Biomedical subjects
Publications and source records attributed to J Wojnar.
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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.
It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versus-host disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P = 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) >1.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P = 0.48). However, the adjusted hazard of increased creatinine >1.5 normal was significantly higher in the imatinib group (HR = 4.09, P = 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR = 0.86, P = 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR = 0.65, P = 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.
We evaluated the feasibility of allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells from siblings (four patients: AML-M4, M2, CLL, MDS); nonoptimal related donors (two patients: AML-M4, CML); and unrelated donors (two patients: CML, ALL, both without engraftment after preceding URDBMT). All patients had high-risk of aGVHD and/or graft failure due to multiple transplantation risk factors. Conditioning treatment was myeloablative (n=7) or nonmyeloablative (n=1). Immunosuppression consisted of CsA (n=8), Mtx (n=5), ATG (n=4). Selected CD34+ cells were transplanted (average 3.91 x 10(6)/kg, range 1.29 to 7.27 x 10(6)/kg) together with 0.01 to 0.5 x 10(7) CD3+ cells/kg to assure proper engraftment. The remaining CD34-negative fraction was cryopreserved for further CD3+ cell add-back. Average recovery and purity of CD34+ cells following CliniMACS selection were 74% and 97%. No severe complications were observed in the first 100 days. Regeneration times were satisfactory in seven of eight patients (87.5%) with ANO > 0.5 g/L and Plt > 50 g/L reached on average on days +26 and +32 (range 15 to 29 and 15 to 67), respectively. In three patients (37.5%) T-lymphocytes were added-back one to three times (due to low numbers of initially transfused CD3+ cells in two patients, in one patient with PRCA caused by ABO incompatibility). One to four additional transplantations of nonselected peripheral cells were performed on days +28 to +270 in consequence of infections (CMV-two patients; parvovirus-one patient), poor regeneration and residual disease (one patient) and prolonged transfusion dependency (one patient). Severe aGVHD grade III or IV developed in three patients (37.5%) following the nonselected cells transplantation. Finally, five patients (62.5%) are alive and in remission (median follow-up 815 days). We conclude that allogeneic transplantation of selected peripheral CD34+ cells (CliniMACS) with controlled add-back of CD3+ cells is an effective, well, tolerated procedure in high-risk patients.
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UNLABELLED: The aim of the study was to compare venous blood gasometry parameters of blood sampled twice from basilic vein on different days and at different hours. In the group of 8 healthy volunteers, parameters of venous blood gasometry sampled from basilic vein before and after exercise of antebrachial muscles, twice--on different days and at different hours were estimated. CONCLUSIONS: 1. In the first and in the second sample venous blood gasometry parameters before and after exercise were different: values of pCO2, pO2, O2sat increased, pH, BE, BEexe and BB decreased and HCO3 was not changed. 2. Venous blood gasometry parameters before exercise in the first and in the second sample and after exercise in the first and in the second sample were not different.
The aim of the study was to evaluate the influence of prednisone therapy on selected parameters of bone metabolism [carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), alkaline phosphatase (AP), parathormone (PTH), and calciuria (Cau) in children with nephrotic syndrome. Twenty patients (aged 4-15 years, mean: 9.2 years) were treated with prednisone. Blood and urine samples were taken: T0--before prednisone treatment; T1--after two weeks of treatment with prednisone 1-2 mg/kg/24 h; T2--after two weeks of treatment with prednisone 1-2 mg/kg/48 h; T3--after 3 months of treatment with prednisone; T6--in 6th month of treatment with prednisone, at dose 0.2-0.4 mg/kg/48 h. Mean values of PICP, ICTP, AP concentration, and PICP/ICTP ratio found in the T1 period were significantly lower, and mean Cau value was higher in comparison to means of these parameters observed before steroid treatment. After two weeks of prednisone administered every 48 hours mean values of PICP, ICTP concentrations and PICP/ICTP ratio were significantly higher than in the T1 period of treatment. There were no significant differences in mean concentrations of PTH before and during everyday doses of prednisone therapy. Mean value of PTH concentration decreased significantly during T2 in comparison with T1 period of prednisone treatment. Our data demonstrate that short-term treatment with high daily doses of prednisone in children with nephrotic syndrome is associated with increase of calciuria and suppression of serum markers of type I collagen's turnover. Changes of PICP, ICTP, and PICP/ICTP ratio depend on a method of steroid administration. Decreased PICP/ICTP ratio during daily steroid treatment may indicate stronger inhibition of bone formation than bone resorption, but significance of PICP/ICTP ratio in later phases of treatment needs further studies. Present study suggests that prednisone influences bone metabolism directly rather than by stimulating the parathyroids.
Among 290 BMT procedures: 74 AML, 78 ALL, 34 CML, 6 SAA, 3 MDS, 42 HD, 35 NHL, 11 MM, and 7 solid tumours (breast or testis cancer) Allogeneic BMT was performed in 76 patients and ABMT/APBCT in 214 patients. Survival, DFS and relapse curves were calculated using the Kaplan-Meier product limit method. Variables potentially affecting survival and DFS were assessed in a multivariate analysis by the Cox proportional hazard model in a stepwise regression. The promising results were obtained in high risk adult ALL in the first CR. DFS in CR1 patients transplanted after full dose induction and high dose consolidation was significantly longer if compared to those who received dose/time reduced or postponed treatment. For CR> or =2 patients and with CNS involvement at diagnosis ABMT offers a salvage therapy that needs further improvement. In relapsed and refractory HD better results are obtained in patients relapsing > 1 year after first CR and in patients with entirely nodal localisation of this relapse. In NHL bone marrow and spleen infiltration at diagnosis appear to be an unfavourable prognostic factor.
Autologous peripheral blood stem cell transplantation (APBSCT) is a method used analogically to autologous bone marrow transplantation (ABMT) to obtain hematological reconstitution following myeloablative therapy in patients with hematological malignancies. We have now applied this procedure in two patients with recurrent high risk Hodgkin's disease. Collection of circulating stem cells mobilised with cyclophosphamide/G-CSF was performed by several leukaphereses on Fenwal 3000, with access through inferior vena cava. Nucleated cells were separated by dextran sedimentation, cryopreserved, and stored at (-) 196 degrees C. Additional marrow collection was performed in one patient. Conditioning regimen consisted of BCNU, etoposide and cyclophosphamide delivered at days -3 and -2. Collected material containing on average 3.6 x 10(8)/kg nucleated cells and 8.0 x 10(6)/kg CD34(+) cells was transfused at day 0. G-CSF was administered following transplantation to one patient to hasten the recovery. Hematological recovery was relatively quick. Neither serious adverse events nor signs of relapse were observed following transplantation. Our results supported by other's reports indicate, that APBSCT enables hematological recovery similarly to ABMT in Hodgkin's disease. The advantage of APBSCT is a possibility to collect material in patients with marrow involvement, hypoplasia or fibrosis. Outcomes obtained following APBSCT are at least as good as following ABMT. High-dose chemotherapy followed by APBSCT or ABMT should be considered in all patients with recurrent Hodgkin's disease sensitive to chemotherapy.
In this article the contemporary methods of positive stem cells isolation have been reviewed, with special regard to their application in the hematological transplantology, and the results of our own studies on isolation with the immunomagnetic method have been presented.
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In 1981-1990, 584 patients with non-Hodgkin malignant lymphoma, 209 women and 375 men, aged between 17 and 75 years, were treated at the I Department of Medicine and Department of Hematology, Silesian Medical Academy in Katowice. In this group the primary localization outside lymph nodes was seen in 26 patients (9 women and 17 men), i.e. 4.6% of all patients with malignant non-Hodgkin lymphomas. Most frequently digestive tract was involved-19 patients (73.1%). Twenty three patients were treated surgically followed by chemotherapy and/or irradiation. Not operated patients were treated with either chemotherapy or both radio- and chemotherapy. Complete remission was achieved in 17 patients (65.4%), partial remission in 4 (15.4%) patients. Five patients did not respond to therapy (19.2%). A mean survival time was 49.4, 14.3, and 6.4 months, respectively.
The results of two different methods of CNS prophylaxis during consolidation were evaluated among fifty one acute lymphoblastic leukemia patients (ALL) treated in 1980-1991 in the Department of Hematology in Katowice. In group I (n = 28) methotrexate (Mtx) was used intrathecally (it) in 6 doses of 18 mg, in group II high dose cytosine arabinoside (Hi AraC)--3g/m2 intravenously (4x) was used with CNS rtg--therapy (18-24Gy). In both groups frequency of CNS relapses was similar 17.8% vs 17.3%; additionally there were no statistically significant differences in RFS: 369 vs. 562 days. The survival of patients with and without CNS relapses was also similar (678 vs. 774 days) and was independent of prophylaxis. The tolerance of both the used methods of CNS prophylaxis was good.
Using RIA method, serum erythropoietin (EPO) levels were measured in 13 patients undergoing autologous bone marrow transplantation (ABMT) and 4 patients with autologous peripheral blood stem cell transplantation (APBSCT) before and at the end of conditioning regiment as well as at the 3rd, 7th, 10th, 14th, 20th i 30th day after ABMT in correlation with actual haemoglobin (Hb) value. Statistically significant increase in EPO level was observed at days 0 to +14 (p < 0.01) with the maximum at day 3. The correlation between increased EPO level and decreased Hb was observed.
Autologous peripheral blood stem cell transplantation (APBSCT) is used similarly to autologous bone marrow transplantation (ABMT) to reconstitute bone marrow following myeloablative therapy in patients with proliferative diseases of the blood. Eight patients with recurrent and refractory lymphoma (3 HD, 4 NHL) and multiple myeloma aged 17-55 were included into the study. Peripheral blood stem cells following their prior mobilisation with cyclophosphamide 4-7 g/m2 and/or G-CFS or Dexa-BEAM + G-CSF were collected by subsequent leukaphereses on Fenwal CS3000. Nucleated cells were separated by sedimentation, cryopreserved in a programmed freezer and then stored at-196 degrees C. Bone marrow has been additionally collected in one patient. Conditioning treatment prior to transplantation consisted of BCNU, etoposide and cyclophosphamide (CBV) in lymphomas and melphalan in multiple myeloma. Collected material with mean cellularity 5.52 x 10(8)/kg and mean CD34+ contents 6.27 x 10(6)/kg was reinfused by central line. G-CSF was given in 5 patients to hasten the bone marrow recovery. All patients fully recovered and left hospital on average 35.5 days following transplantation. No signs of relapse were seen throughout the observation period (mean 349.5 days). Neutrophils > 0.5 G/1 were obtained on day + 20, > 1.0 G/1 on day 30, platelets > 50 G/1 on day 29, > 100 G/1 on day 53, reticulocytes > 0.015 on day 30, erythrocytes transfusions were needed up to day 39. Presented outcomes together with other reports indicate, that APBSCT is a highly efficient way to rescue repeatedly relapsing patients with proliferative diseases of the lymphatic systems, even those presenting with changes in the bone marrow (neoplasmatic infiltrate, hypoplasia or fibrosis).