disco – ULB Münster

1

Article

Reduction of Relapse after Unrelated Donor Stem Cell Transplantation by KIR-Based Graft Selection

Heidenreich, Silke ; Kröger, Nicolaus

2017

ISSN: 1664-3224

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Language: English

In: Frontiers in immunology, 2017, Vol.8, p.41-41

Description: Besides donor T cells, natural killer (NK) cells are considered to have a major role in preventing relapse after allogeneic hematopoietic stem cell transplantation (HSCT). After T-cell-depleted haploidentical HSCT, a strong NK alloreactivity has been described. These effects have been attributed to killer-cell immunoglobulin-like receptors (KIR). Abundant reports suggest a major role of KIR not only on outcome after haploidentical HSCT but also in the unrelated donor setting. In this review, we give a brief overview of the mechanism of NK cell activation, nomenclature of KIR haplotypes, human leukocyte antigen (HLA) groups, and distinct models for prediction of NK cell alloreactivity. It can be concluded that KIR-ligand mismatch seems to provoke adverse effects in unrelated donor HSCT with reduced overall survival and increased risk for high-grade acute graft-versus-host disease. The presence of activating KIR, as seen in KIR haplotype B, as well as the patient's HLA C1/x haplotype might reduce relapse in myeloid malignancies.

Subject(s): Killer cells ; Usage ; Relapse ; Control ; Stem cells ; Transplantation ; Research ; Health aspects ; Diseases ; Immunology ; haplotype ; stem cell ; unrelated ; transplantation ; NK-cell ; killer-cell immunoglobulin-like receptor ; HSCT

ISSN: 1664-3224

E-ISSN: 1664-3224

DOI: 10.3389/fimmu.2017.00041

Source: PubMed Central

Source: Directory of Open Access Journals

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2

Article

Janus Kinase Inhibition for Graft-Versus-Host Disease: Current Status and Future Prospects

Mannina, Daniele ; Kröger, Nicolaus

2019

ISSN: 0012-6667

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Language: English

In: Drugs (New York, N.Y.), 2019-09, Vol.79 (14), p.1499-1509

Description: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment for many hematological malignant and non-malignant diseases. A major complication of the procedure is the donor T-cell-mediated graft-versus-host disease (GvHD). GvHD accounts for about 10% of early mortality after transplantation. GVHD is also the major cause of morbidity and disability in the late follow-up phase of transplanted patients, mainly because of the low response to first-line steroids, and the lack of efficient second-line standard treatments. The increasing knowledge regarding GVHD pathogenesis provides new pharmacological targets, potentially exploitable in clinical practice, in order to prevent and treat this complication. This review provides a description of GVHD pathogenesis, with a focus on the central role of the Janus kinase-related mechanisms. The first inflammatory innate-immunity response is triggered by a JAK/STAT dependent pathway, and JAK inhibition impairs antigen-presenting cell differentiation and activation and downregulates the expression of signals for T-cell triggering. The chronic evolution of alloreactivity, characterized by the long-term maintenance of inflammation and fibrosis, is also dependent on JAK/STAT activation. Based on preclinical data, we reviewed the rationale behind the clinical use of JAK-inhibitors in GVHD, presenting available results of clinical trials and reports, and looked at future implementation of this new promising treatment approach.

Subject(s): Pharmacotherapy ; Internal Medicine ; Medicine & Public Health ; Pharmacology/Toxicology ; Immunity, Innate - immunology ; Inflammation - metabolism ; Janus Kinase Inhibitors - pharmacology ; Animals ; Graft vs Host Disease - drug therapy ; Immunity, Innate - drug effects ; Janus Kinase Inhibitors - therapeutic use ; Humans ; Inflammation - immunology ; Janus Kinases - metabolism ; Graft vs Host Disease - immunology ; Index Medicus

ISSN: 0012-6667

E-ISSN: 1179-1950

DOI: 10.1007/s40265-019-01174-1

Source: Alma/SFX Local Collection

Source: EBSCOhost EJS

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3

Article

Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease

Kröger, Nicolaus ; Solano, Carlos ; Wolschke, Christine ; [et al.]

2016

ISSN: 0028-4793

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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

DOI: 10.1056/NEJMoa1506002

Source: Single Journals

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4

Article

The role of novel agents for consolidation after autologous transplantation in newly diagnosed multiple myeloma: a systematic review

Gagelmann, Nico ; Kröger, Nicolaus

2021

ISSN: 0939-5555

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Language: English

In: Annals of hematology, 2021-02, Vol.100 (2), p.405-419

Description: Despite the increasing inclusion of novel agents within the multiple myeloma (MM) treatment sequence, their role for posttransplant consolidation therapy remains unclear. We systematically reviewed studies evaluating the efficacy of novel agent consolidation. We identified 11 citations on 12 prospective comparative studies, and 5 citations were single-arm or comparative studies with preliminary results. Nine different regimens were evaluated in 5905 patients. Risk assessment yielded serious risk of bias and heterogeneity across study designs was high. Irrespective of the regimen, deepened responses after consolidation were seen and improvements were more pronounced with multi-agent consolidation. Bortezomib, thalidomide, and dexamethasone improved long-term survival versus duplet consolidation, including in patients with high-risk cytogenetics. The addition of daratumumab to triplet regimens yielded modestly improved responses with significantly increased rates of minimal residual disease negativity but survival results were limited by short follow-up. In high-risk MM, responses were not different, whereas progression-free survival appeared to be improved with consolidation therapy, challenging the association of response and overall outcome in this subgroup. Our findings highlight the necessity of longer follow-up and consistent reporting to ensure comparability of studies to enable better evidence assessment and to identify patients benefitting from consolidation therapy.

Subject(s): Multiple Myeloma - diagnosis ; Risk Assessment ; Humans ; Middle Aged ; Hematopoietic Stem Cell Transplantation ; Male ; Transplantation, Autologous ; Consolidation Chemotherapy ; Dexamethasone - therapeutic use ; Multiple Myeloma - therapy ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bortezomib - therapeutic use ; Adult ; Female ; Aged ; Thalidomide - therapeutic use ; Cytogenetics ; Autografts ; Transplantation ; Corticosteroids ; Stem cells ; Multiple myeloma

ISSN: 0939-5555

E-ISSN: 1432-0584

DOI: 10.1007/s00277-020-04316-8

Source: Alma/SFX Local Collection

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5

Article

Is the use of unrelated donor transplantation leveling off in Europe? The 2016 European Society for Blood and Marrow Transplant activity survey report

Passweg, Jakob R ; Baldomero, Helen ; Bader, Peter ; [et al.]

2018

ISSN: 0268-3369

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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

DOI: 10.1038/s41409-018-0153-1

Source: Nature Open Access

Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Source: Alma/SFX Local Collection

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6

Article

Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet

Tiziano Barbui ; Giovanni Barosi ; Gunnar Birgegard ; [et al.]

2011

ISSN: 0732-183X

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Language: English

In: Journal of clinical oncology, 2011-02-20, Vol.29 (6), p.761-770

Description: We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first- and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.

Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Tumors ; Humans ; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative - therapy ; Index Medicus ; Gdln2 ; Special

ISSN: 0732-183X

E-ISSN: 1527-7755

DOI: 10.1200/JCO.2010.31.8436

Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

URL: http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23910898$$DView record in Pascal Francis

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7

Article

The EBMT activity survey report 2017 : a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies

Passweg, Jakob R ; Baldomero, Helen ; Basak, Grzegorz W ; [et al.]

2019

ISSN: 0268-3369

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Language: English

In: Bone marrow transplantation (Basingstoke), 2019-10, Vol.54 (10), p.1575-1585

Description: Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to rise with 45,418 HCT in 41,100 patients [(17,155 allogeneic (42%) and 23,945 autologous (58%)] reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p 〈 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning.

Subject(s): Hematology ; Transplantation ; Surveys ; Reports ; Medical societies ; Hematopoietic stem cells ; Homografts ; Index Medicus ; Haematological cancer

ISSN: 0268-3369

E-ISSN: 1476-5365

DOI: 10.1038/s41409-019-0465-9

Source: Nature Open Access

Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Source: Alma/SFX Local Collection

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8

Article

Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report

Tefferi, Ayalew ; Cervantes, Francisco ; Mesa, Ruben ; [et al.]

2013

ISSN: 0006-4971

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Language: English

In: Blood, 2013-08-22, Vol.122 (8), p.1395-1398

Description: The current document is a revision of the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria for treatment response in myelofibrosis (MF) and represents a collaborative effort by the IWG-MRT and the European LeukemiaNet to objectively assess the value of new drugs in inducing morphologic remission or improvement in MF-associated symptomatic burden (MF-SB). Some of the changes in the current revision include stricter definitions of red cell transfusion dependency and independency and consideration of the Myeloproliferative Neoplasm Symptom Assessment Form as a tool to quantify meaningful changes in disease-related symptoms. Six response categories are listed: complete remission (CR) and partial remission signify treatment effects that are consistent with disease modification, whereas drug-induced improvements in MF-SB were annotated as clinical improvement, anemia response, spleen response, or symptoms response. Additional criteria are provided for progressive disease, stable disease, and relapse. The document also includes recommendations for assessing cytogenetic and molecular remissions, without mandating their inclusion for CR assignment.

Subject(s): Medical Oncology - methods ; Primary Myelofibrosis - diagnosis ; Primary Myelofibrosis - drug therapy ; Myeloproliferative Disorders - therapy ; Europe ; Humans ; Treatment Outcome ; International Cooperation ; Erythrocyte Transfusion - methods ; Remission Induction ; Consensus ; Disease Progression ; Medical Oncology - standards ; Bone Marrow Neoplasms - drug therapy ; Bone Marrow Neoplasms - diagnosis ; Chronic Disease - drug therapy ; Practice Guidelines as Topic ; Index Medicus ; Abridged Index Medicus ; Clinical Trials and Observations ; Brief Report

ISSN: 0006-4971

E-ISSN: 1528-0020

DOI: 10.1182/blood-2013-03-488098

Source: HighWire Press (Free Journals)

Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Source: American Society of Hematology

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9

Article

Development of CAR-T cell therapies for multiple myeloma

Gagelmann, Nico ; Riecken, Kristoffer ; Wolschke, Christine ; [et al.]

2020

ISSN: 0887-6924

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Language: English

In: Leukemia, 2020-09, Vol.34 (9), p.2317-2332

Description: Currently available data on chimeric antigen receptor (CAR)-T cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated multiple myeloma (MM) patients. The CAR-T field in MM is rapidly evolving with 〉50 currently ongoing clinical trials across all phases, different CAR-T design, or targets. Most of the CAR-T trials are performed in China and the United States, while European centers organize or participate in only a small fraction of current clinical investigations. Autologous CAR-T cell therapy against B cell maturation antigen shows the best evidence of efficacy so far but main issues remain to be addressed: duration of response, longer follow-up, prolonged cytopenia, patients who may benefit the most such as those with extramedullary disease, outcome prediction, and the integration of CAR-T cell therapy within the MM treatment paradigm. Other promising targets are, i.a.,: CD38, SLAMF7/CS1, or GPRC5D. Although no product has been approved to date, cost and production time for autologous products are expected to be the main obstacles for broad use, for which reason allogeneic CAR-T cells are currently explored. However, the inherent risk of graft-versus-host disease requires additional modification which still need to be validated. This review aims to present the current status of CAR-T cell therapy in MM with an overview on current targets, designs, and stages of CAR-T cell development. Main challenges to CAR-T cell therapy will be highlighted as well as strategies to structurally improve the CAR-T cell product, and thereby its efficacy and safety. The need for comparability of the most promising therapies will be emphasized to balance risks and benefits in an evidence-based but personalized approach to further improve outcome of patients with MM.

Subject(s): B-Cell Maturation Antigen - immunology ; Immunotherapy - methods ; Multiple Myeloma - therapy ; Humans ; Receptors, Chimeric Antigen - immunology ; Receptors, Antigen, T-Cell - immunology ; Precision Medicine ; T cells ; Evidence-based medicine ; Index Medicus

ISSN: 0887-6924

E-ISSN: 1476-5551

DOI: 10.1038/s41375-020-0930-x

Source: Nature Open Access

Source: Alma/SFX Local Collection

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10

Article

Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis

Kröger, Nicolaus ; Giorgino, Toni ; Scott, Bart L ; [et al.]

2015

ISSN: 0006-4971

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Language: English

In: Blood, 2015-05-21, Vol.125 (21), p.3347-3350

Description: Allogeneic hematopoietic stem cell transplantation (SCT) is the only curative option for patients with primary myelofibrosis (PMF), but information on its net advantage over conventional therapies is lacking. Using ad hoc statistical analysis, we determined outcomes in 438 patients 〈65 years old at diagnosis who received allogenic SCT (n = 190) or conventional therapies (n = 248). Among patients at low risk per the Dynamic International Prognostic Scoring System (DIPSS) model, the relative risk of death after allogenic SCT vs those treated with nontransplant modalities was 5.6 (95% CI, 1.7-19; P = .0051); for intermediate-1 risk it was 1.6 (95% CI, 0.79-3.2; P = .19), for intermediate-2 risk, 0.55 (95% CI, 0.36-0.83; P = .005), and for high risk, 0.37 (95% CI, 0.21-0.66; P = .0007). Thus, patients with intermediate-2 or high-risk PMF clearly benefit from allogenic SCT. Patients at low risk should receive nontransplant therapy, whereas individual counseling is indicated for patients at intermediate-1 risk.

Subject(s): Primary Myelofibrosis - mortality ; Prognosis ; Humans ; Middle Aged ; Kaplan-Meier Estimate ; Proportional Hazards Models ; Hematopoietic Stem Cell Transplantation ; Male ; Primary Myelofibrosis - surgery ; Young Adult ; Allografts ; Adult ; Female ; Index Medicus ; Abridged Index Medicus ; Transplantation ; CME

ISSN: 0006-4971

E-ISSN: 1528-0020

DOI: 10.1182/blood-2014-10-608315

Source: HighWire Press (Free Journals)

Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Source: American Society of Hematology

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