Showing papers by "Eliane Gluckman published in 1991"

Umbilical cord blood hematopoietic stem and repopulating cells in human clinical transplantation.

Abstract: This paper reviews our recent laboratory and clinical studies demonstrating the efficacious use of human umbilical cord blood for HLA-matched allogeneic sibling stem/progenitor cell transplantation in cases of Fanconi's anemia. Future implications and potential problems are discussed with regards to (a) the possibility of maternal cell contamination, (b) the broadness of applicability with regards to other diseases that might be transplanted, and whether such transplants are feasible in adults, as well as in children, and (c) the immunological reactivity of cord blood cells, and whether these cells can be used to cross histocompatibility barriers more easily than that of bone marrow from adults.

Influence of the fractionation of total body irradiation on complications and relapse rate for chronic myelogenous leukemia

Abstract: One hundred eighty patients with chronic myelogenous leukemia, who received an unmanipulated marrow graft from an Human Leucocyte Antigen identical sibling donor, were reported to our group (G.E.G.M.O.) by 21 transplant teams. All were grafted after a total body irradiation-cytoxan conditioning regimen. Of these 180 patients, 126 were non-randomly assigned to single dose total body irradiation ('TBI group) and, 54 to fractionated total body irradiation (FTBI group). With a median follow-up of 40 months, there is no statistically significant difference in the 5-year survival rate between the two groups (51% for the whole population). In a first step we demonstrate by multivariate analysis that total body irradiation fractionation can dramatically decrease the incidence of interstitial pneumonitis. However, a multivariate analysis of potent risk factors for relapse post-transplant strongly suggests that TBI fractionation is also linked to an increased relapse rate. So, a sparing effect of fractionation for lung tissue could be offset by a less effective leukemic stem cell kill. Those results from a retrospective, non-randomized, multiinstitutional study clearly need additional clinical data, ideally from a randomized study.

Case Reports LATE VASCULAR COMPLICATIONS AFTER BONE MARROW TRANSPLANTATION FOR DYSKERATOSIS CONGENITA

Abstract: Two patients ( h and 1 1 years old) received HLA-identical bone marrow transplantation (BMT) for dyskeratosis congenita (DCG). a rare constitutional aplastic anaemia recognized by its association with dermal lesions (cutaneous reticulated hyperpigmentation. nail dystrophy and leucoplakia of the mucous membranes). Conditioning included cyclophosphamide (CY) 60 mg/kg on days 5 and -4, and a single dose total body irradiation on day 1 in one case, and CY 50 mg/ kg on days 5. -4, 3 . and thoraco-abdominal irradiation on day 1 (6 .00 Gy) in the other. Cyclosporine alone was used for prophylaxis of graft-versus-host disease. Rapid and sustained engraftment was seen, and complete chimaerism was proven cytogenetically and/or by erythrocyte markers. IJnfortunately. both patients died of late unexpected vascular complications developing hypertension associated with renal failure (1 years and 18 months after BMT. respectively. Renal post-mortem biopsy findings showed similar lesions. characterized by alteration of the capillary walls of glomeruli, mesangiolysis. arteriolonecrosis and occasional arteriolar luminal thrombosis. The same lesions of thrombotic microangiopathic syndrome (TMAS) have been described after BMT for leukaemia (Antignac et al. 1989; Guinan c’t 01. 1988). In these cases the latent period for nephritis was 2-10 months post BMT. Electron microscopic studies showed subendothelial and mesangial deposits of a n heterogenous material and on immunofluorescence. capillary wall deposition of fibrinogen. IgM and C3 (Antignac et al, 1989). Portal hypertension also appeared in the younger child. The liver biopsy showed marked centrolobular lesions (complete obliteration of terminal venules by fibrosis. dilated sinusoids lined by fibrosis and portal to central bridging) similar to those described as late changes of venocclusive disease (VOD) (Shulman et al. 1980). These changes were associated with portal and trabecular fibrosis. Post-mortem histology of the lung showed luminal narrowing by fibrosis of some terminal lung venules or concentric subintimal vessel wall thickening in others, displaying pulmonary VOD. In contrast to other cases reported in the literature (Mahmound et a] . 1985: Conter et al, 1988: Oberling. oersonal communication). our Datients did not show any ROW TRANSPLANTATION FOR DYSKERATOSIS

Clinical value of PCR in diagnosis and follow-up of leukaemia and lymphoma: report of the third Workshop of the Molecular Biology/BMT study group.

Abstract: The proceedings of the third workshop of the molecular biology/bone marrow transplantation (BMT) study group held in January 1991 in Verona, Italy. This workshop was convened to review progress in the application of molecular techniques to the diagnosis and follow-up of patients with chronic myeloid leukaemia (CML) as well as other haematologic malignancies. The results of polymerase chainreaction studies in 157 CML patients 1-90 months post BMT suggest that leukaemia is frequently detectable for the first 12 months but rarely detected thereafter except in patients known to have a high risk of relapse. In the acute leukaemias and lymphomas there is a rapidly increasing number of leukaemia-specific as well as clone-specific molecular markers now available for the detection of minimal disease. It may be possible to coordinate multi-center prospective studies to investigate the role of these markers in the diagnosis and follow-up of haematologic malignancies.

Perforin and granzyme B: predictive markers for acute GVHD or cardiac rejection after bone marrow or heart transplantation.

Abstract: Monitoring of human allografts requires to use histological, immunohistochemical and functional techniques to characterize graft infiltrating cells. Granzyme B and perforin gene expression is of major importance in functional studies. Those proteins are present in the cytoplasmic granules of cytotoxic T lymphocytes and are secreted during granule exocytosis at the effector/target cell interface. Gene expression of both proteins has been studied by in situ hybridization using specific riboprobes on serial sections of biopsies in two pathological models. Our results show that cells infiltrating early skin lesions of patients with acute GVHD after bone marrow graft are exclusively composed of T cells, among which some of them express granzyme B and perforin genes. Similarly the presence of granzyme B and perforine-expressing cells in endomyocardial biopsies of heart transplanted patients has been associated to early and severe crisis of rejection. In contrast, the absence of functional markers in lymphoid infiltrates was coinciding with less aggressive and late episodes of rejection. Taken together, our data indicate that granzyme B and perforin gene expression in skin infiltrating lymphocytes during GVH or within heart infiltrating cells during crisis of rejection are in favor of severe processes. The study has allowed to predict during heart transplantation the apparition of a rejection crisis and to show the necessity for treating the patient with immunsuppresive drugs. This is also the case for patients with GVHD at the time of the first skin rash.

Stem Cell Harvesting from Umbilical Cord Blood: A New Perspective

Abstract: Newborn blood contains a large number of hematopoietic stem/progenitor cells. In human ontogeny, hematopoiesis occurs first in the yolk sac, later in the fetal liver, and then in the bone marrow [26]. The volume of bone marrow in newborns is, in fact, so large that it is nearly equal to the marrow space occupied by hematopoietic cells in adults. The spleen, lymph nodes, and even kidneys may contain too few developing hematopoietic stem cells. During fetal life and at birth, communication of hematopoietic sites through the blood is very active and immature precursors of blood cells and their progenitors are present in peripheral blood. Transplantation of fetal liver cells has been used with limited success because of the limited number of cells infused, the HLA disparity between donor and recipient, and the occurrence of graft vs host disease (GVHD) when the fetus was older than 21 weeks [10]. Peripheral blood stem cells have been used for autologous transplantation in various malignancies, but the concentration of progenitor stem cells is so low that collection of an appropriate number requires multiple leukophereses, utilization of the rebound observed during recovery after chemotherapy, and stimulation by growth factors [30, 31]. The utilization of human cord blood for hematopoietic reconstitution was suggested by E. Boyse, who showed that lethally irradiated mice could be reconstituted with neonatal mouse blood. This led to a cooperative international study to evaluate human cord blood as an alternative source of hematopoietic stem cells for transplantation in humans.

Influence of various conditioning regimens on the outcome of bone marrow transplantation for leukemia.

Abstract: Allogeneic bone marrow transplantation is widely used for the treatment of leukemias. Relapse is one of the main complications. Various types of conditioning have been used. Most teams use a combination of cyclophosphamide and different modalities of total body irradiation. In some regimens, high dose alkylating drugs like Busulfan are substituted for radiation. None of these regimens has modified significantly the long term disease free survival, indicating the need for prospective randomized trials.