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  • American Society of Hematology  (35)
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  • American Society of Hematology  (35)
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  • 1
    In: Blood Advances, American Society of Hematology, Vol. 7, No. 13 ( 2023-07-11), p. 2972-2982
    Abstract: Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2023
    detail.hit.zdb_id: 2876449-3
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  • 2
    In: Blood, American Society of Hematology, Vol. 119, No. 14 ( 2012-04-05), p. 3256-3262
    Abstract: We studied the impact of risk stratification–directed interventions for minimal residual disease (MRD) on relapse and disease-free survival (DFS) prospectively in 814 subjects with standard-risk acute leukemia receiving allotransplantation in first or second complete remission. A total of 709 subjects were MRD− after transplantation (Group A); 105 subjects were MRD+, 49 received low-dose IL-2 (Group B), and 56 received modified donor lymphocyte infusion (DLI) with or without low-dose IL-2 (Group C). Posttransplantation immune suppression for GVHD was also modified based on MRD state. The cumulative risk of relapse was significantly less and DFS was significantly better in subjects in Group C than in subjects in Group B (P = .001 and P = .002, respectively), but was not different from subjects in Group A (P = .269 and P = .688, respectively). Multivariate analyses confirmed that MRD state and modified DLI were significantly correlated with relapse (P = .000, odds ratio [OR] = 0.255 and P = .000, OR = 0.269) and DFS (P = .001, OR = 0.511 and P = .006, OR = 0.436, respectively). These data suggest that risk stratification–directed interventions with modified DLI in patients with standard-risk acute leukemia who are MRD+ after transplantation may improve transplantation outcomes.
    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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  • 3
    In: Blood Advances, American Society of Hematology, Vol. 3, No. 21 ( 2019-11-12), p. 3406-3418
    Abstract: Overexpression of WT1 and PRAME are common in MDS patients with thrombocytopenia. Both are independent poor prognostic factor for outcome. The evaluation of WT1/PRAME transcript analysis can better risk-stratify the patients, thus guiding individualized treatment.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 2876449-3
    detail.hit.zdb_id: 2915908-8
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  • 4
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5264-5264
    Abstract: Background Bone disease is an important determinant of quality-of-life and survival of persons with plasma cell myeloma (PCM). Biomarkers of bone disease could be useful to predict risk and monitor therapy. In our prior analyses OCSTAMP (osteoclast stimulatory trans-membrane protein) mRNA levels were identified as increased above normals in persons with PCM. OCSTAMP encodes a membrane-anchored cell surface receptor promoting nucleation of osteoclasts involved in bone resorption and osteoclast differentiation. Aims Measure levels of OCSTAMP mRNA in subjects with PCM and interrogate clinical associations. Methods OCSTAMP mRNA levels were quantified by quantitative real-time polymerase chain reaction (RT-qPCR) in 224 bone marrow samples from 160 subjects with PCM including 160 newly-diagnosed; 55 in remission and 9 with recurrent PCM. Results were compared with 42 normals and data expressed as ratio of OSSTAMP mRNA/ABL mRNA. Associations with clinical variables were interrogated and comparisons analyzed using the Chi-square test. Results OCSTAMP mRNA levels were significantly greater than normals in 111 subjects (69%, [95% confidence interval l[CI], 62-77%] , P 〈 0.001) with newly-diagnosed PCM, in 5 (56% [23,88%]; P=0.39) relapsing after initial therapy and in 12 in remission (22% [11-33%; P 〈 0.001). mRNA levels in samples from newly-diagnosed subjects (median, 0.52%; range, 0-121%) were significantly higher than in samples from subjects in remission (0.01%; range, 0-4.7%) or normals (0.02%; range, 0-0.10%; both p 〈 0.001). Levels in subjects in remission and normals were similar (p=0.85). Median OCSTAMP mRNA level was used to dichotomize subjects into low (median 0.06%; range, 0-0.51%) and high (3.8%; range, 0.54-121%) cohorts (P 〈 0.001). Subjects in the high cohort were more likely to be in Durie/Salmon stage-3 (p=0.035), to have serum albumin concentrations 〈 35g/L (p=0.036), have serum C-reactive protein (CRP) concentrations ≥8mg/L (p=0.03) and have ≥1 pathological bone fractures (p=0.002). Conclusions OCSTAMP is highly transcribed in persons with newly-diagnosed and recurrent PCM compared with normals whereas persons in remission have similar levels to normals. OCSTAMP mRNA levels correlate with several clinical variables including Durie/Salmon stage, serum albumin C-reactive protein levels and likelihood of pathological bone fractures. OCSTAMP mRNA levels are potentially useful as a biomarker if our data are validated. Figure. 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: 2018
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  • 5
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 162-162
    Abstract: Abstract 162 Background and Aims. The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) in the first chronic phase (CP) in the imatinib era have not previously been evaluated. This prospective cohort study was designed to compare the medical outcomes and quality of life (QOL), with imatinib versus allo-HSCT from an HLA-matched sibling donor for CML in the first CP including the early CP (ECP; a CML duration 〈 12 months) and the late CP (LCP; a CML duration ' 12 months). Patients and methods. From April 2001 to April 2010, patients treated consecutively at the Peking University People's Hospital, Peking University Institute of Hematology were nonrandomly assigned to treatment with imatinib or allo-HSCT according to whether the patient had an HLA-matched sibling donor; those with an HLA-identical sibling donor were assigned to the allo-HSCT group, and the others were assigned to the imatinib group. QOL of surviving patients still in the imatinib and allo-HSCT groups was measured by the Medical Outcomes Survey Short Form 36 (MOS SF-36) at the end of the study evaluation period in April 2011. Results. In total, 463 patients were recruited, 209 patients were assigned to the allo-HSCT group and 254 patients were assigned to the imatinib group, respectively.Based on a ten-year follow-up period, a multivariate analysis revealed that allo-HSCT was an independent adverse prognostic factor for event-free survival (EFS; estimated HR=2.4, P=0.002 and estimated HR=0.31, P 〈 0.001) and overall survival (OS; estimated HR=6.9, P 〈 0.001 and estimated HR=26.2, P=0.001) for the total population (n=463) and the patients in the ECP (n=348), and an independent favorable predictor of progression-free survival (PFS; estimated HR=3.2, P=0.020) for the total population. Imatinib was superior to allo-HSCT, with six-year EFS and OS rates of 83.6% vs. 76.6% (P=0.041) and 96.4% vs. 82.0% (P 〈 0.001), respectively, for the entire cohort and 90.3% vs. 74.3% (P=0.001) and 99.4% vs. 80.2% (P 〈 0.001), respectively, for the patients in the ECP, despite six-year PFS rates of 90.7% vs. 96.6% (P=0.014), respectively, for the entire cohort and 95.9% vs. 97.3% (P=0.303) respectively, for the patients in the ECP. Both treatments resulted in similar EFS and OS rates in those in the LCP (n=115), with a probability of six-year EFS rate of approximately 80% and six-year OS rate of more than 90%. More LCP patients in the imatinib group experienced relapse compared with those in the allo-HSCT group, with six-year PFS rates of 86.0% vs. 100% (P=0.035), respectively. There was no correlation between the EBMT risk score and EFS, OS or PFS in the patients receiving allo-HSCT. Among the 392 surviving patients who were invited to participate in the QOL survey, 295 (75.3%) patients including 180 of 218 (82.6%) in the imatinib group and 115 of 174 (66.1%) in the allo-HSCT group, respectively, completed the questionnaires. A multivariate analysis revealed that there was no correlation between the treatment mode and the physical health for the total, ECP and LCP population, however, allo-HSCT was one of the independent factors associated with good mental health (estimated HR=0.5, P 〈 0.001) in the ECP patients. The Physical Component Summary were comparable between the imatinib group and the allo-HSCT group, however, the Mental Component Summary of the patients experienced allo-HSCT were better than those receiving imatinib for the total (P=0.001), ECP (P=0.015) and LCP (P=0.010) population. Conclusions. We concluded that imatinib confers significant survival advantages and a desirable QOL and is superior to allo-HSCT as the first-line therapy for patients with CML in the ECP. All trials were registered with www.chictr.org as CHiCHTR-TNC-10000955. Disclosure: No relevant conflicts of interest to declare. 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: 2011
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  • 6
    In: Blood, American Society of Hematology, Vol. 142, No. Supplement 1 ( 2023-11-02), p. 6189-6189
    Abstract: Background: Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) had important roles in the treatment of relapse or refractory (R/R) Hodgkin lymphoma (HL). Treatment of refractory disease after BV and -/or ICIs remains a challenge. This study was conducted to evaluate the efficacy and safety of radiotherapy for R/R HL after failure to BV or ICIs. Patients and methods: We retrospectively analyzed patients in two institutions with R/R HL who had failed after first-line therapy, and were refractory to BV or ICIs, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were analyzed. Results: A total of 19 patients were enrolled. First-line systemic therapy consisted of ABVD (84.2%), AVD + ICIs (10.5%) and BEACOPP (5.3%), respectively. After first-line therapy, 15 patients (78.9%) were refractory, and 4 patients (21.1%) relapsed. After diagnosis of R/R HL, 8 patients (42.1%) received BV, and 17 patients (89.5%) received ICIs. RT was delivered in all 19 patients who failed after BV or ICIs. In 16 efficacy-evaluable patients, the ORR and CR rate were 100% and 100%. The median DOR was 17.2 months (range, 7.9 to 46.7 months). 3 patients progressed at outside of the radiation field. The in-field-response rate was 100%. The 12-month PFS and OS were 84.4% and 100%, respectively. No patients were reported with sever adverse events. Conclusion: This study concluded that radiotherapy was effective and safe for refractory HL after BV or ICIs. Further prospective studies were warranted. KEY WORDS: Radiotherapy; Hodgkin lymphoma; Brentuximab vedotin; Immune checkpoint inhibitors; Refractory; Relapse
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2023
    detail.hit.zdb_id: 1468538-3
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2591-2591
    Abstract: Purpose The role of haploidentical related allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia( Ph+ ALL) is still not clear in the imatinib era, and limited data are available from the literature. We aimed to investigate the long-term survival between the haploidentical and matched related transplant in Ph+ ALL patients, and to analyze factors affecting relapse rate in different donor-type with maintenance therapy of imatinib post-transplant. Patients and methods The study population included Ph+ ALL patients receiving allo-HSCT from either haploidentical or matched related donor, and with maintenance therapy of imatinib post-HSCT. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were & gt;1.0 ± 109/L and platelet counts were & gt;50.0 ± 109/L, or if they displayed a high BCR-ABL transcript levels (∼10-2 after initial engraftment) or elevated BCR-ABL transcript levels in two consecutive tests. The imatinib treatment was scheduled for 3-12 months, or BCR-ABL transcript levels were negative at least for three consecutive tests and complete molecular remission was sustained for at least 3 months). Imatinib-resistant defined as: (1) transcript levels of BCR-ABL increased in two consecutive tests at least one-month interval; or (2) detection of point mutations in the BCR-ABL kinase domain (KD) after transplant. Results The total 120 consecutive Ph+ ALL patients received allo-HSCT and maintenance therapy of imatinib post-HSCT in our center between May 2005 to September 2012. Of these, 115 patients receiving a haploidentical (n=81) and matched related (n=34) graft were analyzed. 24 patients were identified as imatinib-resistant during post-transplant period, 13 in haploidentical group and 11 in matched related group. The 5-year cumulative incidence of relapse£¨CIR£©and non-relapse mortality (NRM) among the haploidentical group and matched related group were no different ( 18.2% vs.26.0%, p=0.212; 9.4% vs.7.2%, p=0.687). At a median follow-up of 37.5 months, the 5-year DFS and OS were 72.2% and 81.5% for the haploidentical group, compared with 68.5% and 79.5% for matched related group (p = 0.265, 0.419, respectively). Multivariate analysis showed that RT-PCR-BCR-ABL positive pre-transplant was significant factor for OS in haploidentical transplant (P=0.046). Remission status ( & gt;CR1) at HCT was a significant predictor to CIR in matched related group (p=0.020), but it wasn't a significant factor to impact on CIR in haploidentical transplant group. Imatinib-resistant was a significant factor to affect DFS, OS and CIR in both donor-type groups. Conclusion In the imatinib era, haploidentical HSCT for Ph+ALL achieves identical long-term survival compared with matched related HCT. Remission status ( & gt;CR1) at the transplant does not significantly impact on relapse in haploidentical transplant. Imatinib-resistant is a worse predictor to long-term survival and relapse rate in both donor-type group after HCT. 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: 2014
    detail.hit.zdb_id: 1468538-3
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  • 8
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5271-5271
    Abstract: Background: Cysteine and glycine-rich protein 2 (CSRP2), a member of the CSRP family, is reported to be upregulated in highly invasive breast cancer cells and promote breast cancer cell invasiveness. The expression and clinical implications of CSRP2 have not been explored in B-cell acute lymphoblastic leukemia (ALL). Aims: To investigate the expression of human CSRP2 messenger RNA and explore its clinical implications in adult B-cell ALL. Methods: TaqMan fluorescent real-time quantitative polymerase chain reaction (qPCR) was used to quantify CSRP2 mRNA copy number in bone marrow samples from patients with B-cell ALL and control normal bone marrow samples from healthy allogeneic stem cell transplantation donors (HD). Results: CSRP2 was expressed at significantly higher levels in 232 newly-diagnosed B-cell ALL marrow samples (ND; median 63.8%; range 0-1368.1%) than 43 HD samples (median 0.4%; range 0-1.8%; P 〈 0.001; Fig. 1A); at lower levels in 172 adult B-cell ALL samples (median 58.1%; range 0-1066.1%) than 60 pediatric B-cell ALL samples (median 93.0%; range 0-1368.1%; P=0.02; Fig. 1B); at lower levels in 206 complete remission samples (CR; median 0.8%; range 0-135.0%) than ND samples (P 〈 0.001; Fig. 1C); and at comparable levels in 27 relapsed samples (median 90.9%; range 0.2-716.3%), 17 refractory samples (median 60.8%; range 2.9-548.5%) and ND samples (P 〉 0.05; Fig. 1C). Minimal residual disease (MRD) was assessed by flow cytometry (FCM) in 166 CR samples: CSRP2 expression was significantly lower in the MRD 〈 0.01% group (n=129, median 0.60%, range 0-18.9%) than MRD 〉 0.01% group (n=37, median 3.2%, range 0.1-45.5%; P 〈 0.001; Fig. 1D). Regarding to the association of CSRP2 transcript levels with clinical variables of adult B-cell ALL, patients with MLL rearrangement expressed remarkably higher CSRP2 levels while patients with complex karyotype expressed significantly lower CSRP2 levels than the other subgroups (Fig. 1E). There was no significant association of CSRP2 transcript levels with age, sex, WBC levels, bone marrow blasts or risk group (P 〉 0.05). Longitudinal analysis was performed using 224 marrow samples from 50 patients with B-cell ALL; 27 patients expressed known fusion-gene transcripts (BCR-ABL, n=20; MLL-AF4, n=7) and 23 lacked additional molecular markers. Patients who achieved CR showed significant reductions in CSRP2 during follow-up; patients in relapse exhibited higher CSRP2 expression (Fig. 1F). In a subset of 182 samples, MRD estimates by FCM were also available. Using the threshold of 0.01% to define MRD positivity by FCM and 1.8% to define MRD positivity by CSRP2, there was a good correlation in the MRD-positive estimates by the 2 methods [r=0.751, 95%CI (0.523-0.885); P 〈 0.0001; Fig. 1G]. Furthermore, we measured MRD using CSRP2 compared with BCR-ABL by qPCR in triplicate using standards made by serial dilution (10-1, 10-2, 10-3, 10-4, 10-5) of diagnosis cDNA from 7 patients and the close concordance of results was confirmed by the Spearman coefficient of rank correlation of 0.933 [95% CI (0.879-0.954); P 〈 0.0001; Fig. 1H]. Conclusion: CSRP2 may serve as a novel biomarker and provide a potentially effective clinical indicator for auxiliary diagnosis and monitoring treatment efficacy in adult B-cell ALL. Figure A-F: CSRP2 expression in bone marrow samples from (A) newly-diagnosed (ND) B-cell ALL and healthy donors (HD); (B) adult and childhood B-cell ALL; (C) ND adult B-cell ALL, and patients with complete remission (CR), relapsed and refractory B-cell ALL; (D) patients with MRD determined by FCM 〈 0.01% and 〉 0.01% in patients with CR; (E) ND adult B-cell ALL with different karyotypes; (F) nine patients with de novo disease who experienced CR and then relapsed. G: Correlation between MRD monitored by CSRP2 and that monitored by FCM. H: Correlation between MRD monitored by CSRP2 and that monitored by BCR-ABL in serial dilution of diagnosis cDNA. *: P 〈 0.05; **: P 〈 0.01; ***: P 〈 0.001. Figure. A-F: CSRP2 expression in bone marrow samples from (A) newly-diagnosed (ND) B-cell ALL and healthy donors (HD); (B) adult and childhood B-cell ALL; (C) ND adult B-cell ALL, and patients with complete remission (CR), relapsed and refractory B-cell ALL; (D) patients with MRD determined by FCM 〈 0.01% and 〉 0.01% in patients with CR; (E) ND adult B-cell ALL with different karyotypes; (F) nine patients with de novo disease who experienced CR and then relapsed. G: Correlation between MRD monitored by CSRP2 and that monitored by FCM. H: Correlation between MRD monitored by CSRP2 and that monitored by BCR-ABL in serial dilution of diagnosis cDNA. *: P 〈 0.05; **: P 〈 0.01; ***: P 〈 0.001. 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: 2016
    detail.hit.zdb_id: 1468538-3
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  • 9
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 29-30
    Abstract: Background: C-CAR088, an anti-BCMA CAR T-cell therapy is a novel 2nd generation 4-1BB chimeric antigen receptor T (CAR-T) cell therapy targeting BCMA which is specifically and highly expressed on multiple myeloma (MM) cells. C-CAR088 is manufactured in a serum-free, automated and digital, closed system. Initial, early clinical trial results in patients with R/R MM supported preclinical findings and showed promising efficacy and manageable safety profile (Yao, Blood (2019) 134 (Supplement_1): 50.) Methods: The dose escalation and expansion studies have been conducted at four medical centers in China to evaluate the safety and efficacy of C-CAR088 in patients with R/R MM who were previously treated with at least 2 lines of therapy including proteasome inhibitors (PIs) and IMiDs. C-CAR088 is administered to patients as a single intravenous dose after a standard 3-day cyclophosphamide/fludarabine conditioning regimen. Results: As of July 15, 2020, 24 patients were infused and 21 patients had evaluable data for safety and clinical response at dose levels of 1.0 x 106 CAR-T cells/kg (n=3), 3 x106 CAR-T cells/kg (n=11) and 4.5~6x106 CAR-T cells/kg (n=7). The median vein to vein time was 16 days. The manufacturing success rate was 100%. The median age of patients dosed was 60 years (range: 45-74 years).The median number of prior lines of therapy was 4 (range: 2-12 prior therapies). There were 17 (81%) patients with at least one and 12 (57.1%) patients with at least two high risk cytogenetic tumor changes. Five patients (23.8%) had bridging therapy. C-CAR088 treatment was well tolerated. 20 of 21 (95%) patients had Grade 1-2 CRS and one patient experienced Grade 3 CRS. Median time to CRS was 6.5 days (range: 1-11 days) and median duration of CRS was 5 days (range: 2-10 days). Four patients (19%) received tocilizumab for CRS treatment. Only one patient experienced a Grade 1 neurotoxicity event. No dose-limiting toxicities were observed and all adverse events were reversible. The best overall response (BOR) included 6 complete responses (CRs), 10 very good partial responses (VGPRs) and 4 partial responses (PRs). Median follow-up was 182 days (range: 30-375 days). The median duration of response has not been reached. In the 3 x106 CAR-T cells/kg dose group, 5/11(45%) patients achieved a CR. The C-CAR088 PK profile in peripheral blood showed a trend of a dose dependent profile. AUC0~28day and Cmax increased and Tmax decreased with dose (P & lt;0.05). Conclusion: The clinical trial results in patients with R/R MM treated with C-CAR088 show a favorable safety profile and promising signs of efficacy. We will continue to evaluate these patients to understand the long-term effect of C-CAR088 in multiple myeloma patients. Clinical trial information: NCT04322292、NCT03815383、NCT03751293、NCT04295018 Research Sponsor: Cellular Biomedicine Group, Inc. Disclosures Zhu: Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Zheng:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Yan:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Lv:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Lan:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Yang:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Huo:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Han:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Zhao:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Qin:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Wu:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Yao:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Zhu:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Ren:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Zhang:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Huang:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Humphries:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company. Yao:Cellular Biomedicine Group Inc: Current Employment, Current equity holder in publicly-traded company.
    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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  • 10
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3015-3015
    Abstract: Abstract 3015FN2 Objective: Acute hemorrhagic cystitis (HC), a severe complication of hematopoietic stem cell transplantation (HSCT), being considered mainly as a result of cyclophosphamide (CTX), seriously affects the quality of life of patients. Mesna, whose half-life is about 70min, is widely used to prevent HC. Aim of this research is to explore the effect of continuous intravenous injection of mesna on HC in HSCT. Methods: (1) 108 patients who underwent HSCT in Nanfang hospital from July 2008 to December 2010 were recruited into this study (70 male and 38 female, the median age is 35.00); 106 cases were allogenic HSCT, 2 cases were auto-HSCT. Conditioning regimens were BuCy or TBI-Cy, in which CTX were given 60mg/kg·d, d−3, −2. Intravenous injection of mesna was used to prevent HC continuously (continuous group, n=68) or intermittently (intermittent group, n=40). Graft versus host disease (GVHD) prevention regimen was cyclosporine A+MTX for HLA-matched sibling donors and cyclosporine A+MTX+ATG for unrelated donors or HLA partial-matched related donors. (2) Both groups received the same daily dose of mesna, which is about 150% of CTX daily dosage. In the intermittent group, 25% of mesna's daily dosage was injected at 0h, 3h, 6h and 9h after the use of CTX at each time-point; while in the continuous group, 25% of mesna's daily dosage was injected before the use of CTX, with the rest dosage being continuously injected intravenously for 24hs using micro-infusion pump (25% daily dosage of mesna dissolved in 40ml 0.9% sodium chloride lasting for 8h was given, q8h), from the first dose of CTX till 48hs after the last injection of CTX. Incidences and grades of HC in the two groups were followed up and analyzed. (3) The mesna concentration in urine of two groups was detected by HPLC, with the comparison of trough concentrations being presented by comparing the average peak concentration. Results: (1) Within 30d after transplantation, HC occurs in 13 of the 40 (32.5%) cases in the intermittent group (6 cases of II°, 4 cases of III°, 3 cases of IV°) with none (0%) in the continuous group. Within 60d after transplantation, HC occurs in 16 of 40 (40.0%) cases in the intermittent group (8 cases of II°, 5 cases of III°, 3 cases of IV°) with the mean occurrence time being +14.6d (-1d - +44d); while only 7 of 68 (10.3%) cases (5 cases of I°and 2 of II°) in the continuous group with the mean time of +43.0d (+33d–+54d). There were statistical significances of the incidence (P =0.000), grade/severity (P =0.007) and occurrence time (P =0.005) of HC between the two groups. (2) Logistic regression analysis shows that the HC occurrences relates with the way of using mesna(P =0.025), with continuous mesna injection being a protective factor(OR=0.114, 95% CI=0.017–0.764); while age, sex, 24h mean liquid intake, 24h mean excretion, 24h mean urinary volume (each P 〉 0.1) and HLA matching (P =0.063) were unrelated factors. (3) The urine mesna trough concentration/average peak concentration was 0.219 (0.043–0.399) and 0.643 (0.153–0.868) in the intermittent group and the continuous group, respectively(P =0.031, n=4). Discussion: Early occurrence of HC is mostly related to high dose of cyclophosphamide, while late occurrence of HC can also be related with infection and GVHD, etc. The continuous injection of mesna seems to be a better way for the prevention of HC in HSCT patients, due to its short half-life of mesna. Injection with micro-infusion pump can reduce the liquid intake, especially suitable for those who have heart or kidney dysfunctions. More tests of mesna and acrolein concentration will help to reveal the mechanism. Conclusion: Continuous intravenous injection of mesna is a more efficient method in prevention of HC in hematopoietic stem cell transplantation than routine intermittent intravenous injection. 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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