Search PubMed⌕ Search

Biomedical subjects

J Hansz

Publications and source records attributed to J Hansz.

At least 19 recordsLinked to original sources
PubMed1999

2-chlorodeoxyadenosine (cladribine) in the treatment of hairy cell leukemia and hairy cell leukemia variant: 7-year experience in Poland.

Between January 1991 and December 1997, 103 patients, 97 with typical hairy cell leukemia (HCL) and 6 with HCL-variant (HCL-V) were treated with 2-chlorodeoxyadenosine (2-CdA) given as 2-h infusion for 5 consecutive d at a daily dose 0.12 mg/kg. To our knowledge this is the largest cohort of HCL patients treated with this type of regimen. Median follow-up amounted to 36 months. Fifty-six of 97 patients with typical HCL were newly diagnosed and 41 were relapsed after previous treatment. Splenectomy as a first-line therapy was performed in 23 patients and 18 remaining patients received prednisone, chlorambucil or interferon-alpha (IFN-alpha) alone or in combinations. Seventy-five (77.3%) patients entered CR and 18 (18.6%) achieved PR, giving an overall response rate of 95.9%. The mean time of first CR duration amounting to 32 months (range 3-72) did not correlate to the number of 2-CdA cycles. 2-CdA was equally effective in treatment of newly diagnosed patients and patients who relapsed after previous therapeutic procedures. Relapse of the disease occurred in 20 of 75 patients who achieved CR after 2-CdA and was usually manifested by very discrete changes in peripheral blood counts (neutropenia and/or relative lymphocytosis). The mean progression-free survival (PFS) time in this group was 37.4 (range 10-66) months. Ten of 20 relapsed patients were retreated with 2-CdA given an identical course to the first one. Seven patients entered second CR lasting 19+ (range 8-47) months and 3 experienced PR. This confirms the previous observations that 2-CdA gives no resistance to leukemic clone. Ten remaining patients have not required retreatment so far and remain in a good clinical and hematological state. The results of HCL-V treatment with 2-CdA were poor. Only 2 patients achieved PR and 4 patients did not respond to this drug. Seven patients (5 with typical HCL and 2 with HCL-V) died, 3 of causes unrelated to the disease. Second neoplasms were noted in 5 patients. 2-CdA-related side effects resulted mainly from myelosuppression and infectious complications. In conclusion we confirm the effectiveness of 2-CdA in inducing CR in patients with typical HCL, but this drug is unable to completely eradicate the leukemic clone which results in the relapse of the disease. The real incidence of the relapse rate may be underestimated unless bone marrow biopsy is performed. The results of our study indicate that a 2-h infusion of 2-CdA in HCL patients is at least as effective as a 24-h infusion but more convenient to the patients, and may be given on an outpatient basis.

Adult↗
PubMed1997

The effect of 2-h infusion of 2-chlorodeoxyadenosine (cladribine) with prednisone in previously untreated B-cell chronic lymphocytic leukaemia.

2-Chlorodeoxyadenosine (2-CdA) is a new antimetabolite chemotherapeutic agent active in indolent lymphoid malignancies. In this retrospective study, 69 previously untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL) were treated with 2-CdA administered at a dose of 0.12 mg/kg daily in 2-h intravenous infusion for 5 consecutive days. 45 patients also received prednisone 30 mg/m2 orally each day for 5 days starting with 2-CdA courses. Patients were given 2-6 courses (mean 4.6) of 2-CdA repeated usually at monthly intervals. If a complete response was achieved, no further 2-CdA courses were administered. Guidelines for response were those developed by the NCI Sponsored Working Group. Complete response (CR) was achieved in 26 (38%) and partial response (PR) in 27 (39%) cases, giving an overall response rate of 77%. 16 patients (23%) did not respond to 2-CdA. In the subgroup of 45 patients receiving 2-CdA with prednisone, CR was obtained in 15 (33%) and PR in 20 (44%) patients giving an overall response rate of 78%. CR was achieved in 11 (46%) out of 24 patients treated only with 2-CdA and in 7 cases (29%) PR was observed, giving an objective response rate of 75%. The differences between both subgroups were not statistically significant. However, we observed a relationship between the response and the number of courses of 2-CdA given in patients receiving and those not receiving prednisone. In the subgroup receiving 2-CdA with prednisone, an earlier response to 2-CdA was observed. In this group a response was achieved in 9 (20%) patients after two courses of 2-CdA and in 18 (40%) after four courses. In the subgroup receiving only 2-CdA, 17 (71%) responses were obtained after six cycles.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed1995

[Contemporary possibilities of prognosis in myelodysplastic syndromes].

Myelodysplastic syndromes (MDS) comprise a heterogenous group of closely related, acquired stem cell disorders. Various patterns of clinical evolution have been observed in patients with different subtypes according to the FAB (French-American-British) criteria. The marked differences in clinical outcome among MDS patients have encouraged us to search the alternative variables for predicting leukemic transformation and survival. During the past 10 years different prognostic scoring systems based on age combined with blood and bone marrow parameters have been described. This has enabled the identification of patients with better and worse prognosis among different MDS types. Additionally, studies of cytogenic patterns in MDS patients and widespread availability of bone marrow histological specimens extended the possibility of prognosis in this disease. Similarly, the in vitro culture results of hematopoietic cells using growth and differentiation factors have given very promising results. The high prevalence of RAS mutation in patients with MDS has been defined, but its clinical usefulness is under discussion.

Bone Marrow↗
PubMed1995

[T lymphocytes from patients with Hodgkin's disease suppress erythroid progenitor growth from autologous marrow].

The effect of peripheral blood T lymphocytes from 42 patients with advanced Hodgkin's disease (grade III and IV) on the autologous marrow erythroid colony formation was studied in diffusion chamber culture. It was found, that unfractionated T lymphocytes suppress the BFU-E--(burst forming unit erythroid) and CFU-E--(colony forming unit erythroid)--derived colony formation by releasing an inhibitory activity. The suppression of colony formation was noted already at 0.25 x 10(5) cell concentration. In experiments with 0.5 x 10(5) and 1.0 x 10(5) T cells the inhibitory effect was increased. Subsequently it was shown, that this inhibition was generated by radioresistant, CD8+ and HLA-DR- subset of T cells. In control experiments, T lymphocytes from healthy subjects had no influence on the erythroid colony formation.

Adolescent↗
PubMed1995

[Empiric antibiotic therapy for treatment of infection in patients with severe neutropenia].

Infection is the most frequent cause of death in patients with severe neutropenia. Fever and other signs of infection with neutrophil count below 0.5 G/L require an early and rapid treatment--the empiric antibiotic therapy. This treatment comprises various combinations of bactericidal broad-spectrum antibiotics such as ureidopenicillins, cephalosporins, quinolones and aminoglycosides. If defervescence is not attained within 3 days, modification of the treatment scheme should be done. The addition of vancomycin or teicoplanin, antibiotics active against Gram + cocci, and changing of the beta-lactams should be considered. In the case of persistent microbiologically not recognized infection after 7 days of therapy, empiric antimycotic treatment with amphotericin B is indicated. Duration of the empiric antibiotic therapy is dependent on the granulocyte recovery and the resolution of infection.

Anti-Bacterial Agents↗
PubMed1995

[Cytokines modify 2-chlorodeoxyadenosine (2-CdA) toxicity in acute myeloid leukemia clonogenic cells (L-CFU)].

We investigated the effect of 2-chlorodeoxyadenosine (2-CdA) in concentrations: 10, 20, 50, 100, 150 and 300 nM/l on the clonal growth of acute myeloid leukemia clonogenic cells (L-CFU), after 24 h preincubation with recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha) or interleukin 3 (IL-3) and in conditioned medium obtained from phytohemagglutin stimulated lymphocytes (PHA-LCM). 2-CdA in concentration 300 nM/l significantly reduced (30%) the number of blast colonies in comparison with control experiments (p < 0.05). After preincubation of blast cells with cytokines (20% PHA-LCM, or GM-CSF--100 ng/ml, or IL-3--5 U/ml) an increase of 2-CdA cytotoxic effect on L-CFU clonal growth was observed. In experiments with 2-CdA (300 nM/l) and GM-CSF or PHA-LCM or IL-3 the number of blast colonies was reduced in 70%, 50% and 50%, respectively, (p < 0.05). Preincubation of blasts with IL-1, did not effect the 2-CdA--induced growth inhibition of CFU.

Cell Division↗
PubMed1995

[Effect of 2-chlorodeoxyadenosine, arabinoside cytosine and doxorubicin on acute myeloid leukemia clonogenic cell proliferation].

We examined the influence of 2-chlorodeoxyadenosine (2-CDA) in concentration 300 nM/l alone and in combination with cytosine arabinoside (ara-C; 10(-7) M/l and doxorubicine (drb; 1 microgram/ml) on the proliferation of acute myeloid leukemia (AML) clonogenic cells (L-CFU) in agar/liquid culture system. After preincubation of blast cells with 2-CDA or ara-C as a single agent the number of colonies was reduced, reaching 70% of control (p < 0.05). Exposure of AML blasts to drb resulted in a greater reduction of L-CFU proliferation than in experiments with 2-CDA or ara-C alone (p < 0.05). Coadministration of 2-CDA in conjunction with ara-C or drb, and additionally with ara-C and drb caused the inhibition of L-CFU growth in comparison with control experiments by 52%, 78% and 61%, respectively (p < 0.05). In further experiments we studied the effect of ara-C and drb together with 2-CDA in different concentrations (20, 100 or 300 nM/l). After preincubation with 2-CDA in concentration 20 nM/l no change in blast colony formation was observed in relation to controls which comprised ara-C and drb only (p < 0.05). The increase of 2-CDA concentration to 100 or 300 nM/l in combination with ara-C and drb significantly reduced the growth of AML clonogenic cells (p < 0.05). The greatest, 90%, inhibition of L-CFU proliferation was observed after the exposure of blast cells to ara-C, drb and 2-CDA in concentration 300 nM/l (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Current approaches of treatment for myelodysplastic syndrome (MDS)].

The number of treatment modalities for patients with myelodysplastic syndromes (MDS) has increased, but curative options are still limited. For the majority of patients with low risk there is no standard therapy other than appropriate supportive care. In selected patients anabolic steroids, differentiation inducers such as cis-retinoic acid (RA), interferon alpha or gamma have been claimed to be active. Application of growth factors such as granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), and interleukin 3 (IL-3) improves neutrophil count and diminishes frequency of infectious complications, but responses are incomplete and of short duration. Preliminary results of erythropoietin (Epo) applied in therapeutical doses are disappointing, giving an improvement in 15-20% patients. Epo in large doses produces greater and sustained responses, but this treatment is too expensive. Low-dose cytosine arabinoside (Ara-C) induces a response rate in 25-30% patients, however, no survival advantage has been obtained. Addition of RA or GM-CSF produces response rates comparable to Ara-C alone, but also with no prolongation in survival. Bone marrow transplantation (BMT) offers a good chance of long-term disease-free survival if is performed in an early stage of the disease or in complete remission, however, it is limited to patients below 55 years with an HLA-identical donor. Relatively young, high risk patients not eligible for allogeneic BMT should be considered for treatment with intensive polychemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Activated lymphocytes in the marrow cell suspension decrease the mafosfamide-induced CFU-GM cytotoxicity.

The aim of the study was to assess whether other cells, besides erythrocytes, may influence the cytotoxic effect of mafosfamide (maf) during ex vivo bone marrow purging from residual tumor cells before autologous transplantation. It was shown that the presence of normal granulocytes, blast cells from acute myeloid leukemia-patients (AML) and lymphoma cells from patients with chronic lymphocytic leukemia (CLL) during maf incubation did not change the maf-induced growth inhibition of CFU-GM. Similar observation was made in experiments with resting lymphocytes. However, when phytohaemagglutinin- and pokeweed mitogen-preincubated lymphocytes were present in the marrow cell suspension, significant decline of the maf-related CFU-GM cytotoxicity was observed. These results suggest that besides erythrocytes also the activated lymphocytes in the marrow mononuclear suspension may change the final effect of maf purging.

Antineoplastic Agents↗
PubMed1994

[Treatment outcome of advanced Hodgkin's disease based on using an alternating program ChLVPP (chlorambucil, vinblastine, procarbazine, prednisone) and ABV (doxorubicin, bleomycin, vinblastine)].

Twenty nine patients (7 women, 22 men) with III and IV stage of Hodgkin's disease were treated according to alternating programme ChLVPP/ABV. The results were evaluated in 27 patients. Complete remission was obtained in 41% (11 patients), partial remission in 22% (6 patients). Applied treatment revealed a relatively small toxicity.

Adult↗
PubMed1994

[Use of cytokines in allogeneic bone marrow transplantation].

Presently the following cytokines are applied in allogeneic bone marrow transplantation: GM-CSF (granulocyte/macrophage colony stimulating factor), G-CSF (granulocyte colony stimulating factor), interleukin 3 (IL-3) and interferon-alfa (IFN-alfa). GM-CSF and G-CSF applied after bone marrow transplantation accelerate the granulopoietic reconstitution, whereas IL-3 in addition exerts an effect on platelet recovery. These growth factors show also high efficiency in the therapy of graft failure. INF-alfa is used early after allogeneic bone marrow transplantation in patients with hig risk for relapse. This cytokin is also very effective as single therapy or together with marrow donor leukocyte infusions for the treatment of patients with chronic myeloid leukemia in relapse after allogeneic bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1993

[Production of activity stimulating an increase of clonal granulocytic precursors by normal B lymphocytes under the influence of various mitogens].

The effect of mitogen-stimulated (concanavalin A, Con A; phytohemagglutinin, PHA; pokeweed mitogen, PWM; Staphylococcus aureus Cowan I, SAC I) normal B lymphocytes on the clonal proliferation of granulocytic progenitors from marrow of healthy subjects (CFU-dG) was studied in diffusion chamber culture. PWM-, SAC- and Con A-stimulated B lymphocytes produced an humoral activity that increased the CFU-dG-derived colony formation. The highest growth-stimulating effect was induced by SAC I-preincubated B lymphocytes and to a lesser degree by PWM- or Con A-stimulated B cells. In contrast, PHA-preincubated and unstimulated B lymphocytes revealed no effect on the CFU-dG proliferation.

B-Lymphocytes↗
PubMed1992

Interferon-gamma-mediated suppression of erythroid progenitor growth by a HLA-DR- and CD4-positive subset of T lymphocytes in acute myeloid leukemia.

In this study, we examined the effects of peripheral blood T lymphocytes from patients with acute myeloid leukemia (AML) on marrow-derived erythroid progenitors (BFU-DE and CFU-DE) growth in an in vivo culture by using the plasma clot diffusion chamber (DC) technique. The application of double-compartment chambers (each compartment separated by a membrane filter) makes the investigations of humoral effects of T lymphocytes upon marrow erythroid progenitors proliferation possible. T lymphocytes of AML-patients in the absence of a statistically significant number of monocytes suppressed the growth of BFU-DE and CFU-DE from T lymphocyte- and adherent cell-depleted marrows. The inhibition ability was restricted to the CD4-positive enriched fraction obtained from T cells by using the negative selection technique. In contrast, the CD8-positive enriched fraction had no effect on erythroid colony formation. Autologous and allogeneic BFU-DE and CFU-DE were similarly affected by the CD4-positive T cells. Treatment of T cells with monoclonal antibodies against HLA-DR before cocultures, completely abrogated the suppression of BFU-DE and CFU-DE-derived colony formation. Suppressive activity detected in the CD4-positive T cells was also totally abolished by treatment with anti-interferon-gamma antibodies; whereas the inhibition was retained after 30 Gy radiation. Under these experimental conditions, resting T lymphocytes from healthy subjects did not affect the erythroid colony formation. Our data show that in AML-patients, a circulating HLA-DR-positive, less radiosensitive subset within the CD4-positive T cells is capable of inducing an interferon-gamma-mediated suppression of erythropoiesis, at least in DC culture.

CD4-Positive T-Lymphocytes↗
PubMed1992

[Clonal proliferation of less mature granulocytic precursors (CFU-dG) under the influence of neoplastic B lymphocytes in low grade non-hodgkin's lymphomas].

The effect of peripheral blood lymphoma B cells from low grade malignancy non-Hodgkin's lymphoma patients (Kiel classification: lymphocytic, centrocytic, centroblastic-centrocytic lymphomas) on clonal growth of normal marrow granulocytic precursors (CFU-dG) was studied. Using in vivo diffusion chamber culture method it was shown that all the tested lymphoma cells enhanced the CFU-dG growth by releasing humoral factor(s). The effect of stimulation was cell-concentration and cell-source dependent. The colony stimulating activity produced by centrocytic lymphoma cells had higher potency than that released by centroblastic-centrocytic lymphoma cells, whereas lymphocytic lymphoma cells showed the lowest ability to generate the CFU-dG growth-promoting activity (p < 0.01). It was shown that the CFU-dG growth enhancing effect was independent of marrow-derived macrophages and T lymphocytes (p > 0.05). Normal peripheral blood B lymphocytes used as a control did not show any substantial effect on the granulocytic precursors proliferation.

B-Lymphocytes↗