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  • Cai, Zhen  (8)
  • 1
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5075-5075
    Abstract: Abstract 5075 Multiple myeloma (MM) is a malignant disorder characterized by abnormal proliferation of monoclonal, immunoglobulin producing plasma cells in the bone marrow. Studies with large samples have shown that molecular cytogenetic changes play an important role in the prognosis of MM. Based upon these findings, we tested cytogenetic aberrations of 65 patients with MM by conventional cytogenetics analysis and FISH technique in this study. Retrospective study was done on these cases for clinical features. Methods: This is a retrospective analysis of 65 patients with MM diagnosed between June 2007 and May 2010 including 13 relapsed cases and 52 newly diagnosed patients. Patients received bortezomib-based combination chemotherapy including bortezomib plus dexamethasone (BD) and the triplet combinations (bortezomib, adriamycin, dexamethasone (BAD), bortezomib, cytoxan, dexamethasone (BCD) and bortezomib, melphalan, prednisone (BMP) or traditional chemotherapy including doxorubicin, vincristine plus dexamethasone (VAD), melphalan plus dexamethasone (MP), melphalan, dexamethasone plus thalidomide (MPT)). To further clarify the correlation between cytogenetic and clinical features on patients with multiple myeloma, we used conventional cytogenetics analysis with R-banding technique and interphase fluorescence in situ hybridization (FISH) to describe the molecular cytogenetic characterization of bone marrow nucleated cells from 65 patients. SPSS (version 18.0) software was used for data analysis, χ2 tests or Fisher's exact test was used for betweengroup comparison of the discrete variables and Log- Rank was used for survival analysis. p 〈 0.05 reflects the remarkable significance. Results: 16.9% of patients (11/65) showed abnormal cytogenetic aberrations including 90.9% (10/11) cases with ultra complex aberration and complex aberration via conventional cytogenetics. In addition, we were able to show aberrations in 49.2% (32/65) of patients by interphase FISH analysis. Abnormalities of 13q14, 1q21, 14q32 and 17p13 were detected in 27.7% (18/65), 13.8% (9/65), 16.9% (11/65), and 29.2% (19/65) by FISH, respectively. 1q21 amplification is strongly associated with 13q14 mutation (P=0.008), demonstrating significant correlation between two. Abnormality of 13q14 deletion or 1q21 amplification were associated with lower levels of albumin (P 〈 0.05). Patients with 13q14 deletion frequently had stage III disease by DS and ISS staging, and compared with patients not detected on FISH analysis, they tended to have elevated serum levels of β2-microglobulin at diagnosis (P 〈 0.05). 17p13 deletion coexistent with 13q14 deletion frequently correlate with elevated serum levels of β2-microglobulin and advanced clinical staging. The median progression-free survival (PFS) of patients with 17p13 deletion or 17p13/13q14 aberrations were both 11.0m, significantly lower than patients with no detected abnormality (median PFS 19.0m) (P 〈 0.05). The median overall survival (OS) of patients with FISH negtive results was 38.0m, significantly higher than those with 13q14, 14q32 or 1q21 abnormality and 17p13/13q14 or more than three abnormalities (P 〈 0.05). Conclusions: This study validates myeloma cells are prone to show complex aberration and FISH is superior in the detection of cytogenetic aberrations to conventional cytogenetics analysis for patients with multiple myeloma. 1q21 had significant correlation to 13q abnormality. 17p13 deletion coexist with 13q14 deletion and 14q32 rearrangeent were used to associate with poor prognosis. 17p13 deletion or 17p13/13q14 deletion was associated with poorer PFS while abnormality of 13q14, 1q21,14q32, 17p13/13q14 or more than 3 abnormalities were correlate with poorer OS. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
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  • 2
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4999-4999
    Abstract: Abstract 4999 Objective: Clinical significance of serum free light chain (sFLC) test in the diagnosis, efficacy evaluation, prognosis judgment of first onset of multiple myeloma (MM). Method: Medical records of 39 cases of first-onset MM were gathered in our hospital from 1/2010 to 2/2012, including 25 male and 14 female patients with the median age being 63 years old. sFLC-kappa and sFLC-lambda were determined by immune turbidimetric assay, sFLC-kappa/lambda were calculated and the results were compared with that of immunofixation electrophoresis (IFE) as well as serum protein electrophoresis (SPE) for sensitivity assessment. All patients were treated with chemotherapy followed by sFLC detection and efficacy assessment. Patients with a sFLC results higher than median were marked as high-sFLC, the rest were marked as low-sFLC, and survival analysis were made comparing the two groups. Results: Of the 39 first-onset MM patients, 38 were detected as sFLC- kappa/lambda positive, that's a sensitivity of 97. 4%, higher than IFE (79. 5%), SPE (53. 8%), and uPE (38. 5%). As condition improves after treatment, sFLC gradually decline and sFLC- kappa/lambda level falls back to normal. Evaluation of efficacy by sFLC results has an accuracy of 77. 27%, significantly higher than that of corresponding M protein test£̈ P=0. 009£©. Follow-up survival analysis showed that the OS time and TTP time of low-sFLC group are significantly higher than those of high-sFLC group (P=0. 037, 0. 009 respectively). Conclusion: sFLC detection is a highly sensitive quantitative method, can help the diagnosis of MM, gives a quicker assessment of treatment efficacy, and can predict disease recurrence. When it's the first onset, sFLC level can also roughly forecast the prognosis. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 3
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 5036-5036
    Abstract: Abstract 5036 Multiple myeloma (MM) is a malignant neoplasm of plasma. With conventional chemotherapy, the rates of complete remission (CR) or very good partial remission (VGPR) are still low. Little has been reported on Bortezomib-based therapies specifically in the Chinese pateitns with MM. Here we report our results with combination therapy based on bortezomib in the Chinese population. We investigated the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients. Methods: Between June 2006 and June 2010, 61 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on Bortezomib. Forty-two patients were male and 19 were female. Median age was 59 years (range 37–86 years). Forty-four patients were stage 3 according to the International Staging System, 6 patients were stage 2 and 11 patients were stage 1. The conbinations included dexamethasone, dexamethasone plus subsequent thalidomide and dexamethasone plus cyclophosphamide. In detail, Bortezomib was at the dose of 1.3 mg per square meter IV on days 1, 4, 8, 11 and dexamethasone at 20 mg per square meter IV daily on the day of bortezomib and the day after, with or without daily oral thalidomide that was escalated from 100 mg to 200 mg (BD group or BDT group) or plus cyclophosphamide at 0.2 per square meter IV on days 1 to days 4 (BDC group). Thirty-four patients were in BDT group, 12 in BD group and 15 in BDC group. All patients received a median of three cycles of therapy (range 1–6). The IMWG criteria were used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3. Results: The proportions of patients with very good partial response (VGPR) or better were 38% (13/34), 25% (3/12) and 60% (9/15) in BDT, BD and BDC group, respectively; 44% (15/34), 33% (4/12) and 33% (5/15) achieved partial response (PR). Therefore the overall response (VGPR plus PR) were 82% (28/34), 58% (7/12) and 93% (14/15). Three patients died with severe infection without disease progression. Grade 3–4 toxicities included fatigue (4/34, 1/12 and 4/15), thrombocytopenia (8/34, 3/12 and 5/15), diarrhea (4/34, 2/12 and 2/15) and infection (7/34,3/12,6/15) in BDT, BD and BDC group, respectively. Grade 1–2 neuropathy were occurred in 20 patients (59%), 6 patients (50%) and 9 patients (60%) and grade 3–4 were occurred in 6 (18%), 1 (8%) and 1 (7%) in BDT, BD and BDC group, respectively. Herpes zoster occurred in 6 patients (18%), 1 patients (8%) and 2 patients (13%) respectively. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment. Conclusions: Our preliminary experience in Chinese patients indicated that combination chemotherapy based on Bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC or BDT regimens may be more superior than BD in Chinese population. There were relative lower rates of grade 3–4 neuropathy and DVT/PE in the Chinese patients with MM receved combination chemotherapy based on bortezomib. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4284-4284
    Abstract: Abstract 4284 Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with distinctive biologic and clinical features that is now highly curable. However, there are complicated issues in treatment strategies for induction, consolidation and maintenance that remain to be studied. The optimal regimen and the duration of consolidation is one of the above controversies. Patients and methods: Six patients (4 males, 2 females) were enrolled in this observation with a median age of 28 years (18–36). All were diagnosed de novo APL with demonstration of the abnormal increased promyelocytes of 53–90% accompanied with detection of t(15;17) or PML/RARα rearrangements. At diagnosis, WBC counts were 0.9–4.6×109/L and platelet counts were 13–84×109/L. Induction therapy was composed of all-trans retinoic acid (ATRA) with or without anthracycline or homoharritonine. After achieving complete remission (CR) following the above regimens, consolidation therapy was given monthly consisting single anthracycline agent of idarubincin (8–10 mg/m2/d, day 1–3) or aclarubicin (8–12 mg/m2/d, day 1–7) and alternative ATRA (25 mg/m2/d, day 1–15). After 12–18 months of consolidation, patients received maintenance therapy including methotrexate (12 mg/m2/d, per week) plus 6 mercaptopurine (30 mg/m2/d, qod ×12 days) and alternative ATRA (25 mg/m2/d, day 1–15) for one year. Results and conclusions: At present, all of the six patients are in continuous CR status, four of whom ceased treatment and are undergoing regular monitoring. Preliminary results from our experience demonstrates that single anthracycline and alternative ATRA can act as a valid option with limited toxicity for APL and might be used as a consolidation strategy, particularly for low and intermediate-risk patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 17, No. 4 ( 2011-04), p. 542-549
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
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    detail.hit.zdb_id: 2057605-5
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  • 6
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4211-4211
    Abstract: Abstract 4211 Isolated extramedullary relapse (EMR) of acute leukemia (AL) is a rare occurrence although it appears to be more common following allogeneic stem cell transplantation (allo-SCT). To characterize what has been observed in isolated EMR, we investigated a total of 287 consecutive AL patients (144 acute myeloid leukemia, 138 acute lymphocytic leukemia and 5 acute mixed lineage leukemia) who underwent allo-SCT. Forty-seven (16.4%) patients experienced relapse after allo-SCT. 12 cases (4.2%) experienced relapse of extramedullary sites without concomitant bone marrow involvement. Isolated EMR accounted for 25.5% of the overall initial relapse. The time to relapse after allo-SCT was longer in the extramedullary sites than in the marrow (median, 10 months vs. 5.5 months, P 〈 0.05,). Sites of EMR varied widely including central nervous system, skin, bone, pelvis and breasts. The variables considered for univariate analysis included donor gender, age, primary disease, disease status, cytogenetics/molecular abnormalities, preconditioning regimen, donor type, HLA match, aGVHD and cGVHD. The variables that showed significant correlation with isolated EMR were the cytogenetics abnormalities at diagnosis. The prognosis for patients who develop EMR remained poor but was relatively better than that after bone marrow (BM) relapse (overall survival, 10 vs. 18 months, P 〈 0.05). Compared with local or single therapy, patients treated with systemic in combination with local treatment could yield favorable prognosis. Three patients survived 63, 55 and 49 months after transplant respectively, of whom two received DLI with subsequent chemotherapy and (or) irradiation and one had surgery with subsequent chemotherapy. In conclusion, we observed a significant number of isolated EMR of AL after allo-SCT and intensive approaches combined of local and systemic therapy can produce favorable response which may cure a percentage of these patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: The American Journal of the Medical Sciences, Elsevier BV, Vol. 345, No. 2 ( 2013-02), p. 88-93
    Type of Medium: Online Resource
    ISSN: 0002-9629
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 2083424-X
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  • 8
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5116-5116
    Abstract: Abstract 5116 Multiple myeloma (MM) is a malignant neoplasm of plasma. The rates of complete remission (CR) or very good partial remission (VGPR) for patients received conventional chemotherapy are still low with median overall survival about 3 years. Here we report our results with combination therapy based on bortezomib in the Chinese population and investigat the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients. Metohds: Between 1st Feb. 2006 and 31st Dec. 2010, 102 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on bortezomib. Sixty-four patients were male and 38 were female. Median age was 59 years (range 31–86 years). Forty-two patients were stage 3 according to the International Staging System, 36 patients were stage 2 and 24 patients were stage 1. The combinations included dexamethasone (BD group ), dexamethasone plus subsequent thalidomide (BDT group ) and dexamethasone plus cyclophosphamide (BDC group ) or epirubicin (BDA group ) based on bortezomib. Thirty-five patients were in BDT group, 19 in BD group, 32 in BDC group and 16 in BDA. All patients received a median of three cycles of therapy (range 1–5 ). The IMWG criteria was used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3. Results: The efficacy of the triplet combination therapy based on bortezomib including BDT, BCD and BAD were better than BD group, with response rate greater than or equal to partial remission(≥PR) 85.7%, 90.6%, 93.7% and 68.4%, respectively. The efficacy of BDA and BDC group were significantly superior to BD group (P=0.048,0.050). Bortezomib in combination with chemotherapy was highly effective as treatment for symptomatic multiple myeloma, even only after one cycle. The efficacy for patients received one cycle of BDT, BD, BCD and BAD was 65.7%, 42.1%, 65.6% and 62.5%, respectively. Patients treated with BD had suboptimal responses to those received BDT, BCD and BAD treatment and one cycle of BCD was superior to one cycle of BD (P=0.019).The median follow-up time was 17m (1–60m), including 31m (1–60m) for 35 patients in BDT group and 16m (2–29m) for the remaining 67 patients. The median progression-free survival (PFS ) of BDT group was 15m (9.8–20.2m ) while BD group was 12m (8.1–15.8m), BCD group was 13m (5.9–20.1m ), and BAD group was 12m (7.8–16.2m ), without significant difference. The median overall survival (OS ) of BDT group was 35m (13.2–56.8m ) while BD, BCD and BAD groups was not reached yet. There was no significant difference in OS among groups, but BCD and BAD were superior to BD group (P=0.104, 0.142 ). The frequent treatment-emergent adverse events includes hematologic adverse events such as neutropenia, anemia, thrombocytopenia and the non-hematologic adverse events like fatigue, infection, constipation, diarrhea, pleural effusion and ascites, herpes zoster and peripheral neuropathy. Patients treated with BDT were more likely to show peripheral neuropathy than those treated with BD, BCD and BAD (91.4% vs 73.6%, 68.7%, 74.9% ), but there is no statistical significant difference (P = 0.131), Grade 2 or 3 peripheral neuropathy was occurred in 45.7% of BDT group significantly higher than BD, BCD and BAD groups. (21.0%, 15.7% and 18.7%, P = 0.028 ). Other related adverse events in all the groups had no significant difference. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment. Conclusions: Our preliminary experience in Chinese patients indicated that combination chemotherapy based on bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC, BDA or BDT regimens may be more superior to BD in Chinese population. There were relative lower rates of DVT/PE in the Chinese patients with MM received combination chemotherapy based on bortezomib. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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