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K Warzocha

Publications and source records attributed to K Warzocha.

34 records · Page 2Linked to original sources
PubMed1996

Elevated circulating levels of TNFalpha and its p55 soluble receptor are associated with an adverse prognosis in lymphoma patients.

In 88 newly diagnosed lymphoma patients, tumour necrosis factor alpha (TNFalpha) and soluble TNF type I receptor (p55-R-TNF) were prospectively determined in plasma by immunoradiometric assay (IRMA) and ELISA methods respectively. These 88 patients included 19 with centrocyto-centroblastic lymphoma, 13 patients with other low-grade lymphoma, and 56 with high-grade lymphoma. Median TNFalpha plasma values were 20 pg/ml (range 5-380 pg/ml) in patients versus 7 pg/ml (range 4-9 pg/ml) in 20 healthy control subjects. Presence of TNFalpha level > or = 20 pg/ml was significantly associated with elevated LDH level (P<0.0001), serum beta2-microglobulin level > or = 3 mg/l (P<0.0001), haemoglobin < or = 12 g/dl (P=0.0001), Ann Arbor stage III or IV disease (P<0.005), and with bulky tumour (P=0.01). High level of TNFalpha was also associated with B symptoms (P<0.005), poor performance status (P<0.05), and serum albumin < or = 35 g/l (P<0.05). Levels of p55-R-TNF were also markedly elevated in these lymphoma patients (median of 3.5 ng/ml, range 0.8-18.8 ng/ml) versus 1.45 ng/ml in control subjects (range 1.1-2.3 ng/ml). Level of p55-R-TNF > or = 3.5 ng/ml was significantly associated with poor performance status (P<0.0001), B symptoms (P<0.0001), beta2-microglobulin levels > or = 3 mg/l (P<0.0001), serum albumin < or = 35 g/l (P=0.0001), C-reactive protein > 6 mg/l (P=0.0003), elevated (>20 pg/ml) IL-6 level (P<0.005), haemoglobin < or = 12 g/dl (P<0.005), and bulky tumour (P<0.001). In the whole group of 88 patients, both high TNFalpha and p55-R-TNF levels strongly predicted short progression-free survival (P<0.005 for both variables) and overall survival (P<0.001 and P<0.001 respectively). In multivariate analyses the elevation of p55-R-TNF retained a higher significance over the other variables and therefore improved the predictive value of the International Prognostic Index. This study suggests that elevated TNF gamma and p55-R-TNF levels have high correlation with other adverse prognostic factors in lymphoma patients and may predict a poor outcome.

Aged↗
PubMed1996

Fulminant 2-chlorodeoxyadenosine-related peripheral neuropathy in a patient with paraneoplastic neurological syndrome associated with lymphoma.

2-chlorodeoxyadenosine (2-CdA) has been demonstrated to be a neurotoxic agent when used at significantly greater doses than currently recommended for clinical use. In this report we describe a case of a 37-years-old man lymphoplasmacytoid malignant lymphoma and pre-existing paraneoplastic neurological syndrome who died of an apparent rapidly progressive sensorimotor peripheral neuropathy after completing treatment with two courses of low-doses of 2-CdA.

Adult↗
PubMed1995

2-Chlorodeoxyadenosine (2-CdA) in the treatment of patients with relapsed chronic lymphocytic leukemia.

This study attempts to characterize the response of patients with chronic lymphocytic leukemia (CLL) to the purine analog 2-chlorodeoxyadenosine (2-CdA). We have treated 10 patients with 2-CdA, at a dose 0.05-0.1 mg/kg/daily, for 7 days as a 2-hour infusion. Mean age was 54.6 years (range, 34-68 years). Mean time from diagnosis to treatment with 2-CdA was 37.0 months (range, 8-84 months). All the studied patients had received preliminary therapy consisting of other than 2-CdA chemotherapeutic regimens. Eight out of 10 patients had Rai stage III-IV disease. Four patients had Coombs positive hemolytic anemia before 2-CdA treatment. Seven patients responded to 2-CdA. Two complete remission (CR) and 5 partial remission (PR) were achieved. All patients but one with Coombs positive autoimmune positive hemolytic anemia achieve complete resolution of hemolysis. Severe neutropenia was frequent, and serious infections were noted in 20%, 43% and 50% of cases during the first, second and third course of 2-CdA, respectively. We conclude that 2-CdA is an effective agent in relapsed CLL patients, particularly in cases complicated by autoimmune hemolytic anemia.

Adult↗
PubMed1994

Influence of 2-chloro-2'-deoxyadenosine alone and in combination with cyclophosphamide or methotrexate on murine leukemia L1210.

The influence of 2-CdA administrated alone and in combination with CY or MTX on the survival time of mice bearing L1210 leukemia was investigated. 2-CdA treated mice lived longer than control animals. Survival times of mice receiving combined therapy of 2-CdA and CY were significantly prolonged as compared with mice treated with these agents separately. Survival times of mice treated with 2-CdA and MTX were not significantly prolonged, compared with animals receiving 2-CdA alone.

Animals↗
PubMed1994

[Antitumor immunotherapy].

In this article we present new immunotherapy modalities in clinical oncology. We review various forms of immunotherapy as well as their clinical effectiveness. At present, effects of cellular adoptive therapy are not satisfying. However, much hope is provided by monoclonal antibodies against tumor-associated antigens. Efficacy of monoclonal antibodies may be increased by their conjugation with various cytotoxic molecules. The number of indications for clinical applications of recombinant cytokines, mainly interferons, IL-2 and CSFs is growing. Genetic engineering creates new possibilities also in this case; modification of cytokine molecules as well as production of fusion proteins, i.e. design of quite novel protein structures that combine the function of two or more cytokines. It is very likely that antineoplastic immunotherapy might become, as is the case with gene therapy, one of future powerful tool against cancer.

Adjuvants, Immunologic↗
PubMed1994

[Thrombocytopenia during pregnancy].

Thrombocytopenia is the most frequent cause of acquired hemorrhagic diathesis. In addition to disorders that may cause thrombocytopenia in nonpregnant women, pregnant patients are at risk for the development of thrombocytopenia caused by syndromes such as preeclampsia, which are unique to pregnancy. In this review we discuss the major causes of thrombocytopenia that occur during pregnancy. These include the immune thrombocytopenic purpura, so called "gestational" thrombocytopenia, preeclampsia-associated thrombocytopenia, HELLP syndrome, thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome.

Female↗
PubMed1994

Treatment of chemotherapy-induced or idiopathic bone marrow aplasia with granulocyte colony-stimulating factor (G-CSF).

We report on our experience with the application of recombinant human granulocyte colony-stimulating factor (G-CSF, Neupogen, Hoffmann La Roche) in patients with various types of hematological malignancies, who had chemotherapy-induced myelosuppression, and in patients with idiopathic aplastic anemia. The administration of G-CSF was associated with marked increase in white blood cells counts (WBC) in twelve out of 14 treated patients. In one patient with aplastic anemia the WBC decreased rapidly to the initial value after the cessation of cytokine therapy. Significant increase of platelet number was observed in 6 patients. No toxicity was encountered with the hematopoietic growth factor therapy. Our study points to the fact that G-CSF have a stimulating effect on the regeneration of hematopoiesis, particularly within the granulopoietic compartment. The effect can be obtained both in a case of idiopathic- and cytostatic-dependent marrow aplasia.

Adolescent↗
PubMed1993

Application of hematopoietic growth factors (G-CSF and GM-CSF) in the treatment of chemotherapy-induced or idiopathic bone marrow failure.

Fifteen patients with various myeloid and lymphoid neoplasias after receiving highly myelotoxic chemotherapy were treated with a single daily dose of 5 micrograms/kg of GM-CSF. G-CSF at a daily dose of 5-8 micrograms/kg was used in four patients with severe pancytopenia in the course of acute or chronic lymphoid leukemia treated with cytotoxic agents, and in two patients with idiopathic aplastic anemia. The administration of cytokines was provided for 4-10 days GM-CSF increased the WBC in twelve out of fifteen patients, mainly because of an increase in the number of neutrophils. Six patients receiving GM-CSF demonstrated rapid platelet recoveries. The rapid increase of the WBC was observed in all G-CSF treated patients. In one patient with aplastic anemia the WBC/ANC decreased rapidly to the initial values after the cessation of the G-CSF therapy. Fast platelet recovery was seen in three patients treated with G-CSF.

Adolescent↗
PubMed1992

Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced myelosuppression.

We have studied the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in stimulating haematopoiesis of patients with chemotherapy-induced myelosuppression. Ten patients with various myeloid and lymphoid neoplasias were treated daily with a single subcutaneous dose of rhGM-CSF (5 micrograms/kg/day), for a period of 5-10 days, after receiving highly myelotoxic chemotherapy. The treatment increased the white blood cell count (WBC) in nine of ten patients, primarily because of an increase in the number of neutrophils. Increase in bone marrow myeloid precursor cells, and myeloid to erythroid cell rations accompanied the white-cell response. In spite of this, five patients demonstrated rapid platelet recoveries, and in two patients erythrocyte levels increased after GM-CSF treatment. No toxicity was encountered with the cytokine therapy. Although rhGM-CSF was shown to stimulate haematopoiesis in patients with chemotherapy-induced myelosuppression, additional studies are needed to assess whether the use of GM-CSF will reduce chemotherapy-associated morbidity and improve response rates and survival among patients with neoplasias.

Adolescent↗
PubMed1992

Antileukemic effects of recombinant human tumor necrosis factor alpha (rh-TNF alpha) with cyclophosphamide or methotrexate on leukemia L1210 and leukemia P388 in mice.

We investigated the influence of recombinant human tumor necrosis factor alpha (rh-TNF alpha) administered as a single agent or in combination with cyclophosphamide (CY) or methotrexate (MTX) on the survival time of mice inoculated with lymphoblastic leukemia L1210 or lymphatic leukemia P388. The median survival time of leukemia L1210 bearing mice treated with rh-TNF alpha at doses ranging from 200 to 275 g/kg in daily i.p. injections was longer than that of control animals. Groups of mice with leukemia L1210 receiving rh-TNF alpha combined with either MTX or CY lived longer than animals treated with these agents individually. We observed only slight prolongation of life of animals inoculated with this tumor and treated with rh-TNF alpha at dose of 800 micrograms/kg in four injections on 2, 4, 6 and 8 day of experiment, and no effect when rh-TNF alpha was administered at dose of 200 or 400 micrograms/kg at the same treatment regime. In contrast no significant differences in lifetime were obtained from either simultaneous or sequential treatment of mice bearing leukemia P388. Groups of mice with this tumor treated with rh-TNF alpha in conjunction with either MTX or CY lived longer than controls, or rh-TNF alpha singly treated mice, but their survivals were not significantly prolonged compared with mice receiving cytostatics alone.

Animals↗
PubMed1991

The influence of recombinant human tumor necrosis factor-alpha, alone and in combination with cyclophosphamide or methotrexate, on leukemia L1210 and normal hematopoiesis in mice.

We investigated the influence of rh-TNF administered as a single agent or in combination with CY or MTX on the survival time of mice inoculated with lymphoid leukemia L1210 and the effects of similar treatment on normal hematopoiesis in mice. The MST of rh-TNF--treated mice was longer than that of control animals. The longest survivals were observed in mice treated with 250 and 275 micrograms/kg of rh-TNF. Groups of mice receiving a combination of rh-TNF at doses of 225 or 250 micrograms/kg and MTX lived longer than animals treated with these agents separately. We observed the longest survival time of mice treated with combined administration of rh-TNF at a dose of 250 micrograms/kg and CY, but survival time was not significantly prolonged compared with mice receiving only CY. Additional studies were performed to examine the influence of rh-TNF administered as a single agent or in combination with toxic doses of CY or MTX on the number of granulocytes, lymphocytes, erythrocytes with hematocrit values and hemoglobin concentration, and platelets in peripheral blood, and the number of mononuclear cells as well as multipotential stem cells (CFU-GEMM) in bone marrow. Rh-TNF caused dose-dependent suppression of mononuclear cells and multipotential stem cells in bone marrow. The addition of MTX to rh-TNF caused no enhanced suppression of any of the above mentioned hematological parameters. In contrast, the addition of CY to rh-TNF suppressed erythrocytes and hematocrit values, as compared with rh-TNF alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Plasmablastic lymphoma in a patient with chronic lymphocytic leukemia heavily pretreated with cladribine (2-CdA): an unusual variant of Richter's syndrome.

Patients with chronic lymphocytic leukemia (CLL) may develop a large-cell transformation known as Richter's syndrome (RS). RS usually presents as diffuse large-cell lymphoma (DLCL) or its immunoblastic variant, and it can be recognized simultaneously with CLL or even 23 yr after its diagnosis. We describe an unusual case of CLL treated with cladribine (2-CdA) in whom DLCL of the plasmablastic type (PBL) developed 4 yr after CLL (Rai IV) diagnosis and 1.5 yr after the 10th course of 2-CdA treatment. Immmunologic, cytogenetic, and molecular studies performed at the time of CLL and PBL coappearance indicated that both tumors originated from different B-cell progenitors. Both malignancies were refractory to VAD (vincristine, doxorubicin, dexamethasone)-based chemotherapy, and only partial response was achieved with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) salvage treatment. However, the patient died 6 months after the occurrence of RS due to rapid progression of PBL. This is the first description of a CLL patient who developed an unusual plasmablastic variant of RS. Recently, the PBL entity has been identified among DLCL associated with the human immunodeficiency virus (HIV) infection. We suggest that in our CLL patient heavily pretreated with 2-CdA, PBL arose as a second clone due to the prolonged and severe state of the host's immunosuppression. Overall survival with current strategies is poor, and further insight into the natural history, biology, and treatment of PBL are needed.

Antineoplastic Agents↗
PubMedDate not supplied

Mechanisms of action of the tumor necrosis factor and lymphotoxin ligand-receptor system.

In the past few years, a number of experimental observations have provided more insight into the mechanisms of action of tumor necrosis factor (TNF)/lymphotoxin (LT) ligand-receptor system. This system consists of three ligands, TNF, LT alpha (LT alpha) and LT beta (LT beta), and three membrane-associated receptors, p55, p75 and LT beta-receptor (LT beta-R). Like TNF, LT alpha is a secreted protein which in solution forms a homotrimer molecule, with a conformation similar to that of TNF. LT beta is a transmembrane protein that provides the membrane anchor for the attachment to the cell surface of the heteromeric complex of LT alpha and LT beta. This complex retains a structure related to TNF and LT alpha homotrimers, with the homology regions interacting in a heterotypic fashion. The LT alpha 1:LT beta 2 heteromer has been found to be a predominant form of surface LT. The biological effects of TNF and LT alpha homotrimers are mediated by p55 and p75 receptors, while the heteromeric complex of LT alpha/LT beta transduces its cellular signal via LT beta-R. Membrane-associated receptor affinities as well as final biological effects of TNF/LT can be modulated by the influence of naturally occurring soluble receptors, derived from the cell surface by proteolytic cleavage. The multimerization of receptor cytoplasmic domains upon TNF/LT ligation is postulated to activate the intracellular signal-transduction pathways. One of them is the activation of phospholipase A2 (PL-A2) resulting in the production of arachidonic acid (AA) and other metabolites, including leukotriens, phosphatidycholine-specific phospholipase C (PC-PLC) with subsequent production of diacylglycerol (DAG) and activation of protein kinase C (PKC). As a third signaling pathway, TNF/LT employ the sphingomyelinase (SMase)-mediated hydrolysis of membrane sphingomyelin (SM) to ceramide. The final link in the TNF/LT signaling is activation of nuclear transcription factors, such as NF-kappa B, AP-1, interferon regulatory factors-1 and -2 (IRF-1, IRF-2), and NF-GMa. Since induction of AP-1, IRF-1 and IRF-2 as well as NF-GMa proceeds through translational event, the posttranslational TNF/LT-driven activation of NF-kappa B remains the only cellular event identified so far that serves as a direct target in their signaling cascade.

Animals↗