Biomedical subjects
Publications and source records attributed to Y Bonny.
Explore the source record for details and available documents.
Interstitial pneumonia (IP) is a frequent and serious complication of bone marrow transplantation with a median time of onset about 2 months posttransplant. Most cases result either from toxicity of radiation and chemotherapy or from infection with pathogens such as cytomegalovirus. Described are two patients with chronic graft-versus-host disease (GVHD) who presented with late-onset IP 242 and 632 days posttransplant. Histologic examination of lung biopsy specimens disclosed a lymphoid interstitial pneumonia (LIP) in both cases. The major lymphocyte subset found in bronchoalveolar lavages and lung tissue was OKT8(+) and showed a positive dot staining for acid phosphatase. Contrary to peripheral blood mononuclear cells, most OKT8(+) lymphocytes in the lungs were OKT3(-). Since acute GVHD lesions are mediated mainly by cytotoxic T-lymphocytes, our data suggest that LIP in marrow-grafted patients may be a manifestation of chronic GVHD. It should be distinguished from the more common types of IP encountered following bone marrow transplantation.
In order to study the posttransplant evolution of serum immunoglobulin levels, we measured serum IgG, IgA and IgM levels in 50 recipients of allogeneic bone marrow before transplantation and at different intervals thereafter (days 39, 120, 365 and 730). IgG and IgM levels were depressed for 1 year and IgA levels for 2 years posttransplant. Immunoglobulin deficiency was more severe and prolonged in patients with graft versus-host-disease. Hypogammaglobulinemia may contribute to the frequent infections observed in these patients, especially those with chronic graft-versus-host disease.
Explore the source record for details and available documents.
Langerhans cells (LC) are bone marrow-derived dendritic antigen-presenting cells found in the epidermis. In an effort to determine the origin (host versus donor) of LC at different intervals following bone marrow transplantation, we performed skin biopsies in 16 recipients of sex-mismatched marrow. LC were identified using monoclonal antibody OKT6 in an indirect immunoperoxidase assay and their donor or host origin determined according to the presence or absence of Y body. The presence of Y-positive (donor) LC could be demonstrated in all (6/6) skin biopsies of female recipients of male marrow tested between days 39 and 730 post-transplant. Persistence of host LC in male recipients of female marrow was documented in all (6/6) recipients studied on day 39 and in two out of seven patients tested on day 120 post-transplant. From day 365 onward, no residual host LC could be detected, suggesting that by this time all epidermal LC are donor-derived. Our study demonstrates that host LC usually persist for 39 and up to 120 d following bone marrow transplantation. The relevance of this observation to the possible role of LC and other host dendritic antigen-presenting cells in the graft-versus-host reaction is discussed.
A second example of chronic myeloid leukemia (CML) with the unusual simple variant t(22;22) is reported. In this case, break points are readily identified at bands q13 and q11. The nature of simple variant translocations in CML is discussed in the light of recent knowledge acquired from in situ hybridization of c-Ableson proto-oncogen DNA probes to metaphase spreads of CML patients.
Explore the source record for details and available documents.
Two young adult patients with therapy-induced preleukemic syndrome and Hodgkin's disease as primary malignancy were treated with aggressive antileukemic regimens before the establishment of leukemic conversion. Pretreatment clinical staging procedures did not reveal recurrence of Hodgkin's disease. One of the regimens consisted of an HLA-identical allogeneic bone marrow transplant and the other of high dose cytosine arabinoside. Both therapeutic approaches have proved successful in restoring normal hematopoiesis with reversal to normal karyotypes and unmaintained remissions 556 and 192 days post-treatment. The rationale for such a therapeutic approach in the preleukemic stage of therapy-induced leukemogenesis is discussed.
In Montreal the acquired immune deficiency syndrome (AIDS) was seen in eight Haitian immigrants and one Caucasian woman who had lived with Haitian immigrants for 3 years before the onset of her illness. AIDS was characterized by opportunistic infections alone in seven patients, by opportunistic infection and Kaposi's sarcoma in one patient and by chronic generalized lymphadenopathy in one patient. Five of the patients had presented with Mycobacterium tuberculosis infections 1 to 12 months before the onset of opportunistic infections. All nine patients were found to have recall anergy by skin testing for delayed hypersensitivity. Enumeration of the lymphocyte subpopulations in three patients showed a marked inversion of the ratio of helper to suppressor T lymphocytes. Six of the patients died as a result of the opportunistic infections; autopsies showed no recognizable causes of immunodeficiency. Thus, there is in Montreal a third clustering of AIDS cases in North America related to Haitian immigrants.
In 25 patients receiving allogeneic bone marrow transplants methotrexate was used to prevent acute graft-versus-host disease (GVHD). Acute GVHD, grades 2 to 4, developed in only 5 (20%) of the patients. The incidence of acute GVHD in other series of recipients of bone marrow transplants has ranged from 5% to 76%. A review of the literature suggests that this variation cannot be completely accounted for by age, type of disease treated by transplantation or type of GVHD prophylaxis. However, transfusion of allogeneic lymphocytes that have not been completely inactivated by irradiation (e.g., in platelet and granulocyte preparations) and inadequate isolation-decontamination procedures may increase the probability of GVHD following bone marrow transplantation.
Explore the source record for details and available documents.
Therapy-related leukemias are generally preceded by a preleukemic phase of several months duration, characterized by pancytopenia, abnormal bone marrow findings, and nonrandom chromosomal abnormalities in almost all cases. No specific therapeutic guidelines are recommended in this preleukemic phase or any other type of preleukemia; aggressive combination chemotherapy is usually withheld until the full expression of leukemia. A 22-yr-old man with therapy-related preleukemia following treatment of Hodgkin's disease received as primary treatment ablative chemotherapy followed by marrow transplantation from his histocompatible sister. At day 316, the patient is still in complete bone marrow recovery with a normal donor karyotype. In the light of the very poor results obtained with conventional chemotherapy regimens once the leukemic phase is established, we suggest that bone marrow transplantation, if undertaken before leukemic conversion, may be the treatment of choice in young adults with therapy-related preleukemia.
Explore the source record for details and available documents.
In recent years, chromosomal aberrations in various hematologic disorders have raised a great deal of interest. In fact, several nonrandom chromosomal abnormalities are now recognized to be responsible for a specific type of dyshemopoiesis while others are closely associated with characteristic hematologic features. Monosomy C, later shown to be monosomy 7 by different banding methods, has been described in children in relation to a peculiar myeloproliferative disorder. Retrospective analysis of early cases published in the literature and a recent observation that we wish to report suggest that the most consistent phenotypic expression of monosomy 7 is an increased susceptibility to bacterial infections related to a preleukemic dyshemopoiesis. Acute nonlymphocytic leukemia is the terminal event of this peculiar preleukemic syndrome, and thus suggests that monosomy 7 involves a stem cell already committed to myeloid differentiation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.