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Biomedical subjects

R Or

Publications and source records attributed to R Or.

At least 19 recordsLinked to original sources
PubMed1998

Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases.

Myeloablative conditioning associated with hazardous immediate and late complications is considered as a mandatory first step in preparation for allogeneic blood or marrow transplantation (allogeneic BMT) for the treatment of malignant hematologic disorders and genetic diseases. Immune-mediated graft-versus-leukemia (GVL) effects constitute the major benefit of allogeneic BMT. Therefore, we have introduced the use of relatively nonmyeloablative conditioning before allogeneic BMT aiming for establishing host-versus-graft tolerance for engraftment of donor immunohematopoietic cells for induction of GVL effects to displace residual malignant or genetically abnormal host cells. Our preliminary data in 26 patients with standard indications for allogeneic BMT, including acute leukemia (n = 10); chronic leukemia (n = 8), non-Hodgkin's lymphoma (n = 2), myelodysplastic syndrome (n = 1), multiple myeloma (n = 1), and genetic diseases (n = 4) suggest that nonmyeloablative conditioning including fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan (8 mg/kg) is extremely well tolerated, with no severe procedure-related toxicity. Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose of cyclosporin A as the sole anti-graft-versus-host disease (GVHD) prophylaxis resulted in stable partial (n = 9) or complete (n = 17) chimerism. In 9 patients absolute neutrophil count (ANC) did not decrease to below 0.1 x 10(9)/L whereas 2 patients never experienced ANC < 0.5 x 10(9)/L. ANC > or = 0.5 x 10(9)/L was accomplished within 10 to 32 (median, 15) days. Platelet counts did not decrease to below 20 x 10(9)/L in 4 patients requiring no platelet support at all; overall platelet counts > 20 x 10(9)/L were achieved within 0 to 35 (median 12) days. Fourteen patients experienced no GVHD at all; severe GVHD (grades 3 and 4) was the single major complication and the cause of death in 4 patients, occurring after early discontinuation of cyclosporine A. Relapse was reversed by allogeneic cell therapy in 2/3 cases, currently with no residual host DNA (male) by cytogenetic analysis and polymerase chain reaction. To date, with an observation period extending over 1 year (median 8 months), 22 of 26 patients (85%) treated by allogeneic nonmyeloablative stem cell transplantation are alive, and 21 (81%) are disease-free. The actuarial probability of disease-free survival at 14 months is 77.5% (95% confidence interval, 53% to 90%). Successful eradication of malignant and genetically abnormal host hematopoietic cells by allogeneic nonmyeloablative stem cell transplantation represents a potential new approach for safer treatment of a large variety of clinical syndromes with an indication for allogeneic BMT. Transient mixed chimerism which may protect the host from severe acute GVHD may be successfully reversed postallogeneic BMT with graded increments of donor lymphocyte infusions, thus resulting in eradication of malignant or genetically abnormal progenitor cells of host origin.

Adolescent↗
PubMed1998

Right atrial thrombi are related to indwelling central venous catheter position: insights into time course and possible mechanism of formation.

We studied the effect of central line catheters on thrombus formation in the right atrium (RA), including the incidence and echocardiographic characteristics of the catheter-associated thrombus as well as possible clinical implications in patients. We prospectively studied 55 patients by transesophageal echocardiography within 1 week after Hickman catheter implantation and on a follow-up study at 6 to 8 weeks. We succeeded in imaging the catheter tip in 48 of the 55 patients (87%). In the baseline study 13 had the tip placed in the RA, eight at the superior vena cava-atrium junction, and 27 in the superior vena cava. An abnormal mass, consistent with a thrombus, was found in 12.5% of the patients, all of which were seen within the 13-patient (46%) group with the Hickman catheter tip placed in the RA. Hickman catheter insertion is associated with high incidence (12.5%) of early formation of RA thrombus. The formation of these thrombi is asymptomatic and highly associated (p < 0.001) with the catheter tip position in the RA, in contrast to their positioning in the superior vena cava or in its junction with the right atrium. On the basis of these findings, we recommend that special attention and effort be given to placing of the catheter tip in the superior vena cava and avoiding the RA during the implantation procedure.

Adult↗
PubMed1998

Engraftment following mitoxantrone (Mito) based conditioning for allogeneic bone marrow transplantation (allo-BMT).

Mitoxantrone (Mito) is presently used in an increasing number of malignancies including leukemias, breast carcinomas and solid tumors. With it has come increased incidence of post remission cytopenias and delayed engraftment following autologous bone marrow transplantation (ABMT). We evaluated engraftment in 18 patients who underwent allogeneic BMT (allo-BMT) following a preparative regimen that included high dose Mito (60 mg m2). Sixteen patients with malignant disease (AML 10, ALL 3, CML 2, MDS 1) and two with non-malignant disease (SCID 1, osteopetrosis 1) underwent non-T cell depleted allo-BMT. Fourteen patients with malignancies were transplanted at an advanced stage of disease while only two patients were standard risk patients. Of the 18 patients, 12 were females and six males, with a median age of 30.5 (0.3-48) years. Nine patients, (breast cancer 3, malignant lymphoma 4 and AML 2), who underwent ABMT following preparative regimens with comparable doses of Mito, served as controls. Engraftment following allo-BMT was normal and not statistically different from engraftment following ABMT. Five patients, who underwent allo-BMT, developed >grade II acute graft versus host disease (GVHD) and two developed chronic GVHD. After a median follow up of 28 (6-42) months, five patients are alive (one with disease). In summary, engraftment following high dose Mito and allo-BMT is not statistically different from engraftment following ABMT. Controlled studies with a larger group of standard risk patients are needed to elucidate the role of Mito in conditioning regimens pre-BMT.

Adolescent↗
PubMed1998

Nosocomial colonization, septicemia, and Hickman/Broviac catheter-related infections in bone marrow transplant recipients. A 5-year prospective study.

In this 5-year prospective study of 242 bone marrow transplantation (BMT) recipients from whom daily blood cultures via the indwelling Broviac/Hickman catheter were obtained, there was a median of 35 catheter-days during hospitalization, mean of 40 days, and total of 9,667 catheter-days which were divided almost equally between neutropenic (4,771) and non-neutropenic (4,896) days. One hundred twenty (50%) patients had a total of 161 episodes of nosocomial bacterial or candidal infections. Overall, 81 (33%) patients experienced 100 episodes of catheter-related infections and 90 (37%) patients experienced 112 episodes of septicemia, including 51 episodes of catheter-related septicemia. There was an incidence of 11.59 septicemia episodes, including 5.28 catheter-related septicemia episodes, 2.48 colonization only (without subsequent septicemia), and 2.59 exit site infections only, per 1,000 catheter-days. Over a period of a total of 6,593 afebrile days, 34 (14%) patients developed 40 episodes of colonization, a rate of 6.07 per 1,000 afebrile days, of which 16 developed into septicemia. Twenty-five patients had 1 episode each of exit site infection without bacteremia. There were 10 (4%) septicemia-related deaths, 4 of which were catheter-related; 50% of all deaths involved Pseudomonas aeruginosa. The mortality due to catheter-related septicemic episodes was not greater than that of the non-catheter-related episodes. Neutropenia was found to be a significant risk factor in our study: 76% of the septicemia episodes (85/112) and 65% of the catheter-related infectious episodes (65/100) occurred during neutropenia. There was a higher incidence of septicemic episodes during neutropenia than during non-neutropenic periods, 17.82 versus 5.51 per 1,000 days (p < 0.0001), and a higher rate of catheter-related infections during the neutropenic period, 13.62 versus 7.15 during non-neutropenic days per 1,000 days (0.001). Fourteen of 16 colonization episodes developed into septicemia during neutropenia versus 2/24 during non-neutropenic periods, a rate of 5.47 versus 0.47 per 1,000 afebrile days, respectively (p < 0.0001), and 9/10 deaths occurred during neutropenia.

Adolescent↗
PubMed1998

Use of fiberoptic bronchoscopy in bone marrow transplant recipients.

Bone marrow transplantation (BMT) has become the therapy of choice for a number of malignant and nonmalignant hematologic and nonhematologic disorders. A frequent complication after BMT is pulmonary disease which is associated with a high mortality rate. We examined the results of 79 bronchoscopies performed between May 1991 and May 1995 in 62 patients for the evaluation of pulmonary complications after BMT. In all cases bronchoalveolar lavage (BAL) was performed, in 10% transbronchial biopsy (TBB) was also carried out and in 13% bronchoscopy was followed by open lung biopsy. Positive results were found in 67% of bronchoscopies. Fungal infection (Candida and Aspergillus species) was the most common finding (18%), bacterial infection was found in 13%, mixed (fungal and bacterial) infection in 6%, cytomegalovirus in 11% and Pneumocystis carinii pneumonia in 4%. Diffuse alveolar hemorrhage was detected in 11% of cases. Idiopathic pneumonia syndrome (IPS) was diagnosed by TBB in 3% of procedures. We conclude that BAL is a safe and accurate procedure for the evaluation of pulmonary complications after BMT. TBB should be considered in the absence of thrombocytopenia for the diagnosis of IPS. If bronchoscopy findings are negative, open lung biopsy should be considered.

Adolescent↗
PubMed1998

Thalidomide reduces vascular density in granulation tissue of subcutaneously implanted polyvinyl alcohol sponges in guinea pigs.

The efficacy of thalidomide in the treatment of erythema nodosum leprosum is a well established fact; there is also accumulating evidence of its therapeutic value in a number of other inflammatory and immune-mediated conditions. In addition, thalidomide has been shown to be an inhibitor of angiogenesis induced by basic fibroblast growth factor (bFGF). Nevertheless, its mechanism of action remains speculative. Using guinea pigs, orally administered thalidomide significantly enhanced the response of multinucleated foreign body giant cells (p<0.05) in subcutaneously implanted polyvinyl alcohol sponges. Furthermore, the drug exerted a dual effect in that it reduced vascular density (p<0.05), which was not abolished by recombinant human bFGF, and at the same time amplified the granulomatous response with and without bFGF (p<0.05 and p<0.01, respectively). The results of our experiments represent a further step toward understanding the mechanism of action of thalidomide, with implications for its potential use in wound healing and scar formation as well as in the control of tumorigenesis.

Animals↗
PubMed1998

Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study.

Allogeneic cell therapy (allo-CT) is emerging as an effective treatment for patients relapsing after allogeneic bone marrow transplantation (BMT), indicating that tumor cells resisting chemoradiotherapy may still respond to immunocompetent allogeneic lymphocytes. We investigated possible graft-versus-tumor (GVT) effects in six patients with metastatic breast cancer that would be comparable to the graft-versus-leukemia (GVL) phenomenon occurring after allogeneic BMT in hematologic malignancies. The patients were cytoreduced with high-dose chemotherapy and autologous stem cell transplantation (ASCT), and were treated ambulatory with allo-CT consisting of adoptive transfer of HLA-matched donor peripheral blood lymphocytes (PBL) activated in vivo with human recombinant interleukin-2 (rIL-2). If no graft-versus-host disease (GVHD) developed, allo-CT was augmented with infusion of donor PBL, preactivated in vitro with rIL-2. Treatment was well tolerated, with low therapy-related toxicity in all patients. Two patients developed signs and symptoms compatible with GVHD grade I-II, one of whom shows no evidence of disease at more than 34 months out. In the remaining patients, progression-free survival following allo-CT ranged between 7 and 13 months. Allogeneic cell-mediated, cytokine-activated immunotherapy might be utilized for induction of GVT in metastatic breast cancer. A search for techniques to boost chimerism without severe GVHD is indicated.

Adult↗
PubMed1997

Autologous bone marrow transplantation for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS. Chronic and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation.

Intensive chemotherapy followed by autologous bone marrow transplantation (ABMT) may provide an alternative therapy for young patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS (sAML) lacking a suitable donor. We report the results for 79 patients with MDS/sAML transplanted with autologous marrow in first complete remission (CR). Within the total group of 79, a cohort of 55 patients for whom the duration of first CR was known were compared with a matched control group of 110 patients with de novo AML. The 2-year survival, disease-free survival (DFS), and relapse rates for the 79 patients transplanted in first CR were 39%, 34%, and 64%, respectively. The relapse risk was greater than 55% for all stages and all disease categories. Patients younger than 40 years had a significantly (P = .04) better DFS (39%) than patients older than 40 years (25%). The DFS at 2 years was 28% for the cohort of 55 patients transplanted for MDS/sAML and 51% for those transplanted for de novo AML (P = .025). Relapse rates were 69% for patients with MDS/sAML and 40% for those with de novo AML (P = .007). ABMT for MDS or secondary leukemia results in a lower DFS when compared with similarly treated patients with de novo AML due to a higher relapse rate. The DFS of 28% for these patients suggests that autotransplantation may be a valuable therapy for this disease. The low treatment-related mortality rate of less than 10% supports the view that sufficient numbers of hematopoietic stem cells are present in patients with MDS to allow adequate repopulation after autologous stem-cell transplantation.

Acute Disease↗
PubMed1997

Immunotherapy with recombinant human interleukin-2 and recombinant interferon-alpha in lymphoma patients postautologous marrow or stem cell transplantation.

Immune-mediated effects appear to play a major role in controlling minimal residual disease (MRD). We, therefore, investigated the role of recombinant human interleukin-2 (rIL-2) given concomitantly with interferon-alpha (IFN-alpha) in malignant lymphoma (ML) patients with responding disease following autologous bone marrow or blood stem cell transplantation (ABSCT). Fifty-six patients were included in this investigation. Thirty-two patients had non-Hodgkin's lymphoma (NHL) and 24 patients had Hodgkin's disease (HD). Sixty-one patients (NHL 36, HD 25) served as historical controls. Patients from both groups had similar demographic characteristics, the same stage of disease at presentation, status of disease at transplantation, conditioning regimens, and type of transplant. rIL-2 and IFN-alpha were self-administered in two cycles beginning 2.5 to 10.5 months (median, 4 months) posttransplant and separated by a 4-week interval. Each cycle consisted of IFN-alpha subcutaneously (SC) 3 x 10(6) U/d x 5 d/wk combined with rIL-2 SC 3 to 6 IU/m2/d x 5 d/wk for 4 weeks. The incidence of survival and disease-free survival (DFS) was significantly higher in the group under investigation than in the historical controls (P < .01). Of 56 patients with ML treated with IFN-alpha + rIL-2, 45 patients are DFS (80.4%) after a follow-up of 7 to 78 months (median, 34 months), whereas in the historical controls, 32 of 61 (52.5%) patients are disease free, in a follow-up of 4 to 84 months (median, 23 months) posttransplant (P < .01). Our preliminary results are encouraging and suggest that home administered immunotherapy with IFN-alpha and rIL-2 is relatively well tolerated and may intensify remission in ML patients with MRD following ABSCT.

Adolescent↗
PubMed1997

Isradipine for the prevention of cyclosporine-induced hypertension in allogeneic bone marrow transplant recipients: a randomized, double-blind study.

BACKGROUND: Hypertension and nephrotoxicity frequently occur in patients who receive cyclosporine therapy after bone marrow transplantation (BMT). Isradipine, a calcium channel entry blocker, has been used successfully in cyclosporine-induced hypertension. METHODS: Thirty leukemic patients who received cyclosporine after BMT were randomized to receive isradipine (0.005 mg/kg) from 72 hr before commencement of cyclosporine therapy until day 100 after BMT or placebo. RESULTS: The placebo and isradipine groups were well matched. No differences were found between the isradipine and placebo groups in the level of blood pressure, renal function, marrow engraftment, or mortality. Hypertension incidence was surprisingly low (30% a week after hospital discharge and 10% by day 100 after BMT), and did not differ between the groups. CONCLUSIONS: Isradipine does not harm immunohematopoietic reconstitution after BMT; therefore, it may be used in this setting, although the previously reported incidence of hypertension has been exaggerated.

Adult↗
PubMed1997

Colchicine does not ameliorate bleomycin-induced pulmonary injury in hamsters.

We have evaluated the effect of colchicine, a potential antifibrotic drug, on bleomycin-induced pulmonary inflammation in hamsters. Pulmonary injury was induced by a single intratracheal (IT) instillation of bleomycin (bleo). Four groups of male Syrian hamsters each received one of four treatments: (1) IT bleo and twice daily intraperitoneal (IP) injections of colchicine (col) starting one day before IT instillation of bleo (bleo-col); (2) IT bleo and IP injections of saline (bleo-sal); (3) IT saline and IP colchicine (sal-col); and (4) IT saline and IP saline (sal-sal). Animals were sacrificed 28 days after IT treatment. Lung injury was evaluated histologically, biochemically and by analysis of bronchoalveolar lavage (BAL) fluid. Treatment of hamsters with colchicine did not ameliorate the bleo-induced lung injury, as determined by a semiquantitative morphological index that assesses the severity and extent of the lung injury on a scale of 0-3. Lung hydroxyproline measurements and BAL fluid cell count were also similar in bleo-col compared to bleo-sal hamsters. Colchicine did not prevent the bleo-induced restriction expressed by volume displacement. These results indicate that colchicine does not ameliorate the bleo-induced lung inflammation and fibrosis and call for further controlled investigations to justify the use of this drug in pulmonary disorders.

Animals↗
PubMed1997

Thalidomide-induced perioral neuropathy.

Thalidomide was administered as a therapeutic agent for chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation in a patient with breast cancer. Although side effects of thalidomide have been described earlier, this is the first instance of perioral neuropathy associated with thalidomide treatment. Awareness of this specific side effect may contribute to early diagnosis and appropriate treatment.

Antineoplastic Combined Chemotherapy Protocols↗
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↗