Increase in IgG-secreting lymphocytes following blood transfusion.
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Antibody-Producing Cells↗
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Results for “Lymphocyte Transfusion”
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Graft-versus-host reaction following blood product transfusion.
The observation of graft-versus-host (GVH) reaction after platelet transfusion in a patient with Hodgkin's disease led us to analyze 38 reported cases in the literature, to outline prognostic factors and to characterize patients at risk. Overall mortality was 68 percent. It was higher among children (76 percent) than among adults (62 percent), and among patients with Hodgkin's disease and immune deficiency syndromes (88 percent) than among those with leukemias (23 percent, p less than 0.005). Following blood transfusions from normal donors, mortality was higher (88 percent) than after transfusions from donors with chronic myelocytic leukemia (25 percent, p less than 0.05). Minimal lymphocyte doses necessary to cause GVH reaction are in excess of 10(7)/kg. Adults seem more resistant to homografts than do children, and the host's cellular immune status is of major prognostic importance. Lymphocytes from donors with chronic myelocytic leukemia may be deficient, and after a threshold dose, the number of lymphocytes transfused does not correlate with clinical outcome. Effective prophylactic measures do exist for this complication but satisfactory therapy does not.
Adolescent↗
Involvement of Fas-mediated apoptosis in the hematopoietic progenitor cells of graft-versus-host reaction-associated myelosuppression.
The influence of graft-versus-host (GVH) reaction on the host hematopoietic cells clinically manifests itself both as adverse reactions in transfusion-associated GVH disease (GVHD) and as a therapeutic graft-versus-leukemia (GVL) effect in either donor lymphocytes transfusion (DLT) or allogeneic bone marrow (BM) transplantation. We examined the effect of GVH reaction on the host hematopoiesis in the murine parent-into-F1 (P1 --> F1) model of GVHD. The systemic transfer of 5 x 10(7) of C57BL/6 (B6) splenocytes into (B6xDBA/2)F1 mice (BDF1), which results in acute GVHD, reduced the peripheral blood cell counts, the number of BM cells, and colony-forming unit-granulocyte macrophage (CFU-GM), whereas the injection of 10(8) of DBA/2 cells into BDF1, which results in chronic GVHD, did not affect hematopoiesis 2 weeks after the transfer. To clarify the mechanism of such myelosuppression, we examined the Fas expression in both hematopoietic progenitor cells as well as whole BM cells. The Fas expressions in each fraction significantly increased in BDF1 mice 2 weeks after the induction of acute GVHD, whereas no such effects were observed in the BDF1 mice with chronic GVHD. Furthermore, when such BM cells were incubated with anti-Fas antibody (Jo2), which induces apoptosis through Fas, the fraction of apoptotic cells increased and the number of CFU-GM decreased significantly. The in vivo administration of neutralizing anti-FasL antibody into BDF1 mice receiving with B6 spleen cells thus protected the host mice from BM failure. These results indicate that the functional expression of Fas on hematopoietic cells plays an essential role in the myelosuppressive effect of GVHD.
Animals↗
An attempt at passive transfer of immunity to leprosy patients by transfusion of allogeneic lymphocytes, inactivated with mitomycin C.
An attempt was made to repair cell-mediated immunity in 7 patients suffering from lepromatous leprosy and severe erythema nodosum leprosum by intravenous infusion of 400 million allogeneic blood lymphocytes on 3 occasions. The lymphocytes were obtained from lepromin and tuberculin-positive subjects and were inactivated in vitro by treatment with mitomycin C. Immunotherapy with inactivated lymphocytes only modified the severity of erythema nodosum leprosum, without altering other aspects of the disease.
Blood Transfusion↗
Graft-versus-leukaemia.
The high relapse rate after T-cell depleted bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML) and the ability of donor lymphocyte transfusions to induce stable remission in patients relapsing after BMT has emphasized the importance of alloreacting donor T-lymphocytes in the graft-versus-leukaemia (GVL) effect in this disease. The mechanisms underlying the GVL response and its relationship with graft-versus-host disease are becoming better defined. There is accumulating evidence that the CD4+ T-cell plays a central role in the GVL response. The prominent role of GVL in the cure of CML after BMT may be associated with the fact that CML cells are strongly immunogenic. New transplant strategies are being devised to separate GVL from graft-versus-host reactions. Future developments focus on the identification of leukaemia-specific antigens and the amplification of T-cell responses against them.
Bone Marrow Transplantation↗
Fatal graft-versus-host disease following transfusion of granulocytes from normal donors.
A case of fatal graft-versus-host disease was seen in an adult with acute leukaemia, after transfusion of leucocytes from normal donors. This is the first reported case of graft-versus-host disease following transfusion of normal blood-products to a patient with a disease not usually associated with severe immunoincompetence. The number of lymphocytes transfused was no higher than that given when platelet concentrates are prepared from a single donor.
Graft vs Host Disease↗
CD34+ cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies.
After autologous or allogeneic transplants of peripheral blood stem cells (PBSC), an adequate dose of CD34+ cells is necessary to ensure early and sustained hematopoietic engraftment and favorable clinical outcome. There are no comparable data on the relationship between CD34+ cell dose and recovery after allogeneic bone marrow transplants (BMT). Twenty-eight patients with hematologic malignancies received a BMT from an HLA-identical sibling, using T-cell depletion and cyclosporin for graft-versus-host disease prophylaxis and delayed donor lymphocyte transfusions in an attempt to prevent leukemia relapse. The treatment-related mortality (TRM), primarily due to infections and cytopenias, was significantly higher for 13 patients receiving less than 1 x 10(6) CD34+ cells/kg (64.9% +/- 12.8% v 6.9% +/- 6.4%, P = .003). Survival at a median follow-up of 1 year was also lower in the group receiving less than 1 x 10(6) CD34+ cells/kg (30.8% +/- 12.8 v 74.3% +/- 13.7%, P = .005). The CD34+ cell dose was the only variable significantly associated with TRM. The dose of CD34+ cells also correlated with speed of hematopoistic recovery. Patients receiving more than 2 x 10(6) CD34+ cells/kg showed significantly earlier recovery of monocytes and a trend for earlier recovery of lymphocytes. They achieved platelet and red blood cell transfusion independence earlier, required less granulocyte colony-stimulating factor support during ganciclovir treatment, and spent fewer days in the hospital after transplantation. These results suggest that, for allogeneic T-cell-depleted BMT, the higher CD34+ cell doses may improve outcome in engrafting patients.
Adult↗
An autoradiographic study of the difference between thymus and lymph node lymphocytes shown by transfusion of labelled cells.
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Blood Transfusion↗
The abrogation of sheep erythrocyte tolerance in rats by means of the transfer of allogeneic lymphocytes.
Whereas the transfer of lymphocytes from normal syngeneic donors fails to abrogate tolerance of sheep erythrocytes in rats, lymphocytes from allogeneic donors are effective. When tolerance is abrogated in this situation, the hemolysin-forming cells are predominantly of host origin. Immunological interaction between transfused lymphocytes and host cells is a prerequisite for the abrogation of tolerance. From the time required for abrogation to occur after transfer of the allogeneic cells, it is suggested that tolerance of sheep erythrocytes in rats represents the repression of a specific reactivity in cells rather than the elimination or irreversible inactivation of reactive cells. This explanation implies the existence of specifically tolerant cells.
Animals↗
Transfusion of the patient with acquired immunodeficiency syndrome.
Cytopenias are commonly found in patients infected with human immunodeficiency virus. Thrombocytopenia due to peripheral destruction of platelets is an early manifestation, normocytic anemia and neutropenia are late manifestations. Transfusions are required when symptoms become severe. Chemotherapy of patients with the acquired immunodeficiency syndrome (AIDS) is also cytotoxic and further contributes to the transfusion requirement. Patients with AIDS receiving treatment with zidovudine, in particular, have a high transfusion requirement. Empirically, many centers irradiate blood products transfused to AIDS patients to prevent possible graft-vs-host reaction in the immunologically compromised recipient. Attempts to correct the deficiency of helper T cells with lymphocyte transfusion and marrow transplantation have so far been ineffective. Similarly, therapeutic trials to treat this disease by apheresis of virus-bearing cells has been ineffective and has, therefore, been abandoned.
Acquired Immunodeficiency Syndrome↗
Studies on lymph humoral factor. Biological characteristics of a lymphocytopoietic factor in rat thoracic duct lymph.
The biological characteristics of a lymphocytopoietic factor obtained from rat thoracic duct lymph (Yamashita, Fukumoto & Miyamoto, 1976) were further investigated. The lymph extract from normal rats failed to stimulate both large pyroninophilic cell-proliferation and mitotic response in the spleen and lymph node of the thymectomized, irradiated and marrow reconstituted rat (B rat). This suggests that target or responsive cells for the factor are not marrow-derived (B) cells, but thymus-derived (T) cells. On the other hand, the lymph extract from the lymphopenic lymph-drained B rats showed similar high lymphopoietic activity to those of normal rats, indicating that the existence of a thymus is not essential for the production or secretion of the factor. The fact that lymphocytotic rats produced by syngeneic lymphocyte transfusion are most sensitive to the lymph extract suggests that liver endogenous level of this factor and the responsiveness of target cells are regulated by the number of circulating T lymphocytes.
Animals↗
[Donor leukocyte transfusion in a patient with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation: analysis of natural killer cell activity and T-cell receptor repertoire in bone marrow T cells that exhibited graft-versus-leukemia activity].
Hematologic relapse of chronic myeloid leukemia developed in 37-year-old man 255 days after allogeneic bone marrow transplantation. The patient received a donor lymphocyte transfusion (DLT) twice at a dose of 5 x 10(6)/kg T cells. He achieved complete cytogenetic response (CCR) 14 weeks after DLT, and has remained in a CCR state for 17 months. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. Natural killer (NK) cell activity was elevated. Also, analysis of the T cell receptor (TCR) repertoire disclosed oligoclonal expansion of T cells of the TCR V beta and J beta subfamilies. These observations provide evidence for the clonal expansion of allogeneic T cells that are capable of mediating antileukemic activity without causing GVHD.
Adult↗
Mixed lymphocyte culture--evidence that pretransplant transfusion with platelets induces FcR and blocking antibody production similar to that induced by leukocyte transfusion.
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Binding Sites, Antibody↗
Interleukin-2 in cancer therapy.
Interleukin-2 (IL-2) is a true biological response modifier. Unlike alpha-interferon, which acts directly, IL-2 mediates its antitumor effects through complex indirect effects on the immune system. IL-2 used alone shows documented antitumor activity, which is both dose and schedule related. Antitumor activity may be increased by the use of either IL-2 in combination with other cytokines or monoclonal antibodies or both types of agents in combination with activated effector cytotoxic lymphocytes. In humans, data suggest that IL-2s rapid initial clearance is due to movement into an extravascular compartment from which IL-2 returns more slowly to the plasma. Toxicity appears to be due entirely to IL-2, rather than to transfused lymphocytes. IL-2 administered by continuous infusion is superior to bolus administration. However, at total daily-dose equivalence continuous infusion of IL-2 is both more toxic and more biologically active than bolus administration, with respect to the height of post-IL-2 rebound lymphocytosis, the generation of activated circulating lymphocytes, and lymphokine-activated killer-cell precursors. The question remains unresolved as to whether the toxicity of IL-2 therapy is necessary for the attainment of optimal clinical results. From currently available data, it appears that a minority of patients treated with IL-2 show clinically significant responses, and only 5% to 10% achieve durable complete responses. Nevertheless, these reproducible responses have occurred in tumors refractory to more conventional treatment. The reasons for non-response are unclear, but many avenues of investigation suggest that IL-2 therapy may be made both more active and more tolerable through the use of alternative doses and schedules and the use of IL-2 in combination with defined antitumor effector lymphocytes, with concomitant or sequential administration of other cytokines, or together with monoclonal antibodies.
Animals↗
Lessons from past experience in cancer immunotherapy and their application to cancer and AIDS treatment and prophylaxis.
Passive immunotherapy which we attempted in 1957 using polyclonal antibodies from immunized donors aggravated tumor evolution: we suspected that blocking by Ig, tumor cell antigen epitopes which are necessary to enhance or even maintain the T-lymphocyte effector role in anti-cancer immunity could be the reason for this tumor aggravation by "specific" antibodies. Today the very limited results of monoclonal antibodies in cancer treatment favors this hypothesis. The aggravation of HIV by (some) antibodies suggests that the same phenomenon may also happen in this condition. In 1957, on the other hand, we described the therapeutically beneficial cytostatic targetting effect of polyclonal antibodies, an effect which has often been quoted and widely confirmed. Does the reason for the poor results of monoclonal antibody targetting in tumor treatment reside in cancer antigen heterogeneity? This is what an experiment we conducted with Olsson on AkR leukemia indicated, suggesting that several monoclonals should be simultaneously combined for most patients, to be determined by the antigenic study not only of each tumor but of each localisation. We shifted our cancer immunotherapy approach to an adoptive form in 1959; a), after establishing partial and transient, then total and permanent allogeneic marrow graft and chimerism in man; b), after describing the graft versus leukemia (GvL) action of the graft versus host (GvH) effect in leukaemic mice; c), and the same phenomenon in humans. Our observations on human allogeneic grafted bone marrow GvH and GvL were statistically confirmed in 1979 by the Seattle group. In the 1970s we attempted to induce strong GvL with weak GvH by replacing allogeneic bone marrow graft by allogeneic lymphocyte transfusions without host conditioning. Remarkable results were registered in mice, and in patients with acute leukaemia--5 complete remissions out of 7 patients who developed moderate GvH, and only 3 out of 70 in those who did not develop GvH. As we now know that CD4-, CD8+ lymphocytes are not all MHCl-restricted, we consider that the allogeneic CTL approach is worth trying as reinforcement treatment of (at least) severe hematopoietic malignancies. If it is indeed worthwhile in some severe neoplasias to include the adoptive form of immunotherapy in the multi-treatment program, the replacement of the patient's bone marrow by engrafted allogeneic stem cells has not been proven necessary, as the persistence in "ALL cured" chemotherapy patients of abnormally differentiated cells does not reduce the expectancy of cure.(ABSTRACT TRUNCATED AT 400 WORDS)
Acquired Immunodeficiency Syndrome↗
Early intervention in post-transplant lymphoproliferative disorders based on Epstein-Barr viral load.
Using a real-time quantitative PCR assay, we identified two patients with EBV-related lymphoproliferative disorders at a very early stage. Both had received an unmanipulated bone marrow transplant with anti-thymocyte globulin for conditioning. To estimate virus-specific immunity, the frequencies of EBV-specific CD8+ T cells were measured using an enzyme-linked immunospot assay. The frequencies of EBV-specific CD8+ T cells of the two were 3.2 and 7.7%, respectively, which had possibly expanded in vivo. After withdrawing the immunosuppressive agents or administering donor lymphocytes transfusion, their symptoms regressed in parallel with the viral load.
Adult↗
A single-centre assessment of long-term quality-of-life status after sibling allogeneic stem cell transplantation for chronic myeloid leukaemia in first chronic phase.
A total of 75 patients underwent sibling allogeneic stem cell transplantation (SCT) for chronic myeloid leukaemia in first chronic phase from 1984 to 2000. Of these patients, 51 (68%) were alive at a median follow-up of 98 months (range 34-217 months). Nine (18%) patients relapsed and seven (14%) received donor lymphocyte transfusions. Quality of life (QoL) was assessed cross-sectionally using the EORTC QLQ-C30, a Leukaemia-BMT-specific module and questionnaires on sexual functioning, fertility and late effects. A total of 46 (90%) replied. Scores for Role (P=0.018) and Cognitive (P<0.001) function were significantly lower when compared to an age-adjusted general population. Dyspnoea (P=0.022) and Financial Difficulties (P<0.001) were significantly more common in the SCT group. No difference was found for scores in the Physical, Emotional and Social domains or the overall Global Health Status/QoL. Decreased sexual functioning was found in one-third of respondents. Although most BMT recipients reported a good QoL, a minority have difficulty with reintegration into professional roles and consequent monetary problems. Identified cognitive and sexual impairments highlight the need for long-term access to psychosocial support.
ABO Blood-Group System↗
Outcome of allogeneic stem cell transplantation in children with non-malignant diseases.
BACKGROUND AND OBJECTIVES: After allogeneic stem cell transplantation treatment failures are mostly caused by graft rejection or graft-versus-host disease (GVHD). T-cell depletion is an appropriate tool to prevent GvHD. However, it might be associated with an increased risk of graft rejection, which can be recognized by serial and quantitative characterization of chimerism. Thus, pre-emptive immunotherapy might be helpful to avoid graft rejection. DESIGN AND METHODS: We present the outcome of 56 transplants performed in 53 children with non-malignant diseases. T-cell depletion was conducted in 27/56 grafts. When increasing mixed chimerism over 30% autologous cells occurred low dose donor lymphocyte transfusions (DLT) were performed. RESULTS: During the course of the follow-up 29 out of 53 patients achieved complete chimerism or low mixed chimerism (0-1%) and 28/29 remained in continuous complete remission. Donor engraftment failed in 2/53 patients who died of serious infection. Increasing mixed chimerism was found in 19 out of 56 transplantations. Fifteen of these 19 patients received additional immunotherapy with DLT. Eleven out of the 15 remained in complete remission. One of the 15 patients developed GvHD grade III that turned out to extensive chronic GvHD. The 3-year overall survival was 100% for patients transplanted from matched related or unrelated donors and 75% for patients transplanted from mismatched donors. INTERPRETATION AND CONCLUSIONS: We demonstrated that children transplanted for non-malignant diseases have an excellent overall survival. T-cell depletion is associated with an increased risk of graft rejection. Pre-emptive immunotherapy with DLT, administered on the basis of increasing mixed chimerism, is feasible and might prevent graft rejection.
Child↗