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Biomedical subjects

R Or

Publications and source records attributed to R Or.

At least 127 records · Page 7Linked to original sources
PubMed1995

Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation.

Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre-BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.

Alleles↗
PubMed1995

[Hepatosplenic fungal abscesses in the immunocompromised].

A rare, newly recognized variant of systemic fungal infection is the occurrence of focal hepatosplenic microabscesses in the immunocompromised patient. A patient with persistent unexplained fever should have a CT or ultrasound scan of the abdomen. The presence of multiple splenic lesions strongly suggests fungal disease. If antifungal therapy does not result in complete resolution of fever and splenic lesions, splenectomy is recommended.

Abdomen↗
PubMed1995

Sequential respiratory syncytial virus and cytomegalovirus pneumonia following bone marrow transplantation.

A 6-month-old child with familial hemophagocytic lymphohistiocytosis (FHL) experienced early sequential pneumonia due to respiratory syncytial virus (RSV) and cytomegalovirus (CMV) following bone marrow transplantation (BMT). The patient was deficient in natural killer (NK) cell activity (as found frequently in patients with FHL), and this risk factor may have played a major role in the concomitant infection by the two viral pathogens. Rapid diagnostic methods for both viruses are essential and early specific treatment may serve to ameliorate RSV- and CMV-induced lung injury in these life-threatening infections.

Bone Marrow Transplantation↗
PubMed1995

Assessment of proton magnetic resonance spectroscopy of blood serum as a diagnostic tool in bone marrow transplantation.

The use of proton high-resolution magnetic resonance spectroscopy (MRS) allows the rapid detection and quantitation of modification in the blood serum metabolic profiles in haematooncological patients. This study examines the feasibility of using proton MRS as a diagnostic tool in predicting the outcome of bone marrow transplantation (BMT) at the earliest possible date. Proton spectra of serum samples from 18 BMT patients (11 autologous-BMT and seven allogeneic-BMT), six hematooncological patients that did not undergo BMT and six normal individuals were recorded at 400 MHz. A longitudinal MRS study was carried for these groups and the data were evaluated for statistical significance. It was determined that the MRS results, taken at different time points before and after the BMT treatment, are statistically significant. However, no significant difference was observed in the MRS parameters between the transplanted patients and the control patients. We could not obtain significant correlation between the MRS results and the immunoglobulin level, engraftment parameters or the age, sex, stage of basic disease, conditioning protocols, transplant type, post transplant complications (including death) and outcome.

Adolescent↗
PubMed1995

Successful matched unrelated transplantation from a donor with idiopathic thrombocytopenic purpura (ITP).

The case of a 5 year old male is described who had acute myeloblastic leukaemia (AML M5) and was in third remission when he underwent an allogeneic T cell depleted bone marrow transplantation (BMT). The bone marrow was from an HLA matched unrelated donor (MUD) who suffered from chronic idiopathic thrombocytopenic purpura (ITP). In spite of this, the patient had rapid platelet engraftment post BMT (> 50 x 10(9) l-1 on day 20). He is now 12 months post-transplantation and has normal platelet counts, without any clinical or laboratory evidence of ITP. Autoimmune manifestations such as ITP occurring in bone marrow recipients following BMT have been previously reported. Furthermore, severe and protracted thrombocytopenia is a known complication following MUD transplantation and with its respective high risk of graft versus host disease (GVHD). In this case, no signs of ITP could be detected in the recipient despite the fact that the donor had ITP. Our data suggest that in the absence of an alternative choice, a person with ITP should be considered as an appropriate donor for transplantation.

Adult↗
PubMed1995

Aeromonas hydrophila myonecrosis accompanying mucormycosis five years after bone marrow transplantation.

A 36-year-old man, five years after bone marrow transplantation for aplastic anemia, was admitted with myonecrosis of the forearm after he had immersed his hand in sewage water several days prior to his admission. Blood cultures and specimens taken from the necrotic tissue of the arm all grew Aeromonas hydrophila. Following extension of the infection, the patient underwent amputation of the arm but ultimately died of cerebral mucormycosis. The epidemiology of Aeromonas infections is discussed and the literature of Aeromonas myonecrosis is reviewed.

Adult↗
PubMed1995

Abatement of bleomycin-induced pulmonary injury by cell-impermeable inhibitor of phospholipase A2.

The mechanism of bleomycin (Bleo)-induced pulmonary injury is not fully understood. Elevated levels of lung phospholipase A2 (PLA2) have been previously reported following intratracheal (IT) instillation of Bleo, but the role of this enzyme in the pathogenesis of lung injury is not clear. In this pilot study, we have evaluated the effect of a cell impermeable inhibitor of PLA2 (CME) on Bleo-induced pulmonary inflammation in hamsters. Pulmonary injury was induced by a single IT instillation of Bleo (1 unit/0.5 ml saline). Three groups of male Syrian hamsters were evaluated: 1) BLEO-CME animals received IT Bleo and daily intraperitoneal (IP) injections of CME (1 mumole/kg), starting 1 day before IT instillation; 2) BLEO-SAL animals--received IT Bleo and IP injections of saline and 3) SAL-SAL animals--treated with IT and IP administrations of saline. Animals were sacrificed 14 days after IT treatment and lung injury was evaluated histologically by a semiquantitative morphologic index and by a differential cell count of bronchoalveolar lavage fluid. CME treatment significantly ameliorated Bleo-induced lung injury compared to BLEO-SAL animals (P < 0.05). The percentage of neutrophiles in bronchoalveolar lavage fluid was reduced from 17.7 +/- 3.2% (mean +/- S.E.) in BLEO-SAL group to 7.3 +/- 1.7% in BLEO-CME group (P < 0.05), achieving levels comparable to SAL-SAL control animals. These results suggest that treatment with an extracellular PLA2 inhibitor-CME abates Bleo-induced pulmonary injury. This may indicate an active role of PLA2 in the pathogenesis of interstitial pulmonary fibrosis.

Animals↗
PubMed1995

A longitudinal follow-up of salivary secretion in bone marrow transplant patients.

Salivary gland dysfunction is a common sequela of the bone marrow transplantation procedure. We determined the effect of different bone marrow transplantation protocols on parotid salivary flow rate. Salivary secretion was substantially reduced during conditioning of all the recipients. A gradual flow rate reconstitution could be detected as soon as a few days after the bone marrow transplantation. Eight patients conditioned with total lymph node irradiation and chemotherapy or chemotherapy alone displayed earlier and complete recovery of saliva secretions 2 to 5 months after the grafting. Recovery was delayed and incomplete when total body irradiation was added to the conditioning regimen (seven patients). Six of these patients also developed graft-versus-host disease. The results suggest that total body irradiation induces irreversible damage to the parotid glands resulting in profound xerostomia followed by opportunistic infections. Chemotherapy with or without total lymph node irradiation does not induce such damage.

Adolescent↗
PubMed1995

Involvement of interleukin-2 in immunologic reconstitution following bone marrow transplantation in mice.

Allogeneic or autologous bone marrow transplantation (BMT) is a curative form of treatment for patients with a variety of hematologic disorders. Impaired immune reconstitution following BMT may seriously impede successful outcome. In this study, the immune function of spleen and thymus was investigated in mice exposed to myeloablative total-body irradiation followed by syngeneic BMT. The T cell mitogen-induced proliferation of both splenic and thymic cells was delayed. Spleen cells started to respond only after 21 days, whereas thymic cells remained unresponsive. Kinetic analysis of surface markers revealed the early appearance of spleen cells with the CD3+CD4-CD8- phenotype, and the thymus, despite a low total number of cells, displayed fast recovery of CD3+CD4+CD8+. At the level of mRNA, a mild decrease in interleukin-2 (IL-2) induction following phytohemagglutinin activation of spleen cells correlated with a decrease in IL-2 secretion for only the first 2 weeks following transplantation. The early restoration of IL-2 implies other avenues for investigation of the immune dysfunction and its correction following syngeneic BMT.

Animals↗
PubMed1995

T-cell-depleted allogeneic bone marrow transplantation for acute leukaemia using Campath-1 antibodies and post-transplant administration of donor's peripheral blood lymphocytes for prevention of relapse.

One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation combined with chemotherapy (125 patients) or busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted allografts received in addition total lymphoid irradiation (TLI) for prevention of rejection. Engraftment of neutrophils (> 0.5 x 10(9)/l) and platelets (> 25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of Campath 1M and Campath 1G treated marrows respectively. Rejection was documented in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2 years was 83% for patients transplanted in first CR, 76% in second CR (P2 = 0.34) and 42% in advanced leukaemia (P2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Campath 1G treated marrow, received post-transplant graded increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus-leukaemia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving marrow allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. In patients with advanced disease, post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be beneficial; however, further studies are needed to define the optimal schedule of CMI for safe and effective prevention of relapse following TCD bone marrow transplantation in malignant haematological diseases.

Acute Disease↗
PubMed1995

Successful immunization of autologous bone marrow transplantation recipients against hepatitis B virus by active vaccination.

Patients undergoing autologous bone marrow transplantation (BMT) are severely immunosuppressed. These patients are exposed to various infections agents due to delayed and efficient reconstitution of their immune system. Forty-eight patients with hemato-oncological malignancies were immunized against hepatitis B virus (HBV) following autologous BMT. Twenty one were vaccinated more than 10 days before BMT, 17 on days 1-9 before and 10 day after BMT. Thirty three patients (68.7%) seroconverted within 40 days after autologous BMT after receiving one dose of the vaccine before autologous BMT with a relatively low level of anti-HBs, whereas in 11 no anti-HBV antibodies could be detected. Nineteen patients remained seropositive but in 11 the seroconversion was only transient no correlation was found between permanent or transient seroconversion and basic disease, conditioning regimens, post-transplant therapy, immunotherapy and day of vaccination in relation to autologous and day of vaccination in relation to autologous BMT. Active HBV immunization of patients with malignancy undergoing autologous BMT is feasible and levels of antibodies, although low, are above the conventional protective titers. Therefore active immunization of some patients may reduce hepatitis-related complications in the setting of autologous BMT.

Adolescent↗
PubMed1995

Cytosine arabinoside as a major risk factor for Streptococcus viridans septicemia following bone marrow transplantation: a 5-year prospective study.

The incidence and clinical course of nosocomial septicemia with Streptococcus viridans was evaluated prospectively in 242 consecutive bone marrow transplant (BMT) recipients throughout their 15-213 days' (median 47) hospitalization, including 4-58 days (median 18) of neutropenia. Initial empiric therapy for febrile neutropenia consisted of mezlocillin, gentamicin and cefazolin; glycopeptide was excluded. S. viridans septicemia occurred in 23/209 (11%) subjects with underlying malignant disease, and only during neutropenia with concomitant mucositis: in 20 subjects (four with ampicillin-resistant strains), S. viridans septicemia occurred at onset of febrile neutropenia, 1-5 days (median 4.5) post-BMT. All survived with an uncomplicated clinical course. Thus, glycopeptide seems unnecessary in the initial empiric antibiotic regimen. The other three subjects demonstrated S. viridans septicemia (two with ampicillin-resistant strains) on day 11 post-BMT; two died. The major risk identified was cytosine arabinoside administration in the conditioning regimen (P < 0.01).

Adolescent↗
PubMed1995

Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes.

Allogeneic bone marrow transplantation (BMT) is the treatment of choice for hematologic malignancies resistant to conventional chemotherapy and for patients who are at high risk for relapse. Until recently, no cure could be offered to patients relapsing following allogeneic BMT. We present our long-term observations of the first patient with remission reinduced by allogeneic cell therapy (allo-CT) using donor peripheral blood lymphocytes (PBL). In addition, we review the cumulative international experience with allo-CT used to treat 163 patients, 105 with CML and 58 with other hematologic diseases, who relapsed following allogeneic BMT. The first patient treated by allo-CT was diagnosed with acute resistant pre-B lymphoblastic leukemia (ALL) in extensive third hematologic and extramedullary relapse shortly after BMT. He was given infusions of donor (sister) PBL in multiple increments. Subsequently, he developed mild, reversible graft-vs-host disease (GVHD) in parallel with regression of all hematologic and cytogenetic disease manifestations. More than 8 years after allo-CT, he is disease-free with Karnofsky score 100% and no evidence of residual male cells by PCR. International data show that relapse after BMT was successfully reversed by donor PBL treatment in 97 of 158 evaluable patients; 72/100 (72%) with chronic myeloid leukemia (CML) and 25/58 (44.8%) with other malignant hematologic diseases including acute leukemia, lymphoma, and myelodysplastic syndrome. T cell depletion (TCD) for prevention of GVHD was performed for 60/105 (57%) patients with CML and 31/58 (53.4%) patients with other hematologic malignancies. Complete response after allo-CT was obtained in recipients of both TCD-BMT and unmodified BMT. GVHD due to allo-CT developed in 86/158 (54.4%) of the patients, 63/100 (63.0%) with CML and 23/58 (39.6%) with other hematologic diseases. alpha-interferon (IFN-alpha) was given to 67.9% of patients with CML and 28.1% of patients with other diseases. The cumulative experience shows that allo-CT can successfully reverse chemoradiotherapy-resistant relapse of acute leukemia and even more effectively of chronic leukemia independently of alpha-interferon therapy. Although GVHD was frequent among responders, accompanied occasionally by transient or irreversible marrow aplasia, remissions were also obtained in patients with no GVHD. Allo-CT should therefore be considered as treatment of choice for overt relapse or de novo minimal residual disease post-BMT. Administration of donor peripheral blood lymphocytes in graded increments at an early stage of relapse may be the best approach for combining optimal timing at the stage of minimal disease while controlling and minimizing the risk of GVHD on an individual basis.

Adolescent↗
PubMed1995

Severe migratory polyarthritis following in vivo CAMPATH-1G.

CAMPATH-1G is an IgG2b rat antihuman (CDw52) monoclonal antibody (MoAb) which is currently being used for T cell depletion in the setting of allogeneic bone marrow transplantation (BMT). In addition it elicits substantial lymphoid depletion, an effect which is being explored for remission induction in patients with lymphoid malignancies and for treating patients with various autoimmune disorders, in particular rheumatoid arthritis. Recently, in vivo CAMPATH-1G has been introduced to achieve increased immunosuppression in the pretransplant conditioning, for prevention of graft rejection following T cell depleted BMT. Here we describe a patient with T cell lymphoblastic lymphoma who received in vivo CAMPATH-1G as part of the pretransplant conditioning regimen and who, 6 days after the first dose, developed severe migratory polyarthritis. This is the first report of severe migratory polyarthritis as a very unusual complication following CAMPATH-1G MoAb administration.

Adult↗
PubMed1994

Regulation of CD23 expression by IL-4 and corticosteroid in human B lymphocytes. Altered response after EBV infection.

Cellular CD23 has been implicated in various biologic and pathologic processes. Here, we have studied the regulation of B cell CD23 expression and function by the synthetic corticosteroid, dexamethasone (DEX). We report that DEX acts directly on B lymphocytes to down-regulate IL-4-induced CD23 expression, whereas in parallel the IL-4R is up-regulated. Down-regulation of CD23 occurred at the cell surface and for shed material in culture medium. EBV infection of B cells is linked to development of lymphoproliferative diseases, including lymphoma, and there is evidence that EBV-stimulated CD23 expression may be instrumental in the inappropriate survival of infected cells. We have determined that treatment of EBV-infected cells with IL-4 leads to a synergistic up-regulation of B cell CD23. Furthermore, infection of B cells by EBV introduced a relative resistance to the down-regulatory effects of DEX on IL-4-induced CD23 expression.

B-Lymphocytes↗
PubMed1994

Regulation of B-cell immune responses: predominant role of interleukin-4 in triggering cell proliferation and Ig production in competent B cells.

We established a system for induction of competence in B cells following brief (45 min) exposure to either the combination of phorbol 12,13-dibutyrate (PDB) and ionomycin (I) (PDB/I) or PDB/anti-IgM. B cells, rendered competent in this fashion, were able to respond to PDB in the second or progression phase of culture but did not proliferate on their own. In addition, competent B cells were IL-2- or IL-4-responsive, due to up-regulation of their respective receptors following competence induction. IL-4 was found to have the most effective role in the progression phase to promote DNA synthesis and was able to enhance both IL-2 and IL-4 receptor expression. Whereas provision of IL-4 could induce IgM, IgG, and IgA in the absence of T cells, it did not result in IgE production. IgE production was only achieved in the presence of activated T cells (competent) together with competent B cells. These results indicate that IL-4 has a major role in B-cell immune responses following initial activation and trigger the cells, in the absence of T cells or other factors, to proliferate and differentiate into Ig-secreting cells. For IgE production in competent B cells, however, IL-4 alone could not overcome the requirement for activated T cells.

Antibodies, Anti-Idiotypic↗