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Biomedical subjects

B M Bär

Publications and source records attributed to B M Bär.

13 recordsLinked to original sources

[The success of lymphocyte infusion as treatment of leukemia recurrence following allogeneic bone marrow transplantation depends on low percentage of patient's own lymphocytes].

OBJECTIVE: Evaluation of induction of complete remission with infusion of lymphocytes from the original bone marrow donor in patients with leukaemia which relapsed after allogeneic bone marrow transplantation. SETTING: Division of Haematology, University Hospital Nijmegen and the Red Cross Blood Bank Nijmegen, the Netherlands. DESIGN: Prospective, non-randomized study. METHODS: Twenty-eight patients who relapsed after allogeneic bone marrow transplantation were treated with infusion of lymphocytes from the original bone marrow donor. Lymphocytes were collected by means of leukapheresis. Follow-up was done by frequent checks at the outpatient clinic. RESULTS: Eleven of 15 (73%) patients with relapsed chronic myeloid leukaemia (CML) and only one of 13 patients (8%) with a relapse of acute leukaemia went into complete remission (p < 0.001). Entering complete remission was always preceded by acute or chronic graft-versus-host disease (GVHD). The development of acute and/or chronic GVHD was significantly associated with the origin of T-lymphocytes in the blood of the recipient at the time of infusion. If the T-lymphocytes came mostly from the patient himself, the infusion remained usually without effect. If the T-lymphocytes came mostly from the donor, the patients went into complete remission. CONCLUSION: Patients with a relapse of leukaemia after allogeneic bone marrow transplantation may enter complete remission after infusion of lymphocytes from the original marrow donor. This form of immunotherapy can be successful especially in patients with a relapsed CML with a relatively low percentage of autologous T-lymphocytes at the time of infusion.

Adolescent↗

Erythrocyte repopulation after major ABO incompatible transplantation with lymphocyte-depleted bone marrow.

Forty-four out of 258 allogeneic BMT were performed across the major ABO barrier. Donor erythrocyte repopulation could be evaluated in 30 cases. Fifty-eight patients transplanted with an ABO compatible or minor incompatible graft served as the control group. All patients received a marrow graft depleted of lymphocytes by counterflow centrifugation. Less than 10(8) residual erythrocytes were present in the graft. Cyclosporin A was used as immunoprophylaxis after transplantation. Erythrocyte repopulation was measured using a fluorescent microsphere method. An adapted transfusion policy was applied. Eight out of 30 patients (27%) with major ABO incompatibility had no detectable donor erythrocytes 2 months after BMT. Up to 3 months after BMT donor erythrocyte repopulation was significantly delayed in the ABO incompatible group (P < or = 0.03). Significantly more erythrocyte transfusions were required in the ABO incompatible group (P < 0.001). Six patients with blood group O (20%) developed pure red cell aplasia which resolved in five without therapeutic intervention. In these six patients anti-A antibody titers were persistently high the first 3 months after BMT. This was in contrast with 22 patients with timely recovery of erythropoiesis in whom anti-A and anti-B antibody titers showed a steady decrease after BMT. The incidence of immunohematological complications in these patients who received a lymphocyte depleted major ABO incompatible graft is similar (20%) to the incidence reported in the literature. Serious morbidity related to major ABO incompatibility did not occur.

ABO Blood-Group System↗

Preparation of random donor leukocyte-poor platelets by cytapheresis.

Platelet refractoriness in treatment of multitransfused patients with haematologic malignancies can be delayed or prevented by transfusing leukocyte-poor platelet concentrates. Absence of consensus about the number of residual leukocytes that leads to a delay or prevention of HLA-antibody formation, may be based on a lack of sampling for determination of leukocyte contamination levels in platelet concentrates. From data presented in this study we conclude that if every preparation of platelets is also tested for platelet count, it reduces costs when the pheresis platelets can be split. Transfusion of platelets in patients can also be better evaluated.

Blood Component Removal↗

Donor leukocyte infusions for chronic myeloid leukemia relapsed after allogeneic bone marrow transplantation.

PURPOSE: Treatment options for patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT) are limited. Treatment with lymphocytes from the original marrow donor and the influence on the malignant clone was studied in these patients. PATIENTS AND METHODS: Seven patients with CML that had relapsed after BMT with T-cell-depleted grafts were treated. Six patients received leukocyte infusions from the original marrow donor. One patient received a second BMT with unseparated marrow from the same sibling donor. Chimerism was studied using erythrocyte and cytogenetic markers. Residual leukemic cells were monitored by cytogenetic analysis of the Philadelphia (Ph) chromosome and by polymerase chain reaction (PCR) of the breakpoint cluster region/Abelson (BCR-ABL) fusion gene. RESULTS: In five patients with hematologic relapse, the Ph chromosome disappeared 1 to 3 months after the leukocyte infusions. Cytogenetic analysis and in situ hybridization (ISH) showed only donor cells during further follow-up. Four to five patients became negative for the BCR-ABL translocation by PCR. Graft-versus-host disease (GVHD) always preceded response and was severe in two patients. One patient with cytogenetic relapse showed no response after leukocyte infusions. GVHD after second BMT was of moderate severity. One year after second BMT, PCR for the BCR-ABL translocation was negative. CONCLUSION: Infusion of donor leukocytes is an effective treatment with a low mortality in patients with CML relapsed after BMT with a T-cell-depleted graft. Longer follow-up and more patients will be needed to know whether cure will be permanent.

Adult↗

Influence of the conditioning regimen on erythrocyte chimerism, graft-versus-host disease and relapse after allogeneic transplantation with lymphocyte depleted marrow.

Three different conditioning regimens were applied to 144 patients undergoing allogeneic bone marrow transplantation (BMT) with HLA identical sibling marrow, depleted of lymphocytes by counterflow centrifugation. All regimens consisted of cyclophosphamide and fractionated total body irradiation (TBI). In 49 patients treated with regimen A the total TBI dose was 9 Gy. In regimen B the dose rate of TBI was increased and anthracyclines were added (n = 65). Thirty patients received regimen C with a total TBI dose of 12 Gy but no anthracyclines. The different conditioning regimens did not influence the percentage of patients with detectable recipient CFU-GM prior to infusion of donor marrow. The incidences of mixed erythrocyte chimerism at 6 months after BMT were 73, 33 and 20% for regimens A, B and C respectively. The conditioning regimen influenced significantly mixed erythrocyte chimerism from 6 to 24 months after BMT. Both age and the conditioning regimen influenced significantly the incidence of acute graft-versus-host disease (GVHD) (p = 0.017 and 0.0001 respectively). Acute GVHD greater than or equal to I occurred in 15, 29 and 77% of the patients treated with regimens A, B and C respectively. The incidence of acute and chronic GVHD was significantly higher in complete donor chimeras than in mixed chimeras (p less than 0.001 and p less than 0.01). The probability of relapse was 43% in 32 and 18% in 43 good risk patients treated with regimens A and B respectively (p = 0.07). Longer follow-up is needed to draw conclusions about relapse in regimen C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Reconstitution of antibody response after allogeneic bone marrow transplantation: effect of lymphocyte depletion by counterflow centrifugal elutriation on the expression of hemagglutinins.

The generation of ABO hemagglutinins was used as a model to assess the tempo of reconstitution of antibody responses in recipients of elutriated (CCE) and nonelutriated (nonCCE) HLA matched bone marrow allografts. The study included 29 CCE recipients (10 major, 6 minor, and 1 major/minor ABO-mismatched, and 12 ABO-matched) and 40 nonCCE recipients (14 major, 12 minor, 2 major/minor, and 12 matched). Plasma volume in the graft and in blood product transfusions was uncorrelated with changes in hemagglutinin titers and therefore was excluded as a significant source of antibody. Removal of graft lymphocytes by CCE did not result in prolongation of host-derived hemagglutinins in recipients of major ABO-mismatched grafts. However, CCE resulted in a complete abrogation of the adoptive transfer of donor-derived antibody as detected in recipients of minor ABO-mismatched grafts. Despite the absence of adoptively transferred donor immunity in recipients of CCE grafts, they had hemagglutinin levels comparable with those of recipients of nonCCE grafts by 6 months after transplantation. This demonstrates that recipients of elutriated marrow were competent to mount de novo responses at that time. The strong correlation between donor pretransplant hemagglutinin titer and recipient titer 1 year after bone marrow transplantation in recipients of nonCCE grafts suggests that even late after transplant, antibody remains the product of adoptively transferred memory cells in recipients of grafts containing large numbers of mature lymphocytes.

ABO Blood-Group System↗

Favourable outcome of patients older than 40 years of age after transplantation with marrow grafts depleted of lymphocytes by counterflow centrifugation.

Nineteen patients with a median age of 43 years (range 40-48) were transplanted for acute myelogenous leukaemia (AML), refractory anaemia with excess of blasts in transformation (RAEBt), acute lymphoblastic leukaemia (ALL) in first complete remission, multiple myeloma, and chronic myelogenous leukaemia (CML) in chronic or accelerated phase. Their outcome was compared with that of 35 patients with a median age of 34 years (range 30-39), and a group of patients with age younger than 30 years (median 24; range 16-29) transplanted for the same indications. Donors were human leucocyte antigen (HLA)-identical, mixed lymphocyte culture (MLC) negative siblings. All marrow grafts were depleted of lymphocytes by counterflow centrifugation. The estimated event-free survival at 3 years after allogeneic bone marrow transplantation was 60.7% for patients with age greater than 39 years, 57.8% for patients with age less than 30, and 43.0% for the intermediate age group (P greater than 0.3). The estimated transplant-related mortality showed no tendency to increase with older age of recipients. The incidence of acute GVHD greater than grade 1 was 15.7% in patients with age greater than 39 years, 9.5% in patients younger than 30 years, and 23% in the intermediate age group. The incidence of chronic GVHD was higher in the older patients (39% compared to 24% in patients younger than 30 years, 19% in the intermediate age group). Chronic GVHD resolved completely in five out of seven patients aged 40 years or more. Reduction of the incidence of acute graft-versus-host disease by physical lymphocyte depletion allows allogeneic bone marrow transplantation for patients aged 40-50 years without increase of transplant-related mortality resulting in similar event-free survival in patients older than 40 years compared to those younger than 40 years.

Acute Disease↗

Continuous intravenous administration of daunorubicin and cytarabine for remission induction of poor risk acute myelogenous leukaemias and myelodysplastic syndromes.

Seventeen consecutively admitted poor risk acute myeloid leukaemia (AML) patients and 4 patients with myelodysplastic syndrome (MDS) were treated with a remission-induction regimen consisting of a 7-day continuous intravenous infusion of conventional doses of cytarabine and of three 24-h constant rate infusions of daunorubicin administered intermittently on days 1, 3 and 5. The diagnoses were: relapsed primary AML in 6 patients, secondary AML in 11 patients (9 untreated, 2 relapsed) and MDS in 4 patients. The median age was 50 yr. Five of 6 patients with relapsed primary AML, 3 of 11 patients with secondary AML and 2 of 4 patients with MDS achieved complete remission (CR). The overall CR rate was 48% with a median remission duration of 5 months (range: 0.25-20 months). Few acute toxic side effects were observed thanks to the constant rate of infusion of daunorubicin.

Acute Disease↗

Host and donor erythrocyte repopulation patterns after allogeneic bone marrow transplantation analysed with antibody-coated fluorescent microspheres.

Analysis of erythrocyte populations, using red blood cell antigen differences between host and donor as marker, was performed with a sensitive fluorescent microsphere assay to monitor marrow engraftment and mixed red cell chimaerism after allogeneic bone marrow transplantation (BMT). An adapted transfusion policy, using marker negative erythrocyte transfusions, was required for this analysis. In all patients the marrow graft was depleted of lymphocytes by counterflow centrifugation. Thirty-seven patients were evaluable for donor repopulation at one or more points in the first 6 months after BMT. At 0.5 month donor erythrocytes were detectable in 19 out of 22 patients. At 6 months donor erythrocytes were detectable in 100% of the evaluable patients. In the first 3 months after BMT the average donor erythrocyte repopulation in recipients of major ABO mismatched transplantations was delayed. Thirty-eight patients were evaluable for chimaerism at 6 months or later after BMT. A high incidence of mixed red cell chimaerism was observed varying from 50% to 71% at different points of analysis. Mixed red cell chimaerism with low percentages (less than 1%) of host cells was not related with relapse, nor did high percentages (greater than 10% of host cells necessarily indicate relapse.

ABO Blood-Group System↗

Primary malignant lymphoma of the uterine cervix associated with cold-reacting autoantibody-mediated hemolytic anemia.

A 66-year-old woman presented with autoimmune hemolytic anemia of the cold antibody type as one of the first symptoms of a non-Hodgkin lymphoma (NHL) localized primarily in the uterine cervix. Cold-reacting autoantibody-mediated hemolytic anemia is a rare complication of NHL. Its occurrence as one of the presenting symptoms of NHL is even more unusual. The incidence of a primary malignant lymphoma in the genital tract is low. The combination of these phenomena in one patient make this case unique in the English literature.

Aged↗