Guidelines for safety management of granulocyte transfusion in Japan.

Granulocyte transfusion (GTX) has recently been revived by the ability to stimulate granulocyte donors with granulocyte colony-stimulating factor (G-CSF), resulting in a greatly increased number of cells that can be collected. However, there is a paucity of guidelines for assessing the appropriateness and safety management of GTX. The objective of this study was to establish guidelines for the safety management of GTX appropriate for the clinical situation in Japan. The Japan Society of Transfusion Medicine and Cell Therapy, Granulocyte Transfusion Task Force issued the first version of guidelines for GTX considering the safety management of both granulocyte donors and patients who receive GTX therapy. The current guidelines cover issues concerning: (1) the appropriateness of medical institutions, (2) management of granulocyte donors, (3) quality assurance of granulocyte concentrates, (4) administration of granulocyte concentrates, (5) evaluation of the effectiveness of GTX therapy, and (6) complications of GTX therapy. The simple 'bag separation method' without apheresis may be recommended for granulocyte collection in pediatric patients. The first version of guidelines for GTX therapy has been established, which may be appropriate for the clinical situation in Japan. Care should be taken to perform the safety management of both granulocyte donors and patients who receive GTX therapy.

Granulocyte concentrates: how can we assess their quality?

The use of granulocyte transfusions to treat and prevent life-threatening infection in patients lacking neutrophil numbers or function may become increasingly important in aiding advances in the treatment of haematological malignancies. A critical factor in determining the outcome of granulocyte transfusion is the number of cells transfused, and collection of sufficiently high concentration of cells from donors remains challenging. A number of tests of granulocyte function can be performed in vitro to assess the quality of granulocyte concentrates, which may be useful in helping to optimize granulocyte collection, processing and storage methods. Studies that have examined neutrophil function in granulocyte concentrates to date have tended to focus on the assessment of viability, chemotaxis, phagocytosis and oxidative killing. How useful in vitro tests of neutrophil function are in predicting neutrophil function following granulocyte transfusion remains to be established in conjunction with well-designed clinical trials.

Unrelated donor leukocyte infusions to treat relapse after unrelated donor bone marrow transplantation.

Allogeneic stem cell transplantation (SCT) may cure many patients with hematologic malignancies due to both the intensive conditioning therapy, and in many patients, the potent graft-vs-leukemia (GVL) effect of the donor graft. The GVL effect is mediated in large part by mature T-cells contained in the donor graft and has been defined in detail in animal models of transplantation. The GVL activity has been observed in the clinical setting after SCT from both matched siblings and unrelated donors. The best demonstration and most direct evidence of GVL activity in humans come from the use of donor leukocyte infusions (DLI). For patients who relapse with chronic myelogenous leukemia after matched sibling SCT, infusions of leukocytes collected from the original transplant donor will re-establish complete and durable remission in 60-80% of patients. DLI is less effective for more advanced phases of CML and for patients who relapse with diseases other than CML. DLI after matched sibling SCT is complicated primarily by graft-vs-host disease (GVHD), marrow aplasia, and unfortunately, relapse in some cases. There has been little information regarding the use of unrelated DLI (UDLI). Available data now shows that despite initial concerns that UDLI would result in excessive toxicity, it is an effective approach to relapse after unrelated donor marrow grafting. Response rates are similar to those seen after the use of matched sibling DLI, and many remissions remain durable. Graft-vs-host disease is a frequent complication after UDLI though the incidence and severity of GVHD is also similar to the use of matched sibling DLI. It is not clear that the GVL and GVHD effects can be separated, since the majority of responding patients also develop GVHD. The most effective cell dose for UDLI has not been established, though there does not appear to be either a dose-response or dose-toxicity relationship from UDLI. Although second unrelated donor bone marrow transplantation (BMT) may cure a small minority of patients, GVL induction with UDLI offers a safer and potentially more effective therapy for relapsed leukemia, and offers insights in methods to manipulate the human immune system for therapeutic benefit.

Granulocyte transfusion therapy: update on potential clinical applications.

The clinical usefulness of granulocyte transfusions for treatment or prevention of life-threatening bacterial and fungal infections remains controversial. Clinical benefit has long been limited by insufficient donor stimulation regimens and suboptimal leukapheresis techniques. Methodologic progress, in particular mobilization of neutrophils in healthy donors by administration of G-CSF, has significantly enhanced leukapheresis yields. A newly published study indicates that unrelated community donors can be effectively and safely used as an alternative to related family donors. Furthermore, several recent studies suggest that it may be possible to store granulocyte concentrates for 24 to 48 hours with adequate preservation of neutrophil function. This review summarizes the current role of granulocyte transfusion therapy in infectious diseases and highlights important recent advances.

Donor leukocyte infusions in acute lymphocytic leukemia.

Donor leukocyte infusion (DLI) has well-documented activity in CML but the role of DLI in other diseases is less well defined. To evaluate the strategy in acute lymphocytic leukemia (ALL) we evaluated 44 ALL patients from 27 centers who were treated with DLI. Patients with persistent or recurrent disease received DLI from the original marrow donor (30 matched related, four mismatched family, and 10 matched unrelated). Chemotherapy was given before DLI to 28 patients. Of 15 patients who received no pre-DLI chemotherapy, two achieved complete remissions, lasting 1112 and 764+ days. In four patients who received DLI as consolidation of remission induced by chemotherapy or immunosuppression-withdrawal, duration of remission post DLI was 65, 99, 195 and 672+ days. Of 25 patients who received DLI in the nadir after chemotherapy, 13 survived > or =30 days post DLI but did not achieve remission, seven died within less than 30 days post DLI, and five entered remissions that lasted 42, 68, 83, 90, 193 days. Seven patients who did not respond to the initial DLI received a second DLI; none of these patients attained durable remission. Eighteen of 37 evaluable patients developed acute GVHD and five of 20 evaluable patients developed chronic GVHD. Overall actuarial survival is 13% at 3 years. In conclusion, DLI has limited benefit in ALL. New approaches are needed in this group of patients.

La transfusión de sangre y los componentes sanguíneos / Blood transfusion and blood components

El artículo ofrece una descripción de los aspectos más importantes a tener en cuanta en los procesamientos de las transfusiones sanguíneas y brinda un resumen de las características de la sangre total y de los hemoderivados utilizados con mayor frecuencia

La transfusión de sangre y los componentes sanguíneos / Blood transfusion and blood components

El artículo ofrece una descripción de los aspectos más importantes a tener en cuanta en los procesamientos de las transfusiones sanguíneas y brinda un resumen de las características de la sangre total y de los hemoderivados utilizados con mayor frecuencia (AU)

Immunotherapy with husband's leukocytes to primary habitual aborters and autoantibodies in their sera.

OBJECTIVE: This study was performed to determine whether primary habitual aborters have an autoimmunological tendency and whether immunotherapy with leukocytes induces autoantibodies in their sera. METHODS: We measured the levels of antiphospholipid antibodies (APAs) and antinuclear antibodies (ANAs) in the sera of 65 primary habitual aborters. Among them, 8 primary habitual aborters received immunotherapy with their respective husband's leukocytes; these 8 patients were followed up for autoantibodies in their sera before immunotherapy, at the time of pregnancy permission, during the first trimester of pregnancy, at delivery, and postpartum. RESULTS: Sixty-nine percent of the 65 primary habitual aborters were positive for IgG or IgM antibodies to at least 1 of 6 phospholipids, and 29% of them were positive for ANAs. Although the pregnancy outcomes of the 8 primary habitual aborters after immunotherapy were good, their APAs and ANAs converted to positive after the immunotherapy. CONCLUSION: Immunotherapy with leukocytes should be performed after checking and confirming the absence of autoantibodies in the sera of a habitual aborter.