[Bone marrow transplantation in leukemia in Switzerland. A retrospective analysis by the Working Group on Bone Marrow Transplantation SAKK/Swisstransplant].
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Adolescent↗
Biomedical subjects
B Chapuis
Publications and source records attributed to B Chapuis.
[What has become of preliminary transfusion protocols in kidney transplantation?].
Many studies have demonstrated that pretransplant blood transfusions improved cadaver kidney graft outcome. The nature and the frequency of transfusions-induced lymphocytotoxic antibodies depends of sex, previous pregnancies and kidney grafts, and transfusional patterns. This provoked immunisation is not a hindrance to beneficial effects of transfusions. Numerous reports have investigated the responsible mechanism for this effect. Controversial data concern the optimum number of blood units. In a previous prospective study in patients who received anti-lymphocyte globulins as part of immunosuppressive therapy, we have shown that a multiple transfusions policy does not give better results than only one. Recently, the beneficial effect of transfusions has been questioned, either entirely, or for particular patients according to age, sex, immunosuppressive treatment including cyclosporin or not. This leaded us to reassess benefits of transfusions.
Blood Transfusion↗
Quantity and nature of residual bone marrow T cells after treatment of the marrow with Campath-1.
Precise characterization of T-cell depletion in marrows used for transplantation is necessary for the evaluation of their potential contribution to engraftment and to graft-versus-host disease. A limiting dilution culture method that allows the determination of small numbers of bone marrow T cells is described. It can detect less than one T cell in 10(4) cells. Bone marrow T-cell depletion with the rat monoclonal antibody Campath-1 and fresh human complement results in a median decrease of 1.7 log (range, 1.6-2.1 log) of marrow T cells. A 2.7 to 3.3-log reduction is obtained when peripheral blood T cells are treated. A second incubation with fresh complement removes additional T cells from peripheral blood and from marrow samples, indicating the importance of bystander marrow cells to complement activity. The assay system described also allows the phenotypic study of responding cells growing in culture. These studies demonstrate that, after treatment with Campath-1 plus complement, no T-subset imbalance occurs. Furthermore, the T cells in these cultures are derived from mature T cells contained in the samples.
Antibodies, Monoclonal↗
Detection of anti-non-MHC-directed T cell reactivity following in vivo priming after HLA-identical marrow transplantation and following in vitro priming in limiting dilution cultures.
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Adult↗
[Effect of T-cell depletion of the graft on graft survival and graft vs host disease].
A limiting dilution culture method has been developed which allows the detection of small numbers of residual marrow T cells following their depletion with the monoclonal antibody Campath-I and autologous complement. In seven consecutive patients the degree of T cell depletion obtained was 1.82 (1.27-2.82) log. The number of nucleated cells per kg decreased by 50% and the number of CFU-GM per kg decreased by 60%. In all except one case marrow cellularity was found to be satisfactory 3 weeks after the transplant. Peripheral engraftment of granulocytes (greater than 500/mm3 on day 20, greater than 1000/mm3 on day 27), lymphocytes (greater than 500 on day 39, greater than 1000 on day 66), platelets (greater than 20,000 and self-sustained after day 24) and red blood cells (day to last infusion = 19) indicated a delay in recovery of lymphocytes and possibly granulocytes, but not platelets or red blood cells, compared to the engraftment seen in non-T depleted patients. No correlation between nucleated cells infused, GFU-GM and engraftment was found. However, the extent of T cell depletion apparently affects lymphocyte, and possibly granulocyte, recovery. The delay in lymphoid engraftment is also reflected by nonresponsiveness to alloantigens during the first 6-9 months following marrow grafting in the absence of graft vs. host disease.
Graft Survival↗
[In vivo detection of alloreactive T cells of the donor in graft versus host disease].
A male patient with severe aplastic anemia who had rejected a first T cell depleted graft from his HLA-identical sister was retransplanted from the same donor without T cell depletion and using an intensified conditioning regimen. After 8 weeks acute graft versus host disease (GVHD) developed and peripheral blood mononuclear cells (PBMC) were obtained. After in vitro restimulation and following limiting dilution cloning, 15 proliferative (PLT) and 25 cytolytic (CTL) T cell lines specific for host PBMC but unreactive to donor PBMC were isolated. Only 1 of 10 clones which could be expanded sufficiently for testing recognized a target cell (haploidentical sister), and in only 4 instances could a restriction element be found in a panel study (3 times HLA-A2; once HLA-BW49) of 13 unrelated stimulators. Of the 8 CTL clones testable after expansion, none showed a clear restriction and none recognized any of the family cells. Our data demonstrate that anti-patient reactive PLT and CTL lines can be found in PBMC. In no instance was segregation with HLA found. Only HLA-class I restriction was detectable.
Anemia, Aplastic↗
[Transplantation of allogeneic bone marrow treated in vitro with Campath-1 monoclonal antibody].
Out of 14 bone marrow transplants, 12 patients received transplantations with allogeneic bone marrow after in vitro T-cell depletion with monoclonal Campath 1. The patients also received short term cyclosporin. This small series is in agreement with the results of larger series using T-depleted marrow as far as the prevention of graft versus host disease is concerned, and with respect to mixed chimerism, slow take, late rejection and, possibly, increased risk of recurrence.
Aged↗
[12 years' experience in bone marrow transplantation in leukemic patients in Switzerland].
Between 1974 and December 1985 180 bone marrow transplants were performed in Switzerland for patients with leukemia. They were performed in 4 centers (Basle 133, Zurich 28, Geneva 17, Berne 2). The overall probability of survival at 10 years for all patients is 20%. Results are better for younger patients, for patients transplanted in recent years and for patients transplanted either in the first complete remission of acute leukemia or in the chronic phase of chronic myeloid leukemia.
Adolescent↗
[Intensive treatment and autologous bone marrow transplantation in cases of acute leukemia and lymphoma].
Experience with 19 autologous bone marrow transplantations shows that this approach may produce a high proportion of complete remissions in otherwise resistant tumours. Although most responses are of short duration, they suggest that longterm disease-free survival may be achieved in patients with poor prognosis if treated earlier in the course of disease.
Adult↗
Increased frequency of DR2 in patients with aplastic anaemia and increased DR sharing in their parents.
68 patients with aplastic anaemia, their parents and healthy siblings were typed for HLA-A, B and DR antigens. Among the patients there is an overrepresentation of DR2. The parents of affected children show an increased compatibility at the DR locus. This situation could favour the expression of recessive gene(s) involved in haematopoiesis and located in the HLA locus.
Alleles↗
[Indications and results in bone marrow transplantation].
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Anemia, Aplastic↗
[Clinical characteristics of immature T-type (negative E-rosette) acute lymphoblastic leukemia detected by LAU-A1 monoclonal antibody].
Immature T-ALL is a newly defined subgroup of ALL in which the blasts lack the receptor for sheep erythrocytes (ER) and the usual T-cell markers, but express the 40 kDa pan-T surface antigen recognized by our monoclonal antibody LAU-A1. Patients with immature T-ALL represent 10% of all cases of adult ALL. Leukocyte counts are lower and spleen, liver and lymph node enlargement is less prominent, but mediastinal enlargement is more frequent than in mature (ER-positive) T-ALL. 7 patients with immature T-ALL (median age 42 years, range 13-73) were treated with intensified chemotherapy regimens, and only one 47-year-old female entered a short-lived complete remission. The overall survival of our patients was poor (median 7.5 months, with only one patient surviving at 15 months) and seemed not to be influenced by age. Our study indicates that immature T-ALL can only be accurately identified by the use of monoclonal antibodies recognizing the 40 kDa pan-T antigen, and that immature T-ALL is a separate disease entity typified by a poor prognosis.
Adolescent↗
[Quantitative determination of human bone marrow T cells following in vitro depletion by Campath-1 monoclonal antibody].
Bone marrow T cell depletion is an effective graft vs host disease prophylaxis in allogeneic bone marrow transplantation. Standard methods of identifying T cells are not sensitive enough to determine small numbers of residual T cells following T cell depletion. A rapid and sensitive method, using limiting dilution culture technology and radionucleotide labelling and allowing the detection of 1/10(4)-1/10(5) residual T cells, has been developed. Its usefulness in the evaluation of the number of T cells after monoclonal antibody (Campath-1) + autologous complement marrow treatment is demonstrated.
Antibodies, Monoclonal↗
[Transplantation of allogeneic bone marrow treated in vitro with Campath-1 monoclonal antibody].
5 patients underwent bone marrow transplantation for severe aplastic anemia (2) and acute leukemia (ALL) in first remission (3). Graft versus host disease prophylaxis was performed by depleting T lymphocytes in the donor bone marrow with the rat monoclonal Campath-1 and autologous complement. In addition, patients received cyclosporin A. Engraftment occurred normally in all 5 patients but 1 patient (SAA) had a late graft failure. Two patients suffered mild degrees of GvHD. All patients are currently in complete remission, one having undergone a second transplantation.
Adult↗
[Intensive treatment and autologous bone marrow transplantation in cases of leukemias and lymphomas in relapse].
This study shows that autologous bone marrow transplantation is feasible and can produce a high proportion of complete remission in otherwise resistant tumors. Although most responses are of short duration, they suggest that long-term disease free survival could be achieved in patients treated earlier in the disease course.
Acute Disease↗
[In vivo detection of alloreactive T cells of host origin after rejection of HLA-identical allogeneic bone marrow transplant].
Rejection and graft vs host disease after HLA-identical allogeneic bone marrow transplantation are probably due to in-vivo T-cell reactivity against non-MHC antigens. Peripheral blood lymphocytes from a patient transplanted for aplastic anemia have been obtained during graft failure and tested for their alloreactivity towards unrelated and marrow donor lymphocytes. Their caryotype was determined. Our results demonstrate (1) alloreactive T cells of host origin and (2) the presence of donor-specific host cells in vivo, providing evidence for rejection following in vivo sensitization to non-MHC antigens.
Anemia, Aplastic↗
Anaphylactic reaction to intravenous cyclosporine.
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Adult↗
[Low-dose cytosine arabinoside (ARA-C) in the treatment of acute myeloid leukemia].
Eleven patients over 70 years of age and two patients under 60 years of age with myeloblastic leukemia have been treated with low doses of cytarabine (10 mg per m2 every 12 hours by subcutaneous injection for a median duration of 3 weeks). Four patients of the first group went into complete remission, 2 patients in the older age group and the 2 patients under 60 years of age went into partial remission, while only 3 patients out of 13 (23%) did not respond to this treatment. Sometimes severe cytopenia observed during the induction phase counterbalanced the advantages of treatment (simplicity and absence of systemic toxicity) and suggest an antimitotic effect which is probably associated with differentiation of the malignant clone.
Adult↗