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Biomedical subjects

C Rosenfeld

Publications and source records attributed to C Rosenfeld.

At least 19 recordsLinked to original sources
PubMed1995

A phase I trial of recombinant human interleukin-6 in patients with myelodysplastic syndromes and thrombocytopenia.

To evaluate the hematologic effects of recombinant human interleukin-6 (rhIL-6, Escherichia coli, SDZ ILS 969, IL-6), and determine its toxicity profile, we performed a phase I trial of IL-6 in 22 patients with various myelodysplastic syndromes (MDS), platelet counts < 100,000/microL, and < 5% bone marrow (BM) blasts. Patients received one of four doses of IL-6 (1.0, 2.5, 3.75, and 5.0 micrograms/kg/d) as a subcutaneous injection on day 1, followed by a 7-day wash-out period, and then 28 days of IL-6 therapy. Dose-limiting toxicities of fatigue, fever, and elevated alkaline phosphatase were seen at 5.0 micrograms/kg/d; the maximum tolerated dose was 3.75 micrograms/kg/d. All patients experienced at least grade II fever and all had an increase in acute phase proteins. Eight patients (36%) experienced at least a transient improvement in platelet counts; three fulfilled the criteria for response, whereas five others had clinically significant increases that failed to meet response criteria. Various IL-6-related toxicities prevented more than three patients from receiving maintenance therapy. Two of the three patients who received maintenance IL-6 therapy had a persistent increase in platelet counts, during 3 and 12 months of IL-6 therapy, respectively. Laboratory studies indicated that IL-6 increased the frequency of higher ploidy megakaryocytes but did not significantly increase the number of assayable megakaryocytic progenitor cells, suggesting that IL-6 acts as a maturational agent rather than a megakaryocyte colony-stimulating factor. Although IL-6 therapy can promote thrombopoiesis in some MDS patients, its limited activity and significant therapy-related toxicity preclude its use as a single agent in this patient population. Further studies, combining low doses of IL-6 with other hematopoietic growth factors, are underway.

Acute-Phase Proteins↗
PubMed1995

Allogeneic transplantation combining mobilized blood and bone marrow in patients with refractory hematologic malignancies.

BACKGROUND: Mobilized blood stem cells have been used successfully in autologous transplant recipients to reduce the complications of pancytopenia due to dose-intensive chemotherapy. Reports of cytokine-mobilized blood progenitor cells in allogeneic transplant recipients are rare. STUDY DESIGN AND METHODS: This is a pilot trial of six patients. Patients with advanced hematologic malignancy received bone marrow (median total 2.6 x 10(8) mononuclear cells/kg) followed by four daily transfusions of blood (median total 9.5 x 10(8) mononuclear cells/kg) from HLA-matched sibling donors who were mobilized with recombinant human granulocyte-colony-stimulating factor (5 micrograms/kg/day subcutaneously for 5 days). All patients received cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis. RESULTS: An absolute neutrophil count greater than 500 per mm3 was achieved on Day 12, and platelet transfusion independence was achieved on Day 16. The median day of hospital discharge was Day 23 after transplant. All patients achieved 100-percent donor cell engraftment. Acute > or = Grade III GVHD did not develop in any patients, but all patients developed Grade I (n = 4) or Grade II (n = 2) acute GVHD. Chronic extensive GVHD developed in four of six patients. One patient died of pneumonia 263 days after transplant while undergoing immune-suppressive therapy for chronic GVHD. CONCLUSION: The transfusion of blood stem cells in patients undergoing allogeneic bone marrow transplant is well tolerated soon after transplant, but the development of chronic GVHD may limit the general usage of unmanipulated blood stem cells.

Adult↗
PubMed1995

Pentoxifylline and ciprofloxacin in patients with myelodysplastic syndrome. A phase II trial.

Tumor necrosis factor (TNF) inhibits hematopoietic cell proliferation. The combination of pentoxifylline (PTX) and ciprofloxacin (Cipro) has been previously shown to reduce circulating serum levels of TNF. In this Phase II trial 14 patients with advanced myelodysplastic syndrome were treated with PTX (2,000 mg/day) and Cipro (1,000 mg/day) in order to determine tolerability and effect on peripheral blood cell counts, progenitor cell responsiveness to cytokines and circulating serum levels of interleukin-6 (IL6) and TNF. Toxicity attributed to PTX and Cipro were limited to nausea in 4 patients. Peripheral blood cell counts, platelet transfusion requirements and red blood cell transfusion requirements did not change during administration of PTX and Cipro (daily for 28 days). Marrow progenitor cells of patients entered into trial were less responsive to stimulation with cytokines in vitro at baseline and during the trial compared to normal volunteers. Eight patients had elevated IL6 levels before treatment with PTX and Cipro these levels did not change during therapy. Five patients had elevated TNF levels at baseline. There was a suggestion of decreased TNF levels during treatment with PTX and Cipro (P = .09). In conclusion, PTX and Cipro was well tolerated but no evidence of efficacy was observed.

Adult↗
PubMed1994

Phase I study of recombinant interleukin-1 beta in patients undergoing autologous bone marrow transplant for acute myelogenous leukemia.

A phase I trial was conducted with recombinant human interleukin-1 beta (rhIL-1 beta) in patients undergoing autologous bone marrow (BM) transplantation for acute myelogenous leukemia. rhIL-1 beta was administered at 3 dose levels (0.01, 0.02, 0.05 microgram/kg) by 30 minute intravenous infusion once a day beginning on the day of BM infusion and continuing for a total of 5 doses. A total of 17 patients were entered on the trial, and their results were compared with those of 74 consecutive historical control patients that did not receive colony stimulating factors. Moderate toxicity was observed in all patients. All 17 patients developed fever and chills within 30 minutes after initiation of rhIL-1 beta, and hypotension was observed in 14 of 17 patients 5 to 8 hours after the infusion. A total of 30% of patients required therapy (normal saline or dopamine) for treatment of hypotension. Therefore, dose escalation was discontinued at the 0.05 microgram/kg dose level. The number of days required to achieve an absolute neutrophil count greater than 500 mL in patients who received rhIL-1 beta was less than in historical patients (25 v 34; P = .02). This appeared to correlate with a reduced incidence of infection between days 0 and 28 after BM infusion (12% v 23%; P = .049). Median bilirubin, median creatinine, platelet recovery, and days in the hospital were not different between study patients and historical controls. Survival of patients who received rhIL-1 beta compared with that of historical patients was improved (30% v 20%; P = .04). These possible benefits were achieved at the cost of moderate toxicity during rhIL-1 beta administration.

Adolescent↗
PubMed1991

Eosinophilia resulting from administration of recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in a patient with T-gamma lymphoproliferative disease.

A therapeutic trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was attempted in a patient with neutropenia and frequent infections secondary to T-gamma lymphoproliferative disease (T-gamma LPD). During the 14 days of subcutaneous rhGM-CSF (500 micrograms/m2/day), the absolute eosinophil count increased from 0 to 9,455/microliters. By contrast, the absolute neutrophil count decreased. Toxicity related to rhGM-CSF included arthralgia and nonspecific chest pain. The possible mechanism for the rhGM-CSF induced selective eosinophilia is discussed.

Adult↗
PubMed1991

Flow cytometry of needle aspirates from bone and soft tissue tumors.

Fine needle aspiration specimens from 29 patients with bone and soft tissue neoplasms were analyzed by flow cytometry for DNA index and cell cycle analysis to determine whether such studies were helpful in cytologic diagnosis. Of 15 cases initially cytologically diagnosed as benign, 14 had a DNA index of 1.0, indicating a diploid population. The remaining case diagnosed as cytologically benign had a DNA index of 1.3. Further tissue from this tumor revealed an osteogenic sarcoma. Of the 14 cases initially diagnosed as malignant, 12 were hyperdiploid. Cell cycle analysis showed that malignant tumors had a higher proportion of cells in S phase (15.2% +/- 8.7%) than benign tumors (6.9% +/- 1.6%). Furthermore, high-grade malignancies had a significantly greater number of cells in S phase (18.5% +/- 1.5%) than low-grade tumors (9.9% +/- 6.3%).

Adolescent↗
PubMed1990

Chimerism studies using in situ hybridization for the Y chromosome after T cell-depleted bone marrow transplantation.

In situ hybridization for the Y chromosome (Y-ISH) was used to monitor engraftment in 10 patients with hematological malignancies who had received T cell-depleted marrow transplants from sex-mismatched donors, seven of whom were only partially HLA-matched. In the three patients who engrafted, as the peripheral counts rose, the percentage of host peripheral blood and marrow mononuclear cells decreased steadily, although host cells (less than 1%) could still be detected as late as day 252. The percentage of host granulocytes fell rapidly to less than 0.2%. Seven patients did not achieve full engraftment by day 28. Those with a low percentage of host cells (less than 1%) improved with observation or treatment with steroids, while those with a high or increasing percentage of host cells did not improve even after treatment with GM-CSF or with repeat marrow infusion without reconditioning. In one patient with graft failure, the residual host cells were predominantly CD8+ CD57+ and CD3+ CD56+, phenotypes consistent with non-MHC-restricted cytotoxic T cells. Lack of full engraftment in recipients of T cell-depleted marrow is not always associated with autologous reconstitution and does not always require retransplantation. Y-ISH may be useful for monitoring patients at high risk for graft failure in order to detect adverse trends in mixed chimerism that will alter therapy early after transplantation.

Adolescent↗
PubMed1989

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purged marrows for acute nonlymphocytic leukemia in late remission or early relapse.

Twenty-four patients with acute nonlymphocytic leukemia (ANLL) were treated with high-dose chemotherapy or chemoradiotherapy followed by infusion of autologous marrow purged with 100 micrograms/mL of 4-hydroperoxycyclophosphamide (4HC). The marrow harvests were performed when there were less than 5% blasts in the marrow. Seven patients were transplanted in second complete remission (CR), eight in third CR, one in fourth CR, and eight in early relapse. The median time to achieve 500 neutrophils/microL or 1,000 leukocytes/microL was 30 days. A platelet count of 20,000/microL and 50,000/microL was achieved at a median of 67 and 91 days, respectively. One patient failed to engraft by day 58. There were five other transplant-related deaths: sepsis (one), intracerebral hemorrhage (one), veno-occlusive disease (one), and interstitial pneumonia (two). Four of seven evaluable patients transplanted in early relapse obtained a CR lasting 112, 143, 189, and greater than 615 days. Eight of 11 evaluable patients transplanted in CR have relapsed at a median of 153 days (range, 104 to 311). The actuarial survival for all patients was 19%. There was a trend toward improved relapse-free survival for patients transplanted in remission as opposed to those transplanted in relapse (P = .11).

Actuarial Analysis↗
PubMed1988

Elevated platelet-surface-bound IgM in thrombotic thrombocytopenic purpura.

The level of platelet-surface-bound IgM (PSIgM) was measured during the course of therapy in two patients with thrombotic thrombocytopenic purpura (TTP). Before therapy, both had significantly elevated PSIgM. In both cases the PSIgM dropped after the institution of treatment with plasmapheresis, steroids, and dipyridamole, correlating with a complete response to therapy in one patient and a partial response in the second. This is further evidence that in some cases of TTP, an immune mechanism is present.

Adult↗
PubMed1987

Platelet satellitism: a possible mechanism.

Markedly increased platelet surface-bound IgG was found on platelets collected in citrate and heparin in a patient with platelet satellitism. The level on platelets collected in EDTA was mildly increased. However, neutrophils from this patient collected in EDTA had markedly increased surface IgG due to attached platelets, while no surface IgG was seen in citrate or heparin neutrophils, indicating that the anticoagulant EDTA in some way modified the surface IgG or neutrophil membrane resulting in platelet attachment. This is the first case in which a possible mechanism for platelet satellitism has been identified.

Blood Platelets↗
PubMed1986

Screening monoclonal antibodies against cell-surface antigens. High frequency of natural antibodies.

Two commonly used methods for screening hybridoma supernatants against cell-surface antigens were performed simultaneously on the supernatant culture fluids of different hybridizations, and compared with the detection of Ig secretion. Supernatants reacting with glutaraldehyde-fixed cells (ELISA (Enzyme-linked immunosorbent assay) on fixed cells) are mostly non-specific for the immunogen; in addition, with this method, only half of the antibodies detected by immunofluorescence are identified. These results can be explained by the frequent occurrence of hybridomas secreting antibodies displaying 'natural antibody' properties, which are strongly reactive with intracellular antigens, and apparently made accessible by the fixation procedure. Since artefacts impair the interpretation of results with ELISA on fixed cells, and complement-mediated cytotoxicity usually as a low yield, membrane immunofluorescence remains the best method for screening hybridoma antibodies.

Animals↗
PubMed1985

Protein kinases in human leukemic cells.

Protein kinase activities and cyclic AMP binding capacity were investigated in human peripheral blood cells from leukemic patients and normal controls. Using [gamma 32P] ATP as phosphoryldonor, the phosphorylating activities were not found to be significantly different in either normal or leukemic cells when measured on both artificial basic and acidic substrates. In contrast, the GTP-dependent casein kinase activity, CK2, which is almost undetectable in normal granulocytes, was markedly increased in highly proliferating myeloblastic cells from patients with acute myelogenous leukemia (AML) or with chronic myelogenous leukemia in blastic crisis (BC-CML). Levels of endogenous phosphotyrosine were not higher in leukemic cells than in normal peripheral lymphocytes or granulocytes. Finally, cAMP binding capacity was found to be increased in several types of proliferating leukemic cells, due to a higher amount of the R1-type regulatory subunit of the cAMP-dependent protein kinases. Specific patterns of cAMP binding proteins observed in the different types of normal blood cells were rather blurred in leukemic cells. In conclusion, modifications observed in human leukemic cells seem to be more related to proliferation or blockage in normal differentiation than to their cellular origin.

Adenosine↗
PubMed1985

A new set of monoclonal antibodies against acute lymphoblastic leukemia.

Six monoclonal antibodies produced by immunization of Balb/c mice with common acute lymphoblastic leukemia (cALL) cells were tested against various types of normal and malignant tissues. ALB1 and ALB2 are directed to the cALL antigen (CALLA gp100); ALB6 recognizes a determinant of p24; ALB7, ALB8 and ALB9 have a pattern of reactivity similar to Ba1. None of these antibodies specifically identify cALL but they should be useful tools for diagnosis or depletion of bone marrow in autologous therapy in transplantation. In addition, the example of ALB6 which acts as a platelet aggregating agent, suggests that the study of other cell systems expressing the antigens associated with cALL may shed light on the function of these antigens and subsequently on the physiopathology of the leukemic cells.

Animals↗
PubMed1985

Merocyanine 540 staining of human leukemic cells: relation to stage of disease.

Previous work based on fluorescence microscopic observation has indicated that leukemic leukocytes and immature hematopoietic precursor cells show a greater permeability to the membrane stain, merocyanine 540 (MC) than normal, mature cells and that changes in MC permeability seem to be correlated with failure in membrane maturation during leukemic cell differentiation. In the interest of addressing questions concerning the efficacy of the MC staining reaction as a diagnostic tool in clinical contexts relevant to leukemia, we have looked for any correlations which might exist between the MC staining patterns displayed by circulating leukocytes, cellular morphology and the clinical status of 53 patients with leukemia and non-Hodgkin's lymphoma, using fluorescence activated cell sorting. In 85% of cases, MC staining was found to be correlated with blood status while in 15% of the cases discrepancies were found. These results are discussed in light of changes in the hematologic profiles of the patients during the clinical course.

Diagnosis, Differential↗