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Biomedical subjects

K Kuliczkowski

Publications and source records attributed to K Kuliczkowski.

At least 37 records · Page 2Linked to original sources
PubMed2002

The treatment of acute myeloid leukemia with mitoxantrone, etoposide and low-dose cytarabine in elderly patients - a report of Polish Acute Leukemia Group (PALG) phase II study.

The common dilemma in the treatment of elderly patients with acute myeloid leukemia (AML) is whether to use intensive myelosuppresive therapy with higher risk of treatment related mortality (TRM), but a chance for complete remission (CR), or to treat less intensively in order to prolong survival time with a better quality of life. The aim of this prospective, phase II study was to assess the efficacy and toxicity of low dose combination induction treatment consisted of cytarabine at a dose of 10 mg/m2 every 12 h s.c. for 7 days, VP-16 at a dose of 100 mg/day p.o. for 7 days and mitoxantrone at a dose of 6 mg/m2 i.v daily on days 1-3. Two induction courses were planned. In the group of 44 patients 12 (27%) achieved CR, 4 (9%) patients were in PR and there were 9 (20%) early deaths (ED). Age, performance status, preceding myelodysplastic syndrome, karyotype, WBC and % of blasts in bone marrow were not significant prognostic factors for CR probability. The following initial factors appeared to be related to a shorter duration of survival time from the start of treatment: age >70 (p<0.03), poor performance status (p<0.03), and % of BM blasts 50 (p<0.05). We conclude that, despite promising results in the pilot study the efficacy of this induction treatment is not better than the efficacy of other regimens. The hematological toxicity of this treatment seems to be comparable with "3+7" regimen.

Acute Disease↗
PubMed2001

p16(INK4a) and p15(INK4b) gene methylations in plasma cells from monoclonal gammopathy of undetermined significance.

p15(INK4b) and p16(INK4a) proteins are cell cycle regulators involved in the inhibition of G1 phase progression. High frequency of methylation of both genes has been reported in multiple myeloma (MM), but it remains to be determined how and when these alterations contribute to tumorigenesis. Monoclonal gammopathy of undetermined significance (MGUS) represents an early disease stage in a fraction of MMs. Plasma cells from 33 patients with MGUS and 33 patients with MM were isolated and analyzed for p15(INK4b) and p16(INK4a) methylation by methylation-specific polymerase chain reaction. Selective methylation was found in 19% for p16(INK4a), 36% for p15(INK4b), and 6.5% for both genes in MGUS, and frequencies were similar in MM suggesting that methylation of these genes is an early event, not associated with transition from MGUS to MM. p15(INK4b) and p16(INK4a) gene methylation might contribute to immortalization of plasma cells rather than malignant transformation in the natural history of MM.

Adult↗
PubMed2001

Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia.

The objective of the study was to determine the effectiveness and the toxicity of a combined chemotherapy consisting of cladribine (2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of previously untreated B cell chronic lymphocytic leukemia (B-CLL). From August 1998 to December 2000 2-CdA was administered at a dosage of 0.12 mg/kg for 3 (CMC3) or 5 (CMC5) consecutive days, mitoxantrone at 10 mg/m2 on day 1 and cyclophosphamide at 650 mg/m2 on day 1 to 62 patients with advanced or progressive B-CLL. The cycles were repeated at 4 week intervals or longer if severe myelosuppression occurred. Twenty patients received CMC5 and 42 patients CMC3. Within the analyzed group an overall response (OR) rate (CR+PR) of 64.5% (95% CI: 52.7-76.3%) was reported, including 29.0% CR. There was no difference in the CR rate between the patients treated with CMC5 (30%) and CMC3 (28.6%) (P = 0.9), nor in the OR rate (55.0% and 69.0%, respectively, P = 0.3). Residual disease was identified in seven out of 18 (38.9%) patients who were in CR, including two treated with CMC5 and five treated with CMC3 protocols. CMC-induced grade III or IV thrombocytopenia occurred in 12 (19.4%) of patients, including four (20%) CMC5-treated and eight (19%) CMC3-treated patients (P= 0.8). Neutropenia grade III or IV was observed in seven (35%) and 11 (26.2%) patients, respectively (P = 0.8). Severe infections, including pneumonia and sepsis, occurred more frequently after CMC5 (11 patients, 55.0%) than CMC3 (10 patients, 28.6%) (P = 0.03) Fourteen patients died, including six treated with CMC5 and eight treated with CMC3 (30% and 19%, respectively). Infections were the cause of death in nine patients, including four in the CMC5 group and five in the CMC3 group. In conclusion, our results indicate that the CMC programme is an active combined regimen in previously untreated B-CLL patients; its efficiency seems to be similar to that observed earlier in B-CLL patients treated with 2-CdA as a single agent. However, toxicity, especially after CMC5 administration, is significant. Therefore, we recommend the CMC3 but not the CMC5 programme for further evaluation.

Adult↗
PubMed2001

Rituximab (Mabthera, Rituxan) in patients with recurrent indolent lymphoma: evaluation of safety and efficacy in a multicenter study.

The objective of this multiinstitutional study was to evaluate the safety and efficacy of rituximab at standard four weekly doses in patients with recurrent indolent lymphoma. Thirty-eight patients entered into this study, 63% had follicular lymphoma and 61% had an IPI score of 2 or more. Median disease duration was 3 yr, median number of prior treatments was three, and 66% of patients responded to the immediate past treatment with a median remission duration of 3 mo. A total of 158 antibody doses were given, including two patients who received two courses of four infusions each. One patient developed acute respiratory failure after the second dose and required assisted ventilation. There was no immediate relationship to the antibody infusion and no evidence of infection. This complication resolved and the patient successfully completed the full course of the antibody treatment. Another patient discontinued therapy after the second dose owing to intolerable fever and painful erythema. Sixty percent of the first, and 20% of subsequent rituximab infusions were associated with infusion-related reactions including mild fever, chills, and occasional skin eruptions. Complete and partial responses were achieved in 24% and 35% of 34 evaluable patients, respectively, for an overall response rate of 59%. The median time to progression/relapse in responding patients was 16 mo (95% CI, 6.4, 25.6) compared with a median of 3 mo duration of response to the immediate previous therapy in these patients. Longer response duration post rituximab monotherapy than with previous treatment in this series of heavily pretreated patients suggests a major role for the antibody in the therapy of patients with indolent lymphoma.

Adult↗
PubMed2001

[Cephalosporins in empirical treatment of neutropenic fever].

Neutropenic fever and infection became a significant clinical problem with the common use of chemotherapy of cancer. The cephalosporins are a large group of beta-lactam antimicrobial agents. Because of their broad spectrum of activity and low toxicity, they are excellent choice for initial empirical treatment of fever in neutropenia. The article summarises the role of third and fourth generation cephalosporins in therapy of neutropenic fever.

Antineoplastic Agents↗
PubMed2001

[Coincidence of multiple myeloma and renal clear cell adenocarcinoma].

There are only casuistic reports about the coincidence of renal carcinoma and lymphoproliferative diseases. We report a case of 59-year old patient who simultaneously developed renal clear cell carcinoma and IgG kappa multiple myeloma. After nephrectomy the progression of multiple myeloma was observed. The renal failure occurred and, as a consequence, the introduction of full doses of chemotherapy for multiple myeloma was unable.

Adenocarcinoma, Clear Cell↗
PubMed2001

[E-cadherin in the serum and the peritoneal fluid of women with endometriosis].

Endometriosis, a disease of unclear etiopathogenesis, is a quite common problem in gynecology. It is thought that the retrograde flow of the menstrual debris to the peritoneal cavity plays an important role in the origin of endometriosis but the mechanism of endometrial cells implantation remains unknown. Recently many centers have reported the importance of adhesion molecules in this process. We studied the concentrations of E-cadherin in the serum and the peritoneal fluid of women with endometriosis. Our results show a significant decrease of E-cadherin concentrations in sera and peritoneal fluids in women with endometriosis. We suggest that screening the level of E-caherin may be useful in the monitoring the therapy of endometriosis.

Adult↗
PubMed2001

Cell cycle regulatory proteins and apoptosis in B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: The pathogeny of B-cell chronic lymphocytic leukemia (B-CLL) involves both deregulated proliferation and inhibition of cell death. A particular role in the regulation of these phenomena is played by proteins involved in early G1 phase regulation: pRb kinases: cyclin-dependent kinases (cdk): cdk4 and cdk6 activated by cyclins D, and universal cdk inhibitor p27(Kip1). DESIGN AND METHODS: We determined by flow cytometry the expression of p27(Kip1) and cyclins D (D2 and D3) in populations of peripheral blood lymphocytes obtained from 59 (for p27(Kip1)) and 31 (for cyclins D) previously untreated patients with B-CLL, and compared them with cell cycle parameters, cell viability and apoptosis in 72-hour cultures in medium only. As a control we determined the expression of p27(Kip1), cyclin D2 and D3 in peripheral blood CD5+/CD19+ lymphocytes from 15 healthy donors. RESULTS: p27(Kip1) was present in nearly 100% of lymphocytes in all B-CLL populations tested. Its cellular content estimated semiquantitatively by specific mean fluorescence intensity was higher than in normal CD5+/CD19+ lymphocytes, p27(Kip1) was inversely correlated with patients' age and not correlated with other clinical variables, cell cycle or apoptosis rate. Cyclin D2 was detectable in 25 out of 31, and cyclin D3 in all B-CLL lymphocytes populations studied. In contrast to p27Kip1 present in all CD5+/CD19+ lymphocytes, both cyclins were detected only in a subset of neoplastic cells: 27.5 to 87% (mean 51.2) for cyclin D2 and 20.3 to 98% (mean 76.5) for cyclin D3. In cyclin D2- and D3-positive normal CD5+/CD19+ lymphocytes and B-CLL cell populations, cyclin D3 was expressed in a higher percentage of cells than cyclin D2. Both cyclin D2-and cyclin D3-positive fractions of B-CLL cells were, on average, larger than corresponding fractions of normal CD5+/CD19+ peripheral blood lymphocytes. INTERPRETATION AND CONCLUSIONS: Our results indicate that cyclin D3 plays an important role in the regulation of normal and neoplastic CD5+/CD19+ cells, and point to the possibility of the exit of a number of CLL lymphocytes from quiescence.

Adult↗
PubMed2001

[Serum soluble tumor necrosis factor alpha receptor (s-TNF-alpha R) and acute phase proteins as factors of a disease activity (and also as prognostic factors?) in patients with malignant lymphomas].

It was found that in neoplastic disorders levels of sTNF-alpha R and acute phase proteins are elevated and correlate with disease activity and poor prognosis. The aim of the study was to determine levels of sTNF-alpha R and acute phase proteins in patients with lymphoma at presentation and after treatment and compare with healthy individuals. Serum concentration of sTNF-alpha R was estimated by ELISA method, fibrinogen and haptoglobin by nephelometric method in 46 lymphoma patients and in 14 healthy individuals. Mean sTNF-alpha R concentration in lymphoma group was statistically significantly higher than in healthy individuals (p = 0.00057) and in patients with complete remission (CR) (p = 0.024). Mean concentration of fibrinogen and haptoglobin was significantly statistically higher at presentation of lymphoma than in CR (p = 0.0001, p = 0.0001). We found the correlation between the mean concentration of sTNF-alpha R, fibrinogen and haptoglobin at presentation of lymphoma. There was no difference in the survival time in patients with higher concentration of sTNF-alpha R. Our data indicate the important role of the elevated concentration of sTNF-alpha R, fibrinogen and haptoglobin as factors of disease activity in lymphoma patients but they do not correlate with disease's prognosis.

Acute Disease↗
PubMed2000

Cladribine with or without prednisone in the treatment of previously treated and untreated B-cell chronic lymphocytic leukaemia - updated results of the multicentre study of 378 patients.

Between January 1992 and January 1999, we treated 378 B-chronic lymphocytic leukaemia (CLL) patients with cladribine (2-CdA), and 255 of the patients were also treated with prednisone. A total of 194 patients were previously untreated, and 184 had relapsed or refractory disease after previous other therapy. Complete response (CR) was obtained in 111 (29.4%) and partial response (PR) in 138 (36.5%) patients, giving an overall response (OR) rate of 65.9%. CR and OR were achieved more frequently in patients in whom 2-CdA was a first-line treatment (45.4% and 82.5% respectively) than in the pretreated group (12.5% and 48.4% respectively) (P < 0.0001). The median duration of OR for previously untreated patients was 14.7 months and for pretreated patients 13.5 months (P = 0.09). The median survival evaluated from the beginning of 2-CdA treatment was shorter in the pretreated group (16.3 months) than in the untreated group (19.4 months) (P < 0.0001). A total of 117 (63.9%) patients died in the pretreated group and 63 (32.6%) in the untreated group. In pretreated patients, 2-CdA + prednisone (P) and 2-CdA alone resulted in similar OR (51.0% and 45.0% respectively; P = 0.4). In contrast, in untreated patients, 2-CdA + P produced a higher OR (85.4%) than 2-CdA alone (72.1%) (P = 0.04). Infections and fever of unknown origin, observed in 91 (49.4%) pretreated and 74 (38.1%) untreated patients (P = 0.03), were the most frequent toxic effects. Our results indicate that 2-CdA is an effective, relatively well-tolerated drug, especially in previously untreated CLL.

2-Chloroadenosine↗
PubMed1998

[The concentration of exfoliative adhesion molecules (ICAM-1 and E-Selectin) in serum and peritoneal fluid of women with endometriosis].

It is commonly known that retrograde transport of exfoliative fragments of endometrium to peritoneal cavity during the menstruation is an important factor of the ethiopathogenesis of endometriosis. The mechanism of inplantation of endometrial cells to peritoneal sites still remains unclear. Adhesions molecules are suggested to take part in this process. In our study we tried to establish the concentration of the adhesion molecules (ICAM-1 and E-Selectin) in the sera and peritoneal fluids of women with endometriosis in comparison to the control group. These concentrations were significantly higher in the sera of all patients. We did not find any significant differences between two examined groups although further studies should be carried out.

Adult↗
PubMed1996

Serum soluble interleukin 2 receptor alpha and soluble CD8 levels in patients with gynecological malignancies undergoing radiotherapy.

The phenotype peripheral blood lymphocytes, soluble interleukin 2 receptor alpha (sIL-2R alpha) and soluble CD8 (sCD8) were studied in 30 patients with gynecological malignancies before and after ratiotherapy. The absolute count of CD3+, CD4+, CD8+, CD19+ and CD25+ lymphocytes before treatment was within normal range. The levels of serum sIL-2R alpha and sCD8 were significantly increased before treatment compared to normal controls. After treatment the absolute number of CD3+, CD4+ and CD19+ lymphocyte subsets significantly decreased. The levels of sIL-2 alpha and sCD8 corrected according to absolute lymphocyte count reached normal range. The decrease of tumor mass correlated with the serum levels of sIL-2R alpha and sCD8. Further studies are needed to evaluate the usefulness of these tests in the prognosis and treatment of these diseases. Our study suggests that sIL-2R alpha and sCD8 in our patients probably has not been originating from the proteolytic cleavage of membrane bound receptors from peripheral blood mononuclear cells (PBMC). It can be speculated that sIL-2R alpha and sCD8 originated in these patients from activated tumor-infiltrating lymphocytes or may arise from separate alternatively spliced mRNAs coding for soluble vs. membrane forms.

Adult↗
PubMed1995

Upregulation of p21 RAS levels in HL-60 cells during differentiation induction with DMSO, all-trans-retinoic acid and TPA.

The role of p21 RAS in the proliferation and differentiation of myeloid cells has been studied by analysing the changes in the level of expression of p21 RAS proteins by flow cytometry upon differentiation down the granulocytic and monocytic pathways. Differentiation resulted in upregulated p21 RAS expression despite a marked decline in the number of dividing cells. On the other hand, growth inhibition, without differentiation, resulted in a decline in expression. Cell cycle analysis showed that the increase in p21 RAS occurred throughout the cell cycle. These results suggest that p21 RAS has a role in the process of myeloid differentiation.

Cell Cycle↗
PubMed1995

Decreased production of interferon gamma by anti-CD3 monoclonal antibody and interleukin-2-stimulated peripheral blood mononuclear cells in Hodgkin's disease.

We have examined the production of interferon (IFN) gamma by peripheral blood mononuclear cells (PBMC) in 22 patients with Hodgkin's disease (HD) in active phase of the disease, 12 patients in clinical remission and 16 healthy subjects. The level of IFN gamma in supernatants of PBMC stimulated for 72 h with anti-CD3 monoclonal antibody (mAb), measured by sandwich enzyme immunoassay (ELISA) was 50.4 +/- 2.3 U/ml in active phase; 137.0 +/- 7.4 U/ml in clinical remission patients; and 520.0 +/- 10.0 U/ml in the controls; the difference between the groups was statistically significant. Co-stimulation with interleukin-2 (rIL-2) markedly amplified production of IFN gamma. The mean levels were 220.8 +/- 7.0 U/ml, 590.7 +/- 3.6 U/ml and 2111.1 +/- 17.3 U/ml in active phase HD, clinical remission and controls, respectively, the difference between groups was statistically significant. The patients showed the same kinetic pattern as healthy individuals. Our results indicate that patients with HD have severely impaired TCR/CD3 activation pathway resulting in significantly depressed IFN gamma response to anti-CD3 mAb and anti-CD3 + rIL-2 in vitro stimulation and provide support for the possible clinical use of IFN gamma as an immunopotentiating agent in patients with HD.

Adult↗