Leukocytoclastic vasculitis complicating granulocyte colony-stimulating factor (G-CSF) induced neutrophil recovery in T gamma-lymphocytosis with severe neutropenia.
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Biomedical subjects
Publications and source records attributed to H Pralle.
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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.
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.
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.
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.
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.
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)
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.
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ESR investigations of lyophilized blood of patients with acute lymphatic leukemia exhibit an increase in spin concentration and an additional peak not present in control samples. This peak disappears almost completely concomittantly with a reduction in spin concentration after treating the patients with prednisolone, vincristine, and doxorubicin or after addition of 5mM of CuCl2 to blood samples. The results show that the ESR spectra of lyophilized blood samples can be utilized to follow the effect of therapy. Moreover, they suggest that the leukemic blood possesses a high concentration of antioxidants.
The case of an 18-year-old male patient with aplastic anemia is reported who was successfully treated by platelets from his father, mother and uncle over a period 8 months because of the very rare constellation of HLA-A,B identity in the family. The patient deceased from uncontrollable septicemia.
79 patients with definite ITP were investigated for HLA-A, -B, -C antigens. There was an increased frequencey of HLA-B5 in the entire groups (27.8% vs. 16.5% in controls and for HLA-B12 in male patients. However, after correction for the number of antigens tested, the difference of antigen frequencies became insignificant.
20 patients with hairy cell leukemia were treated between 1966 and 1978. All modalities of treatment for lymphoproliferative disorders have been used in at least some patients. Besides prednisone, vincristine, cyclophosphamide and their combinations as well as irradiation of enlarged spleens, cell depletion was achieved by splenectomy and leukapheresis. Cytostatics had no beneficial effect. Cytostatic therapy exposed some patients to the hazards of severe infections. On the contrary splenectomy lead to the improvement of some blood parameters. Leukapheresis seemed to work nearly identically. The survival of the splenectomized patients was longer than of controls. Because of the variability of the duration of the disease no definite statement could be made concerning the survival of both groups. 12 patients died during the observation period. Splenectomy was followed by one death, 11 patients died of septicemia.
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L-asparaginase therapy is often limited by allergy or toxicity and probably in some cases by antibody mediated inactivation of the enzyme. These problems can be avoided by extracorporeal application of l-asparaginase. As the enzyme is a stable tetramer with high molecular weight it cannot pass through the dialysis membrane in contrast to the amino acid l-asparagin which is destroyed. The resulting l-asparagin depletion of the plasma is sufficient for therapeutic success. Effective extracorporeal l-asparaginase therapy is demonstrated in two patients with ALL who were resistant to other chemotherapy and could not be treated intravenously because of allergy and toxicity.
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