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  • American Society of Hematology  (7)
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  • American Society of Hematology  (7)
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  • 1
    Online Resource
    Online Resource
    A Novel Oral Histone Deacetylase Inhibitor Chidamide Is Highly Effective and Well-Tolerated in Adult Early T-Cell Precursor and Ph-like Acute Lymphoblastic Leukemia
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4011-4011
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4011-4011
    Abstract: Background Early T-cell precursor (ETP) lymphoblastic leukemia (ETP-ALL) is a neoplasm with an unique T-cell immunophenotype indicating limited early T differentiation. Ph-like ALL is a B-cell neoplasm which lack BCR-ABL1 translocation but similar expression-pattern of the BCR-ABL1-positive ALL. The optimal therapeutic approaches for ETP-ALL and Ph-like ALL are poorly characterized. Chidamide is a novel and orally active benzamide class of histone deacetylase inhibitor (HDACi) and approved for peripheral T-cell lymphoma (PTCL). Methods Based on the pediatric-inspired, PEG-L-asparaginase-intensified and MRD-directed PDT-ALL-2016 protocol, we designed two open-label, one-arm, multi-site trials, PDT-ETP-ALL (NCT03553238) and PDT-Ph-Like (NCT03564470), to evaluate the safety and effect of HDACi chidamide for adult ETP-ALL and Ph-Like-ALL group, respectively. The protocols were approved by Institutional Review Broad (IRB). Chidamide at a dose of 10mg/day will be added to ETP-ALL group from induction therapy to consolidation therapy according to PDT-ETP-ALL protocol. Chidamide and dasatinib will be added to HDACi cohort and TKI cohort, respectively, based on cytogenetics and next-generation-sequencing classification, according to PDT-Ph-Like protocol. Primary study endpoint is event-free survival and secondary study endpoints are complete remission (CR) and MRD after induction, adverse event and overall survival. Result Between FEB 2016 to DEC 2017, 24 patients with ETP-ALL were enrolled into PDT-ETP-ALL trial, 4 female patients and 20 male patients, a median age 22 years old (range, 14-22 years old). A total of 33 patients with Ph-like ALL has been enrolled into PDT-Ph-Like trial, 16 female patients and 17 male patients, a median age of 23 years old (range, 14-55 years old) 11 patients in TKI arm and 22 patients in HDACi arm. Ph-like ALL with CRLF2 high-expression, CRLF2/EPO/JAK2 rearrangement, JAK/STAT/IL-7R/SH2B3 mutation, will be assigned to HDACi arm. Targeted next-generation sequencing revealed ETP-ALL patients harbor high rates of mutations in factors involved in cytokine and JAK/STAT signaling pathway (62%), epigenetic regulation (52%) and hematopoietic development (35%). At the same time, we also performed NGS assessment with the same panel of Ph-like ALL patients. Of note, ETP-ALL and Ph-like ALL share the mutations involved in JAK/STAT signaling pathway (JAK1, JAK2, IL-7R) and histone modification (SETD2, KMT2A, EZH2, KMT2C), which might indicate the underlying mechanism of sensitivity of ETP-ALL and Ph-like ALL to HDACi chidamide. Chidadmide was well-tolerated in ETP-ALL and Ph-like ALL patients. Fatigue, nausea, vomit, neutropenia and thrombocytopenia are common chidamide-associated adverse events (AE) with Common Terminology Criteria for Adverse Events (CTCAE) grade I-II. Complete remission and Flow-MRD-negative rate after induction therapy for ETP-ALL and Ph-Like-ALL were 87% and 67%, 77% and 60%, respectively. Six patients with ETP-ALL (25%, 6/24) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 11 patients with Ph-like ALL received allo-HSCT. With a median follow-up of 20 months (range, 7-31 months), estimated 2-year event-free-survival (EFS) of ETP-ALL and Ph-like ALL is 83%, 70%, respectively. Conclusion: Our preliminary data of PDT-ETP-ALL and PDT-Ph-like ALL trials suggest that a novel HDACi chidamide is effective and well-tolerated in adult ETP-ALL and Ph-like ALL, which deserve further extended clinical trial. Disclosures Zhou: CHIPSCREEN: Consultancy. Carter:novartis: Research Funding; AstraZeneca: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-99-113712
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    Efficacy and Safety of Micafungin As Salvage Treatment for Invasive Fungal Disease in Patients with Hematologic Malignancies
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 4628-4628
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4628-4628
    Abstract: Objective To explore the efficacy and safety of micafungin as salvage treatment for invasive fungal disease(IFD) in patients with hematologic malignancies. Methods A retrospective, observational, sequential cohort study was performed between Feb 2012 and June 2015 at southern medical university nanfang Hospital. We selected a group of 51 patients who either refractory or intolerant to first-line antifungal therapies, received micafungin as salvage therapy. Of the 51 patients, IFD was proven in 5 and probable in 46 patients. The predominant cause for treatment switch to micafungin was refractory therapy in 33 patients, followed by intolerance in 15 patients or both in 3 patients. For their first-line antifungal therapies of IFD, 34 patients received voriconazole, 7 patients received itraconazole, 2 patients received amphotericin B,1 patients received caspofungin,1 patients received posaconazole and 6 patients received voriconazole combined amphotericin B. The median duration of antifungal treatment before salvage therapy was 26 days (range, 4 to 57 days). The successful resolution rates、the median time of micafungin treatment, the drug related adverse events and overall survival were assessed. Results All of the patients were treated with 150 mg/d micafungin. The median time of micafungin treatment was 23 days (range,12-72 days). The success rate was 64.7%, including 16 achieved complete response, 17 achieved partial response and 18 patients had no overall response (failure in 9 patients, 2 patient with stable disease and 7 patients died). Only one patient experienced an adverse event. No patient discontinued micafungin therapy due to an adverse event. Conclusions This study demonstrated that micafungin was efficacy and safety as salvage treatment IFD in patients with hematologic malignancies. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.4628.4628
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Role of Surgical Resection in Allogeneic Hematopoietic Stem Cell Transplant Recipients with Prior Pulmonary Aspergillosis
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 5846-5846
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5846-5846
    Abstract: Backgroud: Invasive fungal disease (IFD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with a history of invasive pulmonary aspergillosis (IPA), especially those with residual pulmonary lesions at transplantation, are at high risk for IFD relapse after allo-HSCT. Since antifungal chemotherapy might be unable to eradicate IPA, surgical resection of pulmonary lesions is suggested to decrease the risk of IPA relapse. In this study, we retrospectively analyzed the outcome of patients who had persistent pulmonary cavity lesions or nodule after initial antifungal treatment. Methods: Between January 2007 and June 2014, a total of 129 patients with a history of IPA underwent allo-HSCT at Nanfang Hospital. Fourteen of these patients had persistent cavity lesions or nodule with more than 2cm in diameter in lung (cavity lesion in 10 and nodule in 4) after initial antifungal treatment ( 〉 1 month). Eight of the 14 patients underwent thoracescopic surgery before transplantation including 6 receiving wedge resections and 2 receiving lobectomies. The other 6 patients did not have surgery because of primary underlying diseases (non-complete remission) or multiple sites of lesions. The median duration of initial antifungal treatment pre-transplants were 179 days (range, 92-338 days) and 117.5 days (range, 60-132 days) in the patients with and without surgery, respectively. All the patients were given secondary antifungal prophylaxis (SAP) from the start of the conditioning until 90 days post-transplantation or until eradication of residual lesions. The SAP agents were chosen based on treatment response to initial antifungal therapy. Results: Of the 8 patients undergoing surgery, the underlying primary diseases included acute lymphoblastic leukemia in 5 and acute myelogenous leukemia in 3. The median time from diagnosis of IPA to surgery was 169.5 days (range, 73-330 days). Seven patients received related donor and 1 received unrelated donor transplantation. HLA-matched transplantation was conducted in 6 patients and HLA-mismatched transplantation was conducted in 2. Three patients received standard conditioning and 5 received intensified conditioning. In the 6 patients without surgery, the underlying primary diseases were acute myelogenous leukemia in 3, acute lymphoblastic leukemia in 2 and acute biphenotypic leukemia in 1. Five of these 6 patients underwent related donor transplantation and 1 underwent unrelated donor transplantation; HLA-matched transplants was conducted in 5 patients and HLA-mismatched transplants was conducted in 1. Standard conditioning were given in 3/6 patients and intensified conditioning in 3/6. After transplantation, none of the 8 patients with surgery experienced IFD relapse while 3 of the 6 patients without surgery experienced IFD progressing including 1 died of hemoptysis caused by IPA. The median duration of SAP after HSCT were 96 days (range, 73-119 days) in patients with surgery and 116.5 days (range, 101-183 days) in patients without surgery. The patients with surgery seemed to have the trend of low incidence of IPA relapse than those without surgery after allo-HSCT (P=0.055). Besides, the incidences f IPA relapse were comparative among the patients with surgery and those who achieved complete remission of IPA at transplantation (P=0.595). Conclusions: For patients with persistent cavity or nodules in lung, surgical resection followed by SAP might be effective to decrease the risk of IPA relapse after transplantation. Disclosures Liu: National Natural Science Foundation of China (81270647, 81300445, 81200388): Research Funding; National High Technology Research and Development Program of China (863 Program) (2011AA020105): Research Funding; National Public Health Grand Research Foundation (201202017): Research Funding; Natural Science Foundation of Guangdong Province (S2012010009299): Research Funding; the project of health collaborative innovation of Guangzhou city (201400000003-4, 201400000003-1): Research Funding; the Technology Plan of Guangdong Province of China (2012B031800403): Research Funding; the project of the Zhujiang Science & Technology Star of Guangzhou city (2013027): Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.5846.5846
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    Online Resource
    Online Resource
    Imatinib Mesylate Versus Allogeneic Hematopoietic Stem Cell Transplantation For Patients With Chronic Myeloid Leukemia In Chronic Phase
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 5518-5518
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5518-5518
    Abstract: Following the introduction of the tyrosine kinase inhibitor (TKI) imatinib in treatment of chronic myeloid leukemia (CML) patients, the allogeneic hematopoietic stem cell transplantation (allo-HSCT) scene in CML has changed dramatically. This retrospective cohort study was designed to compare medical outcomes of Imatinib mesylate and allo-HSCT for patients with CML in chronic phase. Patients and Methods From February 2002 to February 2012, 198 patients treated consecutively at the Nanfang Hospital,Southern Medical University were assigned to two groups according to treatment with imatinib or allo-HSCT. One hundred fifteen cases of imatinib group were given imatinib at an initial dose of 400mg daily and the dose was then adjusted according to the patient´s blood and therapy response. All the patients were evaluated for hematologic, cytogenetic and molecular response every 1-3months. Eighty-three cases of allo-HSCT group received myeloablative preconditioning regimen, and methotrexate (MTX) and cyclosporine A (CsA) were used for graft-versus-host disease(GVHD), parts combined with mycophenolate mofetil (MMF) and antihuman thymocyte globulin(ATG). The primary end points of the study were complete cytogenetic response (CCyR), relapse rate, overall survival (OS) and progression-free survival (PFS) after therapy. Results In total, 59 (68.9%) patients treated over 12 months achieved a CCyR after 12 months in imatinib group, while 67 (95.7%) patients in allo-HSCT group. The relapse rates were 14.8% (n=17) in imatinib group and 10.8% (n=9) in allo-HSCT group (P=0.456). Ten-year cumulative OS rates were 93.9% in imatinib group and 77.1% in allo-HSCT group(P=0.015) and ten- year cumulative PFS rates of two groups were 86.1% vs.88.0%(P=0.508). For Sokal rating stratified analysis, the ten-year OS rates of two groups were 96.4% vs.68.0% (P = 0.049) for high-risk patients,92.6% vs. 57.1% (P = 0.019) for intermediate-risk patients , while the ten-year PFS rates of two groups were 89.3% vs. 88.0% for high-risk patients (P = 0.942), 70.4% vs. 85.7% for intermediate-risk patients (P = 0.405).The ten-year OS rates and PFS rates were not significant difference for low-risk patients. The cumulative OS rates of two groups were 94.7% vs. 73.5%(P=0.019)for the patients who were not less than 30 years old,and the cumulative PFS rates of two groups were 84.2% vs. 94.1% respectively (P=0.147). Conclusion Imatinib mesylate treatment is superior to allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in chronic phase. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.5518.5518
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    The E3 Ubiquitin Ligases Siah2 Contributes To Imatinib Resistance In Chronic Myeloid Leukemia In Hypoxia Condition
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 2530-2530
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2530-2530
    Abstract: Severe hypoxia has been shown to favor the self-renewal of human hematopoietic stem cells. Recent studies demonstrate that hypoxia via hypoxia-inducible factor (Hif-1a) can modify the proliferation and differentiation of CML stem cells. The ubiquitin E3 ligase SIAH2 is an important regulator of the hypoxic response as it leads to the ubiquitin/proteasomal degradation of prolyl hydroxylases such as PHD3, which in turn increases the stability of Hif-1a. The Hif-1a has been linked to chemosensitivity while the underlying molecular mechanism remains elusive. Therefore, we comprehensively analysed SIAH2 and Hif-1a role in determining chemosensitivity via signal molecule vascular epithelial growth factor (VEGF) pathway. Methods We tested the level of Siah2, Hif-1a and VEGF in Imatinb-sensitive CML Patients (n=15) and insensitive CML patients(n=10) by real-time reverse transcription PCR and western blot analysis. K562-wild type (K562-W) and K562-imatinib-resistance type (K562-R) cell were cultured for 24h and 48h under the condition of normal and hypoxia concentration of oxygen (1%). Knockdown of SAIH2 by RNA interference ,Cell viability and IC50 under 1% concentration oxygen were tested by cck-8;detected cell cycle and apoptosis by flow cytometry (FCM) ; analyzed the expression levels of Siah2, Hif-1a and VEGF respectively by real-time PCR and western blot. Results The level of mRNA and protein of SIAH2 ,Hif-1a and VEGF were significantly higher in IM- resistant CML patients compared to IM sensitive CML patients, respectively (P 〈 0.05). The similar results were observed in K562-R and K562-W cells(P 〈 0.01). Under 21%,1% oxygen concentration cultured for 24h ,the IC50 of K562-W and K562-R cells was no significant difference (P 〈 0.05),but there was significant difference after cultured for 48h Cell cycle analysis showed that more G0/G1 cells in K562-R than K562-W after cultured for 48h under hypoxia condition(P 〈 0.05). After being cultured in 1% oxygen concentration for 48 hours, we confirmed SIAH2, Hif-1a and VEGF were up-regulated in both cell lines, moreover, it was more obvious in K562-R cells. In SIAH2-sh K562-R cells, the apoptosis was higher than K562-R cells obviously under 1% oxygen concentration for 48 hours(P 〈 0.05);the level of Hif-1a Hardly monitored, and the level of VEGF was also lower. Conclusions There were higher level of SIAH2, Hif-1a and VEGF in IM-resistant CML patients. Under hypoxia condition, K562 cells were likely to improve their resistance to Imatinib .After we Knockdown SAIH2, K562-R Cell apoptosis rate increased significantly, along with low level Hif-1a and VEGF. It indicated that in hypoxia micro-environment, Siah-2 might be one of the critical molecules that induce Imatinib-resistance in CML in the way of maintaining leukemic cell survival and stimulating them into quiescence phase. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.2530.2530
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    Online Resource
    Online Resource
    A Multicenter Randomized Non-Inferiority Study of Homoharringtonine Versus Etoposide in Induction Phase for Chinese Childhood Acute Myeloid Leukemia - a Report from China Children's Leukemia Group (CCLG)
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1356-1356
    Details
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1356-1356
    Abstract: Purpose: Classical introduction therapy of etoposide combined with cytarabine and daunorubicin (DAE) is commonly applied in childhood acute myeloid leukemia (AML), but etoposide has an increasing risk of secondary cancer. In this study the non-inferiority effect of homoharringtonine (H) versus Etoposide was compared in induction phase for Chinese childhood AML treated by CCLG-AML 2015 protocol. Patients and Methods: The total of 818 childhood AML patients (median age of 80 months; range from 1 to 193 months) from CCLG-AML 2015 study group (40 centers) were randomly allocated to two induction arms of DAE and DAH. During the course of induction I, 467 patients in DAE group received daunorubicin and cytarabine (DA) plus etoposide (D: 40 mg/m2 per day on days 1, 3 and 5; A: 100 mg/m2 every 12 hours from day 1 to 7; E: 100 mg/m2 per day from days 1 to 5), and 351 patients in DAH group received the same DA does plus homoharringtonine ( H: 3 mg/m2 per day from days 1 to 5). During the course of induction II, Idarubicin (10 mg/m2 per day on days 1, 3 and 5) was used to instead of daunorubicin, and patients accepted corresponding IAE or IAH treatment. All patients were divided into standard, intermediate or high risk group (SR, IR or HR group) according to CCLG-AML 2015 regimen (table 1). They were assessed by bone marrow (BM) aspiration and morphologically defined complete remission (CR: blasts ≤5%), partial remission (PR: blasts between 6~19%), or non-remission (NR: blasts ≥20%) on days 28 of induction. Results: DAH/IAH group showed non-inferiority for remission rates both in induction Ⅰ (DAE 70.2% vs DAH 76.6%, P = 0.041) and induction Ⅱ (IAE 79.4% vs IAH 87.7%, P = 0.016). Total CR rate at end of induction Ⅰ reached 73.0% and it didn't differ between DAE and DAH group for IR or HR group (IR group: DAE, 73.9% vs. DAH, 77.3%, P = 0.529; HR group: DAE, 53.9% vs. DAH, 62.6%, P = 0.128). But for SR group, CR rate of DAH group is significantly higher than DAE group (DAE, 85.1% vs. DAH, 95.1%, P = 0.013). It has similar results after induction Ⅱ. Total CR rate reached 83.1% and all patients has almost gained CR/PR for SR or IR group, only 2 patients still couldn't obtain remission. There was no significant difference in SR or IR group between two arms, but for HR group, CR rate significantly increased in those who accepted IAH chemotherapy (SR group: IAE, 91.2% vs. IAH, 95.0%, P = 0.398; IR group: IAE, 87.1% vs. IAH, 92.5%, P = 0.275; HR group: IAE, 66.1% vs. IAH, 78.8%, P = 0.050). Conclusion: Homoharringtonine is an effective cytotoxic drug and DAH regimen showed non-inferiority induction effect compared with classical DAE regimen in childhood AML, especially for patients of standard risk group. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2019-127932
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    Online Resource
    Online Resource
    Development of a Pegylated Dimeric Recombinant Factor VIII-Fc Fusion Protein for the Treatment for Hemophilia a Patients
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 3783-3783
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 3783-3783
    Abstract: Hemophilia A is a hereditary bleeding disorder resulting from reduced factor FVIII activity. It occurred in 1/5000 male. Currently, the treatment option is with the factor FVIII replacement therapy. A long-acting recombinant monomeric FVIII-Fc fusion protein product (Eloctate®) has been approved in 2014 by the US FDA, it requires to infuse the drug for every 3 days or twice a week. There is a clinical need to develop longer half-life product to extend the treatment option to once a week infuse for hemophilia A patients. Recently, we have developed a dimeric recombinant factor VIII-Fc (drFVIII-Fc) fusion protein therapeutic candidate, which is entering the clinical development in China. To generate a longer half-life recombinant FVIII product, we have developed a PEGylation method to PEGylated this drFVIII-Fc fusion protein to PEGdrFVIII-Fc. We have analyzed and characterized the fusion protein by various analytic methods, as well as in vivo animal tests. It was shown that PEGdrFVIII-Fc fusion protein has been modified with about five Y type of 40kd PEG; the remaining activity is around 700 IU/mg, and the in vivo tests in cynomolgus monkey demonstrated that the fusion protein has a half-life of about 37 hours. The data also showed that there was no detectable affinity binding activity of vWF to a PEGdrFVIII-Fc fusion protein, as compared with the binding activity of 5.16X10-4M for the molecule of a drFVIII-Fc fusion protein. In conclusion, we are able to generate a PEGylated form of a drFVIII-Fc molecule with the relevant specific activity and has been shown the molecule with the prolonger half-life in the in vivo tests. The further biochemical analysis demonstrated PEGdrFVIII-Fc fusion protein with no detectable vWF binding activity, which might explain why its half-life is longer than vWF's ~15hours half-life in vivo. This molecule is likely to be used as a once-weekly treatment option for hemophilia A patients. Currently, we are in the development stage of an IND filing in China. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-99-112030
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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