Hematopoietic reconstitution and prevention of graft-versus-host disease with UVB-irradiated haploidentical murine spleen and marrow cells.

We investigated in a murine model whether UVB irradiation of lymphohemopoietic cells would prevent the development of graft-versus-host disease (GVHD). Preliminary experiments showed that spleen colony (CFU-S) formation by hemopoietic cells was preserved at UVB doses that eliminated lymphocyte proliferation. In a parent into F1 model, UVB irradiation (5 to 15 mJ/cm2) of spleen cells added to normal marrow cells prevented the development of GVHD, whereas all recipients given untreated spleen cells developed GVHD.

Late failure of autologous marrow grafts in lethally irradiated dogs given anti-class II monoclonal antibody.

We established a model of canine marrow autografts after 9.2 Gy total body irradiation (TBI) to study the role of class II antigens in hematopoietic stem cell growth and differentiation. Twenty dogs were given 9.

UV irradiation of lymphocytes triggers an increase in intracellular Ca2+ and prevents lectin-stimulated Ca2+ mobilization: evidence for UV- and nifedipine-sensitive Ca2+ channels.

UV irradiation induces in vitro and in vivo immunosuppression. Because mobilization of intracellular calcium ([Ca2+]i) represents a central step in cell activation and immune response, we investigated the effect of UV irradiation on Ca2+ homeostasis. Using indo-1 and cytofluorometry, [Ca2+]i kinetics in UVC- or UVB-exposed human peripheral blood leukocytes (PBL) and Jurkat cells were determined in parallel with functional assays.

Some but not all benefits of intravenous immunoglobulin therapy after marrow transplantation appear to correlate with IgG trough levels.

Multiple benefits of intravenous immunoglobulin (IVIG) therapy after marrow transplantation have been reported, including decreased incidence of acute graft-versus-host disease (GVHD), infection, sepsis, cytomegalovirus (CMV) pneumonitis and platelet use. To test the hypothesis that the observed beneficial effects of IVIG are related to the serum IgG levels achieved, we followed IgG levels (pre-infusion, 1 h and 24 h post-infusion) in 45 consecutive marrow transplant recipients. IVIG 500 mg/kg was given weekly for six doses starting day -8 pre-transplant, then every other week for a total of 11 doses.

Transfusions shortly before HLA-matched marrow transplantation for leukemia are associated with a decrease in chronic graft-versus-host disease.

The effect of random red cell transfusions given shortly before allogeneic bone marrow transplantation (BMT) was evaluated in 969 leukemic patients transplanted from an HLA-identical sibling donor. Patients were divided into two groups: 501 who received a transfusion shortly before BMT, and 468 who did not. Both groups had a similar incidence of acute graft-versus-host disease (GVHD), but the recently-transfused group had a significantly lower incidence of chronic GVHD (35.

Conditioning-related toxicity and acute graft-versus-host disease in patients given methotrexate/cyclosporine prophylaxis.

Intensive chemoradiotherapy conditioning regimens and acute graft-versus-host disease (GVHD) are both associated with significant morbidity and mortality after bone marrow transplantation. In this study, we investigated whether the conditioning regimen affected the development of acute GVHD. Thirty-four patients, four with severe aplastic anemia and 30 with a lymphohemopoietic malignancy, were prepared for transplantation either with cyclophosphamide (CY) alone, with CY combined with total body irradiation (TBI) or CY combined with etoposide and either TBI or busulfan.

Inhibition of cluster formation and lymphocyte proliferation by anti-fibronectin antiserum.

Dendritic cells (DC) confer concanavalin A responsiveness to accessory cell-depleted canine lymphocytes. DC-lymphocyte cluster formation is followed by blast transformation and proliferation of lymphocytes. We investigated whether fibronectin, which is known to be involved in cell:cell interactions, might also be involved in the interaction between canine DC and lymphocytes.

Transfusion-induced graft-versus-host disease in patients with malignant lymphoma. A case report and review of the literature.

A case of transfusion-induced graft-versus-host disease (GVHD) occurring in a 31-year-old female with Hodgkin's disease in complete remission is reported. Clinical features are similar to 19 other reported cases of transfusion-induced GVHD associated with malignant lymphoma. The lack of relationship with underlying histology or disease stage and the nearly uniformly fatal outcome underscores the importance of prophylactic irradiation of blood products given to patients with malignant lymphoma undergoing therapy.

Effective ultraviolet irradiation of platelet concentrates in teflon bags.

Several plastic materials used in blood storage were evaluated for their ability to transmit ultraviolet B (UVB) light. A plastic bag manufactured from sheets of transparent Teflon efficiently (78-86%) transmitted UVB light and was employed in subsequent functional studies of lymphocytes and platelets exposed to UVB light while contained in these bags. In vitro experiments showed a UVB dose-dependent abrogation of lymphocyte responder and stimulator functions, with concurrent preservation of platelet aggregation responses.

Ultraviolet B-induced loss of HLA class II antigen expression on lymphocytes is dose, time, and locus dependent.

Ultraviolet B (UVB) irradiation interferes with the afferent and efferent loops of the immune response. One mechanism that has been suggested is the decline of class II histocompatibility antigen expression on the cell surface. However, data in the literature are controversial.

Processing and storage of human bone marrow: a survey of current practices in North America.

We conducted a two-step survey to question 110 transplant centers in the United States and Canada regarding marrow processing and storage policies and procedures. Approximately 65% of the centers surveyed responded to the questionnaires. Major differences with respect to patient diagnoses, amount of marrow harvested, purging method applied, freezing procedure, storage bag, cell concentrations, storage duration, interval until transplantation, cell counting, viability determination and so forth were reported.

Inhibition of the enzyme purine nucleoside phosphorylase (PNP) reduces refractoriness to transfused platelets in a dog model.

To better define the role of T-cells in alloimmunization, we induced purine nucleoside phosphorylase (PNP) deficiency in a dog platelet transfusion model. Short-term administration of eight different drug schedules using several combinations of the PNP inhibitor 8-aminoguanosine and/or deoxyguanosine did not induce significant toxicity in four treated animals as demonstrated by blood chemistries, cell counts, and autologous platelet recovery and survival measurements. However, continuous long-term daily administration of these agents produced significant renal and/or hepatic toxicity leading to death in five of six animals.

Management of acute graft-versus-host disease.

Current graft-versus-host disease (GVHD) prophylaxis is not uniformly successful. Since the development of GVHD has a profound impact on transplant success, treatment is required. The mainstay of therapy has been glucocorticoids (steroids), along with anti-thymocyte globulin, cyclosporine, monoclonal antibodies, and aggressive supportive care, resulting in response rates of 30-50%, dependent upon severity of the disease, type of transplant, underlying diagnosis, prophylaxis given and other factors.

Delayed complications and long-term effects after bone marrow transplantation.

Bone marrow transplantation is being used with increasing frequency and success for an expanding number of indications. At present, more than 1000 patients are surviving more than 5 years and several hundred more than 10 years after transplantation. Extended observation periods have shown that numerous complications have to be expected in these patients, particularly in those given TBI as part of the conditioning regimen.

Incapacitating peripheral neuropathy as a manifestation of chronic graft-versus-host disease.

A 35-year-old caucasian man developed mild and transient signs of chronic graft-versus-host disease (GVHD) 5 months after bone marrow transplantation. At 16 months he presented with painful cramps in hands, feet, and truncal muscles. Electrophysiological studies revealed generalized sensory neuropathy.

Batten's disease: failure of allogeneic bone marrow transplantation to arrest disease progression in a canine model.

We investigated whether the course of canine ceroid lipofuscinosis (CCL), a model of Batten's disease in man, was affected by allogeneic bone marrow transplantation. Four English setters with CCL, 4 1/2 months of age, were given 9.2 Gy of total body irradiation, followed by the infusion of bone marrow cells from healthy DLA identical sibling donors.