Biomedical subjects

T Robak

Publications and source records attributed to T Robak.

At least 37 records · Page 2Linked to original sources

PubMed1997

Autoimmune haemolytic anaemia in patients with chronic lymphocytic leukaemia treated with 2-chlorodeoxyadenosine (cladribine).

Autoimmune haemolytic anaemia (AIHA) is one of the major complications in chronic lymphocytic leukaemia (CLL). Treatment with alkylating agents and the adenosine analogue, fludarabine, might trigger the development of AIHA in CLL patients despite the reduction of leukaemic clone. The influence of 2-chlorodeoxyadenosine (2-CdA) on AIHA in patients with CLL is undefined so far. In a group of 114 patients treated at our clinics with this agent, AIHA with direct antiglobulin test (DAT) positively was observed in 25 (21.9%) patients. In 23 patients AIHA was noticed before the starting of 2-CdA and in 2 patients DAT became positive after 2-CdA treatment. In 6 patients the drug caused complete resolution of haemolysis and DAT became negative. Eight patients exhibited partial resolution of haemolysis with significant improvement in haemoglobin level but DAT test remained positive. In 11 patients there was no response to 2-CdA in relation to autoimmune haemolysis. Two patients with no previous history of haemolysis developed AIHA after 5 and 6 courses of 2-CdA therapy and their DAT became positive 1-2 months after the last course of the drug. One of them entered severe haemolytic crisis and severe thrombocytopenia and died because of haemorrhagy to the central nervous system. In the other patient AIHA was controlled by steroids and chlorambucil treatment. Our study indicates that 2-CdA may suppress autoimmunohaemolytic process in some patients with CLL and trigger the development of AIHA in others.

Adult↗

PubMed1997

2-Chlorodeoxyadenosine (cladribine)-related eosinophilia in patients with lymphoproliferative diseases.

Eosinophilia and allergic skin reactions are uncommon events after 2-chlorodoxyadenosine (2-CdA, cladribine) administration. A multicentre retrospective analysis of eosinophilia in 360 patients treated with 2-CdA for lymphoid malignancies has been made. B-cell chronic lymphocytic leukaemia (B-CLL) was diagnosed in 153, hairy cell leukaemia (HCL) in 68, low-grade non-Hodgkin's lymphoma (LGNHL) in 119, high-grade NHL in 2 and Waldenstrom's macroglobulinaemia (WM) in 18 patients. 2-CdA was administered at a dose 0.12 mg/kg/d in 2-h intravenous infusion for 5 consecutive d. The courses were repeated monthly. Patients with HCL received 1 cycle of 2-CdA, with NHL 2-6 (mean 3.5) cycles and with B-CLL 3-6 (mean 5) cycles. Twenty patients (5.5%), including 5 with HCL, 6 with LGNHL, 7 with B-CLL and 2 with WM, developed peripheral blood eosinophilia. The mean values of absolute eosinophil count were 0.78x10(9)/l (0.58-1.06x10(9)/l), 0.71x10(9)/l (0.52-1.3x10(9)/l), 85 (0.56-1.82x10(9)/l) and 0.75 (0.74-0.76x10(9)/l), respectively. Eosinophilia occurred in 13 patients after 1 course, in 4 after 2 courses, and in 5 after > or =3 courses of the therapy. In 17 cases it resolved spontaneously. Allergic skin lesions with pruritus were noticed in 3 patients simultaneously with an increase in eosinophil count. All of them required antihistaminic drugs and/or corticosteroids. One patient with B-CLL experienced repeated episodes of eosinophilia. The highest incidence of 2-CdA-induced eosinophilia was noticed in patients with MW (11.1%) and HCL (7.4%) who received only 1 cycle of this drug and entered a complete remission. This side effect was less frequently observed in LGNHL and B-CLL, i.e. in 5.0% and 4.6% of cases, respectively. The mechanism of 2-CdA-induced eosinophilia is not clear. It has been postulated that massive tumour cell lysis may trigger a release of IL-5 and probably other cytokines. The allergic mechanism of 2-CdA-induced eosinophilia is also possible, especially in patients with simultaneous skin reactions.

2-Chloroadenosine↗

PubMed1997

Hairy cell leukemia-variant treated with 2-chlorodeoxyadenosine--a report of three cases.

Three patients with B-prolymphocytic variant of HCL (HCL-V) were treated with a chlorinated purine analogue, 2-chlorodeoxyadenosine, at a daily dosage of 0.12 mg/kg in 2-hour intravenous infusion for 5 consecutive days. Partial remission was achieved in only 1 patient, who relapsed after 6 months. Two other patients did not respond to the treatment. HCL-V is a distinct clinicopathological entity which seems to be resistant to various therapeutic modalities. However, further observations are necessary in order to establish the efficacy of 2-CdA in the treatment of HCL-V.

Aged↗

PubMed1997

Circulating interleukin-6 type cytokines in patients with systemic lupus erythematosus.

We investigated the serum concentration of interleukin-6 (IL-6) and the IL-6 family of cytokines (leukemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF) using an enzyme-linked immunosorbent assay (ELISA) in 64 patients with systemic lupus erythematosus (SLE) and 15 healthy controls. We also examined a possible association between the serum levels of these proteins and SLE activity as well as correlations between the IL-6 concentration and the levels of LIF, OSM and CNTF. IL-6 was detectable in all 64 patients with SLE and normal individuals, and the level of this cytokine was significantly higher in patients than in the control group (p < 0.002 ). LIF, OSM and CNTF were detectable in 9 (14.1%), 6 (9.4%) and 51 (78%) patients, respectively, and undetectable in the majority of healthy individuals. We found positive correlation between the serum concentrations of IL-6, LIF, OSM and CNTF and SLE activity. IL-6 and OSM serum levels were also correlated but not IL-6 and LIF or CNTF. In conclusion, an increase in the serum levels of IL-6 and, to a lesser extent of LIF, OSM and CNTF concentrations may be useful markers for SLE activity.

Adolescent↗

PubMed1997

2-chlorodeoxyadenosine (cladribine) induced allergic cutaneous reactions with eosinophilia in a patient with B-cell chronic lymphocytic leukemia.

We present a 68-year old patient with B-cell chronic lymphocytic leukemia (CLL) treated with 2-chlorodeoxyadenosine (2-CdA). This is the first reported patient with B-CLL in whom skin lesions and eosinophilia were observed simultaneously. The most frequent side effect of this drug is myelosuppression with pancytopenia. So far, there have been few reports of cases where either skin reactions or eosinophilia, occurring separately, were observed as side effects from 2-CdA treatment.

Aged↗

PubMed1997

[Biology and clinical pharmacology of tumor necrosis factor alpha].

Tumor necrosis factor-alpha (TNF-alpha) or cachectin is a cytokine with multiple biological actions. TNF-alpha has been implicated as an important mediator of inflammation and as a key element of immune effector cell regulation. This macrophage product has been biochemically characterized and its protein structure defined by molecular cloning of the TNF gene. The availability of human TNF-alpha has allowed the initiation of clinical investigations into the antitumor properties of this factor.

Cloning, Molecular↗

PubMed1997

[Cytokines in rheumatoid arthritis].

In this review we have examined the role of a variety cytokines in the pathogenesis of rheumatoid arthritis (RA) and their possible applications in the treatment of this disease. Cytokines are small protein molecules, released by activated cells which function as chemical messengers between cells of the immune, inflammatory and other systems. The studies using isolated cells from RA synovial membranes indicate that the vast majority of known cytokines are found in RA synovial tissue. These include IL-1, TNF alpha, IL-6, IL-8, TGF beta, GM-CSF and others. TNF alpha and IL-1 are important, "pivotal" molecules in the disease process. TNF alpha has been detected in the serum and synovial fluid of patients with RA, suggesting an important contribution of this cytokine to the development of arthritis. Clinically, TNF-alpha has been also associated with markers of rheumatoid disease activity. Rheumatoid synovial tissue synthesizes large amounts of both forms of IL-1 (IL-1 alpha and IL-1 beta) in vitro. IL-1 can exert a variety of systemic effects, including induction of fever and synthesis of acute phase proteins. It also induces local joint effects mediating production of fibroblast fibronectin and tissue collagenase. IL-6 is found in greater quantities in the synovial fluids from patients with RA compared to osteoarthritis. Synovial fluid IL-6 levels correlate with local IgM rheumatoid factor and systemic acute phase protein production. Chemokines, including IL-8, have potent chemotactic activity for cells of the immune system. IL-8 not only participates in the inflammatory phase of RA, but also participates in the vasculoproliferative phase of this disease. Recent data on the cytokine profile in RA implies that alternative treatment strategies should be considered. Potential approaches for modifying the cytokine network include inhibition of cytokine production or their action, inhibition of signal transduction and administration of suppressive cytokines.

Arthritis, Rheumatoid↗

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↗

PubMed1996

2-chlorodeoxyadenosine (2-CdA) in 2-hour versus 24-hour intravenous infusion in the treatment of patients with hairy cell leukemia.

Forty one patients with hairy cell leukemia (HCL) were treated with 2-chloro-deoxyadenosine (2-CdA) administered in various schedules. Complete remission (CR) was achieved in 31 (76%) patients and partial remission (PR) in 9 (22%). The mean duration of remission (CR + PR) was 25.2 months (range 9-45 months). One patient did not respond to therapy. Twelve out of 16 patients (75%) achieved CR after 5-day intravenous infusions of 2-CdA and 19 out of 25 patients (76%) after 7-day courses. In 19 out of 23 patients (82.6%) CR was achieved after intermittent 2-hour infusions and in 12 out of 18 (66.7%) after continuous 24-hour infusion. The differences were not statistically significant. Side effects of 2-CdA were similar in both groups except for infections, which were less frequently observed in the group treated for 5 days. The results of our study suggest that 2-CdA can be effectively administered to patients with HCL using 5-day courses and a 2-hour daily infusion.

Adult↗

PubMed1996

Intermittent 2-hour intravenous infusions of 2-chlorodeoxyadenosine in the treatment of 110 patients with refractory or previously untreated B-cell chronic lymphocytic leukemia.

The purpose of our study was to determine the effectiveness of 2-CdA in 2-hour intravenous infusions in the treatment of B-CLL. One hundred and ten patients with B-CLL received 1 to 10 courses of 2-CdA (median 2.5) at a dosage of 0.12 mg/kg daily for 5 consecutive days. Eighteen of them were untreated and 92 relapsed or became refractory to previous therapeutic modalities. Complete remission (CR) was achieved in 8 (7.3%) and partial remission (PR) in 35 patients (31.8%) giving an overall response rate of 39.1%. In 3 patients, cross-resistance to fludarabine was noticed. Toxic effects of 2-CdA were more frequently observed in previously treated patients. Hemorrhagic complications due to drug-induced thrombocytopenia were noticed in 25 (22.7%) and severe infections including sepsis in 14 (12.7%) patients.

Adult↗

PubMed1996

The comparison of 2-chlorodeoxyadenosine (2-Cd A) in combination with interferon alpha (IFN alpha) or interferon gamma (IFN gamma) on granulocyte-macrophage progenitor cells (CFU-GM) and clonogenic blasts in (CFU-L) in vitro cultures.

In the present in vitro study we investigated the influence of 2-chlorodeoxyadenosine (2-CdA) and interferon gamma (IFNgamma) on the clonal growth of granulocyte macrophage progenitor (CFU-GM) cells from 10 normal individuals and from 10 patients with chronic myeloid leukemia (CML) and on CFU-L blasts from 10 patients with acute myeloid leukemia (AML). 2-CdA was added to the culture medium at 20nM/l, 40nM/l and 80nM/l concentrations and IFNgamma at concentrations of 10(2)U/ml, 10(3)U/ml and 10(4)U/ml. Both agents were used alone and in combination with these different concentrations. We observed a decrease in the number of colonies formed by CML CFU-GM as well as by AML CFU-L in a dose-dependent manner. The drugs used alone inhibited to a higher degree the growth of CML than of normal CFU-GM progenitors. 2-CdA and IFN gamma showed the greatest additive effect on the growth of CFU-L blasts at the concentrations of 80nM/l and 10(4)U/ml, respectively. We compared our results with previous in vitro studies in which we have demonstrated the synergistic inhibitory effect of 2-CdA and IFN alpha on both normal and leukemic hematopoiesis. We suggest that the greatest inhibitory effect is observed when 2-CdA and IFN alpha at the highest concentration are added together to the culture of AML CFU-L blasts.

Acute Disease↗

PubMed1996

[Treatment of multiple myeloma--present status and perspectives].

Multiple myeloma (MM) remains incurable. Despite many chemotherapy programs for large numbers of patients, there has been little improvement in outcome during the past 25 years. For many years, intermittent courses of melphalan and prednisone have represented the standard chemotherapy for newly diagnosed symptomatic MM. Many other drug combinations have been assessed, including regimens using multiple alkylating agents, and programs with vincristine, or an anthracycline, and have failed to show any superiority to melphalan-prednisone. Interferon alpha (IFN alpha) inhibits plasma cell growth and has induced responses in approximately 15% of previously untreated patients. This cytokine may have a role when used in those patients who have reached a good "plateau phase" with low tumor burden at the end of a chemotherapeutic program or after a transplantation procedure. The results of myeloablative therapy with allogenic or autologous marrow transplantation are promising and suggest possibility of a cure in some patients. Important problem in the management of MM patients is the treatment of complications, especially bone destruction, hypercalcemia, anemia and infections. Experimental modalities, especially immunotherapy, hold promise for use in humans and may also provide further insights into the pathogenesis of MM.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

[Monoclonal antibodies in diagnosis of acute leukemias].

Immunophenotyping has become an essential component for the study of acute myeloblastic (AML) and lymphoblastic (ALL) leukaemias. The recent development of highly specific monoclonal antibodies (Mc Ab) to differentiation antigens (CD) of haematopoetic cells have made it readily available to clinical laboratories in most major hospitals. Immunophenotyping complements standard morphology by providing information on lineage, stage of differentiation and clonality. In addition some of the flow cytometry findings have independent prognostic significance. Monoclonal antibodies useful in defining lineage (B-cell versus T-cell) and stages of differentiation of ALL. It can be also used in identifying characteristic feature of AML and aiding in lineage determination in acute leukaemias that are morphologically undifferentiated. Surface immunophenotyping is especially helpful for recognizing mixed lineage acute leukaemia and diagnosing certain rare entities such as erythroleukaemia (M6), acute megakaryocytic leukaemia (M7) and minimally differentiation acute myeloid leukaemia.

Antibodies, Monoclonal↗

PubMed1996

Cytokines in the treatment of hematological disorders: recent progress and perspectives.

Cytokines are involved in hematopoiesis by regulating proliferation, differentiation and cellular functions of various lineages of hematopoietic cells. There is an increasing range of clinical conditions in which cytokines are involved as therapeutic agents. One of the most advanced and successful applications is the stimulation of hematopoiesis by the colony stimulating factors (GM-CSF and G-CSF) and erythropoietin. Hematopoietic growth factors are effective in accelerating recovery from neutropenia after chemotherapy and bone marrow transplantation and in reducing incidence of infections. Interferon alpha (IFN-alpha) proved a useful therapeutic agent for chronic myelogenous and hairy cell leukemias as well as for multiple myeloma and non-Hodgkin's lymphoma. Interleukin 2 is the only cytokine apart from IFN-alpha accepted as antineoplastic agent. It may be useful as adjuvant therapy in the hematological malignancies. It may be supposed that in the near future new recombinant cytokines will be introduced in the treatment of blood diseases.

Colony-Stimulating Factors↗

PubMed1996

[Clinical pharmacology of 2-chlorodeoxyadenosine (Cladribine)].

2-chlorodeoxyadenosine (2-CdA) is a simple nucleoside derived from deoxyadenosine by substituting chloride for hydrogen in 2' position of the purine ring, which renders it resistant to degradation by adenosine deaminase. Many studies have revealed high efficiency of 2-CdA in the treatment of lymphoid malignancies. Hairy cell leukemia is notably responsive to 2-CdA, with 85% of patients entering complete remissions after treatment of this drug.

Animals↗

PubMed1996

[Cytokines in systemic lupus erythematosus].

In systemic lupus erythematosus (SLE) is a disease characterized by B cell hyperactivity, autoantibody production and immune complex deposition in vital organs. To explain the mechanisms responsible for immune dysregulation in SLE cytokines have received increasing attention. This review has discussed a number of cytokines which appear to be involved in lupus pathogenesis. Recent studies have shown that disease activity and the main symptoms of SLE are associated with increasing serum levels of cytokines such as interleukin-(IL)-1, IL-2, IL-6, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (THF-alpha). Constitutive expression and in vitro induction of specific cytokines are also aberrant in SLE. The presence of IL-1, IL-6 and IFN-gamma in involved kidneys suggests that they have local pathogenic effects. Moreover IFN-gamma, IL-6 and IL-1 modulate spontaneous IgG production by SLE mononuclear cells. During the next several years, the exact role of these cytokine in the pathogenesis of lupus become more fully elucidated.

Animals↗

PubMed1996

[Thrombotic thrombocytopenic purpura successfully treated with plasma exchange].

This study is a presentation of a case of a 43 year old woman suffering from thrombotic thrombocytopenic purpura, the clinical course of which was complicated and in which no improvement was observed after fresh frozen plasma transfusions and treatment with steroids. The complete clinical and haematological remission was obtained only after intensive plasma exchange by therapeutical plasmapheresis.

Adult↗

PubMed1996

Treatment of drug-induced agranulocytosis with colony stimulating factors (G-CSF or GM-CSF).

The application of granulocyte-macrophage and granulocyte colony stimulation factors (GM-CSF and G-CSF) has been progressively increased in the treatment of patients with agranulocytosis. The aim of our study was to compare the time of neutrophil recovery in patients with severe agranulocytosis treated with G-CSF or GM-CSF and the historical control group. We have studied 6 patients with agranulocytosis treated with stimulating factors and 7 patients in historical control group. Most of the patients have been exposed to thiamazole or non-steroid antiinflammatory drugs. Our results demonstrate that patients receiving colony stimulating factor have a significantly shorter period of recovery (the mean time 8.7 +/- 1.98 days) than the historical control group (the mean time 11.0 +/- 2.24 days). We observed also a shorter time of antibiotico-therapy and hospitalization in the group of patients treated with colony stimulating factor.

Adult↗