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Biomedical subjects

W W Jedrzejczak

Publications and source records attributed to W W Jedrzejczak.

At least 19 recordsLinked to original sources

Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR-ABL--positive acute lymphoblastic leukemia-retrospective analysis of Polish Adult Leukemia Group (PALG).

Patients with Philadelphia chromosome-positive (Ph+) and/or BCR-ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR-ABL+ ALL registered in Poland in 1997-2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR-ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed.

Adolescent↗

Addition of cladribine to induction/consolidation regimen does not impair peripheral blood stem cell mobilization and bone marrow harvest for autotransplantation in acute myeloid leukemia patients.

BACKGROUND: The previous study by the Polish Adult Leukemia Group has demonstrated that addition of cladribine to standard DNR+AraC induction potentiates the antileukemic activity. The goal of this study was to compare the efficacy of bone marrow or peripheral blood hematopoietic cell collection in patients who obtained remission after daunorubicine plus cytarabine induction with cladribine (DAC-7) or without addition of cladribine (DA-7) in preparation for autotransplantation. PATIENTS AND METHODS: Sixty-six patients aged 41 years (range, 17-58 years) were included in this study: 33 cases in the DAC-7 and 33 in the DA-7 arm. Hematopoietic cells were collected from the bone marrow (ABMT, n = 29) or from the peripheral blood (ABCT, n = 37) using cytopheresis after administration of AraC (2 x 2 g/m2) on days 1, 3, 5 and subsequent G-CSF (10 microg/kg) from day 7 as mobilization therapy. RESULTS: The numbers of harvested CD34+ cells were similar in the DAC-7 and DA-7 pretreated patients both after harvesting from peripheral blood (2.55 x 10(6)/kg vs 2.5 x 10(6)/kg) and from bone marrow (1.62 x 10(6)/kg vs 1.55 x 10(6)/kg), respectively. The proportion of patients with sufficient material for autologous bone marrow transplantation was higher in the DAC-7 compared with the DA-7 arm. All patients engrafted; hematopoietic recovery was similar in both subgroups. CONCLUSION: Addition of cladribine to a standard DA induction does not impair the harvesting of hematopoietic cells and their engraftment after autotransplantation.

Adolescent↗

Primary lymphoma of the liver -- morphological and clinical analysis of 6 cases. Success of aggressive treatment.

Histological, clinical and immunohistochemical analysis of 6 cases of primary liver lymphomas (PLL) are presented. PLL represents 4.3% of primary malignant liver tumors diagnosed in our department. The patients were relatively young people, who despite the presence of a large tumor, were in good general health status. There were no signs of scirrhosis, and cancer markers were normal. All lymphomas were CD20, CD79a, BAX positive, CD3, CD30, EMA, CD10, CD5, CD59, c-myc, Bcl2, EBV(LMP), CK negative. The proliferation index (Ki67) was high, ranging from 50-100%. In two cases positive staining for Bcl6 and in another one for cyclin D1 was obtained. The major histological type of the tumor was diffuse large B-cell lymphoma. Positive immunohistochemical results with BAX and the lack of Bcl2, c-myc and CD59 are associated with better prognosis. We have not confirmed the value of Bcl6 and CD10 stains as a predictor of poor outcome. Despite clinically advanced stage at the time of diagnosis, if treated appropriately, the primary lymphoma of the liver has relatively good prognosis (five of our patients are alive).

Adolescent↗

Treatment for primary refractory Hodgkin's disease: a comparison of high-dose chemotherapy followed by ASCT with conventional therapy.

Our previously published study showed promising results of autologous stem cell transplantation (ASCT) in patients with primary resistant Hodgkin's disease (HD). Probabilities of overall survival (OS) and progression-free survival (PFS) at 3 years were 55 and 36%, respectively. The present study was undertaken to compare these results with conventionally treated patients and thus evaluate therapeutic options. Retrospective data on 76 adult patients who underwent ASCT were matched with 76 conventionally treated patients from 17 centers. Comparison of clinical characteristics in both groups showed that ASCT patients were younger (24 vs 31.5 years, P=0.001), more frequently presented with 'B' symptoms (P=0.03) and that more patients treated with chemotherapy (CT) had elevated LDH (P=0.03). In univariate analyses, bulky disease (P=0.0043) and complete resistance to standard CT (P=0.051) were found to be risk factors for OS. In a multivariate survival analysis only bulky disease was found to an independent prognostic factor (P=0.005). There was no difference in survival between the treatment groups with 5 years OS 33.7 (CI: 23-46) in the ASCT group and 35.6% (CI: 25-50) for the CT group (P=0.92). We conclude that ASCT is not superior to standard CT for treatment of patients with primary refractory HD.

Adolescent↗

Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study.

To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.

Adolescent↗

[Albumin--biological functions and clinical significance].

Albumin is a simple protein present both in animal and plant physiological fluids and tissues. It plays many important roles including maintenance of appropriate osmotic pressure, binding and transport of various substances like hormones, drugs etc. in blood, and neutralisation of free radicals. Both acute and chronic disorders lead to hypoalbuminemia, oedema and many other disturbances. Albumin preparations obtained by separation of human plasma are used clinically for more than 50 years to reverse hypoalbuminemia and to allow for reversal of abnormalities in substance transport. These problems are discussed through out this paper.

Albumins↗

[Immunosuppressive mechanisms for immunoglobulin function].

The article reviews the evidence supporting and explaining suppressive activity of intravenous immunoglobulin (IVIG) preparations towards human immune system. Besides basic mechanisms also clinical applications and effects in various autoimmune disorders such as idiopathic thrombocytopenia, Guillain-Barré syndrome and others are described. This evidence supports novel application of IVIG as convenient alternative to other immunosuppressive therapies with many more adverse effects.

Autoimmune Diseases↗

[Preliminary evaluation of a method for detection of individual malignant melanoma cells in peripheral blood while monitoring the course of the malignancy and its treatment].

Using reverse transcription and polymerase chain reaction (PCR) with primers specific for tyrosinase the individual melanoma cells were detected in peripheral blood of patients in different stages of disease, after excision of primary lesion and prior and after chemotherapy. No relation between stage of disease (including situations with overt generalized spread of melanoma) and probability of positive PCR reaction detecting transcript for tyrosinase gene was found. Many patients in III and IV stages were negative for prolonged periods. Therefore, this method cannot be used for monitoring of all patients, because many of them are negative prior as well as after chemotherapy. With regard to the effects of therapy, the patients differed one to another and although some persons positive prior treatment became negative thereafter, a similar number of initially negative patients became positive after treatment.

Adult↗

[Gene therapy of blood disorders].

In the article the basic knowledge concerning genes and genetic disorders necessary to understand the methods utilized in contemporary attempts of gene therapy has been reviewed. Then, a classification of gene therapy methods was presented and approaches to somatic gene therapy were discussed with particular attention to the utilization of retroviral vectors and packaging cell lines. Other vector systems such as adenovirus, vaccinia virus, and herpes virus derived have also been mentioned as well as antisense strategy. Reviewed applications concerned mainly inborn gene errors, but strategy of gene-directed, gene-forced suicide of leukemic cells has also been mentioned.

Animals↗

[Studies on the possibility of using lyophilized in vitro autogenic bone marrow derived stromal cells to stimulate healing of bone lesions in the jaws].

The authors describe a new method of stimulation of regeneration of bone tissue using autografts of autologous bone marrow supplemented with autologous bone marrow stromal fibroblastoid cells (with osteogenic potential) grown in vitro and lyophilized allogenic bone. Such composite grafts have been used in the treatment of 10 patients with lesion in jaw bone. Bone healing was evaluated using clinical and radiological parameters and was compared with healing in 30 similar lesions treated using composite grafts of autologous bone marrow and allogenic lyophilized bone as well as the spontaneous healing of 45 post-cystic lesions. These data indicate, that composite grafts of autologous bone marrow supplemented with in vitro grown autologous bone marrow stromal cells and lyophilized allogenic bone have excellent capacities accelerating bone healing. In smaller lesions, composite grafts of fresh autologous bone marrow and allogenic lyophilized bone (which are easier to prepare) are also useful.

Adolescent↗

Kinetics of destruction and regeneration of the haemopoietic system after administration of busulphan and cyclophosphamide followed by bone marrow transplantation. Peripheral blood parameters.

The kinetics of restoration of haemopoiesis was studied in 10 patients prepared for allogenic bone marrow transplantation with busulphan combined with cyclophosphamide. The morphology of peripheral blood after administration of these drugs and transplantation of allogenic bone marrow was similar to that reported elsewhere after irradiation, cyclophosphamide administration and bone marrow transplantation, the cell counts falling almost to zero within several days after the end of the pharmacological preparation, and later rising to normal values within the period from several weeks to several months after transplantation.

Adolescent↗