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B Chapuis

Publications and source records attributed to B Chapuis.

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

The frequency of pretransplant donor cytotoxic T cell precursors with anti-host specificity predicts survival of patients transplanted with bone marrow from donors other than HLA-identical siblings.

Transplantation with bone marrow from other than genotypically HLA-identical donors is associated with an increased incidence and severity of graft-versus-host disease (GvHD). The precise influence of HLA incompatibilities is not easy to analyze as even perfectly matched, HLA-identical unrelated donors might still express HLA differences that remain undetected by conventional typing. To measure T cell activity against serologically detectable and nondetectable HLA antigens, we analyzed the frequencies of CTL precursors (CTLp) between 11 unrelated HLA-matched and five related haploidentical donor/recipient pairs in graft-versus-host direction. Our results show that whenever HLA class I disparities could be identified by serology, high precursor frequencies (1/28,000-1/94,000) were measured. In contrast, in donor/recipient pairs that differed for class II only, no precursors were detected. CTLp were elevated in two out of eight fully matched donor/recipient combinations. These combinations displayed activities as high (1/21,000; 1/52,000) as the combinations that were serologically HLA class I disparate. The incompatibilities detected by the cellular assay were highly significant for the clinical results after transplantation. High CTLp frequencies before transplantation correlated with unfavorable clinical results independent of the incidence of detected HLA differences. Five out of the six patients with high (> 1/100,000) CTLp frequencies died within 120 days after transplantation. GvHD IV was the cause of death for all (3/5) patients who had received an unmanipulated bone marrow. In the group with intermediate or undetectable CTLp frequencies, eight out of 10 patients are alive, seven (CTLp frequency undetectable) without GvHD more severe than grade II, while one patient (CTLp frequency = 1/180,000) suffered from GvHD grade III. One patient rejected the graft and was rescued by an autologous BMT.

Adolescent↗
PubMed1993

Detection of chimaerism after bone marrow transplantation using the double amplification refractory mutation system.

We have developed a highly sensitive double amplification refractory mutation system (double ARMS) for the detection of extremely low levels of mixed chimaerism after bone marrow transplantation. The system we chose for double ARMS analysis is a highly polymorphic region 5' to the human delta-globin gene. Double ARMS analysis was found to correlate well with an established minisatellite system and was shown to demonstrate a very low level of mixed chimaerism in cases undetectable by the latter method.

Base Sequence↗
PubMed1993

Conditioning the leukemic patient before allogeneic BMT: value of intensifying immunosuppression in the context of different levels of T lymphocyte depletion of the graft.

We have studied the value of additional immune suppression in BMT conditioning regimens in 45 patients with leukemia and 4 with myelodysplastic syndrome allografted between 1984 and 1991. A dose of 6 Gy total lymphoid irradiation (TLI) was delivered to 12 of 24 and 15 of 25 patients conditioned with 10 Gy and 12 Gy total body irradiation (TBI), respectively. Thirteen patients also received methylprednisolone (MP) before BMT to enhance immunosuppression. Differences in immunosuppression between the TBI with or without TLI or MP regimens and the influence of different levels of graft T cell depletion were measured in terms of transplant rejection, and complete versus mixed chimerism. The treatment-related complications were evaluated in terms of GVHD and incidence of pneumonitis. The overall transplant rejection rate was 6% (3 of 49). Complete chimerism was not significantly modified by increasing the TBI dose or by additional TLI (p > 0.10) but was more often seen in patients receiving MP given as pre-transplant immunosuppressor booster (p = 0.01). The incidence of GVHD was only influenced by the level of T cell depletion (p = 0.003). All 49 patients received a TBI lung dose in the range 9.5-10 Gy. A crude pneumonitis range of 19% (9 of 47 evaluable patients) was found. Neither the addition of TLI, MP nor the T cell depletion influenced the lung toxicity rate (p > 0.10) but pneumonitis was more frequent in patients with GVHD (p = 0.005).

Adolescent↗
PubMed1993

Safety and efficacy of recombinant human erythropoietin treatment of anaemia associated with multiple myeloma in haemodialysed patients.

Recombinant human erythropoietin (rHuEpo) was used to treat the anaemia of four haemodialysed patients (3 males, 1 female) with advanced multiple myeloma; the type of serum M component was IgG kappa in all cases. During the 6-month period preceding rHuEpo therapy the patients received multiple blood transfusions (range 4-22 units of packed red cells per patient). After the first month of treatment haematocrit increased from 23 +/- 3 (SD) to 32 +/- 4% and during the last 3 months the maintenance dose of rHuEpo was 143 +/- 37 U/kg per week to achieve a mean haematocrit of 35 +/- 1%. After introduction of rHuEpo, blood transfusions were no longer required and the patients reported an improvement in wellbeing. No apparent worsening of multiple myeloma has been observed over the treatment period ranging from 5 to 34 months (cumulative duration of treatment 55 months). Anti-hypertensive therapy was started in one case and increased in two patients. We conclude that rHuEpo appears to be effective and safe in treating anaemia associated with multiple myeloma in patients requiring haemodialysis.

Aged↗
PubMed1993

Adoptive immunotherapy for recurrent CML after BMT.

Three patients with CML who relapsed after transplantation with T-depleted BM from their HLA-identical siblings were treated with transfusions of donor peripheral blood mononuclear cells, in combination with (short) IFN alpha 2 therapy. CML was successfully controlled as shown by the complete disappearance of Philadelphia-positive metaphases within 90 days of treatment. This treatment appears to be very effective as neither bcr-abl transcripts nor markers specific for hematological cells of recipient origin could be detected by very sensitive PCR techniques. Two patients treated in chronic phase are without evidence of disease 300 and 360 days after treatment. The third patient, treated in accelerated phase, died with BM aplasia, 39 days following PBMC infusions. Failure to detect residual donor-derived granulocytes, as was the case in this patient prior to initiating adoptive immunotherapy, may indicate loss of donor-derived BM activity. This may help predict and possibly prevent the occurrence of life-threatening aplasia after successful clearance of malignant hematopoiesis.

Acute Disease↗
PubMed1993

Characterization of pretransplant CTL activity in "perfectly matched" unrelated bone marrow donor/recipient combinations.

To characterize the pre-transplant cytotoxic T cell precursor (CTLp) activity of unrelated bone marrow donors towards their HLA-ABDR compatible recipients, we have established T cell clones from the primary (positive) CTLp cultures. Two "perfectly matched" oligo-typed DR/DQ identical combinations and two A/B identical, DR subtype incompatible combinations have been studied in detail. Analysis of the clones shows that in the first two combinations the alloreactivity was directed towards a subtype of A2 (A205) and a subtype of Bw60 respectively. In the other two cases, where class II incompatibilities were present, we have not yet defined the exact specificity. However, because the majority of recipient specific clones were of the CD8 phenotype, it is very likely that also in these two cases differences in class I are being recognized.

Bone Marrow Transplantation↗
PubMed1992

[Swiss Register for unrelated bone marrow donors: preliminary results].

Bone marrow transplantation from the unrelated volunteer donor is today a realistic possibility for patients lacking an HLA-identical family donor. In 1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate such bone marrow transplants and create the Swiss volunteer donor registry. Thus for a search has been initiated for 71 patients and 16 transplants have been performed. Donor and recipient were HLA-A-, -B- identical by serology and HLA-Dr-identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of basic disease 2 weeks to 2 years and 4 months after the transplant. These results illustrate that unrelated donor transplantation, using careful selection criteria, is a realistic new therapeutic modality.

Adolescent↗
PubMed1992

Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granulocytes and mononuclear cells by the polymerase chain reaction.

To evaluate the clinical relevance of mixed chimerism (MC) after allogeneic bone marrow transplantation (BMT), we developed a method based on amplification of DNA minisatellites by the polymerase chain reaction (PCR). This sensitive method by which MC lower than 1% can be detected is applicable to any patient-donor pair. Furthermore, because the analysis requires only small amounts of DNA, it allowed us to analyze samples early after BMT and during graft rejection. Results were obtained within 48 hours after blood sampling. Determination of MC in granulocytes (GR) and in mononuclear cells (Mnc) was performed in 20 patients treated for various hematologic malignancies. In patients who received untreated BM, recipient cells disappeared rapidly after BMT. In patients transplanted with T-cell-depleted BM, MC occurred in 15 of 16 cases. The percentage of host Mnc was always significantly higher than the percentage of host GR. The evolution of MC in patients who received T-cell-depleted marrow showed distinct patterns depending on whether patients remained in continuous complete remission, relapsed, or rejected their grafts. During complete remission, a relatively stable and significant number of host cells could be detected during the first 2 years after transplantation. Thereafter, their number decreased, but even after 4 years, low numbers of host cells could persist. When the patients relapsed, an increase in host Mnc was monitored without significant changes in the number of donor Mnc. In contrast, after the relapse, donor GR were no longer detected. Two cases of graft rejection were studied. Directly after the onset of the rejection, donor GR and Mnc disappeared rapidly. During that period, no significant changes in the number of host Mnc were detected.

Adult↗
PubMed1992

Effects of ultrasonic and sonic scalers on dental plaque microflora in vitro and in vivo.

The effects of ultrasonic and sonic scalers on the subgingival microflora were investigated in vitro and in vivo. In the in vitro investigation, 27 plaque samples collected from periodontal pockets were submitted to ultrasonic and sonic vibrations for 10, 30 and 60 s. Bacterial suspensions were examined by darkfield microscopy to detect qualitative changes and cultured to evaluate the total number of cultivable bacteria. Microscopic counts following both instrumentations showed a decrease in the proportions of spirochetes and motile rods and an increase in the % of coccoids and rods. The changes were directly related to the time-period of instrumentation. Comparison between both types of instrumentation showed significant differences and more pronounced changes were observed with the ultrasonic than the sonic scaler. Spirochetes and motile rods were reduced to approximately 0.1% after ultrasonic treatment versus 24.7% after sonic instrumentation. Cultural observations showed a marked increase in total number of colony-forming units following both treatments. The clinical investigation included 66 periodontal pockets which were instrumented subgingivally for 10 and 30 s with ultrasonic or sonic scalers. Qualitative changes were similar to those observed in vitro, i.e., reduction in spirochete and motile rod counts as well as the other morphotypes with an increase in coccoid cells. Total counts of bacteria were reduced following debridement. No difference in the microscopic or cultural data was found between ultrasonic and sonic instrumentation.

Adult↗
PubMed1992

Clonal imbalances of serum immunoglobulins after allogeneic bone marrow transplantation: an analysis by high-resolution two-dimensional gel electrophoresis.

The clonality pattern of immunoglobulins (Igs) produced after allogeneic bone marrow transplantation (BMT) was studied by high-resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of serum samples and purified Igs. With this technique, the light (L) chain of a monoclonal Ig usually appears as a single spot. Thus, the degree of clonal diversity of the functional B cells can be appreciated by the electrophoretic pattern of the serum L chains. Furthermore, 2D-PAGE allows a semi-quantitative determination of prominent Ig clones according to the size of L chain spots. We found that serum electrophoretograms of 8/19 patients after BMT (5-9 months) revealed L chain patterns which were similar to those of normal polyclonal Igs, that is, less than five distinguishable small spots among a cloud-like indiscrete L chain spots region ('polyclonal' pattern). A spectrum of clonal abnormalities was observed on the electrophoretograms of 11/19 patients: in five patients, multiple small L chain spots (corresponding to Ig concentrations between 0.2 and 2 g/l) were detected ('oligoclonal' pattern), whereas in six others, 'typical' monoclonal Igs (Ig concentrations > 2 g/l) were observed with (3/19 patients) or without (3/19 patients) multiple small clonal components. Sequential analysis of serum obtained from patients at different times after BMT revealed that imbalanced clonal reconstitution was transient and evolved towards apparently normal polyclonal Ig production. Our observations show that the development of clonal 'gammopathies' after BMT is a frequent, but not obligatory phenomenon. It may reflect a transient restriction of the B cell repertoire either through a limited outgrowth of precursor cells or through selective antigenic pressures.

Antibody Diversity↗
PubMed1991

[The treatment of acute lymphatic leukemia in adults: pilot project with intensive early therapy without a maintenance phase].

Acute lymphoblastic leukemia (ALL) is conventionally treated in three phases: remission induction, consolidation and maintenance. In adults initial remission rates of nearly 80% can be achieved. The 3 to 5 year leukemia free survival is 20 to 40%. Most relapses occur during maintenance, despite continuous therapy for 2 to 3 years. The value of maintenance therapy following intensive induction in adults is not documented. In this pilot study we treated 34 patients with ALL in five Swiss centers between 1986 and 1989 with intensive induction/consolidation therapy alone. Three induction/consolidation courses were applied: course I, 43 days, consisting of daunomycin, vincristine, prednisone, methotrexate, L-asparaginase and intrathecal CNS prophylaxis; course II, 6 days, consisting of high dose cytosine arabinoside and VP-16; course III, three non randomized arms, either allogeneic or autologous bone marrow transplantation (BMT) or high dose cyclophosphamide and repeated intrathecal therapy alone. 32 patients (94%) reached complete remission (CR): 24 after course I (71%), 7 after course II (cumulative 91%) and one after course III only (cumulative 94%). 3 patients had early, relapses before course III, 3 died of infection, and 2 of graft-versus-host disease. One patient had refractory leukemia in all three courses. 26 patients (76%) were in CR after completion of therapy. 16 relapsed within 1 to 17 months (median 5). 10 patients are free of disease after 10 to 44 months (median 24): 5 had had allogeneic BMT, 3 autologous BMT and 2 cyclophosphamide in course III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Acute myeloid leukemia with poor prognosis: treatment with oral 4-demethoxydaunorubicin (idarubicin) and low-dose cytarabine via subcutaneous route].

26 patients with poor risk acute myelogenous leukemia (elderly, in relapse or resistant) were treated with a combination of oral idarubicin (30 mg/m2/d for 3 days) and low dose subcutaneous cytarabine (10 mg/m2 twice a day for 10 days). Of 26 patients, 14 achieved complete remission, 2 partial remission, and 5 died in aplasia (3 without evidence of response, 2 inevaluable); 5 further patients were non-responders. All responses but two occurred among patients treated for AML at presentation or in relapse. Side effects consisted mainly of severe hematologic and moderate gastrointestinal toxicities. The main interest of this regimen is adaptability to outpatient conditions and rapid cytoreduction in patients with hyperleukocytic presentation.

Administration, Oral↗
PubMed1990

[Ultrasonic and sonic scalers in periodontics. A review].

Periodontal treatment aims at the removal of calculus and bacterial deposits from the tooth surface. Sonic and ultrasonic scalers are mainly used during initial therapy and their use is often limited to the supragingival area. Subgingival instrumentation is usually performed with hand curettes. Recent literature shows that clinical and bacteriological results obtained after treatment of periodontal lesions with sonic or ultrasonic scalers are similar to those observed following hand curettage. In addition, recent ultrasonic scalers allow irrigation with sterile or antiseptic solutions. Finally, new inserts are better designed for subgingival instrumentation. Altogether, these observations give a new dimension to these instruments.

Dental Calculus↗
PubMed1988

[Super intensive treatment followed by bone marrow autograft in cases of hematologic neoplasms and solid tumors].

Thirty-one patients underwent autologous bone marrow transplantation (ABMT) after intensive radio and/or chemotherapy. On 18 occasions, bone marrows were treated in vitro with either Asta-Z 7557, Asta-Z 7654 or the rat monoclonal antibody Campath-1M and complement. Sixteen patients were transplanted for acute leukemia: 6 patients were in first complete remission (CR), 5 in CR greater than 1 and 5 in relapse. Twelve out of fourteen evaluable patients have relapsed. Two patients transplanted in CR 2 and CR 1 remain in CR after 9.5 and 12 months respectively. Nine patients were transplanted for aggressive lymphoma: four patients were in CR 1, 2 in CR greater than 1, 1 in first relapse and 2 refractory to best available second line chemotherapy. All 3 achieved CR after ABMT. Nine patients are evaluable: 4 relapsed and 5 remain in CR at 5, 6.5, 21, 25 and 39 months, this last patient transplanted in a refractory state, the others in CR 1. Four patients were transplanted for refractory Hodgkin's disease: 3 patients are evaluable. One patient achieved complete remission which lasted 9 months. Two patients were transplanted for relapsed solid tumors and achieved a partial response. In conclusion, the response rate is encouraging for patients transplanted during active and sometimes refractory phases of the diseases (8/13 evaluable patients achieved CR). However, for the whole group of patients, including those transplanted for acute leukemia in CR 1, the relapse rate was high. Durable remissions were achieved for patients with aggressive lymphoma who were transplanted early in the disease.

Acute Disease↗
PubMed1987

[Genetic factors predisposing to autoimmune diseases. Study of HLA antigens in a family with pernicious anemia and thyroid diseases].

In a family including patients suffering from autoimmune disease (2 propositi: pernicious anemia and Graves' disease, pernicious anemia and autoimmune thyroiditis), we have determined common autoantibodies and tissue antigens (HLA) in 47 patients (26 males and 21 females) from 2 generations. In this family, we have found 4 cases of pernicious anemia, 5 cases of thyroid disease (2 Graves' disease), 3 women with repetitive abortions and 2 cases of melanoma. Patients with autoantibodies, often asymptomatic, are abnormally numerous (44% in generation II, 16% in generation III). A correlation with haplotype A1B8DR3 was found only for Graves' disease. Likelihood of forming autoantibodies appears to be of multifactorial origin. Its mode of transmission remains unknown.

Abortion, Habitual↗