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Biomedical subjects

B Chapuis

Publications and source records attributed to B Chapuis.

At least 55 records · Page 3Linked to original sources
PubMed1997

Massive delayed hemolysis following peripheral blood stem cell transplantation with minor ABO incompatibility.

After hematopoietic stem cell transplantation, delayed immune hemolysis may occur when donor-derived B lymphocytes carried with the graft produce immune antibodies against the recipient's incompatible red cells. We report the occurrence of this syndrome in the context of minor blood group incompatibility between donor and recipient after peripheral blood stem cell (PBSC) transplantation. On day 12 post-transplant there was abrupt onset of hemolysis necessitating supportive treatment with hydration and transfusions. Because, as compared to bone marrow, PBSC grafts are enriched with lymphocytes, more frequent and intense delayed immune hemolysis may be anticipated when using PBSC. This complication is described most often when cyclosporine alone is used for immunosuppression following the graft. The addition of methotrexate, which with CyA forms the classic regimen for the prevention of graft-vs-host disease, may diminish the frequence and severity of this adverse reaction.

ABO Blood-Group System↗
PubMed1996

High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation.

As compared with related HLA-identical sibling donors, bone marrow transplantation (BMT) with phenotypically HLA ABDR-compatible unrelated donors is associated with increased mortality. This may be due to hidden HLA incompatibilities not detected by conventional typing. We have analyzed 44 unrelated patient-donor pairs who were matched for HLA-A, -B, and -DR by routine tissue typing. Our comprehensive HLA typing approach consisted of serology, cytotoxic T-cell precursor (CTLp) tests, T-cell cloning, oligotyping, and DNA sequencing. Using these techniques, we identified numerous HLA allele mismatches not detected by the previously applied routine typing. Twenty-four patient-donor pairs were highly matched and had a low CTLp frequency, whereas the remaining 20 pairs were allele-mismatched for HLA-A, -B, -C, -DR, -DQ antigens and/or had a positive result of the CTLp test. Patient and donor age, diagnosis, and treatment did not differ significantly between the matched and mismatched transplants. The probability for severe acute graft-versus-host disease grades III-IV was 21% in the matched and 47% in the mismatched patients (P = .0464). Transplant-related mortality was 21% and 57% (P = .0072) and actuarial patient survival rates at 3 years were 61% and 13% (P = .0005). We conclude that both HLA class I and class II allele mismatches between unrelated phenotypically ABDR-compatible patient-donor pairs are frequent and associated with increased incidence of posttransplant complications.

Alleles↗
PubMed1996

Analysis of T-cell repopulation after allogeneic bone marrow transplantation: significant differences between recipients of T-cell depleted and unmanipulated grafts.

We have studied the repopulation of the T-cell compartment in 27 patients transplanted with bone marrow from an (HLA)-identical sibling. Significant differences were found between recipients of unmanipulated and T-cell depleted grafts. Analysis of the T cells by a method based on amplification of minisatellite DNA regions showed that without depletion > 99.9% of the clones responding to a mitogenic stimulus after transplantation were of donor origin. In contrast, when the graft had been depleted with Campath-1M plus complement, a significant part of the T cells cloned during the first weeks after transplantation comprised of recipient T cells that had survived the preconditioning. This mixed population of low numbers donor and recipient T cells (19 +/- 31/mm3 at day 14) expanded rapidly (predominantly CD8+ T cells) during the first 2 months, without a significant change of the ratio of recipient/donor T cells. In 11 of 17 evaluable patients a late wave ( > 9 months) of donor T cells occurred. As a consequence, T-cell chimerism changed in favor of donor T cells and the CD4/CD8 ratio that had been reversed ( < 0.5) after the first expansion, normalized (1.5 +/- 0.51). Analysis of the T-cell receptor repertoire showed that in recipients of a T-cell depleted graft, the recipient as well as the donor T cells that repopulated the peripheral T-cell pool during the first month, were the progeny of a limited number of precursors. Because without depletion, when larger numbers of donor T cells had been cotransfused with the marrow, the repertoire was much more diverse, these data show that immediately after transplantation, the peripheral pool is repopulated primarily through expansion of circulating T cells.

Adolescent↗
PubMed1996

Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease.

PURPOSE: To evaluate retrospectively the cumulative risk probability and factors correlated with renal dysfunction after allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From October 1984 to July 1994, 84 patients with malignant hematopoietic diseases received allogeneic BMT after conditioning with high-dose chemotherapy and total-body irradiation (TBI). Seventy-nine patients with normal renal function before conditioning are included in this study. Conditioning included high-dose cyclophosphamide without (n = 46) or with (n = 33) other agents (daunorubicin, busulfan, cytarabine, and thiotepa) followed by TBI. The TBI dose prescribed to the center of the abdomen was 10 Gy for 24 patients, 12 Gy for 32, and 13.5 Gy for 23. In vitro T-cell depletion was undertaken in 48 cases. The post-BMT nephrotoxicity of aminoglycosides, vancomycin, amphotericin, and cyclosporine was assessed. Time to renal dysfunction was defined as the time to a persistent increase of serum creatinine (SCr) level greater than 110 mumol/L. The potential influence of sex, age, diagnosis, chimerism, and graft-versus-host disease (GvHD) on renal dysfunction was also assessed. RESULTS: The 18-month probability of renal dysfunction-free survival (RDFS) for the whole group was 77%. Only TBI dose and presence of GvHD were significantly correlated with renal dysfunction by multivariate analysis. The 18-month probabilities of RDFS were 95%, 74%, and 55% for the patients conditioned with 10, 12, and 13.5 Gy, respectively. The 18-month RDFS probabilities were 88% and 61% for patients without and with GvHD, respectively. Combining both variables, we have defined two risk categories: low-risk (ie, 10 Gy TBI with/without GvHD and 12 Gy TBI without GvHD) and high-risk (ie, 12 Gy TBI with GvHD and 13.5 Gy TBI with/without GvHD). The predicted 18-month RDFS rates were 93% and 52% for the low- and high-risk groups, respectively. CONCLUSION: Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (and dose per fraction) and to the presence of GvHD. Renal shielding should be recommended if a TBI dose greater than 12 Gy (fractionated twice daily over 3 days) is to be prescribed. Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, absence of T-cell depletion), these data suggest that kidney doses greater than 10 Gy should be avoided.

Adolescent↗
PubMed1995

Application of a polymorphic Y microsatellite to the detection of post bone marrow transplantation chimaerism.

A highly sensitive Y-microsatellite amplification system was developed for the detection of post bone marrow transplantation (BMT) chimaerism. The system is able to detect the DNA equivalent of a single male cell in a background of 10(5) female cells. For clinical applications it has the distinct advantage that the polymorphic nature of the PCR product allows the checking of the genuineness of a positive PCR signal by reference to its allelic type. This extra degree of precision enhances the accuracy of Y-PCR for clinical diagnosis.

Alleles↗
PubMed1995

Histoincompatibilities in ABDR-matched unrelated donor recipient combinations.

To get an insight into the degree of major histocompatibility mismatches in donor/recipient (D/R) combinations who were 'ABDR-matched' by serology for class I and by oligotyping for DR1-14 (low resolution typing), we performed additional HLA testing using a combination of molecular, biochemical and cellular techniques. For class II we used extended oligotyping, discriminating all the common DRB1/B3/B5-subtypes. For class I (-subtypes) we used oligotyping (HLA-A2,-A3,-B35,-B41,-B44), sequencing (HLA-B35,-B41,-Cw16), isoelectrofocusing (IEF), primary cytotoxic T lymphocyte (CTL) assays and class I-subtype specific T cell clones. In addition, all combinations were serologically typed for HLA-C. This high resolution typing by the combination of techniques revealed numerous histoincompatibilities. Fifty-three per cent of all 'ABDR-matched' combinations tested (n = 198) appeared to be DR incompatible. Moreover, independent of the presence of a class II mismatch, 47% of the donors tested (n = 131) displayed pretransplant cytotoxic activity against the patient. This activity was found to be rigorously correlated with the presence of class I incompatibilities, predominantly HLA-A,-B subtypes and HLA-C. Thus, although the D/R pairs had been originally matched for AB including serological splits and by generic class II typing, only 28% of the pairs were in fact ABCDR identical. As many as 38% of the D/R pairs were mismatched for one, 14% for two, 13% for three and 6% for four A, B, C or DRB1 antigens. We conclude that the presence of such a high number of histoincompatibilities in a group of relatively well matched D/R pairs will severely hinder the analysis of the role of HLA in marrow transplantation and that conclusions from studies in which D/R pairs are matched by conventional typing must be interpreted with extreme caution.

Bone Marrow Transplantation↗
PubMed1994

HLA-B35-subtype mismatches in ABDR serologically matched unrelated donor-recipient pairs.

We have characterized HLA incompatibilities in a group of 17 B35-positive patients who were ABDR matched (AB serology and oligotyping for DR1-14) with their 28 (unrelated) potential bone marrow donors. High-resolution oligotyping for DR subtypes disclosed that nine combinations were in fact DR mismatched. Cytotoxic T-lymphocyte (CTL) activity was detected in nine combinations (32%). In the group matched for DR subtypes, three (16%) of 19 combinations were CTL positive. Patient-specific cytotoxic activity appeared to be directed against HLA C (two cases) or against a subtype of B35. In the group of DR-subtype-mismatched combinations, CTL activity was found in six (67%) of nine pairs. In all four cases that were studied in detail, however, CTL reactivity appeared to be directed against a variant subtype of B35. We have studied the B35 incompatibilities recognized in five different combinations by specificity analysis of the B35-specific CTLs and by partially sequencing of relevant segments of B35 exon 3. Preliminary data show that, within this relatively small Caucasoid group, at least five B35-variant subtypes could be distinguished. This would make B35 an antigen that will be frequently subtype mismatched, in particular when DR matching is done with low resolution (DR1-14) only.

HLA-A Antigens↗
PubMed1994

Intensive induction/consolidation therapy without maintenance in adult acute lymphoblastic leukaemia: a pilot assessment. Working Party on Leukaemia of the Swiss Group for Epidemiologic and Clinical Cancer Research (SAKK).

Maintenance chemotherapy for up to 3 years is traditionally given to patients with acute lymphoblastic leukaemia (ALL) achieving complete remission. We questioned the value of such maintenance therapy in adult patients treated with intensive induction/consolidation. In a phase II study (SAKK 33/86) 63 patients between 17 and 72 years of age (median 27 years) with newly diagnosed ALL were treated with three intensive cycles of marrow-ablative chemotherapy. All subtypes were included. No maintenance phase was added. 53 patients (84%) entered a complete remission (CR) and 21 (33%) continue to be in unmaintained remission for 11-69 months (median 21 months). The disease-free survival of patients achieving CR and completing all three cycles is 40% at 3 years, with a 95% confidence interval of +/- 19%. These findings are comparable to the results of conventional studies. We conclude that maintenance therapy might not be needed in all adult ALL patients. Its value should be tested in a randomized trial. For patients failing, novel approaches are needed to improve outcome in adult ALL.

Adolescent↗
PubMed1994

Recombinant human granulocyte-macrophage colony-stimulating factor in acquired or chemotherapy-induced neutropenia. An open clinical trial.

This prospective open trial evaluated the efficacy and tolerability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in patients with established neutropenia, considering as the main endpoint the clinical benefit to the patients regarding clearing of infection or resuming chemotherapy as initially planed. Adult patients (n = 28) with absolute neutrophil counts (ANC) < 10(9)/1 for 21 days were given a fixed dose (400 micrograms) of rhGM-CSF subcutaneously, for a total of 35 cycles. Causes of neutropenia were chemotherapy for acute leukaemia, lymphoma, myeloma and solid tumours, complications after bone marrow transplantation (BMT), and neutropenia associated with AIDS. Response (ANC to > 10(9)/l) occurred in 83% of rhGM-CSF cycles (29/35). Median time to response was 2.4 days (mean 6.7 days). Kinetics of response was dependent on diagnosis and treatment history. Fever abated with increasing ANC in 13/17 patients (76%) who entered the trial with hyperpyrexia. Treatment with rhGM-CSF allowed chemotherapy to be resumed on schedule in 7/9 relevant cycles. Toxicity was mild, leading to treatment interruption in only two cycles. In conclusion, rhGM-CSF was well tolerated and associated with a rise in ANC which appeared to result in immediate clinical benefit, including resolution of infection and resumption of scheduled chemotherapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Kaposi's sarcoma following allogeneic bone marrow transplantation.

Localised Kaposi's sarcoma (KS) was diagnosed 240 days after allogeneic bone marrow transplantation (BMT) in a severely immunosuppressed HIV negative patient with genetic predisposition. The tumour was of host origin, based on PCR amplification of DNA minisatellites. Treatment with radiotherapy prompted almost complete regression of the lesions. However the patient subsequently died with relapsed acute myelogenous leukaemia. Contrary to the incidence observed after organ allografts, the advent of KS appears to be exceptional after BMT, since only one case has been reported to date, following reinfusion of autologous marrow.

Bone Marrow Transplantation↗
PubMed1994

Relation between the resolution of HLA-typing and the chance of finding an unrelated bone marrow donor.

The chance of finding an unrelated bone marrow donor depends on the size of the donor registry, the frequency of the patient's HLA phenotype and the degree of histoincompatibility considered acceptable. We have studied 60 unrelated bone marrow donor searches and the probability of finding a donor when increasing HLA-compatibility requirements were applied. For 21 (35%) of the patients no donor could be identified who was (serologically) matched for all six ABDR antigens. For the remaining 39 (65%), a median of two (range 1-20) blood samples from serologically-matched potential donors was obtained for further analysis. Eighteen (30%) patients appeared to be mismatched with all the pre-selected donors because of DR (sub-)type mismatches detected by oligotyping. A further 7 (12%) patients did not have an MLC and/or cytotoxic T lymphocyte precursor (CTLp) negative donor. Thus, a 'perfectly matched' donor was found for 11 (18%) patients. To find a suitable donor for more patients we propose that many or all the potential donors identified in the various registries for a particular patient are simultaneously evaluated as many of the serologically ABDR-matched donors will appear to be incompatible after high resolution HLA-typing. This strategy will not only allow selection of the best matched donor more rapidly but the consequent use of high resolution typing might also lead to the definition of a certain number of acceptable mismatches.

Bone Marrow Transplantation↗
PubMed1994

Malignant histiocytosis in the leukaemic stage: a new entity (M5c-AML) in the FAB classification?

Malignant histiocytosis (MH) is a rare, rapidly fatal disorder, characterized by systemic proliferation of abnormal histiocytes. Most patients present with pancytopenia. We report the case of a patient with MH in the leukaemic stage, who presented extremely pronounced general symptoms and multisystemic involvement. Determination of serum cytokines showed high levels of tumor necrosis factor (TNF), interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1ra). Cytogenetic studies proved the monoclonality of the histiocytic proliferation. These findings strongly suggest that we are dealing with a proliferation of activated macrophages (= histiocytes). By analogy with the monoblastic (M5a) and monocytic (M5b) acute leukaemia of the French-American-British (FAB) classification, we propose a new entity, 'M5c', designating acute histiocytic leukaemia.

Bone Marrow↗
PubMed1993

Characterization of mixed chimerism in patients with chronic myeloid leukemia transplanted with T-cell-depleted bone marrow: involvement of different hematologic lineages before and after relapse.

We have characterized mixed chimerism (MC) in five patients with chronic myeloid leukemia (CML) who received transplants with T-cell-depleted bone marrow (BM) and who relapsed within 4 years after transplantation. To study the possible relation of MC with relapse, we purified different populations of leukocytes and analyzed their donor/recipient origin by a method based on polymerase chain reaction amplification of minisatellite DNA regions. Our results show that before relapse, all hematopoietic recipient cells are T cells, whereas monocytes, B, and natural killer (NK) cells are of donor origin. This observation does not appear to be specific for CML as similar results were found in two control patients with acute myeloid leukemia (AML). At the time of (CML) relapse, recipient granulocytes, monocytes, and erythrocytes appeared and progressively replaced the respective lineages of donor origin. No other lineages seemed to be involved as B cells and NK cells remained of donor origin and no significant changes in the number of recipient T cells were detected. In this respect relapse of CML after BM transplantation (BMT) seems not to be very different from the primary disease in chronic phase before transplantation. Furthermore, we conclude that after BMT, an association between mixed chimerism before relapse and the (CML) relapse does exist because both phenomena are consequences of T-cell depletion of the BM graft. However, this correlation might well be indirect as the MC caused by the recipient T cells appears to be independent of the one caused by the recurrent disease.

Adult↗
PubMed1993

High-resolution histocompatibility testing of a group of sixteen B44-positive, ABDR serologically matched unrelated donor-recipient pairs. Analysis of serologically undisclosed incompatibilities by cellular techniques, isoelectrofocusing, and HLA oligotyping.

We have characterized HLA incompatibilities in a group of 16 B44-positive patients who were serologically ABDR matched with their 23 (unrelated) potential bone marrow donors. After analysis with a combination of cellular techniques, IEF for HLA-A/B and oligotyping for class II and HLA-B44, 44% of the patients revealed one or more HLA incompatibility with at least one of their potential donors. CTL activity was detected in 12 of the 22 combinations tested. CTL incompatibility occurred more frequently in DR subtype-mismatched combinations, but CTL reactivity was always directed against class I. To characterize these incompatibilities between matched unrelated individuals, we analyzed the specificity of T-cell clones from seven primary CTL cultures. In three combinations, CTL reactivity was directed against a subtype of B44. In two combinations, the CTL reactivity was directed against a non-B44 class I subtype. In two of seven combinations, the CTLs recognized an antigen that, though unconditionally associated with B4403, was expressed by 60% of the B4403+ cells only. Because all 12 of these B4403+ targets recognized could be typed for one HLA-C allele only (Cwl-Cw8), we believe that this alloreactivity might be directed against a serologically undefined Cw antigen.

Base Sequence↗