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D Bunjes

Publications and source records attributed to D Bunjes.

At least 73 records · Page 4Linked to original sources
PubMed1993

Measurement of recipient-specific alloreactivity: is GVHD predictable?

Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings. We determined the frequency with which host-specific interleukin-2 (IL-2) -secreting donor T lymphocyte precursors (Tl-p) occurred in 16 pairs of HLA-identical siblings before they underwent marrow grafting. The results were correlated with the development of acute GVHD after BMT. We further analyzed the responding host (and donor) -specific Tl-p with respect to the cell surface phenotype, the influence of previous in vivo priming, and the MHC class restriction of minor histocompatibility (mH) antigen recognition. To investigate whether host-reactive Tl-p are involved in the induction of acute GVHD, we also examined the frequency of host-specific Tl-p at various time intervals after BMT in 14 patients with and without acute GVHD. High frequencies of host-specific Tl-p were detectable before BMT in 8 donors whose siblings later had severe (grade II or III) acute GVHD. Among the donors to 8 patients with mild (grade 0 or I) acute GVHD, low frequencies were found. Various T-cell subsets contributed to the responding Tl-p. The presence of host-specific Tl-p after BMT was significantly correlated with the development of serious (grade II or III) acute GVHD. We conclude that host-specific IL-2-secreting T cells are critically involved in the induction and maintenance of acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Graft rejection by a population of primed CDw52- host T cells after in vivo/ex vivo T-depleted bone marrow transplantation.

We investigated a case of graft rejection after in vivo/ex vivo T-depleted BMT in a patient who had received a HVG-matched, GVH one locus-mismatched, MLC-negative graft from his cousin. In vivo/ex vivo T cell depletion was performed with Campath 1G (CP1G) and Campath 1M (CP1M), respectively. We identified a failure of CP1G to eradicate a CDw52- (Campath-negative) host T cell population as the main cause of treatment failure. The analysis also suggests that significant host-versus-donor reactivity prior to transplant, as detected by limiting dilution analysis, also contributed to graft rejection. The rejecting T cells were bifunctional in that they showed cytotoxic activity and were capable of inhibiting haemopoietic progenitor growth by producing inhibitory lymphokines.

Adult↗
PubMed1993

Frequency of bone marrow T cells responding to HLA-identical non-leukemic and leukemic stimulator cells.

Grafted immunocompetent cells are considered responsible for GVHD as well as for the elimination of residual leukemic cells ('graft-versus-leukemia reactivity', GVLR) in leukemic patients after allogeneic BMT. Clinical and experimental investigations have given contradictory answers to the question whether GVHD and GVLR are two manifestations of the same process or separate immunologic processes. We have addressed this question by analysing the primary in vitro response of BM-derived proliferating and cytotoxic T lymphocyte precursors (PTLp and CTLp) in HLA identical relative pairs (n = 17). PTLp frequency estimation reveals strong responses (> 1 in 5000) on non-leukemic as well as leukemic stimulation in a majority of cases. CTLp amount variably to 10-100% of the proliferating precursor cells. Preliminary specificity analyses show that on non-leukemic stimulation about 90% of colonies exhibit exclusive lysis of the non-leukemic target. At the same time, on leukemic stimulation, about 75% of cytolytic colonies are exclusively reactive against leukemic targets without crossreactivity against nonleukemic targets from the same patient. Our data show that primary in vitro responses in HLA identical sibling pairs may be as strong as those against allo MHC antigens. In addition CTL specifically lysing leukemic or non-leukemic targets may represent an in vitro model of the immunologic non-identity of GVHD and GVLR.

Bone Marrow↗
PubMed1993

Influence of graft-versus-host disease on the eradication of minimal residual leukemia detected by polymerase chain reaction in chronic myeloid leukemia patients after bone marrow transplantation.

To evaluate the remission quality of Philadelphia chromosome (Ph)-positive, BCR/ABL-positive CML patients after allogeneic bone marrow transplantation (BMT) we used the polymerase chain reaction (PCR) to detect BCR-ABL specific RNA in addition to Southern blotting, cytogenetic, and hematological investigation. Fifty-five bone marrow samples of 27 patients in clinical remission were studied by PCR, 0.5 to 99 months (median 8 months) after BMT. The median clinical follow-up of this cohort of patients is 24 months (1-109) after BMT. BCR-ABL transcripts could be detected in 16 out of 27 patients (59%). Risk factors for minimal residual leukemia (MRD) as defined by PCR were the kind of graft-versus-host disease (GvHD) prophylaxis (patients with T-cell-depleted grafts had a higher rate of MRD in comparison to patients treated with methotrexate/cyclosporin A) and the presence or absence of GvHD after BMT (patients without GvHD had a higher incidence of MRD than patients with GvHD). Moreover, the detection of minimal residual leukemia had prognostic significance. Out of 16 patients with minimal residual leukemia as detected by PCR, four patients relapsed clinically and two further cases relapsed cytogenetically. In contrast none of the patients lacking evidence of minimal residual leukemia relapsed. Serial PCR analysis may prove helpful in deciding about further therapeutic interventions (e.g. interferon therapy or adoptive immunotherapy) before leukaemic relapse becomes manifest after BMT.

Adult↗
PubMed1992

Host-specific interleukin-2-secreting donor T-cell precursors as predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings.

BACKGROUND: Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings. METHODS: We determined the frequency with which host-specific interleukin-2-secreting donor T-cell precursors occurred in 16 consecutive pairs of HLA-identical siblings before they underwent marrow grafting. The results were correlated with the development of acute GVHD after transplantation. RESULTS: High frequencies of host-specific T-cell precursors (> or = 1 per 100,000) were detectable before transplantation in eight donors whose siblings later had severe (grade II or III) acute GVHD. Among the donors to eight patients with mild (grade 0 or 1) acute GVHD, low frequencies (< 1 per 100,000) were found. CONCLUSIONS: Analysis of the frequency of such cells before transplantation may be a useful predictor of severe acute GVHD in allogeneic bone marrow transplantation between HLA-identical siblings. It is possible that the patients at risk for serious acute GVHD after marrow grafting may benefit from some alternative form of immunosuppressive therapy.

Acute Disease↗
PubMed1992

ABO-incompatible bone marrow transplantation.

In the past 10 years 201 HLA-identical bone marrow transplantations (BMT) were performed with major ABO incompatibility in 41 (20%) and minor ABO incompatibility in 35 (18%) patients. ABO compatibility between donor and recipient showed no influence on granulocyte and platelet recovery after BMT. Erythrocyte reconstitution was significantly (p < 0.01) delayed for about 1 week in major ABO-incompatible BMT. In addition, a pure red cell aplasia lasting for 2-5 months occurred in 6 out of 21 blood group 0 patients who received transplants of group A. The rate of graft rejection, incidence of graft-versus-host disease as well as the leukemic relapse rate were similar in ABO-compatible and ABO-incompatible BMT. The probability of a 10-year survival after BMT is independent of ABO compatibility between donor and recipient.

ABO Blood-Group System↗
PubMed1990

Neurological outcome after a severe herpes simplex encephalitis treated with acyclovir and beta-interferon. Time course of intracranial pressure.

A severe herpes simplex encephalitis with documented intra-cerebral lesions and brain edema was treated successfully with acyclovir and beta-interferon. The increase in intracranial pressure during the second week was well controlled by ICP monitoring. Life-threatening pressure peaks were avoided through the use of thiopental, osmodiuretics, TRIS, and lidocaine.

Acyclovir↗
PubMed1990

Comparative analysis of in vivo T cell depletion with radiotherapy, combination chemotherapy, and the monoclonal antibody Campath-1G, using limiting dilution methodology.

We have investigated the efficacy of standard conditioning regimens for bone marrow transplantation in depleting functional T lymphocytes in vivo and have compared it with the efficacy of the monoclonal antibody Campath-1G. Using limiting dilution techniques the frequencies of proliferating T cell precursors (PTL), cytotoxic T cell precursors (CTL-p), helper T cell precursors (HTL-p), and mature helper T cells (HTL) were determined before and after treatment. Both total body irradiation and combination chemotherapy with busulfan/cyclophosphamide were highly efficient at depleting PTL, CTL-p, and HTL-p (0-4 days) but spared HTL to a variable extent (0-99.5%). In the majority of patients treated with Campath-1G a similar degree of PTL, CTL-p, and HTL-p depletion was achieved, and, in addition, HTL were effectively removed (greater than 95.5%). These results suggest that Campath-1G could be successfully employed in depleting radio- and chemotherapy-resistant host T lymphocytes prior to T-depleted bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1990

Frequency, specificity, and phenotype of clonally growing human alloreactive interleukin-2-secreting helper T lymphocyte precursors.

Limiting dilution cultures were performed to detect allospecific IL-2-secreting helper T lymphocyte precursors (HTL-p) among human peripheral blood mononuclear cells, E-rosette-purified (E+) and cell-sorter-separated CD4+/8- as well as CD4-/8+ T cell subsets. Split-well cultures were set up prior to restimulation to assess the antigen specificity of the response. Frequencies of alloreactive IL-2-secreting HTL-p in fully HLA-mismatched responder/stimulator cell combinations ranged from 1/200 to 1/900 (among PBMNC), from 1/50 to 1/301 (among E+ T cells), from 1/36 to 1/220 (among CD4+ T cells), and from 1/38 to 1/450 (among CD8+ T cells). Allospecificity of effector T cells was demonstrated by a strong decline of frequencies obtained after restimulation against unrelated third-party antigens. In clonal segregation analysis, the vast majority of IL-2-secreting progeny (80-90%) were exclusively specific for the original stimulating alloantigen. Finally, the allele specificity of human alloreactive HTL-p was revealed by comparing frequency estimates obtained after restimulation with partially identical stimulator/third-party antigen combinations.

Alleles↗
PubMed1990

Graft failure after T cell-depleted bone marrow transplantation: clinical and immunological characteristics and response to immunosuppressive therapy.

We have investigated the clinical and immunological features of 10 cases of graft failure after T cell-depleted marrow transplantation. In addition, the hypothesis that the process of graft failure can be reversed by immunosuppressive therapy with cyclosporin + steroids +/- monoclonal antibodies was tested in seven patients. Early graft failures (before day 50) presented a uniform clinical syndrome with a host T lymphocytosis preceding the loss of the graft. In the majority of cases of late graft failure (after day 50) a syndrome comprising delayed granulopoietic regeneration, fever of unknown origin and abdominal symptoms was observed. Surface marker analysis of peripheral blood and bone marrow lymphocytes implicated a population of CD3+, CD8+, DR+ host T lymphocytes with a frequent co-expression of the Leu7+ antigen in the pathogenesis of graft failure. Immunosuppressive therapy reversed graft failure in the three cases of incomplete graft failure (i.e. with residual reticulocytes) and failed in the four cases of complete graft failure (i.e. no residual reticulocytes).

Antibodies, Monoclonal↗
PubMed1988

[Bone marrow transplantation as therapy in chronic myeloid leukemia].

Between April 1982 and December 1986, HLA-identical bone marrow transplantations were performed on 25 patients with Philadelphia chromosome-positive chronic myelocytic leukaemia (CML), 18 in the chronic phase, 7 in acceleration or blast crisis. Twelve of the 18 patients (67%) in the chronic phase are still alive a median period of 570 days after transplantation, but only two of the seven (29%) in acceleration or blast crisis a median period of 227 days after transplantation (P less than 0.025). The duration of the chronic phase was of great importance for survival after transplantation: 86% of patients in the chronic phase for less than two years survived, but all patients in the chronic phase for over two years died (P less than 0.001). CML relapses occurred in one patient in a late chronic phase and in two in an advanced stage of the disease. These results confirm the unfavorable outcome of bone marrow transplantation in the accelerated phase or blast crisis, as well as in the late chronic phase. Since at present there are no reliable risk factors for the occurrence of acceleration or blast crisis, bone marrow transplantation should be undertaken as early as possible in the chronic phase of CML.

Adolescent↗
PubMed1988

Pathophysiological aspects of predominant preload lowering on pulmonary circulation, gas exchange, and the biventricular function in patients with chronic obstructive lung disease.

A group of 21 patients with various degrees of chronic obstructive pulmonary disease underwent radionuclide ventriculography with hemodynamic monitoring to assess the extent to which pulmonary artery pressures and pulmonary vascular resistance can be lowered by the vasodilator molsidomine. Molsidomine (N-carboxy-3-morpholino-sydnonimin-ethylester) is similar to nitroglycerin in its mode of action. After hemodynamic and radionuclide data acquisition, at rest and during submaximal exercise in the steady state, 2 mg molsidomine was injected intravenously. Rest and exercise measurements were repeated 45 min after molsidomine injection. In patients with mild to moderate disease (group 1), pulmonary artery resting pressures decreased by 12% (p less than 0.05) at rest by 22% (p less than 0.01) during exercise after the administration of the drug. Total pulmonary resistance during exercise decreased significantly (p less than 0.01) as a result of marked decrease of pulmonary artery pressure (PAP) compared with a minimal decrease in cardiac index (CI). In patients with severe disease (group 2), only the resting values of PAP decreased while the relationship between pressure and flow was unchanged. During the exercise period, the preload parameters of the right and left ventricles decreased by an average of 30%. With regard to gas exchange, only the arterial PO2 at rest decreased slightly but significantly (p less than 0.05) after molsidomine, while the coefficient of oxygen delivery was not affected by the drug. However, in four patients arterial PO2 was markedly reduced by the drug. Right ventricular ejection fraction increased significantly (p less than 0.01) both at rest and during exercise in group 1 and during exercise in group 2 after administration of molsidomine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

T-cell depletion versus methotrexate as GvHD-prophylaxis in allogeneic bone marrow transplantation for leukaemia.

Graft-versus-host disease (GvHD) prophylaxis using methotrexate (23 patients) and T-cell depletion of the graft (40 patients) was compared in 63 allogeneic bone marrow transplantations (BMT) for leukaemia. T-cell depletion significantly reduced (p = 0.001) the incidence of GvHD from 68% to 11% and the GvHD-associated mortality from 79% to 5%. Actuarial disease-free survival for low-risk patients (57% with T-cell depletion and 47% with MTX) was not significantly improved, due to graft failure and possibly due to a higher leukaemic relapse rate after T-cell depletion. Prevention of graft failure after T cell-depleted BMT is essential and could also reduce the risk of leukaemic relapse by improved engraftment.

Acute Disease↗
PubMed1988

Norfloxacin for prevention of bacterial infections during severe granulocytopenia after bone marrow transplantation.

48 patients treated with bone marrow transplantation (BMT) received the quinolone norfloxacin (NOR) in a total decontamination (TD-NOR, n = 36) or selective decontamination (SD-NOR, n = 12) regimen and were compared with a historical control group of 48 BMT patients receiving oral non-absorbable antibiotics (TD-NAA, n = 31 and SD-NAA, n = 17). 17/36 patients (47%) of group TD-NOR and 16/31 patients (52%) of group TD-NAA remained free of febrile episodes and infections. 4/12 patients (33%) of group SD-NOR and only 1/17 patients (6%) of group SD-NAA remained free of fever and infections. The use of norfloxacin in selective decontamination resulted in a statistically significant lower incidence of fever days than in patients receiving SD-NAA (p less than 0.001). These data suggest that norfloxacin may replace non-absorbable antibiotics in total and in selective decontamination regimens used for infection prophylaxis in BMT recipients.

Adolescent↗
PubMed1988

Relation of noninvasive parameters and pulmonary artery mean pressure in patients with chronic obstructive lung disease.

A series of 31 patients with various degrees of chronic obstructive pulmonary disease (COPD) underwent radionuclide ventriculography with right heart catheterization. The patients were divided into 2 groups on the basis of their reduction in forced expiratory volume in 1 s (FEV1). In patients with FEV1 greater than or equal to 1,300 ml (group 1) the oxygen partial pressure (PaO2) did not significantly change with exercise, while in patients with FEV1 less than or equal to 1,200 ml (group 2) the PaO2 significantly decreased (p less than 0.05) with exercise. The groups were significantly different from each other as to the correlation between hemodynamic and noninvasive parameters. In the resting state, the correlation between pulmonary artery mean pressure (PAP) and both residual volume to total lung capacity (RV/TLC) and PaO2 was close only in group 2. By contrast, the right ventricular end diastolic wall thickness (RWD) correlated closely with PAP in both groups. With exercise close correlations were observed between PAP and the noninvasive parameters: RWD, PaO2 and right ventricular ejection fraction in both groups. Arterial CO2 partial pressure (PaCO2) was only increased (greater than or equal to 45 mm Hg) in group 2. This parameter correlated moderately closely with PAP both in the resting and the exercise state only in group 2. The predictive value of PaCO2 greater than or equal to 45 mm Hg for estimation of PAP greater than 35 mm Hg during exercise was 100%. We conclude that separation of patients with COPD into groups with different impairments of the lung function parameter FEV1 can improve the correlation coefficients between noninvasive and invasive parameters. The exercise values obviously correlate more closely than the resting values. An increased value of echocardiographically determined RWD seems to be a reliable parameter for prediction of PAP.

Adult↗
PubMed1987

Cytomegalovirus (CMV) infections in patients receiving CMV-IgG-hyperimmunoglobulin prophylaxis after bone-marrow transplantation.

Conditioning therapy with aggressive chemotherapy and irradiation induces a state of transient combined immunodeficiency in bone-marrow transplant recipients. This promotes the occurrence of severe cytomegalovirus (CMV) infections, the most frequent lethal complication after bone-marrow transplantation (BMT) at present. Forty-four BMT recipients received CMV-IgG-hyperimmunoglobulin for CMV prophylaxis intravenously. The efficacy of this prophylaxis and possible risk factors for the occurrence of CMV-induced interstitial pneumonia (IP) were analyzed. Risk factors for the promotion of a CMV-IP were: additional immunosuppressive therapy after BMT, CMV-positive serostatus of the recipient, CMV-seropositive granulocyte transfusion, CMV infection immediately prior to BMT, and HLA-haploidentical BMT. In this study the incidence of graft-versus-host disease was low and was not associated with the incidence of CMV infections. The use of T-cell-depleted grafts did not result in increased CMV infections or IP and may possibly have improved the immunological reconstitution.

Adolescent↗
PubMed1987

Evidence for the involvement of host-derived OKT8-positive T cells in the rejection of T-depleted, HLA-identical bone marrow grafts.

The recent introduction of a variety of techniques for removing T cells from bone marrow grafts has reduced the incidence of graft-versus-host disease (GVHD)-associated morbidity and mortality. Whether this advance will be translated into improved patient survival is unclear at present, mainly because these procedures increase the risk of graft failure. Since 1983 we have transplanted 25 consecutive leukemia patients with HLA-identical sibling grafts purged of T cells by a single incubation with the monoclonal antibody Campath-1 and donor complement. This approach was successful in reducing T cell contamination of the graft and preventing acute and chronic GVHD. In this group of patients two suffered irreversible graft failure and one developed reversible graft failure. In a similarly sized group of patients previously transplanted with unpurged marrow according to the Seattle protocol, no episodes of graft failure occurred. Since other causes of graft failure, such as drug toxicity or viral infections, could be largely excluded, this suggested that the graft failures were specifically related to the purging process. In haploidentical bone marrow transplantation (BMT) O'Reilly has identified residual host-versus-graft activity (HVG) as a cause of graft failure. The causes and mechanisms of graft failure in T-depleted HLA-identical sibling transplants have not been extensively investigated to date. In the three graft failures observed by us, the loss of the graft was preceded by the appearance of a population of activated lymphocytes. We have determined the phenotype and origin of this population and investigated its interactions with donor hemopoietic tissue in vitro.

Antigens, Differentiation, T-Lymphocyte↗