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At least 19 recordsLinked to original sources
PubMed1997

Adoptive immunotherapy with donor lymphocyte transfusions.

Adoptive immunotherapy denotes the transfer of immunocompetent cells for the treatment of leukemia, cancer, or viral disease. It has regained much interest through the success of treating recurrent leukemia after allogeneic bone marrow transplantation with the transfusion of donor lymphocytes. Chimerism and transplantation tolerance toward the donor offer the possibility of adoptive immunotherapy using donor lymphocytes. In animal studies, donor lymphocytes could be transfused into the chimeric animal, if the transfusion was delayed after marrow transplantation. Transfused lymphocytes exhibit a graft-versus-leukemia effect and increase chimerism. Immunity could be transferred and immune reactivity toward new antigens improved. In human patients transfusion of donor lymphocytes was studied in leukemia recurring after marrow transplantation. It was very effective in the treatment of chronic myelogenous leukemia recurring after marrow transplantation. It was also effective in some patients with acute myeloid leukemia, myelodysplastic syndrome and myeloma; in acute lymphoblastic leukemia and lymphoma responses were rare. Responses in solid tumors as breast cancer have been described. Major complications are graft-versus-host disease and myelosuppression. Myelosuppression could be compensated by the transfusion of marrow. Graft-versus-host disease can be modified by the depletion of CD8-positive T cells from the lymphocyte concentrate or by transfusing very low numbers of cells and increasing doses in a stepwise fashion. The role of concomitant treatment with cytokines and activation of T cells by dendritic cells and vaccination remains to be defined.

Animals↗
PubMed1995

Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients.

The immune reactivity of allogeneic lymphocytes plays a major role in the control of leukemia after bone marrow transplantation. In patients with recurrent leukemia after marrow transplantation, chimerism and tolerance provide ideal conditions for adoptive immunotherapy with donor lymphocytes. We studied the effect of donor lymphocyte transfusions on acute and chronic leukemia in relapse after bone marrow transplantation. One hundred thirty-five patients with chronic myeloid leukemia (CML) (N = 84), acute myeloid leukemia (AML) (N = 23), acute lymphoblastic leukemia (ALL) (N = 22), myelodysplastic syndrome (MDS) (N = 5), and polycythemia vera with osteomyelofibrosis (PCV) (N = 1) were treated with transfusions of donor lymphocytes. Patients were monitored for response of leukemia, including in CML, the use of the polymerase chain reaction for bcr/abl mRNA transcripts and for the occurrence of graft-versus-host disease (GVHD) and myelosuppression. Complete remissions were induced by donor lymphocyte transfusions in 54 patients with CML (73%) and in the patient with PCV; complete remissions were also induced in five patients (29%) with AML and a patient with MDS. In contrast, ALL did not respond to adoptive immunotherapy with donor lymphocyte transfusions. Remissions were durable in patients treated for CML in chronic phase (probability of remission: 87% at 3 years). Lymphocyte transfusions were also given to 18 patients with ALL, AML, MDS, and transformed phase CML who were in remission after chemotherapy. These remissions were not durable. Fifty-two patients (41%) developed GVHD of grade 2 or more, and 41 patients (34%) showed signs of myelosuppression. Seventeen patients died without leukemia, 14 patients with GVHD and/or myelosuppression. Donor lymphocyte transfusions exert strong effects against myeloid forms of leukemia and induce durable remissions in CML.

Adolescent↗
PubMed1994

Recurrent abortions and lymphocyte transfusions.

Normal pregnancies depend on successful implantation of the placenta in the uterus. The trophoblast which forms the ultimate interface between the fetal and maternal tissue seems to lack the foreign (allo) antigens (namely HLA/TLX) required to induce immunological rejection reactions in the mother. It was previously believed that the trophoblast expressed paternal allo antigens and that successful pregnancies were dependent on so called 'kind' (non-cytotoxic or non-complement binding) blocking antibodies in order to protect the fetal unit from maternal cytotoxic T-cells and -antibodies. Blocking antibodies attached to paternal antigens on the trophoblast were assumed to prevent maternal cytotoxic T cell and cytotoxic antibodies from recognising the trophoblast as foreign tissue. On this assumption it was reasoned that transfusions of paternal HLA-expressing lymphocytes would increase maternal antipaternal HLA (TLX) blocking antibodies and thus be beneficial to women who experienced multiple miscarriages. There is, however, no scientific evidence for a specific immune response after lymphocyte transfusions that fulfil this function. Immunological tests, as for example mixed lymphocyte culture (MLC), on peripheral blood lymphocytes do not seem to reflect the local immune state in the uterus, either in the pregnant or the non-pregnant state. Since the trophoblast forms the ultimate interface between fetal and maternal tissue, its structure, secretions, and interaction with the decidua must be of definite importance for implantation of the blastocyst and growth of the embryo.

Abortion, Habitual↗
PubMed1975

Restoration of immunocompetency by lymphocyte transfusion.

A female patient with metastatic osteosarcoma was given a lymphocyte transfusion from her brother, cured of the same histologic type of tumor ten years earlier. Prior to the transfusion the patient was anergic. Following lymphocyte transfer cutaneous reactivity to DNCB was restored. Skin reactivity to mumps and varidase antigens was specifically transferred. Whole lymphocyte transfer is a feasible method for restoring immune competence in the anergic cancer patient.

Adolescent↗
PubMed1987

Clinical and immunological restoration in patients with AIDS after marrow transplantation, using lymphocyte transfusions from the marrow donor.

The diagnosis of transfusion-associated acquired immunodeficiency syndrome (AIDS) was made in 2 patients who developed delayed opportunistic infections and severe cytopenias--56 months for the former (patient 1) and 22 months for the latter, (patient 2) following bone marrow transplantation (BMT) for aplastic anemia. In the third case, grafting for acute leukemia (patient 3) (HIV) infection was probably responsible for the failure of hematological and immunological reconstitution 8 months after allogeneic BMT. Each patient received 6 lymphocyte transfusions from the marrow donor for 3 weeks, combined with a 3-month course of low-dose recombinant alpha interferon. This treatment was followed by recombinant gamma interferon for 3 months. We showed that these 3 patients could resume a normal life for 9 months, at least, and that hematological restoration was observed. Our treatment succeeded in correcting the defect of proliferative response to Candida and the impairment of gamma interferon generation for 4 months in one patient and for more than 12 months in the other two recipients. Nevertheless T4 lymphocyte levels increased only slightly and HIV can still be isolated from the patients' blood. At the time of writing, patients 1 and 3 remain in good health with a partial immunological restoration while patient 2 has died of neurological impairment 2 years after the AIDS diagnosis. Although we cannot generalize this successful therapeutic approach to all patients with AIDS, the results may provide an interesting model of the potential effect of lymphocyte transfusions and the role of interferon therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[The study of the biological activation induced by the lymphocyte transfusion--the induction of the bio-reproducing protein (BRP)].

A small amount of allo-lymphocytes were transfused to tumor bearing hosts to introduce tumor antigen. We found the lymphocyte transfusion significantly effective for the treatment of cancer, of animals and of human as well. We also found that by using a small amount of anti-cancer agents together, this treatment was effective for peritonitis/pleuritis carcinomatosa. Furthermore, we took the ascites and/or the pleural fluid from those peritonitis/pleuritis carcinomatosa patients at their remission stage, and fractionate the fraction V by the alcohol fractionation method from the supernatant of the fluid, and transfuse it back to the patient for the purpose of improving hypoproteinemia, and we found the fraction effective for the cure of the cancer. We designated this fraction the bio-reproducing protein (BRP). The clinical test treatments using the BRP were performed for terminal stage cancer of digestive system, respiratory system, mammary, and others with the efficacy of 76 percent. The detail analysis of the characteristics and the working mechanism of the BRP is in progress.

Adult↗
PubMed1997

Sequential molecular monitoring of chimerism in chronic myeloid leukemia patients receiving donor lymphocyte transfusion for relapse after bone marrow transplantation.

Recent observations of chimerism in patients relapsed following an allotransplant suggest the persistence of immunotolerance, thus offering a biologic rationale for the use of donor lymphocyte transfusion (DLT). In this study, we have analyzed by PCR amplification of several VNTR regions, sequential bone marrow and peripheral blood DNA samples in four patients who received DLT for CML relapse after bone marrow transplantation. Prior to DLT, all patients showed mixed chimerism in peripheral blood cells while two had mixed chimerism and two no chimerism in the BM. None of these four patients showed evidence of chimerism at the cytogenetic level (all had 100% +ve metaphases). After DLT, a complete hematologic and molecular remission (ie disappearance of the BCR/ABL fusion transcript) was obtained in the two patients who had bone marrow mixed chimerism prior to DLT. The two patients without evidence of marrow chimerism prior to DLT converted to a pattern of mixed chimerism after DLT, but both developed a severe bone marrow aplasia occurring at day 56 and 36, respectively. With regard to the sequential analysis of bone marrow chimerism after DLT we observed that: (1) the disappearance of BCR/ABL +ve cells paralleled the conversion to a pattern of full donor chimerism; and (2) the time interval to achieve CR was inversely correlated with the percentage of donor DNA in bone marrow. In conclusion, we have shown here that the assessment of bone marrow pre-DLT chimerism by PCR analysis might predict the response in patients with favorable characteristics, and also might identify patients at high risk of developing severe myelosuppression.

Adult↗
PubMed2005

Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome.

PURPOSE: To improve the effect of allogeneic stem-cell transplantation by sequential use of intensive chemotherapy, reduced-intensity conditioning (RIC), and prophylactic donor lymphocyte transfusions (pDLTs) in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). PATIENTS AND METHODS: In a prospective study of 75 consecutive patients (median age, 52.3 years), high risk was defined by progressive or refractory disease (n = 59), second remission after early relapse (n = 8), or first remission with poor prognosis based on cytogenetics or delayed response to induction therapy (n = 8). Unfavorable karyotypes were found in 49% of informative patients, and 68 patients had medical contraindications against standard conditioning. Fludarabine (30 mg/m2), cytarabine (2 g/m2), and amsacrine (100 mg/m2) for 4 days were used for cytoreduction. After 3 days of rest, RIC consisted of 4 Gy total-body irradiation, antithymocyte globulin, and 80 to 120 mg/kg cyclophosphamide. Thirty-one patients had an HLA-identical sibling donor; 44 patients had an unrelated and/or HLA-mismatched donor. pDLT was given from day +120 in patients who were not receiving immunosuppression and were free of graft-versus-host disease (GvHD). RESULTS: Complete remission was induced in 66 patients (88%). With a median follow-up of 35.1 months (range, 13.6 to 47.6 months), 2-year overall and leukemia-free survival were 42% and 40%, respectively. Outcome of patients with refractory disease or with complex cytogenetic aberrations was identical to that of better prognostic subgroups. Survival was best in patients who received high CD34+ cell numbers, and in patients with limited GvHD. CONCLUSION: Sequential use of intensive chemotherapy, RIC transplantation, and pDLT represents a promising approach to the treatment of high-risk AML and MDS, particularly in patients with most unfavorable prognoses.

Adolescent↗
PubMed2000

Successful graft-versus-leukemia effect of second bone marrow transplantation on relapsed leukemia cutis that was refractory to intensive chemotherapy and donor lymphocyte transfusions in a patient with acute monocytic leukemia.

We report a patient with acute monocytic leukemia (AMoL; M5) who received a second bone marrow transplantation (BMT) with graft-versus-leukemia (GVL) effect on relapsed leukemia cutis, which had been refractory to intensive chemotherapy and donor lymphocyte transfusions (DLTs). A 21-year-old woman was diagnosed with AMoL and achieved complete remission after intensive chemotherapy. The patient received a nonmanipulated allogeneic BMT from her HLA-identical father. Skin tumors developed in her upper extremities, chest, and thigh 11 months after BMT. Leukemia cutis was confirmed by skin biopsy. There was no evidence of relapse in bone marrow. The patient received several courses of chemotherapy and DLTs for the skin relapse, but the skin tumors persisted. The patient then received a second BMT from the same donor. On day 80, grade II acute graft-versus-host disease developed, and the remaining skin tumors were eradicated on day 98, most probably because of GVL effect.

Adult↗
PubMed1986

Hypothesis: blocking factors and human pregnancy: an alternative explanation for the success of lymphocyte transfusion therapy in abortion-prone women.

Recent evidence has demonstrated that the non-specific immunosuppression that develops during pregnancy is not due to the de novo synthesis of immunosuppressive factors (ISF) but is a result of the activation of pre-existing molecules. The latter are present in normal sera as inactive complexes with a molecule which is specifically depleted following conception resulting in the activation of the ISF; the depleted molecule is termed the pregnancy-depleted immunoregulatory factor (pdIRF). Since non-specific ISF are detected in various diseases, it is proposed that the ISF-pdIRF relationship observed in pregnancy is a universal phenomenon and that the depletion of pdIRF and the activation of ISF can be achieved by a variety of stimuli. It is further proposed that abortion-prone women fail to adequately deplete their pdIRF levels so that the ISF are not activated. However, owing to the universal nature of the system, lymphocyte transfusion therapy supplies the necessary stimuli so that the pdIRF levels are depleted and the ISF activated which ensures a successful outcome to the pregnancy.

Abortion, Habitual↗
PubMed2003

Imminent allograft rejection prevented by donor lymphocyte transfusions: report of two pediatric cases.

Gradual allograft rejection after initial good engraftment may occur with simultaneous autologous reconstitution particularly in patients receiving nonmyeloablative conditioning. Careful post-transplant follow-up of the chimerism status can reveal these cases early on, when the immunological balance may still be shifted to the donor cells. We describe two children with nonmalignant diseases, in whom imminent rejection of their sibling allografts was prevented with donor lymphocyte transfusions (DLT). DLT dosing and timing need to be individually guided by monitoring of the chimerism status.

Child↗
PubMed1998

Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated lymphoproliferative disorder of the brain.

EBV-associated lymphoproliferative disorder (LPD) is a rare but serious complication in marrow transplant recipients. A 31-year-old Japanese woman in the second chronic phase of CML received an allogeneic BMT from her HLA 2-locus-incompatible 62-year-old father. Around day +200, she developed EBV-LPD of the right parieto-temporal lobe which caused slowly progressive left hemiparesis. Two courses of donor lymphocyte transfusions (DLT) of 10(6)CD3+ T cells/kg of body weight failed to suppress her central nervous system (CNS) EBV-LPD. The patient died of recurrent blastic crisis of CML. This case suggests that DLT may be ineffective for the treatment of CNS EBV-LPD.

Adult↗