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  • American Society of Hematology  (12)
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  • 1
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1857-1857
    Abstract: Abstract 1857 Background: Circularly permuted TRAIL (CPT) is a recombinant mutant of human Apo2L/TRAIL developed by Beijing Sunbio Biotech Co. Ltd. as a targeted therapy for multiple myeloma and other hematologic malignancies. CPT is a dual pro-apoptotic receptor agonist that directly activates both pro-apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). CPT selectively induces apoptosis in a variety of cancer cells, while sparing most normal cells in the preclinical models. Objective: The safety, pharmacokinetics and preliminary efficacy of CPT in relapsed or refractory multiple myeloma patients (Ral/Ref MM) has been evaluated. Methods: This is a phase Ib, multiple-center, open-label, single/multiple dose-escalation study,18 patients were enrolled in the single dose-escalation study, and 29 patients were recruited in multiple dose-escalation study (including some patients from single dose-escalation study of CPT). Five escalation dosage levels include 5.0, 6.5, 8.0, 10.0 and 15.0 mg/kg/day. Patients received single dose of CPT, or once daily for 5 consecutive days (multiple dose) of each 21-days cycle. Patients receiving multiple doses were treated up to 4 cycles. The clinical response was evaluated at the end of each cycle by an independent review committee according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT). Results: In single dose-escalation study, no dose limiting toxicity (DLT) and maximum tolerated dose (MTD) was observed. The most common treatment-related adverse events (≥10%) were elevated AST, fever, elevated LDH, leucopenia and shivers. In multiple dose-escalation study, the most common treatment-related adverse events(≥10%) were fever, leucopenia, elevated AST, fatigue and vomit. No significant difference of related adverse event was observed among the different dose groups. Two patients (33.3%) experienced laboratorial or clinical tumor lysis syndrome in 15.0 mg/kg multiple dose. The efficacy was evaluated in 27 patients, 1 patient achieved complete response (CR), 4 partial response (PR), 4 minor response (MR) and 12 no change (NC). No response better than MR was observed in 5.0mg/kg and 6.5mg/kg group. In 8.0mg/kg, 10.0mg/kg and 15.0mg/kg groups, the overall response rate (CR+PR %) was 33.33%, 16.67% and 33.33%, respectively. The disease control rate for five dose groups was 50.00%, 66.67%, 83.33%, 83.33% and 100% respectively, indicating that the optimal dose for CPT may be between 8.0 and 15.0mg/kg. PK results are linear at dose range from 5 mg/kg to 15 mg/kg with CL of 32.47±9.33 ml/h/kg, Vd of 51.89±9.20 ml/kg and t1/2 of 1.16±0.22h. No drug accumulation was observed in repeated administration. No anti-drug antibodies were detected after 1 to 4 cycle's treatment. Conclusion: CPT was well tolerated up to 15mg/kg with promising efficacy in patients with Ral/Ref MM. The MTD has not been reached. A randomized phase 2 trial in patients with Ral/Ref MM is ongoing. Disclosures: Yang: Beijing Sunbio Biotech Co., Ltd.: Employment. Zhu:Beijing Sunbio Biotech Co., Ltd.: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 2
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 47-48
    Abstract: Background: Current definition of multi-hit multiple myeloma (MM) is based upon the number of high-risk cytogenetic abnormalities (CA). But we may overlook the influence of standard-risk CA and different concurrent patterns. In fact, standard-risk t(11;14) and del(13q) may bring extra danger when concurrent with other CA. And the concurrency of two secondary CA may do more harm to patients than that of one secondary CA with one primary CA. This study is to answer whether CA number or pattern exert an impact on outcomes of MM patients. Methods: This study was carried out based on the prospective, non-randomized clinical trial BDH 2008/02. 537 MM patients with complete cytogenetic data were enrolled, of whom 64% (341/537) patients were treated with bortezomib-based three-drug induction therapy, and the remaining patients with thalidomide-based therapy. Autologous stem cell transplantation (ASCT) was recommended post induction therapy in transplant-eligible patients, and all patients received maintenance therapy for two years. CA were divided into primary CA [pCA: any type of IgH breakage], and secondary CA [sCA: del(17p), del(13q), gain(1q) (≥3 copies)] Results: In the era of novel agents, patients with pCA only did not have outcomes different from those patients without any FISH abnormality. Patients with s1 CA or s1+p CA had hazard ratio for PFS or OS of 1.5-2.0. Patients with s2 CA or s2+p CA had hazard ratio for PFS or OS of 2.0-3.0. Patients with concurrent del(13q), del(17p) and gain(1q) (s3 CA) had hazard ratio for PFS of 3.11 and for OS of 3.00. Patients with s3+p CA had hazard ratio for PFS of 4.65 and for OS of 6.16. Based on these results, we divided patients into four subgroups: no CA or only pCA, s1 CA in the presence or absence of pCA, s2 CA in the presence or absence of pCA, and s3 CA in the presence or absence of pCA. Both the PFS and OS decreased in a stepwise fashion with the accumulation of CA (Figure 1). Therefore, we defined double-hit MM as any one sCA in the presence or absence of pCA. Triple-hit MM referred to two sCA plus pCA or not, and quadra-hit MM referred to three sCA plus pCA or not. Furthermore, we confirmed the prognostic independence of CA pattern in the multivariant analysis with International Staging System (ISS) and LDH (Table 1). Conclusion: In this study, we found that the primary CA as a whole lost its adverse effect when treated by bortezomib-based regimens. CA subtype conferred a prognostic value. In details, secondary CA imposed an accumulative risk to patients. For the first time, we indicated that double-hit or triple-hit MM should be defined upon the number of secondary CA. This definition coincides with the "Two-Hit" theory of cancer causation and fits well with MM evolution model. The prognostic significance of CA pattern needs validation in further prospective trials. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
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  • 3
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 1-3
    Abstract: Purpose: Most data on the prognostic impact of cytogenetic abnormalities come from the setting of newly diagnosed multiple myeloma, it remains unclear whether the dynamic changes of cytogenetic aberrations affect the prognostic evaluation in multiple myeloma. Methods: We analyzed the prognostic impact of dynamic changes of cytogenetic abnormalities with a cohort consisting of 80 paired patients with consecutive cytogenetic data both at diagnosis and recurrence among 568 patients with newly diagnosed multiple myeloma. Results : Three patterns of recurrence were established from 80 paired patients: Pattern A (40%) consisted of 32 patients without new cytogenetic abnormalities at the time of progression. Pattern B (15%) consisted of 12 patients harboring new standard risk (SR) cytogenetic aberrations. Pattern C (45%) consisted of 36 patients with new high-risk (HR) cytogenetic abnormalities. The median overall survival (mOS; P & lt;0.001) and median progression-free survival (mPFS; P =0.013) differed significantly among three patterns. Four groups including 60 paired patients were further established according to genetic risk stratification changes. There were 15 patients who kept SR in group 1 (25%); 12 SR patients who evolved into HR group in group 2 (20%); 17 HR patients without new HR cytogenetic abnormalities in group 3 (28%); and 16 HR patients harboring new HR cytogenetic aberrations in group 4 (27%). The mOS (P=0.001) also differed significantly among these four groups. Conclusions: Dynamic cytogenetic changes significantly affected prognostic evaluation in multiple myeloma. Patients harboring new HR cytogenetic abnormalities and escalated genetic risk stratification at relapse had worse outcomes. Figure 1 Disclosures Anderson: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Oncopep and C4 Therapeutics.: Other: Scientific Founder of Oncopep and C4 Therapeutics.; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2958-2958
    Abstract: Abstract 2958 Background: Circularly permuted TRAIL (CPT) is a recombinant mutant of human Apo2L/TRAIL developed by Beijing Sunbio Biotech Co. Ltd. as a targeted therapy for multiple myeloma and other hematologic malignancies. CPT is a dual pro-apoptotic receptor agonist that directly activates both pro-apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). CPT selectively induces apoptosis in a variety of cancer cells, while sparing most normal cells in preclinical models. Objective: CPT as a mono-therapy has shown definitive activities for patients with relapsed or refractory multiple myeloma (Rel/Ref MM) in phase I and phase II studies. The aim of this study is to observe the effect and safety of CPT in combination with thalidomide for Rel/Ref MM patients. Methods: In this multiple-center, open-label, single arm phase II study, 43 Rel/Ref MM patients who had received prior therapies and were resistant to thalidomide were recruited. These patients were divided into three groups, and received CPT 5.0mg/kg, 8.0mg/kg, and 10.0mg/kg on days1–5 of each 21-day cycle, respectively, until having finished six cycle‘s treatment or progression disease or intolerant adverse events. All the patients received thalidomide 100mg daily until to the disease progression or intolerant adverse events. Clinical responses of CPT were assessed by an independent review committee according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT). Results: Among the 43 patients, 41 patients can be evaluated. There were 11, 15 and 15 patients in the three groups respectively. Among the 41 patients, two patients achieved complete response (CR), three showed near complete responses (nCR), four exhibited partial responses (PR), and five obtained minor responses (MR). The total response rates were 34% (including MR or better than MR), or 22% (including PR or better than PR). Among the three groups, the dose of 10mg/kg seemed to be optimal with 26.7% response rate (including PR or better than PR), superior to the other two groups. Duration of response of CPT was not evaluated accurately, because most patients who achieved PR, nCR, or CR were progression free at the end of the trial. The common treatment related adverse events (≥10%) were neutropenia, leucopoenia, fever, AST/ALT/LDH elevation, and thrombocytopenia. The grade 3 non-haematological toxicities were AST elevation (4.65%) and LDH elevation (2.33%). The elevation of AST and LDH seems to be related to tumor lysis, but not to liver injury. The grade 4 haematological toxicities were neutropenia and thrombocytopenia (2.33%, respectively) which might be related to thalidomide. Conclusions: The CPT combined with thalidomide was well-tolerated and an effective regimen for the treatment of Rel/Ref MM. The combination of CPT and thalidomide seems to be superior to CPT alone in CR/nCR response rate. Disclosures: Zheng: Beijing Sunbio Biotech Co., Ltd.: Employment. Zhu:Beijing Sunbio Biotech Co., Ltd.: Employment. Yang:Beijing Sunbio Biotech Co., Ltd.: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 5
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 26-27
    Abstract: Background: Age is a pivotal prognostic factor for multiple myeloma (MM). The risk of evolving from MGUS and SMM to symptomatic MM steadily increases with age. And there are nuances in clinical manifestations and cytogenetic characteristics between young and old patients. The aim of this study is to delineate the clinical and laboratory features and determine the relative contribution of ISS, performance status and cytogenetic abnormalities in each age MM patients. Methods: In this study, 778 MM patients were enrolled in the prospective, non-randomized BDH2008/02 clinical trial between January, 2008 and December, 2016. Briefly, the patients accepted bortezomib or thalidomide-based induction therapy. Transplantation eligible patients accepted ASCT, otherwise they accepted the original regimen consolidation therapy. Subsequently, unless intolerance, patients received either thalidomide-based or lenalidomide-based maintenance therapy for two years. Conventional FISH panel included del(13q), del(17p), gain(1q), t(11;14), t(4;14), t(14;16), and t(14;20). The positive cut-off value for chromosome deletion or gain was 20%, and for chromosome translocation was 10%. A multivariate Cox proportional-hazards model was developed to assess the variables with significant effects on PFS and OS. Explained variation of variables was quantified by RD2. Statistical analysis was conducted by Stata/MP 16.0 (Stata Corp., TX, USA) and SPSS 26.0 (IBM Corp., Chicago, Illinois, USA). Results: Among 778 patients with complete data, 59.5% (463/778) were younger than 60 years old, 31.4% (244/778) were 61-70 years old, and only 9.1% (71/778) were over 71 years old. The median PFS of patients≤60, 61-70 and ≥71 years of age was 36.3, 32.6 and 23.1 months, respectively (P & lt;0.001). The median OS in each age group was 86.2, 60.7 and 34.9 months, respectively (P & lt;0.001) (Figure A-D). The median evaluated glomerular filtration rate of the three groups was 89.1, 74.0 and 66.4 ml/min (P & lt;0.001), respectively. The serum β2-microglobulin level gradually increased with age (P & lt;0.001), along with the proportion of patients with ISS 3 stage. Patients ≥71 years old had a higher proportion of ECOG performance status score 3-4, twice than that of patients ≤60 years old. The incidence of high-risk IgH translocation decreased with age, and was 25.4%, 21.3% and 14.3% across age groups. The incidence of gain(1q) increased with age, and was 43.9%, 47.1% and 54.8%, respectively. The incidence of del(17p) and del(13q) seldom changed with age (Figure E). With age, the risk of high-risk cytogenetic abnormalities did not change significantly, accounting for about 50% in each age group. The risk of ISS gradually decreased, accounting for 36%, 27%, and 14% in ≤60, 61-70 and ≥71 year subgroups, respectively. The risk of the ECOG performance status gradually increased with age, accounting for 10%, 17%, and 36% in the three subgroups (Figure F). The overall response rate of induction treatment gradually decreased with age, and were 90.2%, 81.9%, and 69.2%, respectively (P & lt;0.001). Elderly patients with impaired renal function or more than one high-risk cytogenetic abnormalities might benefit more from bortezomib based treatment than younger patients (Figure G). Conclusion: Age is an important prognostic factor in MM. With age, the risk of MM progression or death steadily grows. Cytogenetic abnormalities are equally important in every age group. The risk of poor performance status increases in elderly patients with a reduction risk in ISS. Elderly patients should focus on the status of frailty and molecular events to determine treatment. Figure Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 6
    Online Resource
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    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 2723-2723
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 2723-2723
    Abstract: Aims To make up the absence of the intact epidemiological data by investigating the clinical epidemiological features of Chinese patients with multiple myeloma in a representative center. Methods: Medical records of patients with MM from January 1990 to December 2007 in our hospital were retrospectively studied, and divided into 2 groups (1990s and 2000s) to make a comparison. Results: Patients A total of 944 cases, who came from 26 Provinces, were enrolled during the past 18 years. 416 of the cases were diagnosed in 1990s, and 528 cases were enrolled after 2000. Presenting and clinical features The median onset age was 58 years with a spike of 55–65 years. There were no significant differences in the median onset age and spike period between the 2 groups, while the percentage of younger ( & lt; 40 years) was lower and elder (≥70 years) was higher in 2000s than those in 1990s (10.2% vs 5.3%, 11.3% vs 15.1%). The ratio of male to female was 2.35:1 in 2000s and 1.72:1 in 1990s.The median onset course was 5 months in 1990s and 4 months in 2000s. The main presenting symptoms were bone pain (60%) and fatigue (50%), followed by infection (20%) and bleeding (6%).534 of 688 (77.6%) previously untreated patients were in D-S stage III. The staging distribution between the two groups were no obvious difference, but patients in 2000s had lower renal insufficiency than those in 1990s (16.32% vs 33.22%). The paraprotein typed was defined in 744 cases. 47.1% were IgG type followed by IgA type (23.9%), light chain type(20.6%). IgD type was identified in 3.2%, biclonal type in 0.97%, IgM type in 0.55% and nonsecretory type in 3.87% of patients. Among the 251 patients who had convention karyotype analysis, 61.4% were normal karyotype, followed by hypodiploidy (11.95%), hyperdiploid (8.8%). Complex karyotypes were seen in 15.9% of patients, □¢13 in 8.8%, abnormality of chromosome 14 in 10.4%. 19.0% of the 100 patients with the FISH detection of 13q− (RB1 probe) was positive. Treatment and response The main treatment regimens in 1990s were MP, M2 and VAD. The response rate (≥PR) were 48.6%, with 14.9% reached ≥VGPR. There were 438 cases accepted successive treatment mainly with MPT, VAD-T/DVD-T and VD(velcade + HD-DXM)-like regimens in 2000s. The total RR were 82.0%, with 31.0% of patients reached ≥VGPR. The total response rate especially ≥VGPR was significantly improved after 2000(P & lt;0.01). Follow-up and survival The median OS of patients in 1990s and 2000s was 30.5 and 42 months, respectively. The median OS of patients in 2000s was significant longer than those of 1990s (P & lt;0.01) Prognostic factors The multivariate analysis of the 438 patients after 2000 indicated that β2-macroglobin, lactic dehydrogenase, 13q− had independent prognostic value for survival. The International Staging System and Durie-Salmon Staging System were effective for Chinese myeloma patients. Conclusions The number of patients admitted to hospital and the percentage of patients received successive treatment are increasing after 2000. Compared with patients in western countries, Chinese MM patients had some specific features: younger onset age, longer course before diagnosis, more invasive performance, advanced clinical stage, more unfavorable prognostic factors. The OS of patients in China was relative shorter than those reported in the western countries during the same period. The OS duration was significantly prolonged after the year 2000 with the application of thalidomide, bortezomib, and autologous haemopoietic stem cell transplantation. The main unfavorable prognostic factors of Chinese patients were similar to that of the western patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 7
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 23-24
    Abstract: Background: Large granular lymphocyte leukemia (LGLL) is one type of chronic lymphocytic proliferative disorders, which commonly manifests as infiltration of large granular lymphocytes in both peripheral blood and bone marrow. LGLL now includes two entities with similar clinical course, treatment strategy and outcomes: T-cell large granular lymphocytic leukemia and chronic lymphoproliferative disorder of NK cells. The standard therapy for LGLL is still elusive. Here, we presented the efficacy and safety of combinatorial oral immunoregulatory regimen thalidomide, prednisone, and methotrexate (TPM regimen) in a prospective phase 2 clinical trial. Methods: We designed this phase 2 investigator-initiated clinical trial (NCT04453345) to evaluate the clinical response and safety of the combination of thalidomide, prednisone, and methotrexate in symptomatic treatment naïve LGLL patients. The TPM regimen includes thalidomide 50-100mg per night, prednisone 0.5-1.0mg/kg qod and methotrexate 10mg/m2 per week. This regimen will be administrated for up to 12 months until disease progression or intolerable. Then, thalidomide maintenance will continue for another year or until intolerance. Meanwhile, we set Cyclosporin A (CsA) alone or plus steroids as control. Treatment dosage for CsA was 3-5mg/Kg/day with or without steroids (prednisone) 0.5-1 mg/Kg/day. The primary endpoint of this study was the complete response rate. Results: From Aug 2013, to Jan 2020, twenty-eight patients were enrolled in this study. The median follow-up time was 26 months (range: 7-96). Twenty-five patients (89%) achieved hematologic and symptomatic response. Among them, 21 patients (75%) achieved complete response (CR) and four patients achieved partial response. The median time to best clinical response was 6 months (2-18). The 3-years progression-free-survival (PFS) rate was 90%, and 3-years overall survival (OS) rate was 92%. The median PFS time was not reached in TPM group. The curative effect was better for TPM treatment group, both for overall response (OR) (TPM 89% (25/28) vs CsA 49% (49/99), P=0.000) and CR (TPM 75% (21/28) vs CsA 20% (20/99), P=0.000). Adverse events were uncommon, two patients had grade 1-2 nausea and one had grade 3 nausea. Two patients had grade 1-2 constipation and one patient experienced grade 1-2 peripheral neuritis. Conclusion: The efficacy of this TPM regimen is higher than the history reports with limited adverse events. The multiple-center clinical trial has been initiated to validate this conclusion. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 8
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 78-78
    Abstract: Abstract 78 Background: Circularly permuted TRAIL (CPT) is a recombinant mutant of human Apo2L/TRAIL developed by Beijing Sunbio Biotech Co., Ltd. as a targeted therapy for multiple myeloma and other hematologic malignancies. CPT is a dual pro-apoptotic receptor agonist that directly activates both pro-apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). CPT selectively induces apoptosis in a variety of cancer cells, while sparing most normal cells in preclinical models. Objective: CPT has shown preliminary activities for patients with relapsed or refractory multiple myeloma (Rel/Ref MM) in phase I study. The aim of this phase II study is to investigate the effect and safety of CPT for Rel/Ref MM patients. Methods: In this multi-center, open-label, single arm phase II study, twenty-seven Rel/Ref MM patients were enrolled to receive CPT treatment alone at the dose of 2.5 mg/kg/day intravenously, once daily for 14 consecutive days of each 21-day cycle. Clinical responses to CPT after 2 cycle's treatment were assessed by an independent review committee according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT). Results: Among the 27 patients, one patient (3.7%) achieved near complete response (nCR) and eight patients (29.63%) exhibited partial response (PR). The overall response rate (ORR) was 33.3%. The median PFS was not reached within 2 cycle's treatment. The drug related adverse events (≥10%) included fever, AST/ALT elevation, leucopenia, neutropenia, rash, thrombocytopenia, and LDH elevation. The severe adverse events were occurred in 3 patients (11%), one of them was CPT-related liver injury. Anti-drug antibodies were detected in 6 patients without reduced efficacy or increased toxicities. Conclusions: The CPT is a very effective and well-tolerated new agent for Rel/Ref MM, and it is worthy to be further studied. Disclosures: Yang: Beijing Sunbio Biotech Co. Ltd.: Employment. Cui:Beijing Sunbio Biotech Co. Ltd.: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 9
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3324-3324
    Abstract: Objective: To investigate the efficiency of our designed protocol with early sequential intensive consolidation chemotherapy followed by autologous stem cell transplantation (ASCT) in first complete remission (CR1)on adult acute lymphoblastic leukemia (ALL) patients who lack of matched sibling donors. Methods: The ALL patients were given a median 4 intensive/ consolidation therapy courses including high-dose of methotrexate, cytarabine and/or cyclophosphamide in CR1, followed by ASCT with total body irradiation (TBI)-based conditioning regimen. A 1 to 1.5 year maintenance chemotherapy with 6-mercaptopurine, methotrexate and vincristine-prednisone in combination with interleukin-2/IFN-α immunotherapy were administered after adequate hematological recovery. Results: A total of 83 patients were enrolled in this study. 78 patients reconstituted hematopoiesis except 5 patients died of early toxicity. By a median 47(3– 218) months follow-up after ASCT, the 5-year probabilities of leukemia free survival (LFS) and overall survival (OS) were 53.2%±5.9% and 54.4%±5.8%, respectively. The 5-year cumulative relapse rate (RR) was 35.7%±6.1%, and no patients relapsed more than 3 years after transplantation. According to the adverse features, age ≥35 years, WBC 〉 30×109/L for B-cell ALL or 〉 100×109/L for T-ALL, Pro-B and early T immunotyping, more than 4 weeks to attain remission, and high-risk karyotypes including t(9;22)/BCRABL, t(4;11)/ALL1-AF4 or t(1;19)/E2A-PBX1, the patients were identified in 3 prognostic risk groups of standard (24, 29.0%), intermediate(32, 38.5%), and high(27, 32.5%) with 0, 1, 2 or high-risk karyotypes adverse features, respectively. The 5-year probabilities of DFS were 80.36%±9.0%, 59.39%±9.2% and 24.78%±8.9% in these 3 group s, respectively. While, the 5-year cumulative incidences of relapse was 16.7%,37.5% and 70.4%, respectively.. The standard and intermediate -risk groups had significantly better OS and LFS than the high-risk group. Conclusion: Theses results indicated our designed protocol with early sequential intensive consolidation chemotherapy followed by autologous stem cell transplantation (ASCT) in first complete remission (CR1) could produced a relatively high log-term survival in standard and intermediate-risk group of adult ALL patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 10
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5836-5836
    Abstract: Objective: To evaluate the efficacy and long-term outcome of the total treatment of induction therapy, ASCT and consolidation and maintenance therapy. Methods: A retrospective analysis was made on in multiple myeloma patients in our center between April 1, 2003 and February 1, 2016. The 157 patietns received autologous hematopoietic stem cell transplantation and review the autologous transplantation of long-term follow-up results. Analysis of the effect of transplantation efficacy, the impact on survival remission of different transplantation depth, transplantation in first line or not, salvage transplantation, prognosis of different staging system and other factors. Results: The baseline characteristics of the patients were shown in table 1. Overall patient ASCT before total effective rate (ORR) was 93.6%, in which the complete remission (CR) ratio was 33.1%. After ASCT, the best treatment response rate of PR was 80.3%, and the rate of CR was 58.6%. 91.69 months of median follow-up, patients with an overall survival (OS) and progression free survival (PFS) respectively 91.69 and 50.76 months; in 2005 before the median OS and PFS 39.0m and 23.0m. In 2005 after respectively and 56.41m 120.90m, P = 0.000. The median OS and PFS in the first line transplantation group and salvage transplantation group were vs 54.21m 39.0m and vs 7.09m 119.0m (P value was 0). 136 cases of patients with R-ISS stage, I, II, III of the patients with the median survival time were 120.90m (n=46), 86.43m (n=69), 35.65m (n=21), there were significant differences between groups, p=0.000. Each period of PFS were 72.11m, 51.84m, 28.09m, I and II, III,, p=0.001 and p=0.03, while there was no significant difference between II and III, p=0.122. The received autologous transplantation as first-line and salvage treatment of patients with subgroup survival analysis, median OS of the R-ISS stage III patients and different 15.84m 35.65m, P = 0.031; two groups of patients the median PFS (phase I: 91.69m vs18.92m; II: vs 16.69m 53.42m; phase III: vs 5.91m 28.52m) have difference (P = 0.000). In the first-line transplantation group, transplantation is more than or equal to PR and did not get effective PR group between OS were significantly different; before transplantation achieved CR, PR but did not obtain Cr and did not get effective PR group between PFS were significantly different; after transplantation and achieved CR CR did not get the patients had a median PFS were 65.57m 48.13m, P = 0.039 and median OS no difference. Accept any kind of noval agent- based chemotherapy were significantly longer OS and PFS than traditional chemotherapy (P = 0.001, P = 0.004) .There was no obvious difference on median OS between based regimen (bortezomib group median OS: NR; thalidomide group:120.90m); PFS in thalidomide group (median PFS : NR vs 54.21m) significantly prolonged (P = 0.010). By comparing the baseline characteristics of the two groups, it was found that the PFS was significantly shorter in the bortezomib group with an extra medullary lesion. Multivariate analysis showed that only R-ISS and the depth of remission before transplantation had effect on OS (p=0.003) and PFS (p=0.036) respectively. Conclusion: The total treatment of novel agent-based chemotherapy and ASCT for transplantation-eligible multiple myeloma patients is effective, further improve the remission rate and remission depth, prolong PFS and OS, the overall median survival up to 120.9m. First line transplantation can significantly prolong the OS and PFS compared with salvage transplantation. R-ISS and pre-transplant remission depth are prognostic factors influencing survival of patients. The total treatment to thalidomide based without extramedullary perhaps makes patients get long-term survival. 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: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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