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Biomedical subjects

W Hunstein

Publications and source records attributed to W Hunstein.

At least 37 records · Page 2Linked to original sources
PubMed1990

Clinical implications of increased plasma levels of CD8 in patients with hairy cell leukemia.

Plasma levels of soluble T-suppressor/cytotoxic antigen (sCD8) were measured at diagnosis or before systemic treatment in 69 patients with hairy cell leukemia (HCL). The 49 nonsplenectomized patients were characterized by high concentrations of sCD8 antigen as compared with 17 controls (P less than .0001). The median sCD8 level in non-splenectomized patients was 1,050 U/mL (range: 160 to 2,400 U/mL) and was significantly higher (P less than .0001) than the median of 275 U/mL (range: 20 to 1,080 U/mL) in splenectomized patients. The relationship of sCD8 to clinical response to subsequent interferon alpha (IFN alpha) treatment was analyzed. Patients who showed subsequent hematologic response with normalization of all blood counts had significantly lower levels of sCD8 concentrations at diagnosis than those who did not (P = .0056). Furthermore, normalization of sCD8 during IFN alpha treatment paralleled the achievement of normal counts in peripheral blood, whereas soluble interleukin-2 receptor (sIL-2R) levels remained high in most patients after 12 to 15 months of treatment. We speculate that activation of suppressor/cytotoxic T cells might play a role in myelosuppression, and its modulation during treatment with IFN alpha correlates with normalization in peripheral blood counts.

Adult↗
PubMed1990

Activation of lymphocytes induced by recombinant human granulocyte-macrophage colony-stimulating factor in patients with malignant lymphoma.

To investigate effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we monitored changes in absolute lymphocyte counts, plasma concentrations of soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor (sCD8) antigens, and phenotypic changes of surface membrane antigens of peripheral mononuclear cells from 14 patients with malignant lymphoma treated with rhGM-CSF. Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high-dose Ara-C (AC) (NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease (HD) were in complete remission and treated with rhGM-CSF to enhance peripheral hematopoietic progenitor cell harvest for autografting. An increase in absolute lymphocyte count at the zenith of leukocyte elevation and a drastic increase in concentration of sIL-2R from a median of 565 U/mL to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was also a moderate increase in sCD8 levels from a median of 277 U/mL to 470 U/mL. Ten patients were available for serial studies of phenotypic changes in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P = .0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells. Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or sCD8 were not observed in four other patients during recovery from intensive chemotherapy without rhGM-CSF support. Our results provide evidence that administration of rhGM-CSF might activate lymphocytes in vivo. The impact of this activation on the remission rate and duration, as well as survival in patients with NHL, warrants further investigation.

Antigens, CD↗
PubMed1990

Prognostic significance of glucocorticoid receptor determination in patients with chronic lymphocytic leukemia and immunocytoma--lack of a positive correlation between receptor levels and clinical responsiveness.

Glucocorticoid receptors (GR) have been suggested to have prognostic significance in patients with CLL treated with chemotherapy containing glucocorticoid. In this study, the GR levels in 65 patients with advanced CLL and immunocytoma (clinical stages III and IV according to Rai) were determined by means of a whole cell assay. The median GR-level was 1,920 bs/c with a range from 0 to 9591. The patients were subsequently treated according to a prospective, randomized trial with either a combination of chlorambucil and prednisolone, or with prednimustine. No significant difference in receptor levels was found between responders (median = 1940 bs/c; n = 47) and nonresponders (median = 1950 bs/c; n = 14). To assess the influence of receptor content on prognosis we have analyzed the relationship between GR content and survival time and duration of response. There was no significant difference in duration of response and in survival between those patients with high (greater than 1920 bs/c) and those with low GR levels (less than 1920 bs/c) (log-rank test). Our data suggest that determination of GR provides no reliable indicator for clinical response to regimens with glucocorticoid as a component in patients with CLL and immunocytoma.

Adult↗
PubMed1990

Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site.

Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue.

Adult↗
PubMed1990

A modified cytotoxicity assay with high sensitivity.

Since adoptive immunotherapy using lymphokine activated killer (LAK) cells and interleukin-2 (IL-2) has been introduced into clinical medicine, there has been a growing interest in cytotoxicity assays. The standard 51chromium release assay has certain disadvantages, in particular limited sensitivity, because of a high, nonspecific background release. We examined the conditions under which tritiated thymidine, which has been used to assess slow macrophage mediated cytolysis, can be utilized to assess the rapid cytotoxic activity of unstimulated PBL and LAK cells. The optimal assay duration for the 3H-thymidine (3H-TdR) release assay is 24 h. Under standard conditions actively proliferating effector cells do incorporate some of the 3H-TdR released by the target cells during this time, leading to false low results. This problem can be abolished by the addition of excessive amounts of cold TdR to the assay medium. We found a good correlation of the results of the TdR release assay and the Cr release assay. Using the very sensitive TdR release assay, unexpected significant cytolysis of the so-called 'NK resistant' Daudi cells by unstimulated PBL is demonstrated. The modified 3H-TdR release assay is well-suited to monitor the immunological effects of immunotherapy, using IL-2 and LAK cells.

Chromium Radioisotopes↗
PubMed1990

Long-term effects of 2'-deoxycoformycin treatment on cytokine production in patients with hairy cell leukemia.

Deoxycoformycin (DCF) has been reported to cause immediate reduction and dysfunction of T lymphocytes, but the long-term effects on immune functions are still not known. As cytokine production is regulated by T helper-inducer lymphocytes and might represent a parameter for functional integrity of immunocompetent cells, we have measured the production of interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferons (IFN) by peripheral mononuclear cells (PMNC) from 10 patients with hairy cell leukemia 11-24 months after end of therapy with DCF. The patients were in continuous remission at the time of study. Despite an absolute reduction in CD3+ and CD4+ lymphocytes. there were no significant differences in IL-2 or TNF release between patients and controls. Except for a significant reduction in IFN-alpha release stimulated by Newcastle disease virus (NDV), IFN productions induced by other mitogens (phytohemagglutinin, PHA; Concanavalin A, ConA; pokeweed mitogen, PWM) and viral antigens were within normal range. There was also a decrease in proliferative responsiveness to PHA, but responses to ConA, PWM, and other viral antigens were normal. In five of the patients, we have monitored closely the changes in IL-2, TNF, and IFN before, during, and after treatment and could demonstrate a rapid normalization of initially decreased IL-2 release in all cases and also of TNF if the initial production was reduced. This study shows that, even though the absolute number of T lymphocytes and helper cells are reduced in the long-term observation after DCF treatment, the capacity to produce IL-2, TNF, and IFN-gamma was within normal range. Parallel to this observation, no opportunistic infections or frequency of infectious complications occurred in these patients.

Adult↗
PubMed1990

Successful autologous transplantation of blood stem cells mobilized with recombinant human granulocyte-macrophage colony-stimulating factor.

We investigated the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) on the pool of circulating hemopoietic progenitor cells in 11 patients with hematological malignancies of nonmyeloid origin and 1 patient with sarcoma. These patients were eligible for autologous blood stem cell transplantation rather than autologous bone marrow transplantation because sufficient marrow aspirates could not be performed due to damage at the usual sites of bone marrow harvest by previous chemo- and/or radiotherapy. Recombinant human GM-CSF was given as continuous i.v. infusion via central venous line for a median time of 11.5 days (range 5-22 days), during which a median number of six aphereses were performed. In comparison to the pretreatment level the median increase in the number of granulocyte-macrophage colony-forming units (CFU-GM)/ml of peripheral blood was 8.5-fold. In all 12 patients a median decrease of the platelet count of 21% (range 7%-67%) was observed during rhuGM-CSF treatment prior to the start of the apheresis procedures. Six patients were treated with a myeloablative conditioning therapy consisting of total body irradiation and/or high-dose polychemotherapy followed by autografting with blood stem cells. Five of them achieved a sustained engraftment. Recombinant human GM-CSF proved to be highly efficient in increasing the number of circulating progenitor cells in these patients with severely compromised hemopoiesis. Blood stem cells harvested under a rhuGM-CSF treatment are capable of restoring hemopoiesis in man after a myeloablative pretransplant therapy.

Adolescent↗
PubMed1989

Disease-free survival after autologous bone marrow transplantation in patients with acute myelogenous leukemia.

Autologous bone marrow transplantation (ABMT) makes it possible to escalate the dose of cytotoxic treatment to a lethal range. Disease-free survival (DFS) following myeloablative therapy and ABMT has been shown to be superior to conventional treatment in high risk patients with acute myelogenous leukemia (AML). It was the purpose of the present study to compare hematopoietic reconstitution, actuarial DFS, and relapse rate of patients transplanted in first complete remission (CR) of AML with those in second or subsequent CR, and to evaluate transplant related mortality. Fifty-two patients with AML, 22 in first CR (low risk) and 30 in second or subsequent CR (high risk), underwent total body irradiation (12.1 to 16.7 Gy) and cyclophosphamide (CY) treatment (200 mg/kg) followed by ABMT. The autograft was incubated with the active CY derivative Mafosfamide (ASTA Werke, Bielefeld, Federal Republic of Germany) to reduce the number of possibly contaminating clonogenic tumor cells. All patients showed three lineage engraftments with platelet recovery observed as being the slowest. The transplant related death rate was low at 5.8%. There was no significant difference in the kinetics of polymorphonuclear (PMN) cell or platelet reconstitution between the low and high risk patient subgroups. The estimated probability of DFS (relapse) after ABMT in first CR was 61% (36%) compared with 34% (65%) in second or subsequent CR, the longest follow-up being 55 months and 57 months, respectively (median follow-up 31 months and 19 months, respectively). ABMT offers a stable long-term DFS when performed in first CR with no relapses occurring in over a year after transplantation. Six later relapses, however, were seen after ABMT in second or subsequent CR, although DFS was not statistically different from that of first remission patients (P = .72).

Adult↗
PubMed1989

Mitoxantrone and high-dose cytarabine as salvage therapy for refractory non-Hodgkin's lymphoma.

Mitoxantrone (Novantrone, NO) and high-dose cytarabine (Ara-C, AC) have each been shown in monotherapy trials to be active in non-Hodgkin's lymphoma (NHL). In the current study, a combination of the two drugs (NOAC) was administered to 31 patients with advanced NHL refractory to modern sequential chemotherapy regimens. Ara-C was administered at 3 g/m2 as a 3 hour infusion every 12 hours on day 1 (2 doses) and mitoxantrone at 10 mg/m2/day on days 2 and 3. Of the 18 patients with high-grade malignant NHL, six have attained a complete remission (CR) and two, a partial remission (PR). One CR and 5 PRs were achieved among the other 13 patients with intermediate or low-grade NHL. The median time to relapse (TTR) of patients achieving CR was 7 months with a range from 4 to 17 months. Myelosuppression with subsequent infections was the major toxicity of this regimen. The median duration of severe neutropenia (less than 0.5/nl) was 9 days with a range of 0 to 27 days and the median duration of severe thrombocytopenia (less than 20/nl), 5 days with a range of 0 to 35 days. Infectious complications during cytopenia was seen in 45.3% of the courses administered and fever of unidentified origin was seen in 42.3%. About 63% of the patients were hospitalized for intravenous antibiotic or antimycotic treatment. Other side effects were mild and included nausea, stomatitis, and transient tachycardia of greater than 100/min. Thus, this regimen was active in refractory NHL with poor prognosis, and the toxic side effects were not excessive. Evaluation of the activity of this regimen at higher dose levels of Ara-C is warranted.

Adolescent↗
PubMed1989

Long-term endocrine toxicity of myeloablative treatment followed by autologous bone marrow/blood derived stem cell transplantation in patients with malignant lymphohematopoietic disorders.

The effect of myeloablative treatment with autologous bone marrow transplantation (ABMT)/autologous blood derived stem cell transplantation (ABSCT) in patients with acute leukemias or lymphomas was studied in 32 adult patients with a mean observation time of 15.8 months after transplantation. The conditioning regimen consisted of hyperfractionated total-body irradiation (TBI) and high-dose cyclophosphamide or the cyclophosphamide, carmustine, and etoposid (CBV) regimen. In all of the female patients, we observed primary ovarian failure requiring estradiol replacement therapy. In all of the male patients, testosterone levels were normal but follicle stimulating hormone (FSH) levels were increased, suggestive of germinal aplasia which was proved by semen analysis in several patients. In contrast to the reports of other groups, we did not find any abnormalities in thyroid function, most likely because TBI was hyperfractionated. Moderate toxicity to the adrenal cortex was noticed and was more pronounced in women than in men. Our results are similar to findings reported after allogeneic bone marrow transplantation, with the exception of normal thyroid function in our patients. These results should be taken into consideration when counseling patients about the long-term consequences of myeloablative treatment. Cryopreservation of semen should be offered to men before myeloablative treatment. Estrogen replacement should be initiated after transplantation in women to prevent adverse effects of long-term ovarian failure.

Adult↗
PubMed1989

Evidence for an osteoblast-activating factor in a patient with peripheral T-cell lymphoma and osteosclerosis.

A patient with peripheral T-cell Lymphoma and acquired, systemic osteosclerosis is described. Bone histology showed a spectacular activation of osteoblasts accompanyed by massive new bone formation. Alkaline phosphatase in serum was elevated and increased to greater than 2000 U/l when the lymphoma became refractory to chemotherapy. In the patient's serum an osteoblast-activating factor could be demonstrated using a rat osteogenic osteosarcoma cell line (ROS 17/2.8). The factor was absent during remission of the tumor. We conclude that osteosclerosis was a paraneoplastic syndrome in this patient due to the secretion of an osteoblast-stimulating factor by the T-cell lymphoma. This situation is similar to the secretion of osteoclast-activating factors described in B-cell lymphomas, particularly multiple myeloma. The characterization of such a factor could be of therapeutic relevance.

Adult↗
PubMed1989

Effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) on normal peripheral B lymphocytes and B lymphoblastoid cell lines.

The role of the granulocyte-macrophage colony-stimulating factor (GM-CSF) for the proliferation and differentiation of normal and leukemic myeloid cells has been extensively investigated. We examined whether rhuGM-CSF has any functional effect on normal purified B cells and cell lines from patients with B cell non-Hodgkin's lymphomas (NHL). Normal B cells were prepared by combining E-rosetting followed by two non-adherence procedures. Further B cell enrichment was achieved by complement-mediated lysis with a panel of antibodies directed against various T cell antigens. Alternatively, we incubated the cells with monoclonal antibodies recognizing specific antigens on monocytes/macrophages and T cells followed by a separation with immunomagnetic beads coated with sheep anti-mouse IgG. With these different separation procedures B cell populations with a various content of monocytes/macrophages were obtained. An optimal enrichment of B cells up to 80-90% was achieved by combining E-rosetting, non-adherence, and separation with immunomagnetic beads. The proliferative response to rhuGM-CSF (0.01-1000 ng/ml) was assessed in a [3H]-thymidine uptake assay. RhuGM-CSF alone or in combination with anti-IgM or SAC did not cause any proliferative effect in normal B cells. Even in the presence of 35% monocytes (CD11+) as accessory cells no stimulatory effect could be measured. Similarly, the malignant B lymphoma cells did not show any proliferative response to rhuGM-CSF. To assess a potential differentiation-inducing capacity the Ig production was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1989

Therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea.

Treatment of the myeloid blast phase of chronic granulocytic leukemia is still a major problem in clinical hematology. Alternate-day plicamycin and hydroxyurea treatment was reported to induce remissions in the majority of patients with myeloid blast phase by Koller and Miller in 1986 Subsequently we treated eight patients according to this regimen. Complete remissions could not be achieved and no prolongation of median survival was observed. In two patients treatment had to be discontinued due to severe toxicity.

Adult↗