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  • 1
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 41, No. 11 ( 2009-11), p. 1234-1237
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
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    SSG: 12
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  • 2
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 33-33
    Abstract: Background: Acute myeloid leukemia (AML) and myelodysplasia (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable option for patients suffering from high-risk AML/MDS. However, there were still many patients relapsed after allo-HSCT, especially for some patients are MRD positive before transplantation. Novel therapy to prevent replase is urgently needed. Both BCL-2 inhibitor, venetoclax (VEN) and hypomethylating agent, decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration DEC has been shown to ameliorate GVHD and boost GVL post-transplantation. Several clinical trials have also shown that venetoclax plus decitabine can be a safety and effective salvage treatment for patients with AML/MDS relapsing after allo-HSCT. We therefore conducted a prospective study (ChiCTR1900025374) to exam the tolerability and efficacy of a maintenance therapy low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for MRD positive high-risk AML/MDS patients. To our knowledge, this is the first report of venetoclax combined decitabine in this setting. Methods: Six patients with MRD positive high-risk AML (n=5) /MDS(n=1) post transplantation were recruited. Around day 100 post transplantation, all patients received LDEC (15mg/m2 for 3 days) followed by VEN (200mg) on day 1 to 21. Two months is a cycle. The primary end points of this study were rates of Overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), incidence of cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD) and incidences of viral infection after allo-HSCT. Survival outcomes were analyzed using Kaplan-Meier analysis Results: Two of the six patients were partial remission (PR) before transplantation, and the remaining 4 patients were MRD+ before transplantation. The median follow-up was 16 (11-26.5) months. Both 2-year OS and 2-year EFS were 83%. The median 2-year EFS time was 16(9-26.5) months, and five patients still EFS alive at the time of this writing. The 2-year cumulative incidence of relapse after LDEC+VEN was 17% and 2-year non-relapse mortality was 0%. No tumor lysis syndrome (TLS) was observed. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 adverse events were observed in 33% (2/6). No grade & gt;3 AEs were observed. Acute (any grade) and chronic (limited or extensive) graft-versus-host disease occurred in 67% and 17% of patients, respectively. The 2-year cumulative incidence of CMV viremia and EBV viremia were 33.3% and 16.7%, respectively. Conclusion: We conclude LDEC+VEN can be administered safely after allo-HSCT, without evidence for increased incidence of GVHD, and this combination demonstrates decreased relapse for MRD positive high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent replase for MRD positive high-risk AML/MDS patients, and the clinical benefits need to be assessed in a comparative prospective trial. Figure 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: 2020
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  • 3
    In: International Journal of Cancer, Wiley, Vol. 148, No. 10 ( 2021-05-15), p. 2398-2406
    Abstract: What's new? Evidence suggests that markers of Epstein‐Barr virus (EBV) infection are useful in screening for nasopharyngeal carcinoma (NPC). Few prospective studies, however, have validated the performance of EBV‐based risk scores for NPC. In this prospective validation study with data for more than 51 000 participants, EBV‐based risk score based on the combination of IgA antibodies against viral capsid antigen and EBV nuclear antigen 1 was found to be highly discriminating for NPC over follow‐up periods lasting five years. The findings indicate that EBV‐based scores could be valuable risk‐prediction tools for early NPC diagnosis, leading to improved clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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  • 4
    In: Blood, American Society of Hematology, Vol. 125, No. 10 ( 2015-03-05), p. 1541-1547
    Abstract: Rituximab plus recombinant human thrombopoietin is superior to rituximab monotherapy for corticosteroid-resistant or relapsed ITP patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
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  • 5
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 962-962
    Abstract: A substantial portion of patients with inherited blood disorders such as beta thalassemia, or bone marrow failure syndromes such as aplastic anemia(AA), myelodysplastic syndromes(MDS) require frequent transfusions of red blood cells. Frequent blood transfusions may lead to the excess of plasma non-transferrin -bound iron(NTBI) and iron overload occurs, which will significantly injure bone marrow (BM) function as well as induce organ dysfunctions such as liver cirrhosis, diabetes and cardiac diseases. However, the exact mechanism behind this effect remains elusive and ideal treatment needs to be explored. In our preliminary studies, we have demonstrated free iron catalyzes oxidative damage to hematopoietic cells/ mesenchymal stem cells in vitro and suppresses hematopoiesis in iron overload patients (Zhao et al.,blood, 2010 abstract; Lu et al.,blood,2012 abstract; Lu et al., Eur J Haematol, 2013). Here we observed the hematopoiesis inhibitory effects of iron overload on the basis of estabalished iron overload mice model and preliminarily disscussed the mechanism. In this study, we first established an iron overload mice model by administering different doses(12.5mg/ml,25mg/ml,50mg/ml) iron dextran by intraperitoneal injection every three days for four weeks. To confirm the efficacy of the mice model, the BM, hepatic and splenic iron deposits were observed by morphological study and the labile iron pool level (LIP) of bone marrow mononuclear cells(BMMNCs) was detected using the calcein-AM fluorescent dye. It was found that iron deposits in BM cells of iron overload mice, liver and spleen were markedly increased and the BMMNCs LIP level was much higher than that of normal control mice. The above results showed that the iron-overloaded mice model has been established successfully. Next we observed whether iron overload (25mg/ml) could affect the hematopoiesis of BM. The colony-forming cell assay was performed by culturing BMMNCs in MethoCult M3434 methylcellulose medium to evaluate hematopoietic progenitor cells(HPCs) proliferation function. The competitive repopulation assay and single-cell colony cultures of sorted hematopoietic stem cells (HSCs,CD34-Lin- sca1+c-kit+cells,LSK+)were used to validate HSCs function. The counts of BMMNCs have no significant difference. However, It was found that hematopoietic colony-forming unit (CFU-E, BFU-E, CFU-GM and CFU-mix) was much lower than that of normal control(P 〈 0.05)(Fig.1). Notely, the number of LSK+ cells (*103/femur) was decreased significantly in iron overload mouse (26.43±3.28) compared with normal control(40.12±5.21) and the single-cell colony formation(/60wells) was reduced significantly in iron overload mouse(28.54±3.33) compared with normal control(47.93±4.82) (P 〈 0.05). The long-term and multilineage engraftment capability of the iron-overloaded HSCs was weaken after transplantation. We then explored the possible mechanism of this inhibitory effects. Our previous studies have shown that iron overload could elevated reactive oxygen species (ROS) levels of mesenchymal stem cells and HSCs in vitro. Similarly, the intracellular ROS levels were analyzed by a flow cytometer. It was found that ROS level in iron overload BM was increased by 3.32 folds in erythroid cells, 1.51 folds in granulocytes and 4.80 folds in LSK+ cells,respectively. And also, the expression of p53, p38MAPK and p16Ink4a mRNA remained significantly elevated, which indicated that ROS related signal pathway was involved in the deficient hematopoiesis of iron overload BM. In addition, we also observed the effects of iron overload on the mice with deficient hematopoiesis exposed to 4Gy total body irradiation(TBI), which was more similar to clinical pathological conditions such as AA or MDS. It was found that BM damage caused by iron overload was aggravated in pathological conditions (primary findings were not shown). In conclusion, our study confirmed that iron overload injures the hematopoiesis of BM by enhancing oxidative stress in mice, which would be helpful to further study on the mechanism and would provide an experimental basis to find new therapeutic targets for the treatment of iron overload in patients with hematopoietic dysfunction.Figure 1Results of hematopoietic colony forming unit of different groups(*P 〈 0.05)Figure 1. Results of hematopoietic colony forming unit of different groups(*P 〈 0.05) 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: 2013
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  • 6
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1059-1059
    Abstract: Abstract 1059 Adoptive transfer of activated T and NK cells has had significant clinical benefits in certain tumor models. Cytokine induced killer (CIK) cells are a group of cells that possess both T and NK cell like recognition of target cells. These cells are generated after extensive ex vivo manipulation of PBMCs. Maintenance of not only CIK cells but other activated effector T and NK cells in culture is vital for their effective transfer and development following adoptive immunotherapy. IL-21 is the newest member of the common γ chain family which has been shown to increase cytotoxic factors and cytokine secretion in immune cells without over stimulation. Such qualities make IL-21 a suitable agent in immunotherapy of tumors. IL-21 has shown effective antitumor function and is currently going clinical trials for tumors such as renal cell carcinoma, melanoma and lymphoma. Our previous experiment showed that like in T cells and NK cells, IL-21 significantly improves the cytotoxicity of CIK cell on K562 cells and primary leukemic cells from patients. Although proliferation of cells in a CIK cell pool was not observed we found that it helped maintain and grow the CD3+ and CD56+ phenotype. Our present experiment aims to explain the mechanism through which IL-21 promotes CIK cells survival and cell cytotoxicity. In our experiment, blood from healthy donors was collected and PBMCs were transformed into CIK cells following 14 days of culture using appropriate methods. The cells were then stimulated with IL-21 for a defined period of time and subjected to MTT assays to measure cellular viability and cytotoxicity to K562 cells. To elucidate the mechanism of action of IL-21, CIK cells were checked for the level of mRNA expression of perforin, Granzyme B, FasL, INF-γ, TNF-α,Granzyme A,NKG2D, TNF-β using RT-PCR. Furthermore the expression of significantly important cytotoxic factors and cytokines was measured through flow cytometry and ELISA. Western blot was performed to check the involvement of JAK/STAT pathway following stimulation. We found that IL-21 doesn't enhance in vitro proliferation of CIK cells, but does increase the number of cells expressing the CD3+/CD56+ phenotype. IL-21 can also significantly increase the cytotoxic potential of CIK cells to K562 cells. It does so with significantly increased production of perforin which increased almost 2 folds from (0.5592±0.1457) to (0.9831±0.1265); Granzyme B also by almost 2 folds from (0.4084±0.1589) to (0.7319±0.1639) and FasL which increased by almost 2 folds from (0.4015±0.2842) to (0.7381±0.2568). Increase in secretion of cytokines such as INF-γ was observed from (25.8±6.1)ng/L to (56.0±2.3)ng/L; and TNF-α from (5.64±0.61)ug/L to (15.14±0.93)ug/L while no significant difference was observed in the expression of Granzyme A,TNF-β and NKG2D. Measurement of IL-21R receptor on CIK cell surface following IL-21 stimulation caused a more than two folds increase in expression of IL-21R from 1.88% to 4.25%. We further affirm that JAK/STAT is actively involved in IL-21 signalling. STAT3 and STAT5b could be potential signalling mechanisms taking part in IL-21 enhanced cytotoxic potential of CIK cells. Using this information we have concluded that increased expression of perforin, Granzyme B, FasL, IFN-γ and TNF-α plays a significant role in IL-21 enhanced cytotoxic potential of CIK cells and STAT-3 and STAT-5b signaling pathway are involved in the processes. Our data indicate that IL-21 is a potent enhancer of antitumor function of CIK cells. As CIK cells and IL-21 have both been shown to increase patient survival or tumor free periods in certain hematological malignancies using them in conjunction might be therapeutically more beneficial. 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
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  • 7
    Online Resource
    Online Resource
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 2097-2097
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2097-2097
    Abstract: Abstract 2097 Iron is a useful component of cytochromes, oxygen-binding molecules and some enzymes due to its capacity to accept and donate electrons readily. However, excessive iron accumulation can damage tissues and cells by catalyzing the conversion of superoxide and hydrogen peroxide to free radical species that can attack cellular membranes, proteins and DNA. Recent multiple data revealed that iron chelation therapy was effective in treating cytopenia in iron overload disease, which supported the idea that iron overload affected hematopoiesis in bone marrow(BM). Based on these findings, We demonstrated that iron overload suppressed hematopoiesis by inhibiting hematopoietic stem/progenitor cells and the effects could be restored by iron chelation or anti-oxidants(Zhao et al., Blood, 2010, 116:4247a). However, it is unclear whether iron overload can impair BM hematopoiesis by injuring the microenvironment. As an important component of the BM microenvironment, Mesenchymal stem cells (MSCs) secrete a large amount of cytokines and extracellular matrix protein which provides a favorable platform for the localization, self-renewal, and differentiation of hematopoietic stem cells. Here we hypothesize that iron overload impairs BM microenvironment by affecting the function and survival of MSCs which is mediated by ROS. In this study we first established an iron overload model of MSCs by adding ferric ammonium citrae (FAC) to the culture medium. To confirm this model, the labile iron pool (LIP) level of MSCs was detected using the calcein-AM method. We found that the LIP of MSCs was significantly higher than control and reached the highest level when cultured at 400μmol/L FAC for 12h. Next we analyzed whether iron overload can affect proliferation, apoptosis and function of MSCs by the following experiments. Firstly, the proliferation of MSCs was evaluated using population doubling time (DT). Under iron overload, the population doubling time (DT) of MSCs was 24.43± 2.72 hours, which was signifcantly longer than control(16.03± 2.31 hours; P=0.015). However, the difference wasn't significant after two passages (P=0.936). Possible explanation could be that the injury to MSCs is reversible following decreased concentration of iron after passaging. Secondly, the apoptosis of MSCs altered by iron overload was measured by staining Annexin V/PI, and we found the apoptosis rate was higher in the iron overload group(12.75±0.32%) than control (3.63±0.80%)(P 〈 0.05). Finally, mono-nuclear cells were purified from umbilical cord blood and co-cultured with MSCs to assess the hematopoiesis-supportive function of MSCs. Iron overload group showed decreased hematopoietic support capacity than control. Taken together, these findings proved iron overload impaired hematopoietic microenvironment by decreasing proliferation, inducing apoptosis and injuring the hematopoietic support capacity of MSCs. We then explored the possible mechanism that may take part in this process. It has already been reported that iron overload may result in the generation of reactive oxygen species (ROS). Similarly, we found that ROS level of MSCs could be positively correlated with the concentration of FAC and reached its highest level when cultured at 400μmol/L FAC for 12h. Finally, Western blot analysis of whole cell lysates from umbilical derived MSC using antibodies recognizing known ROS-related signaling pathways revealed robust increases in phospho-p38, p53 in response to FAC compared with control, with inhibition of these signaling pathways noted in response to NAC or GSH at suitable dose, suggesting that antioxidant can inhibit ROS-induced signaling pathway in iron overload. In conclusion, Our finding indicates that iron overload can injure hematopoiesis by enhancing oxidative stress in MSC. Our data further suggests creatively that antioxidant and cytotherapy may be an effective method in curing deficient hematopoiesis in iron overload. 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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  • 8
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  Allergy Vol. 75, No. 7 ( 2020-07), p. 1699-1709
    In: Allergy, Wiley, Vol. 75, No. 7 ( 2020-07), p. 1699-1709
    Abstract: The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has recently spread worldwide and been declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases. Methods Electronic medical records of 11 patients with COVID‐19 were collected, and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed. Results The clinical course of the eleven cases demonstrated the complexity of the COVID‐19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe. Conclusion All different clinical characteristics of COVID‐19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.
    Type of Medium: Online Resource
    ISSN: 0105-4538 , 1398-9995
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2003114-2
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  • 9
    In: Allergy, Wiley, Vol. 76, No. 2 ( 2021-02), p. 510-532
    Abstract: The pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID‐19 children with different severities and allergic status. Methods Data extracted from the electronic medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results, and radiological images of 182 hospitalized COVID‐19 children, were summarized and analyzed. Results The median age was 6 years, ranging from 3 days to 15 years, and there were more boys (male‐female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort, and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground‐glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia (manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase, and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10, and TNF‐α. There were no differences in treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing, and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID‐19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID‐19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy, and asthma. Demographics and clinical features were not significantly different between allergic and nonallergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D‐dimer, and aspartate aminotransferase levels compared with all patients. Immunological profiles including circulating T, B, and NK lymphocyte subsets, total immunoglobulin and complement levels, and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subset numbers, and serum cytokine levels. Conclusion Pediatric COVID‐19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and nonallergic COVID‐19 children in disease incidence, clinical features, and laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS‐CoV‐2 infection and hardly influenced the disease course of COVID‐19 in children.
    Type of Medium: Online Resource
    ISSN: 0105-4538 , 1398-9995
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2003114-2
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  • 10
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 48-48
    Abstract: Background: The persistence or recurrence of minimal residual disease (MRD) after chemotherapy predicts relapse of B-cell acute lymphoblastic leukemia (B-ALL). CD19-directed chimeric antigen receptor-modified T (CD19 CAR-T) cells have shown excitable response in B-ALL. Recently, some studies have shown that ALL patients with lower burden had higher CR rate and lower risk of CRS after CAR-T therapy (Park, et al, NEJM. 2018; 378(5):439-448. Lee, et al, Blood.128 (22):Abstract 218.). However, its role in chemotherapy-refractory MRD-positive B-ALL remains unclear. Here we aimed to assess the effectiveness and safety of CD19 CAR-T in MRD-positive B-ALL patients. Methods: Since January 2018, a total of 14 B-ALL patients with persistent (n=8) or recurrent (n=6) MRD were enrolled in the CAR-T clinical trials (ChiCTR-ONN- 16009862 and ChiCTR1800015164). The patients were from two different clinical trials about CAR-T. If patients were treated in an MRD positive state, they would be included in this analysis. All the patients received one or more infusions of autogenous CD19 CAR-T. Results: Median age was 37.5 (13-62) years and 7 patients were female. The median dose of infused CAR-T cells was 6.78´106cells/kg, and 5 patients received more than one infusion. After one cycle of CAR-T infusion, 12 patients achieved MRD-negative remission, leading a response rate of 85.7%. Of the subgroup of 5 Ph-positive patients who subsequently underwent transplantation, 2 patients died due to transplant-related toxic effects, whereas the other 3 patients all currently alive without leukemia. Of the subgroup of 9 Ph-negative patients, 8 patients did not undergo subsequent transplantation (Figure 1). Three patients finally suffered CD19-positive relapse and 1 patient suffered CD19-negative relapse. Importantly, 4 patients (50%) are in ongoing molecular remission without transplantation, with a duration of response averaging 22.9 months (range: 12.1-28.6 months). The most frequent adverse events were fever and hematopoietic toxicities. Ten patients (71.4%) had grade 1 or 2 cytokine release syndrome (CRS) and no patients died of CRS. At a median follow-up time of 599.5 days (range: 172-915 days), the probability of 2-year relapse-free survival and 2-year overall survival was 61.2%±14.0% and 78.6%±11.0%, respectively. Conclusion: In conclusion, pre-emptive CD19 CAR-T treatment is an effective and safe approach and may confer a sustained remission in B-ALL patients with chemotherapy-refractory MRD. 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: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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