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  • 1
    Language: English
    In: International journal of molecular sciences, 2019-10-28, Vol.20 (21), p.5362
    Description: The significance of measurable residual disease (MRD) in hematopoietic stem cell transplantation (HSCT) is well recognized in different hematological malignancies, but the evidence indicate that pre-transplant MRD status is of particular importance in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In ALL, inadequate response at the level of MRD is a commonly accepted risk factor for relapse and thus an indication for allogeneic HSCT. Similarly, growing evidence from the literature strongly suggest that MRD detected by multiparameter flow cytometry or molecular techniques should be also used for risk stratification in AML at the time of HSCT. Despite the well-defined association of MRD and outcomes of HSCT in acute leukemias, there are still many open issues such as the role of additional pre-transplant consolidation for MRD eradication, the ability of HSCT to overcome negative influence of MRD positivity on survival, the impact of conditioning regimen intensity on MRD clearance post HSCT, and transplantation outcomes or the selection of optimal donor with regards to MRD status. In addition, the role of MRD assessment in guiding post-transplant maintenance treatment should also be addressed in prospective trials. These open issues mostly awaiting further clinical studies will be discussed in our current review.
    Subject(s): Hematologic Neoplasms - therapy ; Recurrence ; Donor Selection ; Hematologic Neoplasms - mortality ; Humans ; Risk Factors ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Combined Modality Therapy ; Hematopoietic Stem Cell Transplantation - mortality ; Transplantation, Homologous ; Leukemia, Myeloid, Acute - mortality ; Neoplasm, Residual ; Flow Cytometry ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - therapy ; Index Medicus ; acute myeloid leukemia ; acute lymphoblastic leukemia ; measurable residual disease ; multiparameter flow cytometer ; hematopoietic stem cell transplantation ; Review ; polymerase chain reaction
    ISSN: 1422-0067
    E-ISSN: 1422-0067
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2019-08, Vol.54 (Suppl 2), p.713-718
    Description: Allogeneic stem cell transplantations (alloSCT) from haploidentical (〉2 HLA mismatch) donors (HaploSCT) are constantly increasing in Europe. From 2005 to 2015 numbers of HaploSCT increased by close to 300%. In parallel, there is a major shift from T deplete (CD34+ megadose) to T replete (non-T deplete) HaploSCT. Graft versus host disease (GVHD) prophylaxis also changed from CD34+ cell purifications to anti-thymocyte globulin (ATG) and lately to post-transplantation cyclophosphamide (PTCy). Novel conditioning regimens have been developed incorporating novel drugs and innovative approaches. Results are persistently improving and currently, registry-based and single-center studies showed no statistical significance difference in transplantation outcome between HaploSCT to alloSCT from unrelated donors and even from HLA-matched sibling donors, although the numbers of those studies are small and the lack of randomized studies available so far. HaploSCT have several advantages and such as the possibility to choose between different potential donors. Parameters to consider in the Haplo donor selection are age, gender, kinship, ABO blood group, CMV status, non-shared HLA Haplotypes and killer cell immunoglobulin-like receptor (KIR). Future goals are to further decrease transplant-related mortality currently mainly due to infection complications and reduce relapse rates especially in patients with high-risk acute leukemia.
    Subject(s): Care and treatment ; Usage ; Acute leukemia ; Graft versus host reaction ; Transplantation ; Risk factors ; Hematopoietic stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: The New England journal of medicine, 2014-09-04, Vol.371 (10), p.895-905
    Description: In patients 65 or younger with multiple myeloma, high-dose consolidation therapy was associated with longer survival and more myelotoxicity than conventional-dose therapy. Lenalidomide maintenance improved progression-free survival but not overall survival. High-dose chemotherapy plus autologous stem-cell transplantation, as compared with conventional chemotherapy, prolongs progression-free survival and overall survival among patients with newly diagnosed multiple myeloma. 1 – 4 and it is currently the standard of care for patients who are younger than 65 years of age. However, since autologous stem-cell transplantation has substantial toxic effects and requires prolonged hospitalization, the comparison with less toxic, orally administered treatments is important. Immunomodulatory drugs and proteasome inhibitors have significantly improved outcomes in patients, regardless of whether they are eligible for transplantation. 5 – 18 These improvements have raised questions about the role of transplantation in comparison with conventional . . .
    Subject(s): Hematologic and hematopoietic diseases ; Immunopathology ; General aspects ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Immunoglobulinopathies ; Medical sciences ; Immunodeficiencies. Immunoglobulinopathies ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Multiple Myeloma - mortality ; Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Transplantation, Autologous ; Consolidation Chemotherapy ; Antineoplastic Agents, Alkylating - administration & dosage ; Thalidomide - analogs & derivatives ; Multiple Myeloma - drug therapy ; Multiple Myeloma - therapy ; Melphalan - adverse effects ; Adult ; Maintenance Chemotherapy ; Neutropenia - chemically induced ; Thalidomide - adverse effects ; Prednisone - administration & dosage ; Prednisone - adverse effects ; Kaplan-Meier Estimate ; Combined Modality Therapy ; Thalidomide - administration & dosage ; Disease-Free Survival ; Melphalan - administration & dosage ; Aged ; Antineoplastic Agents, Alkylating - adverse effects ; Stem Cell Transplantation - adverse effects ; Complications and side effects ; Care and treatment ; Patient outcomes ; Multiple myeloma ; Stem cells ; Transplantation ; Research ; Health aspects ; Autografts ; Chemotherapy ; Cell survival ; Transplants & implants ; Melphalan ; Stem cell transplantation ; Death ; Prednisone ; Drug dosages ; Neutropenia
    ISSN: 0028-4793
    E-ISSN: 1533-4406
    Source: Single Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Clinical cancer research, 2008-05-15, Vol.14 (10), p.3044-3051
    Description: Purpose: CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein belonging to the B7 receptor family present on lymphocytes. The objectives of this phase I study were to assess the dose-limiting toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients with advanced hematologic malignancies. Experimental Design: Seventeen patients were treated with escalating doses of CT-011 ranging from 0.2 to 6 mg/kg. For pharmacokinetic analysis, blood samples were withdrawn from the patients before and immediately after treatment and at 24 hours, 48 hours, and on days 7, 14, and 21. CT-011 blood levels were assessed with a specific ELISA and derived concentrations were used to calculate pharmacokinetic parameters. Activation of the immune system was assessed by measuring peripheral blood CD4 + , CD8 + , and CD69 + lymphocytes. Results: The study showed the antibody to be safe and well tolerated in this patient population. No single maximum tolerated dose was defined in this study. Clinical benefit was observed in 33% of the patients with one complete remission. Pharmacokinetic analyses show that serum C max and the AUC of CT-011 increased proportionally with dose. The median t 1/2 of CT-011 ranged from 217 to 410 hours. Sustained elevation in the percentage of peripheral blood CD4 + lymphocytes was observed up to 21 days following CT-011 treatment. Conclusions: A single administration of 0.2 to 6.0 mg/kg of CT-011 is safe and well tolerated in patients with advanced hematologic malignancies.
    Subject(s): hematologic malignancies ; Monoclonal antibody ; T cells ; Pharmacokinetics ; PD-1 ; Immunotherapy ; Enzyme-Linked Immunosorbent Assay ; Area Under Curve ; Humans ; Middle Aged ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - pharmacokinetics ; Male ; Antineoplastic Agents - administration & dosage ; Antigens, CD - metabolism ; Apoptosis Regulatory Proteins - metabolism ; Dose-Response Relationship, Drug ; Maximum Tolerated Dose ; Antibodies, Monoclonal - administration & dosage ; Antineoplastic Agents - adverse effects ; Hematologic Neoplasms - drug therapy ; Adult ; Female ; Programmed Cell Death 1 Receptor ; Aged ; Antineoplastic Agents - pharmacokinetics
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 5
    Language: English
    In: The New England journal of medicine, 2016-01-07, Vol.374 (1), p.43-53
    Description: Antilymphocyte globulin (ATG) added to the conditioning regimen before allogeneic hematopoietic stem-cell transplantation resulted in a lower rate of chronic graft-versus-host disease at 2 years than the rate without ATG (32% vs. 68%), with no apparent increased risk of relapse. Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic stem-cell transplantation that results in later illness and death and a reduction in quality of life. 1 , 2 Risk factors for chronic GVHD are the use of peripheral blood as a source of stem cells, a history of acute GVHD, and the use of donated stem cells with high numbers of T cells. 3 – 7 In a meta-analysis, the Stem Cell Trialists’ Collaborative Group reported an incidence of extensive chronic GVHD of 47% after peripheral-blood stem-cell transplantation from an HLA-identical sibling. 4 In 2012, more than 70% of the stem-cell transplantations performed in . . .
    Subject(s): Graft vs Host Disease - epidemiology ; Prospective Studies ; Humans ; Immunosuppressive Agents - therapeutic use ; Middle Aged ; Proportional Hazards Models ; Child, Preschool ; Male ; Survival Rate ; Transplantation, Homologous ; Incidence ; Young Adult ; Disease-Free Survival ; Graft vs Host Disease - mortality ; Adolescent ; Antilymphocyte Serum - therapeutic use ; Adult ; Female ; Graft vs Host Disease - prevention & control ; T-Lymphocytes - immunology ; Child ; Chronic Disease ; Prevention ; Treatment outcome ; Graft versus host reaction ; Immunoglobulins ; Dosage and administration ; Analysis ; Graft-versus-host reaction ; Transplants & implants ; Leukemia ; Stem cell transplantation ; Lymphocytes T ; Preventive medicine ; Hemopoiesis ; Globulins ; Risk assessment ; Peripheral blood ; Stem cells ; Bone marrow ; Histocompatibility antigen HLA ; Index Medicus ; Abridged Index Medicus
    ISSN: 0028-4793
    E-ISSN: 1533-4406
    Source: Single Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2020-07, Vol.55 (7), p.1220-1228
    Description: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment available for various hematological malignancies. Ideally, prospective randomized controlled trials (RCTs) should establish the indications for allo-HSCT. In reality, however, RCTs are not feasible due to the rarity of many hematological conditions. In these scenarios, decision analysis, which simulates possible outcomes with different approaches, can help in selecting the treatment strategy predicted to have the best result. Assessment of cost-effectiveness can also be incorporated in computational simulation analysis. In this review, we would like to provide an overview of decision-analytic models that evaluate alternative treatment strategies for patients with hematological malignancies.
    Subject(s): Carboplatin ; Medical colleges ; Transplantation ; Antithymocyte globulin ; Hematopoietic stem cells ; Stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Journal of clinical oncology, 2013-11-20, Vol.31 (33), p.4199-4206
    Description: The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. We conducted an international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT. Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab. This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease.
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Tumors ; United States ; Humans ; Middle Aged ; Antibodies, Monoclonal - adverse effects ; Fatigue - etiology ; Antibodies, Monoclonal - therapeutic use ; Male ; Programmed Cell Death 1 Receptor - antagonists & inhibitors ; Transplantation, Autologous ; Neutropenia - etiology ; Young Adult ; Lymphoma, Large B-Cell, Diffuse - therapy ; Aged, 80 and over ; Lymphoma, Large B-Cell, Diffuse - immunology ; Adult ; Female ; Chile ; Antibodies, Monoclonal - immunology ; Immune Tolerance - drug effects ; Drug Administration Schedule ; Treatment Outcome ; Combined Modality Therapy ; India ; Disease-Free Survival ; Lymphoma, Large B-Cell, Diffuse - blood ; Lymphocyte Count ; Aged ; Hematopoietic Stem Cell Transplantation - methods ; Israel ; Programmed Cell Death 1 Receptor - immunology ; Hema13 ; Hema16 ; ORIGINAL REPORTS
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 8
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2018-09, Vol.53 (9), p.1139-1148
    Description: Hematopoietic cell transplantation (HCT) is an established procedure for acquired and congenital disorders of the hematopoietic system. In 2016, there was a tendency for continued activity in this field with 43,636 HCT in 39,313 patients [16,507 allogeneic (42%), 22,806 autologous (58%)] reported by 679 centers in 49 countries in 2016. The main indications were myeloid malignancies 9547 (24%; 96% allogeneic), lymphoid malignancies 25,618 (65%; 20% allogeneic), solid tumors 1516 (4%; 2% allogeneic), and non-malignant disorders 2459 (6%; 85% allogeneic). There was a remarkable leveling off in the use of unrelated donor HCT being replaced by haploidentical HCT. Continued growth in allogeneic HCT for marrow failure, AML, and MPN was seen, whereas MDS appears stable. Allogeneic HCT for lymphoid malignancies vary in trend with increases for NHL and decreases for Hodgkin lymphoma and myeloma. Trends in CLL are not clear, with recent increases after a decrease in activity. In autologous HCT, the use in myeloma continues to expand but is stable in Hodgkin lymphoma. There is a notable increase in autologous HCT for autoimmune disease. These data reflect the most recent advances in the field, in which some trends and changes are likely to be related to development of non-transplant technologies.
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: British journal of haematology, 2021-01, Vol.192 (2), p.239-250
    Description: Summary Digitalization of the medical record and integration of genomic methods into clinical practice have resulted in an unprecedented wealth of data. Machine learning is a subdomain of artificial intelligence that attempts to computationally extract meaningful insights from complex data structures. Applications of machine learning in haematological scenarios are steadily increasing. However, basic concepts are often unfamiliar to clinicians and investigators. The purpose of this review is to provide readers with tools to interpret and critically appraise machine learning literature. We begin with the elucidation of standard terminology and then review examples in haematology. Guidelines for designing and evaluating machine‐learning studies are provided. Finally, we discuss limitations of the machine‐learning approach.
    Subject(s): prediction models ; haematology ; leukaemia ; machine learning ; artificial intelligence ; Artificial intelligence ; Analysis ; Machine learning ; Index Medicus
    ISSN: 0007-1048
    E-ISSN: 1365-2141
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2019-02-26, Vol.54 (10), p.1643-1650
    Description: Autologous T cells transduced with CD19-directed chimeric antigen receptors have recently been approved by several regulatory agencies for the treatment of relapsed and refractory leukemia and lymphoma, after demonstrating remarkable remission rate in advanced patients. The most common adverse events reported are cytokine-release syndrome (CRS), neurotoxicity, and hematologic toxicity. Here, we focus on early and late cytopenia occurring after CD19 CAR-T cells in 38 patients treated with CD19 CAR-T cells. Neutropenia, thrombocytopenia, and anemia occur frequently (94, 80, and 51%, respectively) after CAR-T cell infusion, and are associated with a biphasic nature, as in 93% of patients hematologic toxicity occurs after 21 days from cell infusion. Late hematologic toxicity was more common in patients with high grade CRS and in patients treated after a recent stem cell transplantation. Interestingly, since these events occur late after the lymphodepleting chemotherapy and after resolution of CRS, we found perturbations in SDF-1 levels to correlate with events of late neutropenia, likely associated with B-cell recovery.
    Subject(s): Care and treatment ; Usage ; Stem cells ; Transplantation ; Non-Hodgkin's lymphomas ; Research ; T cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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