogenetically, 62.5% cases had additional chromosomal abnormalities, and the main associated recurrent additional abnormalities were loss of a sex chromosome (LOS), trisomy 4, del (9q) and trisomy 8. After conventional induction therapy, 62 patients attained complete remission (CR) resulting in the CR rate 82.7%. With a follow-up of 1 to 96 months, 19 cases relapsed at a median time of 10.5 months (range 3 to 42 months). The median overall survival was 20 months, and the estimated 5-year overall survival (OS) rate was 32.3%. In multivariate analyses of prognostic factors, karyotype, extramedullary leukemia, age and post-remission therapy were of prognostic value for OS. Patients with additional chromosomal anomalies had shorter survival compared to those with t (8; 21) only (P = 0.019), no matter which kind of additional karyotype it was. Extramedullary leukemia was an adverse prognostic factor (P = 0.012). Patients aged 15 years or less had a longer survival than those aged more than 15 years (P = 0.045). Patients accepted HSCT in post-remission therapy had better outcome compared to those with chemotherapy only. It is concluded that Chinese AML patients with t (8; 21) had some different characteristics as compared with patients from other countries, a relatively poor outcome was observed in our patients, especially in those with extramedullary leukemia or additional chromosomal abnormalities. HSCT should be recommended to t (8; 21) AML in China, especially to those with adverse prognostic factors.

[Treatment of refractory and relapsed acute lymphocytic leukemia in adults].

OBJECTIVE: To analyze on the efficacy and toxicity of fludarabine and teniposide + mitoxantrone (MIT) regimens on treating refractory and relapsed acute lymphocytic leukemia in adult patients. METHODS: Teniposide 100 mg/d, 5-7 d, MIT 10 mg/d, 2 d and fludarabine regimens [Flu 30 mg/(m(2) . d), 3- 5 d, Cytarabine (Ara-c )1-2 g/(m(2) . d), 5 d; Flu 50 mg/d, 5 d, Ara-c 200 mg/d, 5 d, MIT 4 mg/d, 4 d] were used to treat 42 cases of adults with refractory and relapsed acute lymphocytic leukemia(ALL). G-CSF 5 microg/(kg . d) were used when WBC<1.0 x 10(9)/L. RESULTS: In both the regimens fludarabine and VM (teniposide + MIT), the complete remission (CR) rate was 45% versus 31.8% (P>0.05); the median neutropenia began 6 days after the regimens arresting and lasting 10 versus 7.5 days, P>0.05; thrombocytopenia begin at time of 10 versus 6.5 days (P<0.05) after the regimens arresting and lasting 6 versus 10 days (P>0.05). Fludarabine regimen had less non-haematological toxic effect than that of VM. CONCLUSION: Compared with VM, Fludarabine regimen was a very effective alternative treatment for CR induction in adult patients with refractory and relapsed ALL and low toxicity.

[Analysis of characteristics of 72 cases of t(8;21) acute myeloid leukemia].

OBJECTIVE: To investigate the laboratorial and clinical characteristics of t(8;21) AML, and to compare the differences between patients with additional chromosomal abnormalities and those without additional aberrations. METHODS: Seventy-two cases of t(8;21) AML were analyzed retrospectively, including features of morphology, initial blood cells, cytogenetic G-banding karyotype, immunophenotype, AML1/ETO fusion gene and clinical outcome. In order to compare the characteristics of patients with additional chromosomal abnormalities with those with t(8;21) alone, these patients were divided into two groups according to their karyotype as follows: Group A included patients with t(8;21) alone; Group B included patients with additional aberrations. RESULTS: According to FAB classification, there were 65 cases of M2, 5 cases of M4 and 2 of M5. Cytogenetically, 45 cases (62.5%) were accompanied by additional chromosomal abnormalities. The main additional aberrations included -Y, +4, del(9q). There were no obvious differences between these two groups in their features of age distribution, bone marrow blast cells, Auer rods, eosinophilia, immunophenotype, as well as central nervous system leukemia occurrence and complete remission rate of induction, but a male prevalence and a lower initial WBC were observed in Group B. With a follow up of 1-96 months, the median survival time was much longer in group A (65 months) compared with group B (12 months), but there was no difference between the four main subgroups of group B. The estimated 3-year survival was (63.9+/-11.2)% in group A compared with (20.9+/-9.2)% in group B. CONCLUSION: Additional chromosomal abnormality is an adverse factor for prognosis of t(8;21) AML. The median survival time of patients with additional aberrations was much shorter than that of those without.

[Clinical study of Philadelphia chromosome-positive acute lymphoblastic leukemia].

OBJECTIVE: To study the clinical characteristics and therapeutic outcome of Ph+ acute lymphoblastic leukemia (ALL). METHODS: Thirty previously untreated cases of Ph+ B-ALL were diagnosed in our institute. The patients were treated with combination chemotherapy of CODP +/- L regimen, Imatinib (400 approximately 600 mg/d) was continuously given to those who couldn't reach CR. Fourteen patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR, while 16 received consolidation of intensive chemotherapy. RESULTS: Thirty (32.6%) of 92 ALL patients were diagnosed as Ph+ ALL, with a median age of 25.5 (14 - 60). Among them Ph+ as the sole anomaly was seen in 16 patients, and Ph+ with additional chromosome abnormalities in 14. Besides the B cell markers, 23 (76.7%) patients had CD34+ and 13 (43.3%) CD13+ and/or CD33+. Nineteen of the Ph+ ALL patients underwent molecular analysis; 13 (68.4%) expressed P190 and 6 (31.6%) P210. Increased WBC (> 30 x 10(9)/L) was found in 22/30 cases while WBC > 100 x 10(9)/L in 9/30 cases. The chemotherapy complete remission rate was 68.8% in patients with only Ph+ versus 28.6% in those with additional chromosome abnormalities. All seven refractory/relapsed patients reached CR with Imatinib therapy. The total complete remission rate was 73.3% in all Ph+ ALL patients. The median remission duration was shorter in patients with additional chromosome than in those with only Ph+ (1 vs 7 months, P < 0.05), and so was the survival period (7 vs 9 months, P > 0.05). The remission duration was significantly longer in patients received allo-HSCT than in those received chemotherapy only (8 vs 0.5 month, P < 0.05), and so was the survival period (12.5 vs 6 months, P < 0.05). CONCLUSION: Additional chromosome abnormalities negatively affect the prognosis and therapeutic effect of Ph+ ALL patients. Imatinib is effective for the induction therapy of Ph+ ALL. The survival period of patients who received allo-HSCT was obviously longer than those who received chemotherapy only.

[MICM classification and prognostic analysis of 80 adolescents with acute lymphoblastic leukemia].

OBJECTIVES: To explore MICM classification and adverse prognostic factors in adolescents with acute lymphoblastic leukemia (ALL). METHODS: The MICM classification, clinical characteristics of 80 adolescents with ALL admitted to our hospital from January 1998 to December 2002 were retrospectively analyzed. Survival data were estimated by the Kaplan-Meier method and the prognostic factors were analyzed with the COX regression model. RESULTS: In the 80 patients, B-ALL and T-ALL accounted for 69.12% and 26.47%, respectively. The percentage of Ph(+)ALL was 18.37% (9/49), and that of hyperdiploidy was 4.08%. Patients at diagnosis with high leukocyte counts (> 50 x 10(9)/L) accounted for 27.94%. Among the 78 cases treated with VDP(L) or CODP(L) regimens, 73 (91.03%) obtained CR in 4 weeks. After a median follow-up of 24 months, the estimated 3-year disease-free survival (DFS) rates of patients receiving chemotherapy or allo-HSCT were (32.55 +/- 16.50)% and (69.58 +/- 8.72)%, respectively (P < 0.05). In COX analysis, high initial leukocyte counts (> 50 x 10(9)/L) and Philadelphia chromosome positivity were adverse prognostic factors for long-term survival. CONCLUSIONS: MICM classification has important clinical and prognostic significance in the risk-directed therapy of adolescents with ALL. The adverse prognostic features for these patients were high leukocyte counts, less incidence of chromosome hyperdiploidy and Ph chromosome positivity.

[Effect of the tetra-arsenic tetra-sulfide (As4S4) on the corrected QT interval in the treatment of acute promyelocytic leukemia].

OBJECTIVE: To evaluate the effect of tetra-arsenic tetra-sulfide (As4S4) therapy on the corrected QT interval (QTc) in the acute promyelocytic leukemia (APL) patients. METHODS: Ninety cases of APL treated with As4S4 were divided into two groups--the remission induction group and maintenance therapy group. Blood arsenic concentration was measured and a 12-lead electrocardiogram (ECG) was simultaneously performed before treatment and after remission in the induction group, and before and 2, 4, 6, 8, 10 courses after the treatment in the maintenance therapy group. QT interval on each ECG was measured and corrected by the Bazett formula. RESULTS: Oral administration of As4S4 could lead to the prolongation of QTc both in remission induction and maintenance therapy groups. QTc prolongation was related to the doses of As4S4 and blood arsenic levels. QTc prolongation and its variation range were increased with accumulative doses of As4S4 and the blood arsenic levels. In ten courses maintenance therapy patients, the average abnormal rate of QTc was 37.7%. Blood arsenic concentration was increased slowly with courses, but the variation had no statistical difference (P > 0.05). All the patients whose QTc was abnormal (> or = 440 ms) had neither symptoms nor serious cardiac events, such as ventricular tachycardia and Torsade de pointes and could complete the As4S4 therapy. CONCLUSION: Although As4S4 therapy can lead to QTc prolongation in the treatment of APL patients, it does not preclude the completion of the therapy.