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The Yale Journal of Biology and Medicine 1990The clinical pathologic syndrome of graft-versus-host disease (GVHD) is usually a sequela of bone marrow transplantation. This disorder occurs as a result of recognition... (Review)
Review
The clinical pathologic syndrome of graft-versus-host disease (GVHD) is usually a sequela of bone marrow transplantation. This disorder occurs as a result of recognition by engrafted donor-derived lymphocytes of "foreign" recipient transplantation antigens. GVHD may also result from engraftment of lymphocytes from other sources, including (1) transfusion of lymphocytes containing blood components, (2) transplacental maternal fetal transfusion, and (3) passive transfer of lymphocytes in solid organ transplantation. The recipients are usually severely immunodeficient and thus incapable of rejecting the transfused lymphocytes. This syndrome may, however, also develop in immunologically competent patients receiving blood products from individuals with histocompatibility antigens not recognized as foreign.
Topics: Diagnosis, Differential; Dose-Response Relationship, Immunologic; Graft vs Host Disease; Humans; Leukocyte Transfusion; Risk Factors; Transfusion Reaction; Ultraviolet Rays
PubMed: 2293503
DOI: No ID Found -
Cytotherapy Nov 2017Granulocyte transfusions (GTXs) have been used to treat and prevent infections in neutropenic patients for more than 40 years, despite persistent controversy regarding... (Review)
Review
Granulocyte transfusions (GTXs) have been used to treat and prevent infections in neutropenic patients for more than 40 years, despite persistent controversy regarding their efficacy. This narrative review attempts to complement recent systematic reviews by the Cochrane Collaboration and provide both historical context and critical assessment of the most significant clinical studies published over the years. The data suggest that properly collected and promptly infused granulocytes are active against infections, both bacterial and fungal. The most important question that remains unanswered is in which patients the administration of granulocytes will be beneficial. The preponderance of evidence suggests that granulocyte transfusions may be efficacious in few select cases as a temporizing measure to control an infection that is expected (or proven) to be refractory to optimal antimicrobial treatment, and that could otherwise be controlled by marrow recovery, which is expected to happen. In this regard, they are best considered a "bridge" that grants enough time for the recipient to develop their own response to the infection. The challenges to use GTXs successfully are both clinical, in terms of timely identifying the patients who may benefit, and logistical, in terms of optimal selection of donors and collection technique.
Topics: Anemia, Aplastic; Case-Control Studies; Child; Controlled Clinical Trials as Topic; Granulocytes; Humans; Infection Control; Infections; Leukocyte Transfusion; Neutropenia; Tissue Donors; Treatment Outcome
PubMed: 28916227
DOI: 10.1016/j.jcyt.2017.08.012 -
Best Practice & Research. Clinical... Dec 2016Management of relapsed leukemia following allogeneic transplantation is challenging. Intensive chemotherapy, donor lymphocyte infusions (DLI), or second transplantation... (Review)
Review
Management of relapsed leukemia following allogeneic transplantation is challenging. Intensive chemotherapy, donor lymphocyte infusions (DLI), or second transplantation have some value, but most reported series describe only a limited number of patients surviving beyond 2 or 3 years following relapse. Additionally, understandable selection-bias of reports describing the outcomes of intensive management approaches for relapsed leukemia confound generalizability to a broader population. However numerous reports suggest that second allogeneic transplantation for relapsed leukemia following an initial transplant may produce extended disease control and survival for patients with favorable performance status, remission at the time of second transplant, and most importantly a long interval between initial transplant and relapse. Reduced intensity conditioning for second allografts may be preferable and little data exists to suggest that a new donor will improve disease control by inducing a stronger graft-versus-leukemia effect. Improved measures to prevent the first relapse, however, may protect more patients and produce a greater fraction enjoying extended leukemia-free survival.
Topics: Allografts; Disease-Free Survival; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Lymphocyte Transfusion; Recurrence; Survival Rate
PubMed: 27890260
DOI: 10.1016/j.beha.2016.10.011 -
Best Practice & Research. Clinical... Jun 2008Donor leukocyte infusion (DLI) is used after both myeloablative and non-myeloablative stem-cell transplantation to treat and prevent relapse, to establish full donor... (Review)
Review
Donor leukocyte infusion (DLI) is used after both myeloablative and non-myeloablative stem-cell transplantation to treat and prevent relapse, to establish full donor chimerism, and to treat and prevent infections. The major treatment-related complication of DLI is graft-versus-host disease (GVHD). The presentation and treatment of GVHD after DLI is similar to its presentation and treatment after stem-cell transplantation, with some notable exceptions. While GVHD and graft-versus-tumor (GVT) effects are highly correlated after DLI, some patients experience remission without GVHD. Studies to define tumor-specific target antigens and GVT effector cells, as well as strategies of donor T-cell manipulation and optimization of DLI dose and schedule, may ultimately lead to the consistent ability to separate GVHD from GVT activity, improvement in the safety and specificity of DLI, and enhancement of the anti-tumor activity of donor T cells.
Topics: Graft vs Host Disease; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Leukocyte Transfusion; Lymphocyte Depletion
PubMed: 18503987
DOI: 10.1016/j.beha.2008.02.007 -
Pediatrics and Neonatology Apr 2008Critically ill children in pediatric intensive care units are commonly indicated for blood transfusion due to many reasons. Children are quite different from adults... (Review)
Review
Critically ill children in pediatric intensive care units are commonly indicated for blood transfusion due to many reasons. Children are quite different from adults during growth and development, and that should be taken into consideration. It is very difficult to establish a universal transfusion guideline for critically ill children, especially preterm neonates. Treating underlying disease and targeted replacement therapy are the most effective approaches. Red blood cells are the first choice for replacement therapy in decompensated anemic patients. The critical hemoglobin concentration may be higher in critically ill children for many reasons. Whole blood is used only in the following conditions or diseases: (1) exchange transfusion; (2) after cardiopulmonary bypass; (3) extracorporeal membrane oxygenation; (4) massive transfusion, especially in multiple component deficiency. The characteristics of hemorrhagic diseases are so varied that their therapy should depend on the specific needs associated with the underlying disease. In general, platelet transfusion is not needed when a patient has platelet count greater than 10,000/mm3 and is without active bleeding, platelet functional deficiency or other risk factors such as sepsis. Patients with risk factors or age less than 4 months should be taken into special consideration, and the critical thrombocyte level will be raised. Platelet transfusion is not recommended in patients with immune-mediated thrombocytopenia or thrombocytopenia due to acceleration of platelet destruction without active bleeding or life-threatening hemorrhage. There are many kinds of plasma-derived products, and recombinant factors are commonly used for hemorrhagic patients due to coagulation factor deficiency depending on the characteristics of the diseases. The most effective way to correct disseminated intravascular coagulation (DIC) is to treat the underlying disease. Anticoagulant therapy is very important; heparin is the most common agent used for DIC but the results are usually not satisfactory. Antithrombin III, protein C, or recombinant thrombomodulin has been used successfully to treat this condition. For reducing the risk of organism transmission and adverse reactions resulting from blood transfusion, the following measures have been suggested: (1) replacement therapy using products other than blood (e.g., erythropoietin, iron preparation, granulocyte colony-stimulating factor); (2) special component replacement therapy for specific diseases; (3) autotransfusion; (4) subdividing whole packed blood products into smaller volumes to reduce donor exposure; (5) advances in virus-inactivating procedures. To avoid viral transmission, vapor-heated or pasteurized products and genetic recombinant products are recommended. Cytomegalovirus (CMV)-seronegative blood, leukoreduced and/or irradiated blood are recommended for prevention of CMV infection, graft-versus-host-disease and alloimmunization in neonate and immunocompromised patient transfusion. There is no reason to prescribe a plasma product for nutritional supplementation because of the risk of complications. The principle: complications of transfusion must be avoided, the rate of blood exposure should be reduced and the safety of the transfused agents or components should be maintained must always be kept in mind.
Topics: Anemia; Blood Transfusion; Child; Critical Illness; Erythrocyte Transfusion; Exchange Transfusion, Whole Blood; Humans; Leukocyte Transfusion; Platelet Transfusion
PubMed: 18947009
DOI: 10.1016/S1875-9572(08)60004-2 -
Science Translational Medicine Jul 2021Clinical outcomes from granulocyte transfusion (GTX) are disadvantaged by the short shelf life and compromised function of donor neutrophils. Spontaneous neutrophil...
Clinical outcomes from granulocyte transfusion (GTX) are disadvantaged by the short shelf life and compromised function of donor neutrophils. Spontaneous neutrophil death is heterogeneous and mediated by multiple pathways. Leveraging mechanistic knowledge and pharmacological screening, we identified a combined treatment, caspases-lysosomal membrane permeabilization-oxidant-necroptosis inhibition plus granulocyte colony-stimulating factor (CLON-G), which altered neutrophil fate by simultaneously targeting multiple cell death pathways. CLON-G prolonged human and mouse neutrophil half-life in vitro from less than 1 day to greater than 5 days. CLON-G-treated aged neutrophils had equivalent morphology and function to fresh neutrophils, with no impairment to critical effector functions including phagocytosis, bacterial killing, chemotaxis, and reactive oxygen species production. Transfusion with stored CLON-G-treated 3-day-old neutrophils enhanced host defenses, alleviated infection-induced tissue damage, and prolonged survival as effectively as transfusion with fresh neutrophils in a clinically relevant murine GTX model of neutropenia-related bacterial pneumonia and systemic candidiasis. Last, CLON-G treatment prolonged the shelf life and preserved the function of apheresis-collected human GTX products both ex vivo and in vivo in immunodeficient mice. Thus, CLON-G treatment represents an effective and applicable clinical procedure for the storage and application of neutrophils in transfusion medicine, providing a therapeutic strategy for improving GTX efficacy.
Topics: Aged; Animals; Cell Death; Granulocyte Colony-Stimulating Factor; Humans; Leukocyte Transfusion; Mice; Neutropenia; Neutrophils
PubMed: 34321317
DOI: 10.1126/scitranslmed.abb1069 -
Blood Jan 2013
Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Humans; Leukemia-Lymphoma, Adult T-Cell; Lymphocyte Transfusion; Male; Salvage Therapy
PubMed: 23287623
DOI: 10.1182/blood-2012-11-464628 -
Experimental Hematology Apr 2017Allogeneic hematopoietic cell transplantation (allo-HCT) represents the only curative therapy for many haematological malignancies. Its curative potential is mostly... (Review)
Review
Allogeneic hematopoietic cell transplantation (allo-HCT) represents the only curative therapy for many haematological malignancies. Its curative potential is mostly attributed to the graft-versus-leukemia effect (GvL), which is mainly driven by donor T-cells. Donor lymphocyte infusions (DLI), likewise a second allo-HCT, have become a standard approach to treat AML and MDS relapses post allo-HCT. Although DLI have been used in this setting for decades, its effectivity and toxicity are still unpredictable in many patients. Over these recent years, new DLI strategies and therapies have been developed for AML and MDS. In this review, we will overview the recent use of DLI for AML and MDS, with up to date information from novel studies and research lines.
Topics: Animals; Combined Modality Therapy; Graft vs Host Disease; Graft vs Leukemia Effect; HLA Antigens; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Lymphocyte Transfusion; Myelodysplastic Syndromes; Retreatment; Tissue Donors; Transplantation, Homologous; Treatment Outcome
PubMed: 28027963
DOI: 10.1016/j.exphem.2016.12.004 -
The Cochrane Database of Systematic... Apr 2016Despite modern antimicrobials and supportive therapy bacterial and fungal infections are still major complications in people with prolonged disease-related or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite modern antimicrobials and supportive therapy bacterial and fungal infections are still major complications in people with prolonged disease-related or treatment-related neutropenia. Transfusions of granulocytes have a long history of usage in clinical practice to support and treat severe infection in high-risk groups of patients with neutropenia or neutrophil dysfunction. However, there is considerable current variability in therapeutic granulocyte transfusion practice, and uncertainty about the beneficial effect of transfusions given as an adjunct to antibiotics on mortality. This is an update of a Cochrane review first published in 2005.
OBJECTIVES
To determine the effectiveness and safety of granulocyte transfusions compared to no granulocyte transfusions as adjuncts to antimicrobials for treating infections in people with neutropenia or disorders of neutrophil function aimed at reducing mortality and other adverse outcomes related to infection.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 2). MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 11 February 2016.
SELECTION CRITERIA
RCTs comparing people with neutropenia or disorders of neutrophil dysfunction receiving granulocyte transfusions to treat infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, language or publication status.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by the Cochrane Collaboration.
MAIN RESULTS
We identified 10 trials that met the inclusion criteria with a total of 587 participants. We also identified another ongoing trial. These trials were conducted between 1975 and 2015. None of the studies included people with neutrophil dysfunction. The studies differed in the type of infections they included. Six studies included both children and adults, however data were not reported separately for children and adults. The two newest studies gave granulocyte colony stimulating factor (G-CSF) to donors; both were stopped early due to lack of recruitment. Three studies re-randomised participants and therefore quantitative analysis was unable to be performed.Overall the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcomes being imprecise.There may be no difference in all-cause mortality over 30 days between participants receiving therapeutic granulocyte transfusions and those that did not (six studies; 321 participants; RR 0.75, 95% CI 0.54 to 1.04; very low-quality evidence). There were no differences between the granulocyte dose subgroups (< 1 x 10(10) per day versus ≥ 1 x 10(10) per day) (test for subgroup differences P = 0.39). There was a difference in all-cause mortality between the studies based on the age of the study (published before 2000 versus published 2000 or later) (test for subgroup differences P = 0.03). There was no difference in all-cause mortality between participants receiving granulocyte transfusions and those that did not in the newest study (one study; 111 participants; RR 1.10, 95% CI 0.70 to 1.73, low-quality evidence). There may be a reduction in all-cause mortality in participants receiving granulocyte transfusions compared to those that did not in studies published before the year 2000 (five studies; 210 participants; RR 0.53, 95% CI 0.33 to 0.85; low-quality evidence).There may be no difference in clinical reversal of concurrent infection between participants receiving therapeutic granulocyte transfusions and those that did not (five studies; 286 participants; RR 0.98, 95% CI 0.81 to 1.19; low-quality evidence).There is insufficient evidence to determine whether there is a difference in pulmonary serious adverse events (1 study; 24 participants; RR 0.85, 95% CI 0.38 to 1.88; very low-quality evidence).None of the studies reported number of days on therapeutic antibiotics, number of adverse events requiring discontinuation of treatment, or quality of life.Six studies reported their funding sources and all were funded by governments or charities.
AUTHORS' CONCLUSIONS
In people who are neutropenic due to myelosuppressive chemotherapy or a haematopoietic stem cell transplant, there is insufficient evidence to determine whether granulocyte transfusions affect all-cause mortality. To be able to detect a decrease in all-cause mortality from 35% to 30% would require a study containing at least 2748 participants (80% power, 5% significance). There is low-grade evidence that therapeutic granulocyte transfusions may not increase the number of participants with clinical resolution of an infection.
Topics: Adult; Cause of Death; Child; Granulocytes; Humans; Infections; Leukocyte Transfusion; Neutropenia; Randomized Controlled Trials as Topic
PubMed: 27128488
DOI: 10.1002/14651858.CD005339.pub2 -
Blood Dec 2008Allogeneic transplantation of hematopoietic cells is an effective treatment of leukemia, even in advanced stages. Allogeneic lymphocytes produce a strong... (Review)
Review
Allogeneic transplantation of hematopoietic cells is an effective treatment of leukemia, even in advanced stages. Allogeneic lymphocytes produce a strong graft-versus-leukemia (GVL) effect, but the beneficial effect is limited by graft-versus-host disease (GVHD). Depletion of T cells abrogates GVHD and GVL effects. Delayed transfusion of donor lymphocytes into chimeras after T cell-depleted stem cell transplantation produces a GVL effect without necessarily producing GVHD. Chimerism and tolerance provide a platform for immunotherapy using donor lymphocytes. The allogeneic GVL effects vary from one disease to another, the stage of the disease, donor histocompatibility, the degree of chimerism, and additional treatment. Immunosuppressive therapy before donor lymphocyte transfusions may augment the effect as well as concomitant cytokine treatment. Possible target antigens are histocompatibility antigens and tumor-associated antigens. Immune escape of tumor cells and changes in the reactivity of T cells are to be considered. Durable responses may be the result of the elimination of leukemia stem cells or the establishment of a durable immune control on their progeny. Recently, we have learned from adoptive immunotherapy of viral diseases and HLA-haploidentical stem cell transplantation that T-cell memory may be essential for the effective treatment of leukemia and other malignancies.
Topics: Antineoplastic Agents; Benzamides; Blood Donors; Graft vs Host Disease; Graft vs Host Reaction; Graft vs Leukemia Effect; Humans; Imatinib Mesylate; Immune Tolerance; Immunotherapy, Adoptive; Leukemia; Lymphocyte Transfusion; Lymphocytes; Piperazines; Pyrimidines; Transplantation Immunology; Tumor Escape
PubMed: 19029455
DOI: 10.1182/blood-2008-03-077974