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Biomedical subjects

R Or

Publications and source records attributed to R Or.

At least 109 records · Page 6Linked to original sources
PubMed1996

Low molecular weight heparin stimulates megakaryocytopoiesis in bone-marrow transplantation patients.

The use of low molecular weight heparin (LMWH) as prophylaxis for veno-occlusive disease of the liver has been studied in patients undergoing bone marrow transplantation (BMT). The present study analyzes the effect of LMWH on the time course of platelet recovery after BMT. Significantly accelerated platelet recovery in conjunction with lessened requirements of platelet transfusions was observed in the LMWH-treated patients.

Anticoagulants↗
PubMed1996

Bronchiolitis obliterans presenting as subcutaneous emphysema and pneumomediastinum: a case report.

We describe a woman post allogeneic bone marrow transplantation (BMT), who presented to the emergency room with subcutaneous emphysema and pneumomediastinum as the first manifestation of bronchiolitis obliterans complicating mild chronic graft versus host disease (GVHD). In contrast to other patients with pneumomediastinum described in the literature, this patient suffered from only mild GVHD. She did not receive methotrexate as GVHD prophylaxis, and the pneumomediastinum was a presenting manifestation rather than a terminal event. In addition, this is the first description of subcutaneous emphysema with this setting. Therefore, bronchiolitis obliterans should be highly suspected in post-BMT patients presenting with pneumomediastinum and subcutaneous emphysema, and prompt therapy should be initiated.

Acute Disease↗
PubMed1996

Predominant 45,X,--Y karyotype in donor cells after allogeneic BMT: cytogenetic and molecular analysis.

We describe two women; one (patient 1) with the diagnosis of acute myeloblastic leukemia (AML), the second (patient 2) with myelodysplastic syndrome (MDS). Both patients underwent allogeneic bone marrow transplantation (BMT), from their HLA-matched brothers. Cytogenetic analysis after the BMT revealed a chromosomal mosaicism in both patients, with the karyotype 46,XX/45,X with no sign of the Y chromosome. The origin of the clone with monosomy X was determined using cytogenetic analysis including heteromorphism and segregation of DNA polymorphic markers. The results led us to the conclusion that in both patients the origin of the 45,X clone was that of the donors. Patient 1 had MDS-like syndrome after the BMT and was stabilized in the chimeric state; to date she is doing well. Patient II also had MDS. However, in her case, it was her primary disease. The graft in patient II was rejected and she died 6 months after BMT.

Adult↗
PubMed1996

Second transplantation using allogeneic peripheral blood stem cells in a beta-thalassaemia major patient featuring stable mixed chimaerism.

Allogeneic bone marrow transplantation (BMT) for beta-thalassaemia major carries the risks of disease recurrence due to residual thalassaemic stem cells or true immune-mediated rejection. We report a thalassaemic patient who displayed stable mixed chimaerism with only 5% donor-derived cells for about 5 years after BMT. Displacement of host cells was accomplished by ambulatory non-myeloablative conditioning and allogeneic G-CSF mobilized peripheral blood stem cell transplantation from the same donor, resulting in full reconstitution. Patients featuring stable mixed chimaerism after BMT may benefit from allogeneic cell therapy with immunocompetent lymphocytes and stem cells, whilst avoiding supralethal conditioning.

Bone Marrow Transplantation↗
PubMed1996

Teething and acute graft vs. host disease: a clinical observation.

A 5-month-old girl, treated with bone marrow transplantation for severe combined immunodeficiency, developed two episodes of severe acute graft vs. host disease (GVHD) while teething. A dramatic improvement in GVHD was noted after the completion of tooth eruption. It is suggested that the release of interleukin-1, associated with the traumatized gingival tissue, is the triggering mediator for the GVHD.

Acute Disease↗
PubMed1996

Salivary immunoglobulins in recipients of bone marrow grafts. III. A longitudinal follow-up of CMV specific antibodies.

Cytomegalovirus (CMV) infection is a major complication of BMT. The oral cavity is a common route for CMV infection, whose protection is provided by salivary anti-CMV antibodies. We developed an ELISA assay for the detection of CMV-specific antibodies in parotid saliva. Saliva of patients receiving BMT from CMV-positive donors was transiently reconstituted with IgG and IgA anti-CMV antibodies shortly after transplantation. The concentration of these antibodies gradually decreased during the 2 months after transplantation and increased again around day 80. A remarkable rise in the salivary concentrations of IgG and IgM anti-CMV was observed shortly after i.v. administration of Sandoglobulin. These results demonstrate, for the first time accurate monitoring of CMV-specific antibodies in saliva using a quantitative ELISA assay. The study suggests that secretion of CMV-specific antibodies in saliva of immunocompromised patients can be reconstituted by donor-derived B and plasma cells transferred with the BM or by i.v. administration of pooled Ig.

Adolescent↗
PubMed1996

Hydronephrosis in children after bone marrow transplantation: case reports.

Hydronephrosis post-bone marrow transplantation (BMT) diagnosed in five children, was caused by hemorrhagic cystitis and blood clots in the bladder, congenital uretro-pelvic junction stenosis and ureteral obstruction due to adenoviral infection. Patients received conservative therapy to treat the symptoms. However, hydronephrosis did not change the outcome of BMT. Therefore, we suggest less aggressive procedures to treat children with hydronephrosis.

Adolescent↗
PubMed1996

Oral tuberculosis following autologous bone marrow transplantation for Hodgkin's disease with interleukin-2 and alpha-interferon immunotherapy.

A patient with Hodgkin's disease (HD) underwent autologous bone marrow transplantation (ABMT). Six months later while receiving interleukin (IL)-2 and alpha-interferon immunotherapy, he developed a painful lesion in his oral cavity with a fistula in the buccal area. Excision biopsy disclosed necrotizing granulomatous inflammation with acid-fast bacillus. The patient received a 9-month course of isoniazide, rifampin and pyrazinamide, and recovered. The possible pathophysiological mechanism is discussed.

Adjuvants, Immunologic↗
PubMed1996

In vivo CAMPATH-1 followed by T cell-depleted bone marrow transplantation: a potential new mode of therapy for hepatitis-associated severe aplastic anemia (SAA).

Bone marrow transplantation (BMT) has been previously reported as a successful mode of treatment for hepatitis B and associated severe aplastic anemia (SAA). Non-A, non-B, non-C hepatitis is one of the causes of SAA. The etiology of SAA caused by non-A, non-B, non-C hepatitis is unknown. There is evidence that the immune response and, specifically, T cells and monocytes have a major role in both HCV- and HBV-induced liver damage. The liver damage caused by non-A, non-B, non-C hepatitis may be associated with similar mechanisms. We describe an 8-year-old girl who developed SAA post-non-A, non-B, non-C hepatitis infection. She was treated by in vivo CAMPATH-1G antibodies followed by T cell depleted HLA-matched BMT and cyclosporin A, resulting in gradual improvement and almost normalization of liver function. We suggest that treatment with CAMPATH-1G followed by T cell-depleted BMT and cyclosporin A could be a novel mode of therapy for viral non-A, non-B, non-C hepatitis-induced liver damage and associated SAA.

Anemia, Aplastic↗
PubMed1996

Soluble IL-6 receptors (sIL-6R) in hematological patients receiving immunotherapy with IL-2/IFN-alpha or donor lymphocytes following bone marrow transplantation.

Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin-6 (IL-6) which may display antitumor activity. Therefore, we evaluated sIL-6R levels in the sera of 15 patients who received cytokine-mediated immunotherapy with (IL-2/IFN-alpha), and 15 patients who received cell-mediated immunotherapy post-BMT, in an attempt to reduce the relapse rate. sIL-6R levels were evaluated pre-, during and post-cytokine or cell-mediated immunotherapy, using IL-6R-specific monoclonal antibodies (McAb) and double-sandwich ELISA. In normal controls, sIL-6R levels were found to be 20 +/- 3 ng/ml. sIL-6R levels increased significantly during IL-2/IFN-alpha immunotherapy in comparison to pre- or post-immunotherapy levels (74 +/- 9 ng/ml vs 46 +/- 6 ng/ml, and 50 +/- 9 ng/ml, respectively) (n = 15) (P < 0.05). sIL-6R levels also significantly increased following donor lymphokine activated killer (LAK) cells, given in addition to IL-2, in comparison to base line levels (87 +/- 3 ng/ml vs 60 +/- 2 ng/ml) (n = 6) (P < 0.05). Increased levels of sIL-6R were observed in BMT patients treated with immunotherapy.

Adolescent↗
PubMed1996

Stimulation of immune reconstitution by interleukin-7 after syngeneic bone marrow transplantation in mice.

Successful outcome of autologous bone marrow transplantation (BMT) is severely handicapped by susceptibility to infection and by a high rate of relapse. While quantitative aspects of the immune system generally return to normal within the first 3-4 months after BMT, the recovery of qualitative immune functions is prolonged. Since interleukin-7 (IL-7) has growth-promoting and differentiating effects on pre-B cells and immature thymocytes, its role in the recovery of immune functions was investigated in BALB/c mice after syngeneic BMT (sBMT). After sBMT, mice treated with human recombinant IL-7 (rIL-7) showed an 11.9-fold increase in thymic cellularity associated with an enhanced response to a mitogenic stimulus compared with the controls. rIL-7 significantly increased RAG-1 expression and promoted V beta 8(D)J gene rearrangement of the T cell receptor in the thymus. Further, the cytokine boosted survival after challenge with influenza virus following sBMT. The finding that rIL-7 induces differentiation and proliferation of immature thymocytes and counteracts post-BMT immune deficiency makes it a promising medium for clinical application in BMT patients.

Animals↗
PubMed1996

Mucosal melanoma following autologous stem cell transplantation for non-Hodgkin's lymphoma (NHL).

The incidence of secondary malignancy following autologous stem cell transplantation (ASCT) is increasing. We describe a patient with stage IVB Hodgkin's disease who developed primary amelanotic malignant melanoma of the tongue 18 months following autologous stem cell transplantation. She was treated by partial glossectomy and supra-omohyoid neck dissection followed by cytokine-mediated immunotherapy. Malignant melanoma of the skin is a frequent secondary solid tumor seen in patients undergoing stem cell transplantation. However, mucosal melanoma which is rare by itself (0.2-8%) has never been reported in NHL patients following ASCT. Early diagnosis and initiation of combined local and systemic treatments including immuno-therapy may improve the outcome of this rare but lethal complication.

Adult↗
PubMed1996

Activated allogeneic cell therapy (allo-ACT) for relapsed chronic myelogenous leukemia (CML) refractory to buffy coat transfusions post-allogeneic bone marrow transplantation.

We describe a 17-year-old male patient with chronic myelogenous leukemia (CML) in hematologic and cytogenetic relapse 4 months post-non-T cell-depleted allogeneic bone marrow transplantation for accelerated CML. Two sequential buffy coat transfusion with donor peripheral blood cells (8.9 and 4.8 x 10(7) cells/kg), the second transfusion in combination with in vivo activation of donor cells by human recombinant interleukin-2 (rIL-2) 6 x 10(6) IU/m2 subcutaneously for 3 days, failed to induce remission . The patient responded to an infusion of donor peripheral blood lymphocytes (3.4 x 10(7) cells/kg) pre-activated in vivo with rIL-2 and additionally activated in vivo with rIL-2, 6 x 10(6) IU/m2/day subcutaneously for 3 days. Elimination of the Philadelphia (Ph) clone was confirmed by cytogenetic analysis showing a normal male karyotype and by disappearance of the bcr/abl transcript, using the polymerase chain reaction (PCR). At present, the patient is 26 months post-treatment with no evidence of disease, but with chronic graft-versus-host disease. Our data indicate that allogeneic activated cell therapy (allo-ACT) may provide antitumor effector cells that successfully induce graft-versus-leukemia (GVL) effects even when cell therapy with donor buffy coats was insufficient.

Adolescent↗
PubMed1996

Allogeneic cell-mediated immunotherapy using donor lymphocytes for prevention of relapse in patients treated with allogeneic bone marrow transplantation for hematological malignancies.

Two major causes of treatment failure in allogeneic BMT for leukemia are graft versus host disease (GVHD) and leukemic relapse. Acute GVHD, mediated by alloreactive donor T lymphocytes originating from the transfused marrow is the most significant cause of transplant-related morbidity and mortality, despite the use of combined prophylaxis with cyclosporine and methotrexate. Effective prevention of GVHD can be accomplished by depletion of donor immunocompetent T cells from the marrow prior to its infusion. Depletion of lymphocytes, however, prevents the immune mediated interaction of donor T cells against residual host tumor cells--the graft versus leukemia (GVL) effect, which significantly contributes to the curative effect of allogeneic BMT. It is still unsettled to what extent GVH and GVL are unseparable or closely related phenomena, and a major question remains whether it would be possible to retain the beneficial antileukemic effects of donor T cells and at the same time prevent or control the risk of GVHD. We have adopted a policy by which an allogeneic BMT is conducted with T cell depleted marrow to minimize the risk of severe acute GVHD, followed by stepwise administration of fresh unirradiated donor lymphocytes for prevention of leukemic relapse. Our data show that the overall relapse free survival was significantly better for patients receiving preventive posttransplant donor lymphocytes, predominantly when transplant was performed in 1st or 2nd CR.

Adolescent↗
PubMed1996

Soluble tumor necrosis factor (sTNF) receptors: a possible prognostic marker for bone marrow transplantation-related complications.

Involvement of tumor necrosis factor (TNF) in bone marrow transplantation (BMT)-associated complications has been documented. Biological response to TNF requires interaction with specific cell membrane receptors. Extracellular domains of these receptors are released into body fluids as soluble molecules, and participate in the bioactivity of TNF. Serum levels of p55 and p75 soluble tumor necrosis factor receptors (sTNFR) were determined in 34 patients with different diseases who underwent BMT. Sequential studies initiated 10 days before BMT and continued up to 110 days post-transplantation showed that p55 and p75 sTNFR levels were elevated significantly in patients who subsequently developed major transplant-related complications (TRC). Moreover, both sTNFR levels were increased 2- to 3-fold over control values during post-BMT febrile periods in those patients who at a later stage suffered major TRC. These results indicate that the serum level of sTNFR may be used as a prognostic marker for major TRC in BMT.

Adolescent↗
PubMed1995

Elevated inflammatory cytokine levels in bone marrow graft rejection.

Graft rejection and graft failure represent major obstacles in allogeneic bone marrow transplantation (BMT). Cytokines possibly play a central role in the inflammatory and allospecific components of allograft rejection. Therefore, we evaluated inflammatory cytokine levels following BMT in 12 consecutive patients with graft rejection (GR). Seven of the patients underwent BMT from siblings (6 matched and 1 mismatched), 4 patients received bone marrow from other family members (3 mismatched and 1 matched), and 1 patient underwent HLA-matched unrelated BMT. Nine of 12 had a sex-mismatched BMT and 5/12 had an ABO-mismatched BMT. Nine of 12 underwent T cell-depleted (Campath anti-CDw52 moAb) BMT. Rejection was defined as marrow hypoplasia with a peripheral white blood cell count < 0.5 x 10(9)/L 21 days after BMT, in conjunction with the absence of donor cells by polymerase chain reaction analysis using a sex-mismatched probe and/or a tumor-specific probe (BCR/ABL). Twenty-five patients who underwent uneventful BMT with no GR served as controls. The levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1 (IL-1) were evaluated by a high sensitive RIA or an enzyme immunoassay. The levels of TNF and IL-6 were found to be higher in 10/12 and 7/7 evaluated GR patients, respectively, as compared with controls (P < 0.05). The level of IL-1 was high only in 2/12 patients. TNF elevation occurred in all patients immediately after GR. TNF and IL-6 levels were significantly higher for patients with early rejection (< 35 days after BMT) as compared with patients with late rejection (> 35 days after BMT) (P < 0.049 and P < 0.006, respectively). Eight patients engrafted after the second transplant (2 only transient). All 6 patients with stable engraftment are alive (4 with basic disease), while the 4 patients who did not engraft and the 2 patients with only transient engraftment died. In the 6 patients with no engraftment or only transient engraftment, the elevated TNF levels remained high; in the 6 patients who had stable engraftment after retransplant, TNF levels, but not IL-6 levels, decreased. In conclusion, a majority of the patients with GR displayed high levels of inflammatory cytokines (TNF and IL-6). Dysregulation of inflammatory cytokines may be involved in the pathogenesis of GR.

ABO Blood-Group System↗
PubMed1995

Bacterial pneumonia in recipients of bone marrow transplantation. A five-year prospective study.

Bacterial pneumonia as an important complication of bone marrow transplantation (BMT) has not been subjected to comprehensive analysis. Two hundred fifty-five consecutive allogeneic and autologous BMT recipients, ranging in age from 1 month to 53 years, were prospectively followed for 3 days to 3 years (median, 108 days) for development of bacterial pneumonia. Etiology, place acquired, chest radiography, and outcome were recorded and the association between bacterial pneumonia and demographic and clinical variables was analyzed. Thirty-seven (15%) patients experienced 52 episodes of bacterial pneumonia: onset of 13 episodes occurred within 30 days after transplantation, 10 episodes occurred on days +31 to +100, and 29 episodes occurred thereafter. Bacterial pneumonia was the terminal event or contributed to fatal outcome in 8 patients (22% of bacterial pneumonia cases, 3% total study population). Mortality due to hospital-acquired pneumonia (6/21) was significantly higher than (P = 0.03). Bacterial pathogens were identified in 27 (52%) episodes. During the first 100 days after BMT, hospital-acquired Gram-negative bacteria predominated, caused mainly by Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter lwoffi, and Enterobacter cloacae. After day +100, community-acquired, Gram-positive bacteria predominated, particularly Streptococcus pneumoniae. Haemophilus influenzae occurred periodically. Considering all episodes, significant association was found between bacterial pneumonia and veno-occlusive disease (VOD) (P < 0.01) and chronic graft-versus-host disease (GVHD) (P < 0.02). For culture-positive episodes, the association between bacterial pneumonia and VOD was significant (P < 0.001) and borderline for acute GVHD (P = 0.07). It is concluded that VOD and GVHD are positively associated with post-BMT bacterial pneumonia. Its incidence, etiology, risk factors, and outcome are important considerations in its prevention and treatment.

Adolescent↗