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Littérature scientifique sur le sujet « Hematological malignancie »

Auteur : Grafiati

Publié le 14 mars 2023

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Articles de revues sur le sujet "Hematological malignancie"

Miao, Miao, Wu Depei, Aining Sun, Ying Wang, Lingzhi Yan et Qian Wu. « The Efficacy and Safety of Recombinant Human Thrombopoietin in Patients with Hematological Malgnancies After Allogeneic Hematopoietic Stem Cell Transplantation ». Blood 118, n^o 21 (18 novembre 2011) : 4565. http://dx.doi.org/10.1182/blood.v118.21.4565.4565.

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Abstract Abstract 4565 OBJECTIVE: To evaluate the efficacy and sefety of recombinant human thrombopoietin(rhTPO) prior to engraftment in adults with hematological malignancie who received allogeneic haematopoietil stem cell transplantation(Allo-HSCT). METHODS: This sutdy was a randomized, controlled clinical trial,38 patients were hematological malignancie, inclulding acute and chrinic myeloid leukemia, acute lymphoblastic leukemia, lymphoma.They received Allo-HSCT and were randomly divided into groups(group A 19 cases, group B 19 cases).The group A was no-rhTPO as control, the group B were received rhTPO 15000U/d from +1 day, and continued until the untransfused platelet count was >70×109/L for two consecutived days. Patients received platelete transfusion when they developed severe thrombocytopenia<20×109/L. Efficacy and sefety of rhTPO on the outcome of Allo-HSCT were evaluated. RESULTS: In both group A and B, platelet decrease after Allo-HSCT had no sognificant difference. The platelet engraftment duration of group A and B was 15.68±1.36(range 11–31) days and 13.47±0.72(range 9–21) days, respectively. The amount of platelet transfusion of group A and B was 4±0.55(range 20–130) units and 2.89±0.36(range 0–50) units, respectively. The effects of rhTPO on neutrophil engraftment, hepatic function, renal function, alloergic reations and acute GVHD were not found. CONCLUSION: The platelet engraftment duration of group B was shorter than that of group A(t=27.2, p<0.001), the amount of need platelet transfusion was significently less than those in the group A.There was a statistically significant difference in platelet engraftment and platelet transfusion needed(t=2.523, p<0.05). Administration of rhTPO prior to platelet engraftment after Allo-HSCT seem to be efficacy and safe. Disclosures: No relevant conflicts of interest to declare.

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Dong, L., X.-Y. Zhai, Y.-L. Yang, L. Wang, Y. Zhou, H.-Y. Shi, B.-H. Tang et al. « P110 Population pharmacokinetics and dosing optimisation of imipenem in children with haematological malignancie ». Archives of Disease in Childhood 104, n^o 6 (17 mai 2019) : e63.3-e63. http://dx.doi.org/10.1136/archdischild-2019-esdppp.148.

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BackgroundImipenem/cilastatin is widely used for the treatment of children with serious infections. Currently, there is lack of pharmacokinetic studies of imipenem in children with hematological malignancies. Given the significant impact of disease on pharmacokinetics and increased resistance, we aimed to conduct a population based pharmacokinetic study of imipenem and optimize the dosage regimens for this vulnerable population.MethodsAfter treated with IMP/CS, blood samples of children were collected and the concentration of imipenem were quantified using HPLC-UV. Then, population level pharmacokinetic analysis was conducted using NONMEM software.ResultsData from 56 children (age range: 2.03–11.82 years) with haematological malignancies were collected to conduct a population based pharmacokinetic analysis. In this study, a two-compartment model that followed first-order elimination was found to be best suitable. The parameters of current weight, age and creatinine elimination rate were significant covariates that influenced imipenem pharmacokinetics. As a result, 52.0%, 65.2% and 76.6% of children reached the pharmacodynamic target (70% fT>MIC) against sensitive pathogens with an MIC of 0.5 mg/L at 15, 20 and 25 mg/kg q6h of imipenem, respectively. However, only 17.2% of children achieved the pharmacodynamic target against Pseudomonas aeruginosa with an MIC of 2 mg/L at a dose of 25 mg/kg q6h.ConclusionPopulation pharmacokinetics of imipenem was assessed in children. The current dosage regimens of imipenem are underdose for resistant pathogens including Pseudomonas aeruginosa and Acinetobacter baumannii. However, for sensitive pathogens, imipenem has an acceptable pharmacodynamic target rate at a dosage of 25 mg/kg q6h.Disclosure(s)Nothing to disclose.

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Zinzani, Pier Luigi, Enrico Derenzini, Cinzia Pellegrini, Luigi Rigacci, Alberto Fabbri, Federica Quirini, Vittorio Stefoni et al. « Fludarabine and Mitoxantrone Followed by Yttrium-90 Ibritumumab Tiuxetan in Untreated Patients with Follicular Lymphoma. Long Term Efficacy and Toxicity Results of the FLUMIZ Trial. » Blood 118, n^o 21 (18 novembre 2011) : 1604. http://dx.doi.org/10.1182/blood.v118.21.1604.1604.

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Abstract Abstract 1604 We previously reported the results of a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus radioimmunotherapy (RIT) [FLUMIZ (Fludarabine, Mitoxantrone, Zevalin) trial], demonstrating that this combination was safe and very effective in untreated patients with follicular non-Hodgkin lymphoma. We are now providing long term efficacy and toxicity results of this combination strategy. Sixty-one patients with stage III and IV untreated follicular lymphoma were enrolled between June 2004 and April 2006, at 13 Italian institutions. Briefly, treatment schedule was the following: oral fludarabine 40 mg/m2 on days 1–3, intravenous mitoxantrone 10 mg/m2 on day 1 every 28 days for six cycles, followed by one course of yttrium-90 (90Y)-labelled ibritumumab tiuxetan (Zevalin), which consisted in two weekly infusions of Rituximab 250 mg/m2 followed by a weight based dose of 90Y-ibritumumab tiuxetan. Primary endpoints at the time of the first analysis were complete response and hematological toxic effects, secondary endpoints were overall survival (OS) and progression free survival (PFS). Fifty-seven patients were treated with RIT after the completion of six courses of fludarabine and mitoxantrone (FN) regimen. Four patients were excluded because of disease progression (n=1) and bone marrow infiltration > 25% (n=3) at the end of the FN regimen. Median follow up at the time of the last analysis was 52 months (range 24–75). Five-year PFS was estimated to be 68%, 5-year OS was estimated to be 93.0%. Noteworthy, late hematological side effects such as myelodisplastic syndromes or acute myeloid leukemias have not been observed so far. All patients had a complete hematological recovery after the completion of the sequential treatment. 16 patients relapsed during the follow-up period and 4 patients died due to disease progression. 22 patients (38%) are in first complete remission after more than 4 years of follow-up. All relapsed patients underwent second line chemotherapy and high dose chemotherapy with stem cell rescue was performed in 4 patients. These results confirm the long term efficacy and safety of 6 cycles of fludarabine and mitoxantrone followed by consolidation with 90Y-ibritumumab tiuxetan: the 5-year PFS and OS compare favourably with the results of chemoimmunotherapy alone in untreated follicular lymphoma, with no increased incidence of secondary hematologic malignancie Disclosures: No relevant conflicts of interest to declare.

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Clemmensen, Signe B., Jennifer R. Harris, Jonas Mengel-From, Wagner H. Bonat, Henrik Frederiksen, Jaakko Kaprio et Jacob v. B. Hjelmborg. « Familial Risk and Heritability of Hematologic Malignancies in the Nordic Twin Study of Cancer ». Cancers 13, n^o 12 (16 juin 2021) : 3023. http://dx.doi.org/10.3390/cancers13123023.

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We aimed to explore the genetic and environmental contributions to variation in the risk of hematologic malignancies and characterize familial dependence within and across hematologic malignancies. The study base included 316,397 individual twins from the Nordic Twin Study of Cancer with a median of 41 years of follow-up: 88,618 (28%) of the twins were monozygotic, and 3459 hematologic malignancies were reported. We estimated the cumulative incidence by age, familial risk, and genetic and environmental variance components of hematologic malignancies accounting for competing risk of death. The lifetime risk of any hematologic malignancy was 2.5% (95% CI 2.4–2.6%), as in the background population. This risk was elevated to 4.5% (95% CI 3.1–6.5%) conditional on hematologic malignancy in a dizygotic co-twin and was even greater at 7.6% (95% CI 4.8–11.8%) if a monozygotic co-twin had a hematologic malignancy. Heritability of the liability to develop any hematologic malignancy was 24% (95% CI 14–33%). This estimate decreased across age, from approximately 55% at age 40 to about 20–25% after age 55, when it seems to stabilize. In this largest ever studied twin cohort with the longest follow-up, we found evidence for familial risk of hematologic malignancies. The discovery of decreasing familial predisposition with increasing age underscores the importance of cancer surveillance in families with hematological malignancies.

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Asare, Mariette, Jeanne E. Hendrickson et Christopher A. Tormey. « Determination of Red Blood Cell Alloimmunization Rates in Transfused Patients with Hematologic and Oncologic Malignancies ». Blood 128, n^o 22 (2 décembre 2016) : 1463. http://dx.doi.org/10.1182/blood.v128.22.1463.1463.

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Abstract Introduction: Patients with hematological and oncological malignancies are among the most frequent recipients of chronic red blood cell (RBC) transfusion therapy. One of the risks associated with chronic RBC exposure is the development of blood group antibodies. However, there are few extensive studies of alloimmunization rates associated with hematological or oncological malignancies in adult patients despite the frequency with which they are transfused. As such, the aims of this study were: 1) to determine the alloimmunization rate associated with malignant conditions in general, 2) to establish and compare alloimmunization rates for individuals with different forms of hematological and oncological neoplasia, and 3) to determine if any oncological disorder(s) appeared to predispose individuals to alloimmunization such that antibody mitigation measures could be employed for these diagnoses. Methods: Patients included were those undergoing type and screen testing at the study site (n=18,750 unique, active subjects in our facility's transfusion record database). For each of these subjects, the electronic medical record was retrospectively reviewed to determine if a history of a hematologic or oncologic malignancy was present. Disorders grouped as 'hematologic malignancies' in this study included: acute leukemia (myeloid or lymphoid), mast cell diseases, multiple myeloma, myelodysplastic syndromes, myeloproliferative disorders, and non-Hodgkin lymphoma (T- or B-cell). 'Non-hematologic' cancers in this study were broadly grouped as follows: bladder, colon, head/neck, lung, prostate, skin, soft tissue/sarcoma. If a patient had a history of any of the above neoplastic diseases, further inclusion in the study required: 1) that the patient undergo at least one RBC unit transfusion after their diagnosis was established and 2) that at least one follow-up antibody screen test be performed after their first RBC transfusion post-diagnosis. When these additional inclusion criteria were met, the following data were collected for each subject: malignancy type, race/ethnicity, gender, and the number and specificity of antibodies detected. Ratio data were compared using the chi-square test with Yates' correction for continuity; P values <0.05 were considered significant. Results: A total of 69 patients became alloimmunized after their diagnosis of a malignancy; these patients were overwhelmingly male (66/69; 95.7%) and most identified as white, non-Hispanic (50/69; 72.5%). The alloimmunization rate among patients with any malignancy diagnosis was 1.5% (69/4687), which was significantly lower than the general, historical alloimmunization rate at our facility (443/18750; 2.4%; P=0.0019). Of total transfused patients with a malignancy, most were diagnosed with a non-hematological disorder(4371/4687; 93.3%) and such malignancies were associated with an alloimmunization rate of 1.3% (55/4371) following transfusion. By comparison, the alloimmunization rate for transfused patients with hematological malignancies was 2.8% (14/501), which was significantly higher (P=0.011). When alloantibody development was analyzed on a disorder-by-disorder basis, the five highest alloimmunization rates were seen in: myelodysplastic syndromes (8/71; 11.2%), soft tissue cancers (3/50; 6.0%), acute leukemia (1/34; 2.9%), renal cancer (3/113; 2.7%), and myeloproliferative disorders (2/75; 2.7%). Alloimmunization rates under 2% were observed for all other hematological and non-hematological malignancies encountered in our patient population. Conclusions: RBC alloimmunization rates in transfused patients with malignancy were significantly lower than historical controls, suggesting that the immunosuppressive nature of these disorders and/or their associated therapies may play a role in limiting blood group antibody development. Hematologic disorders were associated with higher alloimmunization rates than non-hematologic malignancies, which may reflect a larger transfusion burden in these illnesses (a factor to be evaluated in future analyses). Overall, only myelodysplastic syndromes and soft tissue malignancies were associated with antibody formation rates substantially higher than historical controls. Therefore, consideration for prophylactic antigen matching to prevent alloimmunization may be warranted for these conditions. Disclosures No relevant conflicts of interest to declare.

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Liao, Yongkang, Shijun Xiong, Zaid Ur Rehman, Xiaoli He, Hongling Peng, Jing Liu et Shuming Sun. « The Research Advances of Aptamers in Hematologic Malignancies ». Cancers 15, n^o 1 (1 janvier 2023) : 300. http://dx.doi.org/10.3390/cancers15010300.

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Currently, research for hematological malignancies is very intensive, with many breakthroughs. Among them, aptamer-based targeted therapies could be counted. Aptamer is a targeting tool with many unique advantages (easy synthesis, low toxicity, easy modification, low immunogenicity, nano size, long stability, etc.), therefore many experts screened corresponding aptamers in various hematological malignancies for diagnosis and treatment. In this review, we try to summarize and provide the recent progress of aptamer research in the diagnosis and treatment of hematologic malignancies. Until now, 29 aptamer studies were reported in hematologic malignancies, of which 12 aptamers were tested in vivo and the remaining 17 aptamers were only tested in vitro. In this case, 11 aptamers were combined with chemotherapeutic drugs for the treatment of hematologic malignancies, 4 aptamers were used in combination with nanomaterials for the diagnosis and treatment of hematologic malignancies, and some studies used aptamers for the targeted transportation of siRNA and miRNA for targeted therapeutic effects. Their research provides multiple approaches to achieve more targeted goals. These findings show promising and encouraging future for both hematological malignancies basic and clinical trials research.

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Yang, Xiao-Jing, Ya-Ming Xi et Zi-Jian Li. « Icaritin : A Novel Natural Candidate for Hematological Malignancies Therapy ». BioMed Research International 2019 (28 mars 2019) : 1–7. http://dx.doi.org/10.1155/2019/4860268.

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Hematological malignancies including leukemia and lymphoma can severely impact human health. With the current therapies combined with chemotherapy, stem cell transplantation, radiotherapy, and immunotherapy, the prognosis of hematologic malignancies improved significantly. However, most hematological malignancies are still incurable. Therefore, research for novel treatment options was continuing with the natural product as one source. Icaritin is a compound extracted from a traditional Chinese herb,Epimedium Genus, and demonstrated an antitumor effect in various neoplasms including hematological malignancies such as leukemia, lymphoma, and multiple myeloma. In hematological malignancies, icaritin showed multiple cytotoxic effects to induce apoptosis, arrest the cell cycle, inhibit proliferation, promote differentiation, restrict metastasis and infiltration, and suppress the oncogenic virus. The proved underlying mechanisms of the cytotoxic effects of icaritin are different in various cell types of hematological malignancies but associated with the critical cell signal pathway, including PI3K/Akt, JAK/STAT3, and MAPK/ERK/JNK. Although the primary target of icaritin is still unspecified, the existing evidence indicates that icaritin is a potential novel therapeutic agent for neoplasms as with hematological malignancies. Here, in the field of hematology, we reviewed the reported activity of icaritin in hematologic malignancies and the underlying mechanisms and recognized icaritin as a candidate for therapy of hematological malignancies.

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Ren, Anqi, Xiqin Tong, Na Xu, Tongcun Zhang, Fuling Zhou et Haichuan Zhu. « CAR T-Cell Immunotherapy Treating T-ALL : Challenges and Opportunities ». Vaccines 11, n^o 1 (12 janvier 2023) : 165. http://dx.doi.org/10.3390/vaccines11010165.

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T-cell acute lymphoblastic leukemia (T-ALL), a form of T-cell malignancy, is a typically aggressive hematological malignancy with high rates of disease relapse and a poor prognosis. Current guidelines do not recommend any specific treatments for these patients, and only allogeneic stem cell transplant, which is associated with potential risks and toxicities, is a curative therapy. Recent clinical trials showed that immunotherapies, including monoclonal antibodies, checkpoint inhibitors, and CAR T therapies, are successful in treating hematologic malignancies. CAR T cells, which specifically target the B-cell surface antigen CD19, have demonstrated remarkable efficacy in the treatment of B-cell acute leukemia, and some progress has been made in the treatment of other hematologic malignancies. However, the development of CAR T-cell immunotherapy targeting T-cell malignancies appears more challenging due to the potential risks of fratricide, T-cell aplasia, immunosuppression, and product contamination. In this review, we discuss the current status of and challenges related to CAR T-cell immunotherapy for T-ALL and review potential strategies to overcome these limitations.

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YAEGASHI, HIROSHI, TAKAHIRO NOHARA, KAZUYOSHI SHIGEHARA, KOUJI IZUMI, YOSHIFUMI KADONO, TOMOYUKI MAKINO, KANAME YAMASHITA, KOUSHIRO OHTSUBO, HIROKO IKEDA et ATSUSHI MIZOKAMI. « Survival Outcomes of Patients With Primary Mediastinal Germ Cell Tumors : A Retrospective Single-institutional Experience ». Cancer Diagnosis & ; Prognosis 2, n^o 3 (3 mai 2022) : 352–59. http://dx.doi.org/10.21873/cdp.10116.

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Background/Aim: Primary mediastinal non-seminomatous germ cell tumors (PMNSGCTs) are occasionally complicated by a hematologic malignancy, as with somatic-type malignant tumors called germ cell tumors with somatic-type malignancy (GCTSTM) and are known to have a poor prognosis. Patients and Methods: Data obtained between September 1997 and February 2020 for patients with mediastinal germ cell tumor at our institution were retrospectively analyzed. Key outcome measures included survival rates and the clinical features of non-seminoma cases. Results: Of 16 patients, 9 had pure seminoma, and 7 had non-seminoma. At the median follow-up of 56.2 months, the 5-year survival rate was significantly higher in patients with seminoma (100%) than in those with non-seminoma (37%) (log-rank test, p=0.0153). Regarding PMNSGCT, two patients evolved into GCTSTM and three had concomitant hematological malignancies. Conclusion: Patients with PMNSGCTs, GCTSTM complications, and hematologic malignancies showed poor survival, suggesting the need for the development of treatment strategies.

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Krishnan, Gayathri, et Anupam Pande. « 985. Fusarium Infections in Patients with Hematological Malignancies ». Open Forum Infectious Diseases 8, Supplement_1 (1 novembre 2021) : S583—S584. http://dx.doi.org/10.1093/ofid/ofab466.1179.

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Abstract Background Fusarium is a ubiquitous mold that can cause invasive and disseminated fusariosis in immunosuppressed patients, especially those with hematological malignancies. The risk factors associated with mortality of patients with Fusarium infections have not been adequately assessed in literature. In this study, we sought to explore the characteristics, clinical outcomes, and risk factors for mortality in Fusarium infections in patients with hematological malignancies. Methods This is a retrospective study of adult hematological malignancy patients admitted to surgical/medical wards or critical units at an academic medical center from January 2010 to January 2021 and diagnosed with proven invasive Fusarium infections through positive microbiological culture data from a biopsy, surgical specimen or sterile site. Primary end point was 30-day mortality. Statistical analysis was done using Fischer’s exact test and Mann-Whitney U test. Results 31 patients with hematological malignancies were identified with proven Fusarium infections during the 10-year period (13,390 total unique patients with diagnosis of hematologic malignancies). Two were excluded due to incomplete data. Demographic characteristics, type and status of hematological malignancy, chemotherapy, exposure to steroids, neutropenia, lymphopenia, antifungal prophylaxis, and other factors were analyzed. Mean age at diagnosis was 52.6 years. 16/29 (55.2%) had undergone stem cell transplant prior to infection with median duration of 150.5 days (range 12 to 1503) prior to infection. The most common pathologies were invasive sinusitis and disseminated cutaneous infection in 13/29 (44.8%) patients. Blood culture was positive in 5/29 (17.2%). Overall mortality was 86.2% with 30-day mortality of 44.8% and 1-year mortality of 83%. Death was attributed to fusariosis in 12/25 (48%). Median duration to death was 56 days (range 2 to 1627 days). Risk factors for 30-day mortality were assessed (table 1). The table describes risk factors for 30-day mortaity for fusarium infections in patients with hematological malignancies. statistical analysis done using fischer’s exact test Conclusion Fusarium infections result in morbidity and mortality in patients with hematological malignancies. A variety of host and disease factors dictate eventual outcome of Fusarium infections in these patients. Lack of neutrophil recovery is a significant risk factor for 30-day mortality in this population. Disclosures All Authors: No reported disclosures

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Thèses sur le sujet "Hematological malignancie"

Akarca, Ayse. « Immunohistochemical studies for identification of biomarkers in haematological malignancies : An approach for potential novel therapeutic targets ». Doctoral thesis, Università di Siena, 2021. http://hdl.handle.net/11365/1127626.

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Lymphoid neoplasms are a subgroup of haematological malignancies that affect circulating lymphocytes. The clinical and biological heterogeneity of lymphoid neoplasms can lead to difficulty in accurate diagnosis in this group of diseases. The advancement in effective and feasible detection platforms has enabled novel biomarkers to improve diagnosis and prognosis, in addition to assist in patient stratification and personalised treatments for these diseases. Although there have been improvements in high-throughput diagnostic techniques, the conventional immunohistochemistry (IHC) remains the most widely used platform for biomarker assessment in the field of tissue pathology. As this conventional technique has certain limitations, multiplex IHC (MIHC) approaches have found ways to overcome these challenges, therefore becoming the main focus of immunotherapy for lymphoid neoplasms. This particular effective and proficient technology can simultaneously target multiple molecule/protein of interest within the tumor microenvironment to determine the status of immune cell activation and the presence of protein expression. MIHC is advantageous in providing information about the underlying immune evasion mechanisms, which play a vital role in the development of prognostic and diagnostic biomarkers. This thesis focuses on the novel use of IHC/MIHC approaches and their current role in biomarker development to be used in diagnosis, prognosis, and the potential treatment strategies within haematological malignancies in specific lymphoid neoplasms.

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Schouten, Hendricus Constantinus. « Chromosomal abnormalities in hematological malignancies ». Maastricht : Maastricht : Datawyse ; University Library, Maastricht University [Host], 1991. http://arno.unimaas.nl/show.cgi?fid=5640.

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Runarsson, Gudmundur. « Biosynthesis of leukotriene B₄ in hematological malignancies / ». Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-386-8/.

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Gorkin, David Uscher. « Hematological malignancies : the possible role of BCL11A ». Thesis, Boston University, 2004. https://hdl.handle.net/2144/32867.

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Thesis (B.A.)--Boston University. University Professors Program Senior theses.
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
2031-01-01

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Buldini, Barbara. « Flow cytometry application in hematological malignancies of childhood ». Doctoral thesis, Università degli studi di Padova, 2008. http://hdl.handle.net/11577/3425984.

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The PhD research work was performed, for the first part (1 year) at the Pediatric Haematology-Oncology Department, Fondazione IRCCS Policlinico San Matteo, Pavia University and for the second part (2 years) at the Pediatric Haematology-Oncology Department, Padova University, two excellent setting for a specialized training in pediatric haematology-oncology. The PhD program was targeted in both a clinical and laboratory research experience in order to perform a translational research on pediatric patients affected by a wide range of hematological disorders, both malignant and non-malignant. The efforts were coordinated to study the biology and therapy of pediatric Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS).

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Kim, Mee Hye. « Optimisation and application of comparative genomic hybridisation (CGH) in cancer cytogenetics ». Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272858.

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Cherif, Honar. « Infections in patients with hematological malignancies : etiology, trends and management / ». Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-501-1/.

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Hishizawa, Masakatsu. « Identification of tumor-associated antigens in hematological malignancies by SEREX ». Kyoto University, 2006. http://hdl.handle.net/2433/143835.

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Romano, Alessandra. « High resolution molecular karyotyping and proteomic analysis in hematological malignancies ». Thesis, Universita' degli Studi di Catania, 2011. http://hdl.handle.net/10761/96.

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Il presente lavoro di tesi ha applicato i risultati della genomica funzionale in termini traslazionali a due neoplasie ematologiche: le sindromi mielodislastiche (MDS), e il loro potenziale ventaglio di evoluzione a leucemia mieloide acuta, e l'altrettanto ampio spettro di gammopatie monoclonali, fino alla condizione di mieloma multiplo (MM). In entrambi i casi, infatti, le recenti acquisizioni derivanti dall`applicazione dei nuovi farmaci hanno evidenziato la necessita' di indirizzare l`approccio terapeutico contemporaneamente alle cellule neoplastiche e a quelle del microambiente. Nelle MDS l`ultima generazione delle piattaforme Affymetrix, capace di identificare polimorfismi di singoli nucleotidi (SNP) e alterazioni del numero di copie (CNA) sul genoma e' stata utilizzata al fine di identificare CNA somatici e germinali associati a tumore e perdite di eterozigosita' (LOH) e piu in gerale anomalie genomiche ricorrenti, particolarmente nelle MDS ad alto rischio di trasformazione in leucemie mieloidi acute. Un singolo paziente e' stato studiato nel tempo seguendo l'evoluzione clinica della sua MDS in leucemia acuta, con l'obiettivo di definire le univoche caratteristiche del clone neoplastico attraverso un approccio bioinformatico. Per il MM, abbiamo sviluppato un saggio ex-vivo capace di identificare il segnale associato a trattamenti diversificati di campioni di midollo a fresco, confermando come in ogni paziente si abbia un pattern singolare di attivazione, in presenza di una risposta generalmente differenziata tra plasmacellule neoplastiche ed elementi del microambiente. Grazie a una tecnica globale proteomica (RPMA) abbiamo identificato vie di trasduzione del segnale che si attivano come meccanismo compensatorio al trattamento farmacologico, potenzialmente responsabili di chemioresistenza sia nelle MDS che nel MM, sostenute dai segnali di autofagia e sopravvivenza. In particolare sono stati identificati: - Msi-2 come potenziale biomarcatore di staminalita' e aggressivita' nelle MDS, - la via di PLC 1Tyr783, SrcTyr416 and STAT-5Tyr694 responsabile di alcuni effetti collaterali del trattamento con Azacitidina nelle MDS, - il livello di fosforilazione di NFkB quale potenziale mediatore di chemioresistenza al Desametasone nel MM, - la via di AkT/mTOR quale marcatore di aggressivita` delle plasmacellule nel MM, - una patologica compartimentalizzazione di serotonina nel MM nel sangue periferico e midollare, correlata alla malattia ossea mielomatosa. Nell`insieme, i nostri dati suggeriscono nuove potenziali applicazioni in campo diagnostico e prognostico, e/o nuovi approcci terapeutici per MDS e MM, attraverso un approccio integrato genomico e proteomico.
In this work we focused on two hematological malignancies to apply the translational meaning of functional genomics: myelodysplastic syndrome (MDS) and its potential evolution to frank acute myeloid leukaemia, and the broad set of monoclonal gammopathies up to multiple myeloma (MM). In both diseases the recent advances obtained thanks to the application of novel therapeutic agents have enlighten the need to target at the same time both neoplastic and surrounding microenvironment cells. In MDS we applied the last generation of Affymetrix single nucleotide polymorphism (SNP)/copy number aberrations (CNA) platform to distinguish somatic and germline tumor-associated CNAs and loss of heterozigosity (LOHs) to identify possible recurring genomic abnormalities in high risk MDS evolving to AML. In particular in one patient, strictly followed in the clinical evolution from MDS to AML, we were able to define the unique features of the aberrant clone through a bioinformatic-based strategy. For MM, we developed ex-vivo assay to identify signalling associated with differential treatments of fresh bone marrow aspirate samples, confirming the unique constellation of activation in the single patient, and the general trend of a differential behavior among neoplastic and surrounding cells. Thanks to a global proteomic technique (RPMA) we identified compensatory pathways potentially responsible of chemoresistance, in both MDS and MM, sustained by the activation of autophagy and pro-survival signalling. In particular, we identified: - Msi-2 as potential biomarker of stemness and aggressivity in MDS, - PLC-y1Tyr783, SrcTyr416 and STAT-5Tyr694 as compensatory pathway responsible of side effects of treatment with azacitidine in MDS, - NFkB status as potential mediator of chemoresistance to dexamethasone in MM, - Akt/mTOR as biomarker of aggressiveness of plasmacells in MM; - an abnormal compartmentalization of serotonin in MM peripheral blood and bone marrow, related to bone disease. Taken together, our data provide potential insights into diagnosis, prognosis, and/or treatment strategies for MDS/AML and MM, through an integrative genomic and proteomic approach.

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BANDINI, CECILIA. « FUNCTIONAL GENOMIC APPROACHES TO SENSITIZE HEMATOLOGICAL MALIGNANCIES TO PROTEASOME INHIBITORS ». Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/708377.

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Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma (MM) and mantle-cell lymphoma (MCL). Nevertheless, patients continuously relapse or are intrinsically resistant to PIs.Here, to identify druggable targets that synergize with PIs, we carried out a functional screening in MM cell lines using a shRNA library targeting cancer driver genes. The Isocitrate Dehydrogenase 2 (IDH2) and Lysin Specific-Demethylases 1 (LSD1) genes were identified as top candidates, showing a synthetic lethal activity with the PI Carfilzomib (CFZ). We first validated the role of IDH2 in mediating PIs sensitivity. Combinations of the pharmacological IDH2 inhibitor AGI-6780 with FDA approved PIs significantly increased apoptotic cell death in ten MM cell lines, both sensitive and resistant to PIs. Combined treatments triggered synergistic cytotoxicity also in others hematological malignancies, such as Burkitt’s lymphoma, mantle cell lymphoma and diffuse large B-cell lymphoma. Importantly, CFZ/AGI-6780 treatment increased death of primary MM cells from nine patients and exhibited a favorable cytotoxicity profile towards normal human cells. Mechanistically, CFZ/AGI- 6780 combination decreased TCA cycle activity and ATP levels, due to enhanced IDH2 enzymatic inhibition. Specifically, CFZ treatment decreased nicotinamide phosphoribosyltransferase (NAMPT) expression, a rate-limiting enzyme required for IDH2 activation, through the NAD+-dependent deacetylase SIRT3. Consistently, combination of CFZ with either NAMPT or SIRT3 inhibitors impaired IDH2 activity and increased MM cells death, thus phenocopying CFZ/AGI-6780 effects and putting the proteasome in a direct link with IDH2 inhibition. Moreover, inducible IDH2 knock-down enhanced the therapeutic efficacy of CFZ in xenograft mouse models of MM, resulting in inhibition of tumor progression and extended survival. Finally, preliminary results also showed that LSD1 may represent a potential therapeutic target to combine with PIs. Indeed, genetic inhibition of LSD1 increased sensitivity to CFZ in MM cell lines, both sensitive and resistant to PIs. Remarkably, treatment with the non-competitive LSD1 inhibitor SP2509 significantly increased CFZ efficacy in eighth out of ten MM cell lines, both sensitive and resistant to PIs. However, GSK2879552 and GSK-LSD1, two LSD1 enzymatic inhibitors, did not display synergistic activity with CFZ, thus establishing the basis for future research of non-canonical functions of LSD1 or alternative SP2509 targets. In conclusion, our data demonstrate that IDH2 inhibition increases the therapeutic efficacy of PIs, thus providing compelling evidence for treatments with lower and less toxic doses and broadening the application of PIs to other malignancies. Moreover, preliminary results suggest LSD1 targeting as an alternative promising strategy to enhance PIs sensitivity in multiple myeloma.

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Livres sur le sujet "Hematological malignancie"

Czader, Magdalena, dir. Hematological Malignancies. Totowa, NJ : Humana Press, 2013. http://dx.doi.org/10.1007/978-1-62703-357-2.

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service), SpringerLink (Online, dir. Rare Hematological Malignancies. Boston, MA : Springer Science+Business Media, LLC, 2008.

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Ansell, Stephen M., dir. Rare Hematological Malignancies. Boston, MA : Springer US, 2008. http://dx.doi.org/10.1007/978-0-387-73744-7.

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Faguet, Guy B. Hematologic Malignancies. New Jersey : Humana Press, 2000. http://dx.doi.org/10.1385/1592590748.

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Hoogstraten, Barth, dir. Hematologic Malignancies. Berlin, Heidelberg : Springer Berlin Heidelberg, 1986. http://dx.doi.org/10.1007/978-3-642-82734-1.

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Bhargava, Manorama. Hematologic Malignancies. Singapore : Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-33-4799-1.

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R, Durant J., Hoogstraten B et International Union Against Cancer, dir. Hematologic malignancies. Berlin : Springer, 1986.

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Barth, Hoogstraten, et Durant John R. 1930-, dir. Hematologic malignancies. Berlin : Springer-Verlag, 1986.

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Hentrich, Marcus, et Stefan K. Barta, dir. HIV-associated Hematological Malignancies. Cham : Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-26857-6.

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Ortolani, Claudio. Flow Cytometry of Hematological Malignancies. Oxford, UK : Blackwell Publishing Ltd., 2011. http://dx.doi.org/10.1002/9781444398069.

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Chapitres de livres sur le sujet "Hematological malignancie"

Neymark, Niels. « Hematological Malignancies ». Dans Assessing the Economic Value of Anticancer Therapies, 156–82. Berlin, Heidelberg : Springer Berlin Heidelberg, 1998. http://dx.doi.org/10.1007/978-3-642-72123-6_11.

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Gautier, Marc, et Harvey Jay Cohen. « Hematologic Malignancies ». Dans Geriatric Medicine, 337–54. New York, NY : Springer New York, 1997. http://dx.doi.org/10.1007/978-1-4757-2705-0_25.

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Girnius, Andrea, Saulius Girnius et Lesley Gilbertson. « Hematologic Malignancies ». Dans Consults in Obstetric Anesthesiology, 251–54. Cham : Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-59680-8_72.

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Gagnon, Patrick J., Celine Bicquart Ord et Carol Marquez. « Hematologic Malignancies ». Dans Radiation Oncology Study Guide, 325–51. New York, NY : Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-6400-6_12.

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Ribera, Josep-Maria. « Second Malignancies ». Dans HIV-associated Hematological Malignancies, 235–37. Cham : Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-26857-6_21.

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Lamoth, Frédéric. « Epidemiology and Risk Factors of Invasive Fungal Infections ». Dans Hematologic Malignancies, 1–12. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-57317-1_1.

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Matthaiou, Dimitrios K., et George Dimopoulos. « Intensive Care ». Dans Hematologic Malignancies, 147–53. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-57317-1_10.

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Busca, Alessandro, Silvia Corcione et Francesco Giuseppe De Rosa. « Gram-Positive Infections ». Dans Hematologic Malignancies, 155–60. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-57317-1_11.

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Bassetti, Matteo, Elda Righi et Murat Akova. « Gram-Negative Infections ». Dans Hematologic Malignancies, 161–79. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-57317-1_12.

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Sprute, Rosanne, Philipp Koehler et Oliver A. Cornely. « Herpes Viruses ». Dans Hematologic Malignancies, 181–89. Cham : Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-57317-1_13.

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Actes de conférences sur le sujet "Hematological malignancie"

Kuttikrishnan, Shilpa, Kirti S. Prabhu, Tamam Elimat, Ashraf Khalil, Nicholas H. Oberlies, Feras Q. Alali et Shahab Uddin. « Anticancer Activity of Neosetophomone B, An Aquatic Fungal Secondary Metabolite, Against Hematological Malignancie S ». Dans Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2021. http://dx.doi.org/10.29117/quarfe.2021.0106.

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Cancer is one of the most life threatening diseases, causing nearly 13% death in the worldwide. Leukemia, cancer of the hematopoetic cells is the main cause of cancer death in adults and children. Therapeutic agents used in treatment of cancer are known to have narrow therapeutic window and tendency to develop resistance against some cancer cell lines thus, proposing a need to discover some novel agents to treat cancer. In the present study we investigated the anticancer activity of Neosetophomone B(NSP-B), an aquatic fungal metabolite isolated from Neosetophoma sp against leukemic cells (K562 and U937). MTT results demonstrated a dose dependent inhibition of cell proliferation in K562 and U937 cell lines. Annexin staining using flow cytometry indicated that NSP-B treatment cause a dose dependent apoptosis in leukemic cells.Western blot analysis showed that NSP-B mediated apoptosis involves sequential activation of caspase 9, 3 and poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore NSP-B treatment of leukemic cells resulted in upregulation of pro-apoptotic proteins (Bax) with downregulation of anti-apoptotic proteins ( Bcl-2 ).Thus, present study focuses on exploring the mechanism of anticancer activity of NSP-B on leukemic cells, raising the possibility of its use as a novel therapeutic agent for hematological malignancies. Results: We sought to determine whether NSP-B suppresses the growth of leukemic cell lines. We tested a panel of leukemic cell lines with different doses of NSP-B. Cell viability decreased in a concentration-dependent manner in K562 and U937 cell lines. NSP-B induced apoptosis in K562 and U937 cell lines via downregulation of anti-apoptotic proteins and enhancement of pro-apoptotic proteins. NSP-B induced the activation of caspase cascade signaling pathway. Altogether our results suggest that the NSP-B plays an important role in apoptosis in leukemic cell lines .Conclusions: Our data provides insight on anticancer activities of NSP-B in leukemic cell lines (K562 and U937). NSP-B inhibit cell viability via inducing apoptosis. The NSP-B mediated apoptosis occurs via downregulation of anti-apoptotic proteins and enhancement of pro-apototic proteins, thereby activating the caspase-cascade signaling. Further studies are required to elicit role of NSP-B in regulating molecular pathway involved in the progression of cancer. Taken together, above results suggest that NSP-B may have a future therapeutic role in leukemia and possibly other hematological malignancies.

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« Nanotechnology for Human Hematological Malignancies Treatment ». Dans International Conference on Biotechnology, Nanotechnology and Environmental Engineering. International Academy of Arts, Science & Technology, 2015. http://dx.doi.org/10.15242/iaast.a0415036.

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Mikami, Yu, Daiya Takai, Masafumi Horie, Satoshi Noguchi, Hirotaka Matsuzaki, Kosuke Makita, Hideyuki Takeshima, Yasuhiro Yamauchi, Go Tanaka et Takahide Nagase. « Respiratory manifestations in hospitalized patients with hematological malignancies ». Dans Annual Congress 2015. European Respiratory Society, 2015. http://dx.doi.org/10.1183/13993003.congress-2015.oa2907.

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Tertemiz, Kemal Can, Aylin Ozgen Alpaydin, Seda Salman et Inci Alacacioglu. « Diagnostic yield of bronchoalveolar lavage in hematological malignancies ». Dans Annual Congress 2015. European Respiratory Society, 2015. http://dx.doi.org/10.1183/13993003.congress-2015.pa2646.

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Heikkinen, Tuomas, Kati Kämpjärvi, Sirpa Leppä, Peter Hokland, Heikki Kuusanmäki, Satu Mustjoki, Marjatta Sinisalo, Caroline Heckman, Mika Kontro et Pia Vahteristo. « Abstract 1169 : Somatic MED12 mutations in hematological malignancies ». Dans Proceedings : AACR 107th Annual Meeting 2016 ; April 16-20, 2016 ; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-1169.

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Borgovan, Theo. « Abstract 1016 : A new biomarker in hematological malignancies ». Dans Proceedings : AACR Annual Meeting 2021 ; April 10-15, 2021 and May 17-21, 2021 ; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1016.

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Laklaai, Z., K. Channoune, N. Zaghba, H. Benjelloune et N. Yassine. « Radiological aspects of thoracic involvement in hematological malignancies ». Dans ERS International Congress 2022 abstracts. European Respiratory Society, 2022. http://dx.doi.org/10.1183/13993003.congress-2022.3226.

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« Study of hematologic malignancy vaccines ». Dans International Conference on Medicine, Public Health and Biological Sciences. CASRP Publishing Company, Ltd. Uk, 2016. http://dx.doi.org/10.18869/mphbs.2016.117.

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Albrecht, S., H. Male, H. W. Barkman, V. R. Sethapati et M. T. Cunningham. « Prognosis of Hematologic Malignancies in Pleural Fluid ». Dans American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a4199.

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Spicuzza, Lucia, Emanuela Cannata, Lisa Angileri, Giovanna Russo, Andrea Di Cataldo et Nunzio Crimi. « Risk factors for impaired pulmonary function in adult survivors of childhood hematological and non-hematological malignancies ». Dans ERS International Congress 2020 abstracts. European Respiratory Society, 2020. http://dx.doi.org/10.1183/13993003.congress-2020.1664.

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Rapports d'organisations sur le sujet "Hematological malignancie"

Press, O. W. Improved radioimmunotherapy of hematologic malignancies. Office of Scientific and Technical Information (OSTI), mars 1992. http://dx.doi.org/10.2172/5376292.

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Press, O. W. Improved radioimmunotherapy of hematologic malignancies. [Final report]. Office of Scientific and Technical Information (OSTI), mars 1992. http://dx.doi.org/10.2172/10141667.

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Press, O. W. Improved radioimmunotherapy of hematologic malignancies. Final technical report. Office of Scientific and Technical Information (OSTI), août 1996. http://dx.doi.org/10.2172/373849.

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Press, O. W., et D. F. Barofsky. Improved radioimmunotherapy of hematologic malignancies. Progress report, 1988--1991. Office of Scientific and Technical Information (OSTI), décembre 1991. http://dx.doi.org/10.2172/10112383.

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Liang, Zuohui, Jie Liu, Hongxia Jin, Yirong Teng, Shuangyan Xu, Weimin Yan et Yun Zhu. Potential correlation between eczema and hematological malignancies risk : a systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, juin 2022. http://dx.doi.org/10.37766/inplasy2022.6.0097.

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Press, O. W. Improved radioimmunotherapy of hematologic malignancies. Progress report, November 1, 1993--October 31, 1994. Office of Scientific and Technical Information (OSTI), août 1994. http://dx.doi.org/10.2172/10187100.

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Ji, Conghua, Rongchen Dai, Hanting Wu, Qiushuang Li, Shan Liu, Peijie He, Juan Liang et Qing Guo. Efficacy and safety of hematopoietic stem cell transplantation for hematologic malignancies : A protocol for an overview of systematic reviews and meta-analyses. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, mai 2021. http://dx.doi.org/10.37766/inplasy2021.5.0064.

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Zhao, Kangjia, Jiwen Sun, Nanping Shen, Mengxue He, Haishan Ruan, Geng Lin, Jiali Ma et Yanhua Xu. Treatment-Related Adverse Events of Chimeric Antigen receptor T-Cell (CAR-T) Cell Therapy in B-cell hematological malignancies in the Pediatric and Young Adult Population : A Systematic Review and Meta-Analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, juillet 2022. http://dx.doi.org/10.37766/inplasy2022.7.0034.

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