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W Hunstein

Publications and source records attributed to W Hunstein.

At least 19 recordsLinked to original sources
PubMed1992

Regional administration of lymphokine-activated killer cells can be superior to intravenous application.

A patient with liver metastases of human lymphocyte antigen (HLA) class II-negative malignant melanoma was treated with several cycles of adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells. The authors evaluated the efficacy of regional transfer of LAK cells versus systemic intravenous administration. Initially, the patient was treated according to a regional treatment protocol, consisting of perfusion of the spleen with interleukin-2 and transfer of LAK cells into the portal vein; a partial remission was observed. Because of technical problems, interleukin-2 and LAK cells were administered intravenously in a second treatment cycle. This systemic treatment course resulted only in a minor mixed response of the hepatic metastases. A third treatment course was administered with the use of intravenous interleukin-2 infusion and arterial perfusion of the liver with LAK cells. The patient had separate hepatic arteries to both lobes of the liver as an anatomic variation. Because most of the tumor mass was present in the right lobe of the liver, a third of the LAK cells were injected into the right hepatic artery and the remaining cells were administered intravenously. The lesions in the right lobe of the liver regressed, but disease progression occurred in the left lobe. A fourth treatment cycle, consisting of intravenous infusion of interleukin-2 and arterial perfusion of both lobes of the liver with LAK cells, resulted in a complete response of all hepatic lesions, which has lasted 18 months to date. Because, in this patient, tumor regression was observed only in anatomic areas of the liver, which were perfused with LAK cells, it is suggested that the regional administration of LAK cells was essential for successful treatment.

Adult↗
PubMed1992

Elevated TNF receptor plasma concentrations in patients with rheumatoid arthritis.

Two types of tumor necrosis factor receptors have been characterized, both capable of transmitting the signal and exerting the biological functions of TNF and lymphotoxin. We measured the plasma concentrations of two types of TNF binding proteins (sTNFR-A and sTNFR-B) in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) using an enzyme-linked binding assay. In normal controls (n = 43), mean plasma concentrations were 1030 +/- 55 and 1461 +/- 59 pg/ml for sTNFR types A and B, respectively. In 67 patients with moderate RA, mean levels were 1422 +/- 82 pg/ml (type A) and 2088 +/- 109 pg/ml (type B); in 34 patients with severe RA, 2588 +/- 279 pg/ml and 4494 +/- 550 pg/ml, respectively, were measured (P less than 0.0001 compared to normal controls). Concentrations of both type A and type B sTNFR were highly correlated in severe RA (R2 = 0.7) but not in SpA or normal controls. T lymphocytes in synovial fluid of patients with RA expressed predominantly type A TNF receptors on their surface; in some patients a weaker expression of type B receptors was also detectable. Soluble TNF binding proteins in patients with RA were able to neutralize TNF in a cytotoxicity assay, demonstrating their ability to act as "TNF-inhibiting factors". We conclude that both types of TNF receptors are parameters of disease activity in RA and may also act as TNF antagonists.

Arthritis, Rheumatoid↗
PubMed1992

The interleukin-2 receptor in human monocytes and macrophages: regulation of expression and release of the alpha and beta chains (p55 and p75).

Human monocytes constitutively express the intermediate-affinity interleukin-2 receptor (IL2R) p75, while freshly isolated monocytes lack the low-affinity IL2R p55 (Tac antigen, CD25). Lipopolysaccharide (LPS) upregulates expression of p75 and effectively induces surface expression of CD25 on human monocytes within 18 h, as detected by two-colour FACS analysis on 59.5 +/- 7.6% of cells. IL2-binding studies using biotinylated IL2 reveal the presence of a functional high-affinity receptor on LPS-activated monocytes. Soluble CD25 (sCD25) is not released into supernatants of elutriation-purified monocytes cultured for 24 h with 100 ng/ml LPS. When these monocytes are cultured for up to 7 days in the presence of serum to induce differentiation into macrophages, increasing amounts of sCD25 can be measured in the 24-h supernatants induced with LPS (173 +/- 86 U/ml at day 7), whereas the percentage of CD25+ cells (14.8 +/- 14.1% at day 7) is significantly lower than in monocytes. Thus, the cell surface expression and release of CD25 is differentially regulated in activated monocytes and macrophages.

Humans↗
PubMed1992

Deficiency in interferon production of peripheral blood leukocytes from patients with non-Hodgkin lymphoma.

In search for a rationale for the use of interferons (IFNs) in treatment of non-Hodgkin lymphoma (NHL), we have investigated the IFN system of 13 patients with low-grade NHL, 15 patients with high-grade NHL, and 20 patients with chronic lymphocytic leukemia or leukemic immunocytoma (CLL/IC). Production of IFN induced by phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), Corynebacterium parvum, Herpes simplex virus (HSV), Newcastle disease virus (NDV), and interleukin 2 (IL-2) were studied in the peripheral leukocytes from the patients and from 21 control persons by means of a whole blood technique. All three groups of patients with NHL had significantly reduced production upon stimulation by NDV (p ranged between 0.0038 and less than 0.0001) compared to controls. Similarly, C. parvum also induced lower titers of IFN in the leukocytes of patients with non-leukemic NHL (p = 0.0015 for low-grade NHL and p = 0.0038 for high-grade NHL). When stimulated by PHA, the IFN response of all groups of patients was within normal range. With the exception in low-grade NHL, Con A also induced normal titers of IFN in the patients with NHL. The levels of IFN induced by PWM, HSV, and IL-2 were very low and no differences between controls and patients could be found. As NDV and C. parvum induce mainly IFN-alpha and the mitogens PHA and Con A mainly IFN-gamma, our results suggest that there is a deficiency in the IFN-alpha response in the patients with NHL but normal response in IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) subsequent to chemotherapy improves collection of blood stem cells for autografting in patients not eligible for bone marrow harvest.

Fourteen patients with relapsed Hodgkin's disease responded to a salvage therapy with Dexa-BEAM (dexamethasone, BCNU, etoposide, Ara-C and melphalan). In seven patients a continuous i.v. infusion with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was started subsequent to Dexa-BEAM (+rhGM-CSF) while the other seven patients received no hemopoietic growth factor (-rhGM-CSF). It was our objective to study the impact of rhGM-CSF on the collection of blood-derived hemopoietic stem cells in patients with extensive prior chemo- and radiotherapy not eligible for marrow harvest. Compared to baseline, we observed a significant increase of colony-forming units granulocyte-macrophage (CFU-GM) in the peripheral blood of patients receiving rhGM-CSF (p less than 0.05). On average, the yield of total nucleated cells and CFU-GM collected per single leukapheresis was 2.2 and 2.4-fold higher in the rhGM-CSF-treated patients respectively (p less than 0.05). With rhGM-CSF the interval from the start of chemotherapy to the end of blood stem cell collection could be reduced by 6 days (p less than 0.05). Following the CBV pretransplant regimen (cyclophosphamide, BCNU, etoposide), the reinfusion of rhGM-CSF-exposed stem cells resulted in a shorter time of leukocyte recovery (p less than 0.05). The number of CFU-GM/kg body weight transplanted was found to be predictive for the time of neutrophil recovery (p less than 0.05). In patients with bone marrow hypoplasia or fibrosis, rhGM-CSF as part of an effective salvage therapy improves the collection of blood stem cells that are capable of restoring hemopoiesis after high-dose pretransplant therapy.

Adult↗
PubMed1992

Induction of intracellular and plasma 2',5'-oligoadenylate synthetase by pentostatin.

Similar to interferon alpha, pentostatin is highly effective in hairy cell leukemia and moderately active in other chronic lymphoid malignancies. In ten patients with hairy cell leukemia (HCL) and seven patients with other B-cell chronic leukemias (BCL), we have studied the intracellular 2',5'-oligoadenylate synthetase (2,5OAS) activity of the mononuclear cells before, 4 h, 24 h, and 48 h after pentostatin administration. In patients with HCL the median level of intracellular 2,5OAS increased 4.6-fold at 4 h and 11.5-fold at 24 h compared to the pretreatment value. Among the other seven patients, the median intracellular 2,5OAS remained unchanged in three patients and rose slightly by 2 to 14 times in four patients. Eleven patients (eight with HCL and two with BCL) responded to pentostatin. The median increase in 2,5OAS among the responders was 13.0-fold (range 4.8-30.0) whereas that among non-responders was 2.2-fold (range 0.2-6.3). The difference was highly significant (p less than 0.0001). In five of the total seventeen patients, the plasma levels of 2,5OAS activity were also determined and changes in plasma levels paralleled those measured intracellularly. To determine if the elevation of 2,5OAS is mediated by induction of interferon alpha, the expressions of mRNA for interferon alpha and beta were investigated by means of reverse transcription and polymerase chain reaction using the corresponding sense primers. In none of the five patients thus studied could we find an induction of mRNA for interferon alpha or beta in the leukemic cells during treatment with pentostatin. Thus, response to pentostatin correlates with induction of 2,5OAS directly and the 2',5'-oligoadenylate system seems to be involved in cytotoxicity.

2',5'-Oligoadenylate Synthetase↗
PubMed1991

Etoposide in acute leukemia. Past experience and future perspectives.

Etoposide as a single agent is active in relapsed and refractory acute myelogenous leukemia (AML), with complete responses (CR) rates of 10% to 25%. The drug has been safely combined with cytarabine, azacytidine, vinca alkaloids, and anthracyclines, inducing remission rates of 20% to 60% in patients with previously treated AML. The experience with etoposide in acute lymphoblastic leukemia is less extensive, but the drug seems to be active in combination with cytarabine or aclacinomycin. In addition, etoposide is combined with cytarabine and anthracyclines for the primary treatment of AML. The response rates thus achieved are comparable with those obtained with standard regimens. A Phase I/II trial was initiated to study the efficacy of the NOVE combination (mitoxantrone [10 mg/m2/d, days 1 to 5] plus etoposide [100 mg/m2/d for 3, 4, or 5 days] in patients with refractory AML. The results showed that extended duration of etoposide administration is associated with higher CR rates. Overall, a CR rate of 43% was achieved in 61 patients. A sequential regimen with IDAC (idarubicin/cytarabine) and NOVE was designed for primary treatment of adult patients with AML. Cycles of IDAC or NOVE are applied depending on response. The results of the pilot study with this strategy were encouraging with 18 of 20 patients achieving CR. Further studies are under way to verify the efficacy of this strategy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Peripheral blood mononuclear cell collection from patients undergoing adoptive immunotherapy or peripheral blood-derived stem cell transplantation and from healthy donors.

The demand for collection of mononuclear cells from the peripheral blood of patients for therapeutic purposes is rapidly increasing. Automated blood cell separators are usually designed for collection of blood components from healthy donors. We reviewed safety and efficiency of collection data of a new procedure for the Fenwal CS 3000 blood cell separator in 125 collections from normal donors and 101 collections from patients after IL-2 pretreatment or chemotherapy. The new procedure set red blood cell spillovers to occur at 3.5 minute intervals, using procedure 1 with the interface detector set at 1,000 and the standard granulocyte and collection chambers. Despite significant anemia and thrombocytopenia in a large number of patients no serious procedure-related side effects occurred. The lymphocyte yield was 4.74 +/- 1.6 x 10(9) per 5 liters of blood processed in normal donors and 24.2 +/- 12.0 x 10(9) per 10 liters of blood processed after IL-2 treatment. After chemotherapy the lymphocyte yield was 4.5 +/- 3.1 x 10(9) per 10 liters of blood processed; the collection efficiency was found to be significantly lower in this group. The main problem was the platelet loss of 35.6 +/- 12% of the initial count in normal donors, 40.3 +/- 14.1% after IL-2 treatment, and 42.1 +/- 18.0% after chemotherapy. The platelet loss is, however, closely related to the preapheresis platelet count; patients with thrombocytopenia lose fewer platelets than normal donors. Therefore the procedure was found to be safe for patients with a platelet count as low as 20/nl. This report provides a basis for safe, effective mononuclear cell collection from patients with very abnormal peripheral blood counts.

Adolescent↗
PubMed1991

Decrease in soluble CD8 antigen levels in splenectomized patients as an index for reduced suppressor/cytotoxic cell activity.

To investigate the effect of splenectomy on lymphocyte subpopulations we monitored changes in serum concentrations of soluble suppressor/cytotoxic (sCD8) and soluble helper/inducer (sCD4) antigen in 11 splenectomized patients. Indications for splenectomy were hereditary spherocytosis in 2, idiopathic thrombocytopenic purpura in 2, gastric carcinoma in 4, Hodgkin's disease in 2 and pancreatitis in 1 patient. Lymphocyte subpopulations were also analyzed by means of conventional immunophenotyping with monoclonal antibodies to CD4 and CD8. We consistently found an early postoperative drop of sCD8 and sCD4 levels within the first week after splenectomy, paralleling changes in the percentages of CD4+ and CD8+ lymphocytes. While alterations of lymphocyte subsets in the peripheral blood were completely reversible and sCD4 levels returned to preoperative values, sCD8 concentrations remained suppressed even 3 months after splenectomy. SCD8 levels at the nadir and those 3 months after splenectomy were significantly lower than preoperative values (P = 0.003, P = 0.149 respectively). Since sCD8 levels reflect suppressor/cytotoxic cell activity, we suggest that suppressor cell activity is reduced in splenectomized patients.

Adult↗
PubMed1991

Autologous transplantation of an immunomagnetic bead purged marrow in patients with relapsed acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL) the expected duration of a second complete remission (CR) following conventional aggressive multi-drug treatment is rather short, and long-term survival is rarely seen. Myeloablative consolidation treatment with ABMT in second CR is thought to benefit "high risk" patients thus allowing the escalation of cytoreductive treatment into a lethal range. In three patients with relapsed ALL bone marrow was collected in the very early second remission phase. The autografts were incubated with a panel of monoclonal antibodies bound to magnetobeads (DYNABEADS M450). The pretransplant regimen consisted of total body irradiation (TBI) (14.4 Gy) and cyclophosphamide (CY) (50 mg/kg b.w. x4). Following autologous transplantation of those immunomagnetobead purged marrow grafts, complete hematologic reconstitution was seen in all three patients. They are alive and disease-free for +26, +24 and +17 months post transplant, which is also proven by the absence of detectable gene rearrangements after transplantation. In two of them disease-free survival exceeds the duration of the preceding remission y 20 and 12 months respectively, which is a definitive parameter for therapy effectiveness. Therefore, "high dose" consolidation treatment in very early second CR followed by autologous transplantation of purged bone marrow seems to allow long-term disease-free survival. The technique of ex vivo immunomagnetic bead purging, i.e. the "direct" and "indirect" method of binding monoclonal antibodies to magnetobeads is described.

Antibodies, Monoclonal↗
PubMed1991

Utilization of recombinant human GM-CSF to enhance peripheral progenitor cell yield for autologous transplantation.

Evidence has accumulated which indicates that efficacy of chemotherapy correlates with dose intensity and with total dose. For most cytotoxic agents, the major limiting factor for escalation of dose intensity is myelotoxicity. Attempts have been made to circumvent myelotoxicity by autologous bone marrow transplantation. Recently, it has been demonstrated that progenitors enriched from the peripheral blood can also be used successfully for autografting. The concentration of progenitor cells in peripheral blood is lower than that in bone marrow but myelosuppressive chemotherapy or hematopoietic growth factors, or a combination of both can be exploited to enhance the progenitor cell yield. The studies reported here are sequential. In the first study, eight patients with advanced Hodgkin's disease received myelosuppressive regimen consisting of cytarabine (100 mg/m2/12h SC days 1 to 5) and daunorubicin (45 mg/m2/d, days 3 and 4). Progenitor cell leukapheresis was performed during the rebound phase of hematopoiesis. All eight patients were treated with super-dose chemotherapy with progenitor cell transplantation. One patient died of CNS toxicity 48 days after transplantation but all other seven had sustained engraftment. In the second study, human recombinant GM-CSF (at 250 micrograms/m2/d as continuous infusion) was administered to twelve patients. Leukapheresis was started at a white blood count (WBC) of greater than 10 x 10(9)/L and the dosage of rhGM-CSF adjusted to keep the WBC between 10 x 10(9)/L and 20 x 10(9)/L. The median duration of rhGM-CSF application was 11.5 days and a median number of six leukaphereses performed. The median increase in the number of granulocyte-macrophage colony forming units (CFU-GM)/ml of peripheral blood was 8.5 fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Assessment of bone marrow infiltration by magnetic resonance imaging in patients with hairy cell leukemia treated with pentostatin or alpha-interferon.

The bone marrow of five patients with progressive hairy cell leukemia was examined histologically and by magnetic resonance imaging in a prospective study. Iliac crest biopsies and magnetic resonance scans were performed before and after nine months of therapy with pentostatin (four patients) and alpha-interferon (one patient). T1-weighted scans were evaluated quantitatively and in terms of their visual appearance in three regions of interest (lumbar spine, pelvis and femur). In contrast to bone marrow histology, it was possible to detect differences in the degree of infiltration between these marrow regions in four patients by magnetic resonance imaging. After treatment, three patients had no residual bone marrow infiltration as determined histologically; in parallel, the magnetic resonance images had normalized. The remaining two patients achieved partial remission: marrow infiltration was estimated to be 20% histologically, corresponding well to the signal reduction obtained by magnetic resonance imaging. These data suggest that magnetic resonance imaging of the bone marrow is a sensitive method for assessing responses to treatment with pentostatin and alpha-interferon in patients with hairy cell leukemia.

Adult↗
PubMed1990

[Menetrier's disease: brain infarction as an unusual first symptom].

A 43-year-old patient was admitted to hospital with an apoplectic stroke caused by an angiographically confirmed partial stenosis of the arteria cerebri media branch. We diagnosed Ménétrier's disease, documented by gastroscopy and histology, after having eliminated other causes for the apoplexy. We suggest a direct causal relationship between the stroke and Ménétrier's disease, since high incidences of thromboembolic complications have been reported in association with this rare disease. After conservative therapy with H2-blockers, laboratory values returned to normal. In the two years following diagnosis, the patient reported no recurrence of neurologic complications.

Adult↗