Leukocytoclastic vasculitis complicating granulocyte colony-stimulating factor (G-CSF) induced neutrophil recovery in T gamma-lymphocytosis with severe neutropenia.
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Adult↗
Biomedical subjects
H Pralle
Publications and source records attributed to H Pralle.
Effective natural interferon-alpha therapy in recombinant interferon-alpha-resistant patients with hairy cell leukemia.
To explore the relationship between anti-interferon-alpha (anti-IFN-alpha) antibodies and loss of clinical responsiveness to IFN-alpha treatment, we examined sera from 59 patients with hairy cell leukemia who responded to therapy with recombinant IFN-alpha-2a (rIFN-alpha-2a). During the first 2 years of therapy, 10 patients developed rIFN-alpha-2a-neutralizing and 15 rIFN-alpha-2a-binding antibodies. Nine of the 59 initially responding patients became resistant to rIFN-alpha-2a and suffered a relapse of the disease at 7 to 24 months of treatment. All nine relapsing patients tested positive for both neutralizing and binding antibodies with titers above 400 INU/mL, while none of the antibody-negative patients relapsed. Six patients with detectable binding antibody titers below 400 INU/mL continued to respond to treatment. By measuring the IFN kinetics and the levels of the IFN-induced Mx-homologous protein in mononuclear cells after a single injection each of rIFN-alpha-2a and nIFN-alpha the IFN antibodies of eight of the nine resistant rIFN-alpha patients were found to be highly specific for rIFN-alpha-2a. Therefore, these eight patients were switched to natural IFN-alpha (nIFN-alpha) therapy at doses of 3 million IU, three times a week. All eight patients responded to treatment with nIFN-alpha, achieving durable objective responses similar to those obtained previously with rIFN-alpha-2a. These data clearly demonstrate that rIFN-alpha antibody-positive patients can effectively be treated with nIFN-alpha.
Adult↗
[Immunologic studies in patients with ovarian carcinoma during radio-chemotherapy. I. Studies of lymphocyte subpopulations].
In this article we have studied the behaviours of different lymphocyte subpopulations (T11, T8, T4, B4 and B1) in the peripheral blood of 60 patients suffering from ovarian cancer during radio- and chemotherapy with the APAAP-technique. The most important results of our study are that compared with the chemotherapy the radiotherapy causes greater lymphocyte depression, that the subpopulations of T-lymphocyte with the exception of T8 show greater radio-sensitivities than B-lymphocyte, that T8-subpopulation is not radio-sensitive, and that the T11-, T4-, B4- and B1-subpopulations of the patients at stage I and II can recover from the depression caused by radiation much better than the corresponding subpopulations of the patients at stage III and IV.
Adult↗
[The implantation of Hickman catheters. A new function of interventional radiology].
Hickman catheters are used mainly in patients with hematologic diseases, especially lymphatic and myelotic leukemias, and malignant lymphomas. They facilitate the administration of chemotherapeutics, hyperosmolar solutions and other substances with local toxicity as well as frequent taking of blood samples. Usually Hickman catheters are placed by surgical cut-down on a jugular vein. In lieu of this surgical placement, we recommend the implantation of Hickman catheters by means of interventional radiology techniques. In a period of 13 months 78 Hickman catheters were placed in 67 patients, 37 catheters (= 47%) stayed more than one month, 8 catheters (= 10%) stayed 5 to 8 months in the central venous system, 26, respectively 6, of these catheters are until now in situ. Lethal or life threatening complications did not occur. There were no infections at the introduction site of the catheter. The main complications were: pneumothorax without drainage: 3.2%, pneumothorax with drainage: 3.2%, slipping back of the tip of the catheter: 4.8%, thrombosis of the subclavian vein: 3.2%, fluid in the pleural cavity: 1.6%. In correspondence to the literature the complications of Hickman catheter placement by means of interventional radiology are less serious than by means of surgical cutdown. Further advantages are: general anesthesia can be avoided (less strain on severely ill patients, no problems to wean from assisted ventilation in patients with respiratory insufficiency), the smooth curve of the implanted catheter avoids sharp kinking and occlusion of the lumen, very small skin incisions are sufficient (lesser risk of hematomas in patients with thrombopenia), time and cost are reduced in comparison to surgical placement.
Adolescent↗
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↗
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↗
[Lymphocyte subpopulations in patients at risk of sepsis in a surgical intensive care unit].
Infection remains a major cause of morbidity and mortality in intensive care medicine. The increased susceptibility of the severely injured patient to sepsis and consecutive multiorgan failure has been attributed to abnormalities in cell-mediated immunity. The purpose of our study was to determine changes in the pattern of lymphocyte subpopulations in severely injured patients and to relate these changes to any development of sepsis and to outcome (indirect immunofluorescence with monoclonal antibodies). During 14 months we investigated 28 patients (ages 15-65 years) suffering from severe multisystem trauma (22 cases) or diffuse peritonitis (6 cases), 6 of whom (21.4%) developed sepsis and multiorgan failure; 4 of these 6 septic patients died. According to the clinical data, patients developed sepsis between the 3rd and 6th days after trauma. We therefore defined days 1-3 as the preseptic phase, days 3-6 as the phase of sepsis development, and days 4-10 as the phase of septic disease. In the preseptic phase there was no statistically significant difference in the pattern of the eight lymphocyte subpopulations measured between patients who later developed sepsis and those who did not. During the phase of sepsis development, however, the patients who did develop sepsis showed significantly reduced numbers of CD2-, CD8-, and CD20-positive cells (P = 0.0003; P = 0.009; P = 0.012). The number of helper cells (CD4) was also decreased, but the difference between the two groups failed to reach statistical significance (P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Plasma levels of soluble CD8 antigen and interleukin-2 receptor antigen in patients with hairy cell leukemia, relationship with splenectomy and with clinical response to therapy.
A soluble form of CD8 antigen (sCD8) has been shown to be released by activated CD8 + lymphocytes. Measurements of sCD8 may serve as an index of suppressor/cytotoxic cell activity. To assess the clinical significance of this observation in response to malignancy, we have investigated the sCD8 concentrations in 38 patients with hairy cell leukemia (HCL) not yet treated with any systemic therapy. The median plasma sCD8 level of the 20 nonsplenectomized patients was 1,025 U/ml and was significantly higher than that in the 18 patients who had previous splenectomy (median = 200 U/ml, p less than 0.0001), or in 14 normal controls (median = 350 U/ml, p less than 0.0001). Compared to controls, splenectomized patients had also significantly lower levels of sCD8 (p less than 0.01). The median concentration of soluble interleukin-2 receptor (sIL2R) in nonsplenectomized patients was 14,500 U/ml and was in the same range as in splenectomized patients (15,000 U/ml). There was no overlap in sIL2-R levels between controls (median = 300 U/ml) and patients. Investigation of serial plasma samples in 7 patients who received deoxycoformycin (DCF) and 11 patients treated with interferon alpha (IFN-alpha) showed a normalization of sCD8 levels and a decrease of sIL2R concentrations in those patients who showed hematological improvement. Normalization of sIL2R was, however, only observed in patients with complete remission. Our observation indicates that splenectomy might cause a reduction of the activation of suppressor/cytotoxic cells in patients with HCL. Treatment with either DCF or IFN-alpha also modulates the sCD8 levels to normal range. Measurements of sCD8 and sIL2-R might give more insight into the pathogenesis of HCL and serve as parameters for monitoring different phases of the disease and response to therapy.
Antigens↗
Establishment and characterization of a permanent human IgA2/kappa myeloma cell line.
A human myeloma cell line designated LOPRA-1 has been established from ascites fluid containing malignant plasma cells of a patient with IgA2/kappa multiple myeloma. The cultured cells which are Epstein-Barr virus (EBV) negative have retained the morphological, cytochemical, ultrastructural and immunophenotypical features of well-differentiated plasma cells. They express the plasma cell antigen PCA-1, the antigens CD28 (Kolt-2) and CD38 (OKT10), the transferrin-receptor (OKT9), and some epitopes of the CD24 antigen (HB8, VIB E3), but are negative for surface immunoglobulins. HLA class II antigens (HLA-DP, -DQ, -DR) and other B-cell markers such as CD10 (CALLA), CD19 (B4), CD20 (B1), CD21 (B2), CD22 (HD39), CD23 (MHM6), CD37 (BL14) and CD39 (G28-8) as analysed by both flow cytometry and immunocytochemistry (PAP/APAAP). With respect to immunoglobulin synthesis, two stable clones were selected by single cell cloning: clone LOPRA-1/5 synthesizes large amounts of alpha 2 heavy and kappa light chains, but secretes only small amounts of these molecules, whereas clone LOPRA-1/4 is clearly devoid of intracellular immunoglobulin heavy and light chains and thus appears to be a chain loss variant. Cytogenetic analysis revealed a pseudotriploid phenotype with several structurally abnormal marker chromosomes: 3n + -, 70, XX, -X, -1, -4, -6, -8, -8, -13, -16, +7, +18, +21, +i(1q), +i(1q), +6q-, +3mar.
Cell Line↗
[Alpha interferon in the therapy of hairy cell leukemia. Results of 3 prospective multicenter studies in West Germany].
Within 19 months of recruitment 51 centers enrolled 84 patients in our prospective multicenter trial for low-dose IFN alpha-2c for HCL (1.2 x 10 IU/m x 28 days s.c.- or lower). Induction therapy of 84 days was followed by maintenance with 2 weekly doses. Patients who reached stage Jansen I or A were then randomized to 2 arms either to receive further IFN or to stop treatment. Reinduction was reinstituted whenever any patient lost Jansen stage A or I. Only 3 patients failed. But enrollment was discontinued when it became apparent that fatalities in splenectomized (SX) patients due to septicemia outnumbered deaths given in the literature. Low-dose IFN administered daily might compromise host defense. Our next study aimed at improving the safety of IFN for SX patients. Pulsatile IFN on 7 consecutive days within a 28-day period was given to all SX patients. A randomization of non-SX patients either to receive daily or pulsatile IFN should provide proof of the efficiency. The intermissions ought to be as suitable for in-vitro investigations as for observations concerning the capacity of IFN to produce 'induction of inducers'. Pulsatile treatment has so far been safe in 13 splenectomized patients. Central diagnostic procedures remained the same during both studies. It seems important to us to use an intermittent schedule for the injection of IFN in SX patients and to restrict splenectomy to selected patients.
Aged↗
T-cell prolymphocytic leukemia (T-PLL) with unique surface phenotype.
Leukemic cells of a 19 year old patient with prolymphocytic leukemia of T-cell type (T-PLL) were characterized by surface markers and immunologic functions. Phenotypic analysis using a large panel of monoclonal antibodies corresponding to the clusters (CD) of differentiation antigens established on the Leukocyte Typing Workshops I and II revealed a unique T-cell phenotype not yet reported in the literature: CD1 (T6)-, CD2 (T11)+, CD3 (T3)+, CD4 (T4)-, CD5 (T1)-, CD6 (T411)+, CD7 (Leu9)+, CD8 (T811)-, CD10 (J5)-, CD11 (M22)+, CD12 (M67)-, CD13 (My7)-, CD14 (Mo2)-, CD16 (Vep13, 3G8, Leu11)+, CD18 (MHM23)+, CD19 (B4)-, CD20 (B1)-, CD25 (TAC)-, MHC-class II (HLA-DR, HLA-DQ)-, NKH1A+, Leu7-. Despite the expression of surface structures associated with natural killer (NK) function (CD16, CD18, NKH 1 A) the T-PLL cells were inactive in NK assays in vitro. Low in vitro ADCC activity was detectable. This unusual T-PLL phenotype might help to identify a new distinct T-cell differentiation stage.
Adult↗
[Primary treatment of hairy cell leukemia with low-dose human recombinant interferon-alpha-2c (Hr-IFn alpha 2c) in comparison with therapy following splenectomy. Interferon (IFn-alpha 2c) in HCL before or after splenectomy].
Within less than 14 months of recruitment 32 centers enrolled 97 patients in a multicenter trial for low-dose treatment of hairy cell leukemia (1.2 X 10(6) IU/m2 X 28 days s.c. with dose reduction according to clinically judged improvement) or ultra-low dose treatment (1.2 X 10(5) IU/m2, s.c. daily increasing to a well-tolerated dose) with Hr IFn-2c (arg). Induction therapy was limited to 84 days. Patients who reached the clinical stage Jansen I or A were then randomized to 2 arms either to receive further IFn (1.2 X 10(6) IU/m2 s.c.) twice a week or to be taken off treatment. For both arms induction therapy was reinstituted whenever a patient lost the criteria of Jansen stage A or I. The study included obligatory central diagnostic procedures and several special investigations. During the first year of the study a special problem evolved in the group of 34 patients with recurrent disease after splenectomy. Ten of them died, 9 of septicemia and 1 of bleeding complications, whereas only 1 death occurred in those patients who received IFn before splenectomy. The risk factors and the response to therapy in the two groups will be analyzed in order to define the criteria that will be needed for the proper choice of primary treatment for HCL. It appears important to us to restrict splenectomy to selected patients.
Clinical Trials as Topic↗
[Prospective controlled study of therapy of chronic myeloid leukemia (CML)].
The current status of the prospective German multicenter study on the therapy of chronic myelogenous leukemia (CML) is reported. After three years 188 of the projected 300 patients have been randomized. The duration of the study will be 8 years. The clinical characteristics of the randomized patients correspond well to those reported in the literature. Risk factors are distributed equally in both arms. One problem is the relatively high drop-out rate of about 12% thus far. Survival curves for the two treatment arms will be presented, although at present the number of patients having reached the end of the chronic phase is too small to allow definitive evaluation.
Adult↗
A prospective multicenter trial with human recombinant alpha 2c-interferon in hairy cell leukemia before and after splenectomy.
Our multicenter study on the treatment of hairy cell leukemia (HCL) started in December 1984 and the present data cover the time up to June 30, 1986. Ninety-seven patients were enrolled. For induction of response daily doses (6 micrograms) of low dose human recombinant alpha 2c-interferon (arg) was chosen. Further dose reduction (3 micrograms) was possible for patients who improved within the first 3-4 weeks. Patients with known risk factors started at lower doses (0.6 microgram daily). As infections are known to be the main cause of death in HCL, splenectomy was not mandatory before treatment. Thirty-nine patients received treatment with interferon. Nevertheless, infections remained the major cause of death in the study. The protocol did not prevent fatal infections in nine of the 34 splenectomized patients. The regimen proved safe for all but one of the nonsplenectomized patients. According to this experience, new criteria are needed for the choice of primary treatment in HCL. In our opinion splenectomy should become restricted to selected cases.
Antineoplastic Agents↗
[Thrombophilia: 2 different pathogenetic mechanisms].
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Female↗
High dosage desferrioxamine therapy in a female patient with acquired aplastic anaemia and transfusion siderosis.
A 32 year old woman with severe aplastic anaemia required frequent transfusions and consequently developed hyperferrioxaemia (54 microMol/l) and hyperferritinaemia (1,700 ng/ml). For the treatment of transfusion siderosis she was given 18 high dose courses each comprising 35 g of desferrioxamine. Because of pre-existing thrombocytopenia (platelet count 5 X 10(9)/l) the iron chelating agent was given by continuous intravenous infusion over 3 1/2 days. High dose desferrioxamine had to be abandoned because of severe bone pain. The desferrioxamine infusions achieved a negative iron balance, iron loss after each infusion being 100 to 200 mg in the urine and 400 mg in the faeces. Serum iron and ferritin concentrations fell almost to normal. This report shows that faecal iron excretion must be taken into account in assessing the balance of iron input and output during desferrioxamine treatment.
Adult↗
[Changes in lymphocyte subpopulations in relation to anesthesia procedure].
44 patients undergoing comparable gynaecological operations received either halothane- modified neuroleptanaesthesia or a combination of epidural and NLA. Monoclonal antibodies were used to determine 8 different lymphocyte subpopulations in blood samples drawn before and after anaesthesia and on the first postoperative day. Cell populations were counted by fluorescent microscopy. Halothane anaesthesia produced both a depression of T-cells (72.67% preoperatively to 52.79% postoperatively) and of the helper/suppressor ratio (1.46 to 1.10); meanwhile activated T-cells increased from 2.33% to 6.83%. After neuroleptanaesthesia as well as after halothane the HLA-DR positive cells decreased (21.05% to 19.29%; 25.22% to 20.29%). The B-cell fraction was elevated from 2.33% to 6.83% following combined anaesthesia. The potential of the anaesthetics to produce subsequent alterations in host defense is discussed.
Adult↗
[A comparison of staging classifications of plasmacytoma].
In 152 patients treated with cytostatic agents for multiple myeloma the prognostic value of seven staging systems was evaluated: Carbone et al. Acute Leukemia Group B, Southeastern Cancer Study Group, Durie and Salmon, Alexanian, Merlini et al., British Medical Research Council. The staging systems of the ALGB and SECSG, both dividing patients into "good risk"- and "poor risk"-groups gave significantly different survival curves. Nevertheless, the differences were rather small. In the systems of Carbone et al., Merlini et al., Alexanian, and Durie and Salmon some of the differences in the survival curves were statistically significant while others were not. Our data best fitted into the British Medical Research Council staging system, the survival curves of all three stages showing significant differences with median survival time dropping from 83 months in stage A to 52 months in stage B and 26 months in stage C. Nevertheless, none of those systems was clearly superior to single risk factors especially creatinine and hemoglobin.
Evaluation Studies as Topic↗