Search PubMed⌕ Search

Biomedical subjects

R Or

Publications and source records attributed to R Or.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interleukin-7-enhanced cytotoxic T lymphocyte activity after viral infection in marrow transplanted mice.

Lethally irradiated BALB/c mice were reconstituted by syngeneic bone marrow transplantation (BMT), and injected with recombinant interleukin 7 (rIL-7), recombinant interleukin 2 (rIL-2), or saline 10 days post-transplantation. Intranasal infection with A/PR8/34 influenza virus 2 weeks after BMT was associated with the highest survival rate in the rIL-7 treated group. The protective mechanism elicited by rIL-7, as manifested by very low virus titers in the lung, involves T and B cell functions. High hemagglutinin inhibition antibody levels were observed on days 7 and 12 post-challenge in the rIL-7 mice. Moreover, the anti-influenza cytotoxic T lymphocyte activity was induced primarily by rIL-7, leaving the effect of rIL-2 on the same level as that of the control. Thus, rIL-7 promotes both T cell-mediated function and B cell production during the immunodeficient state after BMT. This cytokine may prove a potential immunotherapeutic modality in BMT recipients.

Animals↗
PubMed1997

Invasive fungal infections in lymphoma patients receiving immunotherapy following autologous bone marrow transplantation (ABMT).

Invasive fungal infections are quite rare (1-5%) following conventional ABMT for malignant lymphoma. Two high-risk lymphoma patients (one non-Hodgkin's lymphoma (NHL) and one Hodgkin's disease) underwent ABMT followed by immunotherapy as part of an experimental therapy given to 12 lymphoma patients aiming to prevent relapse following transplantation. The post-immunotherapy course in both patients was complicated by invasive fungal infections (pulmonary mucormycosis and generalized aspergillosis). The association between invasive fungal infection and immunotherapy following ABMT for malignant lymphoma patients is discussed.

Adult↗
PubMed1997

A fludarabine-based protocol for bone marrow transplantation in Fanconi's anemia.

Allogeneic bone marrow transplantation (BMT) is an effective therapy for Fanconi's anemia (FA). However, mortality and transplant-related complications are usually high due to increased sensitivity to the alkylating agents and radiation commonly used for pre-transplant conditioning. Fludarabine monophosphate is a purine analogue that has been proven effective as a conditioning agent for chronic lymphocytic leukemia patients. We report a child with FA in leukemic transformation with thrombocytopenia and 20% myeloblasts who underwent successful BMT following conditioning with fludarabine/ATG/cyclophosphamide. The regimen was well tolerated, no transplant-related complications were observed, and engraftment was rapid. The child is currently 10 months post-BMT, in excellent clinical condition with a normal blood count, 100% chimerism and no sign of graft-versus-host disease (GVHD). We suggest that this fludarabine-based regimen may be effective in the conditioning of standard, as well as transforming, FA patients for BMT.

Antineoplastic Agents↗
PubMed1997

Should soybean agglutinin purging be performed in breast cancer patients undergoing autologous stem cell transplantation? A retrospective analysis of 48 patients.

High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) has gained an increasing role in the treatment of high-risk Stage II-III and/or metastatic breast cancer patients. Several investigators reported on a high rate of tumor cells contaminating the bone marrow and peripheral blood stem cell collection. Nevertheless, the clinical implication of reinfusion of tumor cells with the stem cells to the relapse rate is still uncertain. In this retrospective analysis we compare the outcome and the toxicity of 29 patients with high-risk Stage II-III and 19 metastatic breast cancer patients who underwent HDC with ASCT. Thirteen patients underwent transplant with soybean agglutinin (SBA)-purged graft, while 35 consecutive patients received unmanipulated graft. Engraftment was significantly faster for the nonpurged transplant. No differences in disease-free survival, freedom from relapse, or overall survival were noted in both groups during a median follow up time of 14 months. We conclude that tumor cell purging using SBA in breast cancer patients is not warranted. New purging methods are needed to assess the role of tumor cell purging in breast cancer patients.

Adult↗
PubMed1997

The use of tretinoin as oral mucositis prophylaxis in bone marrow transplantation patients: a preliminary study.

OBJECTIVE: The examination of prophylactic efficacy of tretinoin on oral mucositis, post bone marrow transplantation (BMT). PATIENTS AND METHODS: The study population consisted of 11 patients undergoing BMT. Six tretinoin topically-treated patients (0.25 mg daily of 0.1% tretinoin cream) were matched with five non-treated control patients comparing mucositis severity, duration and analgetic (morphine) requirements. Concomitant follow-up included conditioning parameters associated with mucositis and engraftment. RESULTS: The mean of oral mucositis peak scores was significantly lower in the tretinoin-treated patients vs the non-treated patients (score 1.5 vs 3.6; P < 0.02). In the majority of cases the duration of the most severe phase of oral mucositis was shorter in the tretinoin-treated group as compared with the control. Only one patient in the experimental group required morphine analgesics compared with four patients in the control group. CONCLUSIONS: This preliminary study indicates that the severity of oral mucositis, both objective and subjective, in BMT patients may be reduced by 0.1% topical tretinoin cream, 0.25 mg, administered daily from the beginning of the BMT conditioning regimen until marrow engraftment.

Administration, Topical↗
PubMed1997

Noncardiogenic pulmonary congestion following bone marrow transplantation.

We report a 36-year-old female who developed acute pulmonary congestion as the first presenting sign of venoocclusive disease (VOD), complicating an otherwise successful bone marrow transplantation (BMT). Left ventricular function was normal by echocardiography. Conservative therapy included oxygen, Lasix, and low dose dopamine. Hepatic toxicity, the typical presenting feature of VOD, occurred in our patient 72 h after pulmonary congestion. VOD occurs in 20-50% of BMT patients and is the result of widespread endothelial damage as a result of chemoradiotherapy. The dominating clinical feature is liver toxicity. Pulmonary manifestations of VOD have not been described as presenting features, and in fact have been noted as rare and late sequelae of BMT. Therefore, in the setting of preserved left ventricular function, acute pulmonary congestion early after BMT may represent the onset of VOD.

Adult↗
PubMed1997

Hepatobiliary graft-versus-host disease manifested by common and hepatic biliary duct obstruction.

BACKGROUND: A 26-year-old patient presented with ascending cholangitis 8 months after allogeneic bone marrow transplantation for immunoblastic lymphoma. METHODS AND RESULTS: Endoscopic retrograde cholangiopancreatography showed common and hepatic biliary duct obstruction that was attibuted to chronic graft-versus-host disease. CONCLUSION: This case indicates that hepatobiliary disease related to chronic graft-versus-host disease may involve major bile ducts causing obstruction.

Adult↗
PubMed1996

Microsatellite instability and p53 mutations in therapy-related leukemia suggest mutator phenotype.

During the last decade the frequency of therapy-related acute leukemia (t-leuk) and myelodysplastic syndrome (t-MDS) has been increasingly observed. Over the past 15 years, we treated 56 patients with t-leuk who had received prior chemotherapy (39%), radiotherapy (11%), or both (45%). The drugs received included alkylating agents and topoisomerase II inhibitors. The primary tumors included hematological malignancies (49%) and solid tumors such as breast or ovarian cancer. The median age at diagnosis of the primary tumor was relatively young (43 years +/- 18). Twelve patients had more than one primary tumor and 31 patients had a family history of malignancy. Karyotypic abnormalities were found in 91% of the patients. Prognosis was uniformly poor, with an overall median survival of 10 months. Twelve of the 18 patients examined (67%) had a multidrug resistance phenotype. P53 genes of the leukemic cells, as well as the original tumors, were analyzed in 21 patients using polymerase chain reaction (PCR) with single-stranded conformation polymorphism analysis followed by sequencing. P53 mutations were identified in 38% of these patients, a relatively high prevalence compared with other forms of MDS or de novo acute myeloid leukemia. Mutations were nongermline and restricted to the leukemic cells. We identified different p53 mutations in the various primary tumors of individual patients. The presence of a mutator phenotype was assessed by PCR analysis of microsatellites in eight loci (one trinucleotide repeat sequence, four dinucleotide, and three mononuclear repeat sequences). Microsatellite instability in two to seven loci were found in 15 of 16 (94%) of the patients. This instability is compatible with a mutator phenotype, which predisposes the patients to the development of malignancies including t-leuk.

Adult↗
PubMed1996

Soluble interleukin-6 receptors in hematology patients undergoing bone marrow transplantation.

Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin (IL)-6, which may display antitumor activity. We evaluated sIL-6R and IL-6 levels in the sera of 24 patients following transplantation (allogeneic, n=17; autologous, n=7). Five patients developed acute graft-versus-host disease (AGVHD), three had early graft rejection, and three had an early relapse following bone marrow transplantation (BMT). Soluble IL-6R levels were evaluated at day - 10, day 0, day of engraftment, and during BMT-related complications, using IL-6R-specific monoclonal antibodies (mAb) and double-sandwich ELISA. In normal controls, sIL-6R and IL-6 levels were 20+/-3 ng/ml and 0.01+/-0.005 ng/ml, respectively. Soluble IL-6R levels increased in direct correlation with engraftment in the uneventful allogeneic transplants (17.7+/-2.1 ng/ml at day 0 to 49.7+/-2.6 ng/ml at day of engraftment, n=6, P<0.05) as well as in the autologous transplants (26.8+/-2.82 at day 0 to 66.4+/-12.9 at day of engraftment, n=5, P=0.01). In contrast, IL-6 levels declined with time during the conditioning period and showed only a modest elevation following BMT. Increased levels of sIL-6R and IL-6 were found in the patients who developed AGVHD (23.8+/-4.2 and 0+/-0 ng/ml at day 0 to 79+/-6.9 and 0.26+/-0.04 ng/ml, respectively, at time of AGVHD, n=5, P=0.01). No correlation was found between the severity of AGVHD and sIL-6R levels. In the three patients with early relapse, sIL-6R levels increased from 30+/-0 ng/ml at day 0 to 90 ng/ml (P=0.05) and IL-6 levels increased from 0 to 0.16+/-0 ng/ml, respectively. The mean elevation of sIL-6R in the patients with early relapse and AGVHD was significantly higher than the mean elevation in the patients with the relatively smooth engraftment (P<0.05). Contrary to these findings, in the three patients with graft rejection, sIL-6R levels decreased while IL-6 was found to be elevated. Basic disease, conditioning regimen, type of transplant, GVHD propylaxis, and T cell depletion had no effect on sIL-6R or IL-6 levels. In summary, sIL-6R levels positively correlated with engraftment. Both sIL-6R and IL-6 levels were found to be significantly elevated in patients who developed AGVHD or early relapse following BMT. Therefore, the sIL-6R level may be used as a tool for assessing engraftment and transplant-related complications following BMT.

Acute Disease↗
PubMed1996

Control of neuroblastoma cell proliferation and differentiation by human bone marrow.

BACKGROUND: Neuroblastoma (NB) is one of the few tumors known to undergo spontaneous regression. Its progression, however, often leads to bone marrow (BM) metastasis. Proliferation and differentiation of human NB cells may be regulated in vitro by a variety of biologic agents, some of which are released by low-density BM and peripheral blood (PB) cells. Little is known regarding BM cell-derived control of NB cell growth and differentiation. METHODS: The proliferative and differentiative responses of NB cells, to BM cell-, and to PB cell-derived conditioned medium (CM) were evaluated in comparison to cytokine-induced responses. RESULTS: CM from unstimulated cultures of low density BM and PB cells, from healthy donors, from newborn infants, and from NB patients, significantly and reproducibly stimulate NB cell growth in vitro. The intensity of CM-induced stimulation was not attained by recombinant human tumor necrosis factor (rhTNF), interferon (rhIFN), or granulocyte-monocyte colony stimulating factor (rhGM-CSF); and although epidermal growth factor (rhEGF) and transforming growth factor alpha (rhTGF alpha) were strongly stimulatory, neutralizing antibodies against each of these agents did not affect CM-derived activity. In contrast to growth stimulation, differentiation of CM-treated NB cells, was reproducibly suppressed, as reflected in abrogation of neuronal cell morphology as well as of neurofilament and neuron specific enolase expression. CONCLUSIONS: Spontaneous regression of NB tumors, on one hand and BM metastasis on the other may be associated with the extent and nature of the NB cell response to regulatory activity released by BM and PB cells.

Bone Marrow↗
PubMed1996

Low molecular weight heparin for the prevention of veno-occlusive disease of the liver in bone marrow transplantation patients.

Hepatic veno-occlusive disease (VOD), a common complication of bone marrow transplantation (BMT), is a result of intensive conditioning by chemo-radiotherapy. Endometrial injury causes fibrin deposition in the affected hepatic venules, leading to abnormal laboratory parameters followed by lethal full-blown disease. Previous studies have shown that unfractionated heparin can prevent VOD in BMT patients. Since low molecular weight heparin (LMWH) preserves the antithrombotic, but not the anticoagulant, activity of unfractionated heparin, we initiated a pilot study to determine the safety of LMWH for the prevention of VOD. Sixty-one patients undergoing BMT (allogeneic, n=24; autologous, n=37) were randomized to receive subcutaneous injection of enoxaparin (40 mg/day x 1) or a placebo prior to BMT conditioning and until day 40 after transplantation or discharge from the hospital. LMWH administration did not influence marrow engraftment, nor was it associated with bleeding tendency. Hemorrhagic events occurred significantly less frequently (P=0.025) were shorter duration (P=0.006) in the LMWH group than in the placebo group. Time to platelet recovery was significantly shorter (16.5 vs 29.6 days, (P=0.0075), and platelet transfusion requirements were lower (p=0.05) in the LMWH patients. VOD parameters occurred less frequently in the experimental group, including duration of elevated bilirubin levels (P=0.01) and incidence of hepatomegaly (P=0.04). LMWH, which seems to enhance platelet recovery, may be safely administrated to BMT patients in an attempt to prevent VOD of the liver.

Adult↗
PubMed1996

Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) is the only effective treatment for hematologic malignancies resistant to conventional chemotherapy. Until recently, no cure existed for patients who relapsed post-BMT. We present our long-term observations on remission induction, after relapse post-BMT, by allogeneic cell therapy (allo-CT) and the feasibility of remission induction in allo-CT-resistant patients by activation of antileukemia effector cells with recombinant human interleukin-2 (rhIL-2) in vitro and in vivo. The longest observation of successful allo-CT (event-free survival, greater than 8 years) was made in a patient with resistant pre-B lymphoblastic leukemia who received infusions with graded increments of donor (female) peripheral blood lymphocytes (PBL) as soon as bulky hematologic and extramedullary relapse was noticed early post-BMT. The patient is currently without evidence of residual host (male) cells as determined by polymerase chain reaction (PCR). Of 17 patients with acute and chronic leukemia in relapse after BMT, 10 were reinduced into complete remission. Four patients with cytogenetic relapse responded to allo-CT alone, while five of six patients with overt hematologic relapse responded only after additional activation of donor with rhIL-2. Allo-CT can, therefore, successfully reverse chemoradiotherapy-resistant relapse of both acute and chronic leukemia. Moreover, in patients resistant to donor lymphocyte infusion, remission can be accomplished by additionally activating donor PBL in vitro and/or in vivo with rhIL-2. Based on our observations, after BMT, allo-CT should be considered the treatment of choice for patients with hematologic malignancies resistant to conventional anticancer modalities. Allogeneic activated cell therapy (allo ACT) should be considered for patients with tumor cells resistant to allo-CT. Although allo-CT, followed if indicated by allo-ACT, can be effective for patients with overt hematologic relapse, reversal of persistent minimal residual disease or documented molecular/cytogenetic relapse early after BMT may also be considered as a possible indication for allo-CT.

Adolescent↗
PubMed1996

Nosocomial coagulase-negative staphylococcal infections in bone marrow transplantation recipients with central vein catheter. A 5-year prospective study.

The purpose of this study was to examine coagulase-negative staphylococcal infections in bone marrow transplantation (BMT) patients with central vein catheters by investigating incidence, clinical relevance, risk factors, methicillin resistance, clinical impact of initial empiric antimicrobial therapy without vancomycin, and management of documented catheter-related infections. A 5-year prospective study was conducted with daily evaluation of 242 BMT patients during hospitalization, including clinical assessment and blood culture via the Hickman/Broviac catheter. If fever or infected appearance occurred, peripheral blood cultures or exit site cultures, respectively, were done. Results showed a septicemia incidence of 7.0%, including in 6 patients following colonization, in 1 patient with tunnel infection, in 1 patient with thrombophlebitis, in 1 patient with exit site infection, and in 8 patients with septicemia of unknown origin. Total colonization incidence was 7%, with colonization only in 11 patients who had 16 episodes; incidence of exit site infection was 3.7%. Age > or = 18 years was the only identified risk factor for developing staphylococcal infection (P = 0.03). Despite a methicillin resistance rate of 45% and omission of vancomycin from the routine initial empiric antimicrobial regimen, the clinical course of coagulase-negative staphylococcal infections was relatively benign. A single patient, who experienced marrow rejection, died on day +31 with septicemia and only one patient experienced microbiological failure with recurrent colonization. Bacteria grown in both aerobic and anaerobic bottles were more likely true bacteremia than contaminant (P = 0.03). We conclude that the hazard of coagulase-negative staphylococcal infection does not mandate inclusion of a glycopeptide in the initial empiric antimicrobial regimen in BMT patients, even during febrile neutropenia. Hickman/Broviac-related staphylococcal infections, except for tunnel infection or thrombophlebitis, can usually be treated successfully without removing the catheter.

Adolescent↗
PubMed1996

Normalization of serum lactic dehydrogenase in beta-thalassemia patients following bone marrow transplantation.

Serum lactic dehydrogenase (LDH) levels are mildly elevated in beta-thalassemia major due to ineffective erythropoiesis. We reviewed the charts of 15 consecutive thalassemic children who underwent allogeneic, T-cell-depleted bone marrow transplantation (BMT) in our department during the last 3 years. Eleven patients had successful engraftment and are alive and well without evidence of disease, according to physical examinations, blood counts, and polymerase chain reaction (PCR) tests, with a median follow-up of 2 years. Two patients died due to transplantation-related complications, and two rejected the graft and received their backup autologous marrow. The LDH levels in the transplanted patients gradually decreased from an average of 952 +/- 155 IU/L 10 days pre-transplant (N = 300-620) to 426 +/- 56 IU/L at the day of transplantation, and stayed at approximately the same level post-transplant (489 +/- 55 IU/L). By contrast, the LDH levels reverted to the pre-transplant value in those patients who rejected their marrow. The significance of this clinical observation for the pathophysiologic mechanism of intramedullary hemolysis and ineffective erythropoiesis in beta-thalassemia major is discussed.

Bone Marrow Transplantation↗