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A B Skotnicki

Publications and source records attributed to A B Skotnicki.

At least 19 recordsLinked to original sources
PubMed2005

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↗
PubMed2004

Efficacy and safety of fludarabine and cyclophosphamide combined therapy in patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL)-Polish multicentre study.

The aim of this study was to investigate the efficacy of a combination of fludarabine (F) and cyclophosphamide (C) in the treatment of patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL). Between November 1999 and December 2001, 63 patients with B-CLL (median age 60 years) received a regimen that consisted of F 25 mg/m2 and C 250 mg/m2, days 1-3, intravenously, every 4 weeks, for a maximum of 6 courses, Response and toxicity were assessed according to current criteria (NCI-WG and WHO). Complete and partial remissions were achieved in 17.5% and 55.6% of patients, respectively; 19% of patients had stable disease and 7.9% of patients showed disease progression. The median follow-up was 16.5 (range 1.5-32) months. The median duration of progression-free survival (PFS) has not been reached among patients treated with FC regimen as second-line therapy. The median PFS was 13 (range 8-26) months in the 19 responding patients treated with FC regimen as third-line therapy. The most frequent side-effects were neutropenia (45%), thrombocytopenia (42%) and infections (57%). We conclude that the combination of fludarabine and cyclophosphamide demonstrated significant efficacy in pretreated, advanced B-CLL patients, with tolerable toxicity.

Adult↗
PubMed2004

Clinical efficacy, safety and pharmacokinetic properties of the factor VIII concentrate Haemoctin SDH in previously treated patients with severe haemophilia A.

Clinical efficacy, safety and pharmacokinetic properties of the high-purity double-virus inactivated plasma-derived factor VIII concentrate Haemoctin SDH (pdFVIII) were evaluated in three prospective open-label uncontrolled studies in previously treated patients (PTPs) with severe haemophilia A. The pharmacokinetic properties assessed at baseline and after 3 months of treatment are in accurate accordance with published data and remain unchanged over time (study A, n = 12). Mean terminal elimination half-life was 11.8 and 11.9 h, mean incremental recovery (IU dL(-1)/IU kg(-1)) was 2.3 and 2.0, respectively. Long-term efficacy and safety, in particular the potential immunogenicity, were investigated in a total of 53 PTPs (studies A and B) treated prophylactically and on-demand, as required. PdFVIII has shown to be effective in preventing and controlling bleeding episodes; 23.5% of patients were free of bleeding events. A total of 177 haemorrhages occurred with 74.0% resolving after a single infusion, 87.6% within two infusions. 98.3% of responses reported on haemorrhages were rated as 'excellent' or 'good'. Moreover, 'excellent' haemostatic efficacy has been demonstrated in 10 surgical procedures including general and severe orthopaedic interventions (study C). No complication occurred in any surgery. Few adverse events were reported, one patient developed a high-titre FVIII inhibitor without clinical relevance. In all three studies, over 6 million units were administered in nearly 4300 infusions, approximately 94% units or infusions were given for prophylaxis and only 6% for treatment on-demand. In conclusion, pdFVIII has shown to be effective, safe and well tolerated in long-term prophylaxis and treatment on-demand as well as after minor and major surgical procedures.

Adolescent↗
PubMed2003

Acute lymphoblastic leukemia in elderly: the Polish Adult Leukemia Group (PALG) experience.

This is a retrospective, multicenter study to evaluate biological features and outcome of elderly patients diagnosed with acute lymphoblastic leukemia (ALL) during the last 10 years in ten hematological centers in Poland. Eighty-seven patients aged 60 years or older were studied. To our knowledge, this is one of the largest group of elderly patients with ALL evaluated. We have not observed differences in immunological subtypes and Ph chromosome incidence as compared with younger adult ALL presented in the literature. Induction chemotherapy was administered in 75 patients. We observed complete remission (CR) in 34 (45%, 95% CI: 33-56%) patients. Induction death occurred in 11 (15%) patients. Thirty patients (40%) showed primary resistance to chemotherapy. Median overall survival (OS) of all patients was 150 days. Median disease-free survival (DFS) of responding patients was 180 days. We observed four long-term survivors (DFS longer than 3 years) in our group of patients. Factors influencing OS were CR achievement, female gender, and WBC below 30 x 10(9)/l. Male gender was the only prognostic factor negatively affecting probability to achieve CR. We have not observed any differences in either biology or outcome between patients aged 60-69 years and those aged more than 70 years. ALL of the elderly is a rare disease with poor prognosis. Further clinical trials evaluating the disease features, outcome, and new therapeutic approaches are warranted.

Aged↗
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

[Hemorrhagic cystitis related to the high-dose conditioning therapy in a bone marrow recipient].

Hemorrhagic cystitis (HC) is the syndrome of hematuria combined with symptoms of lower urinary tract irritation in the absence of bacterial infection or generalized hemorrhagic diathesis. HC often occurs as a difficult complication after autologous as well as allogeneic hematopoietic cell transplantation (HCT). It may be secondary to pretransplant preparative regimen (chemotherapy and/or radiation therapy) or viral infection by adenovirus, JC and BK viruses. The most effective treatment for HC has not been established yet. We report a case of a 17-year-old male with common acute lymphoblastic leukemia (cALL) in second CR, who was treated with high-dose chemotherapy (BuCy conditioning regimen) followed by autologous bone marrow transplantation (ABMT), complicated by hemorrhagic cystitis on day 0 (several hours after infusion of transplant material). The immediate use of increased dose of 2-mercaptoethane sulfonate sodium (mesna), bladder irrigation and intensive hydration with forced diuresis resulted in resolution of macroscopic hematuria on day +3 after the transplant and urinary tract recovery with normalization of urine analysis parameters on day +7.

Adolescent↗
PubMed2001

[Veno-occlusive disease--an important complication in hematopoietic cells transplantation].

Hemopoietic stem cell transplantation is frequently used in clinical practice. However, many severe complications limit its usage. One of the most important is veno-occlusive disease of the liver (VOD). The key pathophysiologic event is a damage to epithelium during chemotherapy. Gradual development of intrahepatic portal hypertension leads to clinical manifestations (jaundice, liver enlargement, ascites). Many risk factors has been identified (pre-transplant liver disturbance, chemotherapy and conditioning, drugs). The diagnosis is based on clinical criteria and exclusion of other diseases. Laboratory, haemodynamic, ultrasound studies and histopathology are very important in diagnosis. In pharmacological prophylaxis heparin is widely used. Therapy requires strict fluid and electrolyte balance. Some patients can benefit from transjugular intrahepatic portosystemic shunt (TIPS) or liver transplantation. Defibrotide gives more hope for patients but further investigations are needed.

Anticoagulants↗
PubMed2000

Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial.

The efficacy and toxicity of cladribine (2-CdA) + prednisone (P) versus chlorambucil (Chl) + P were compared in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia (CLL) in a randomized, multicenter prospective trial. Eligible patients were assigned to either 2-CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2) per day for 5 consecutive days or Chl 12 mg/m(2) per day and P 30 mg/m(2) per day for 7 consecutive days. Three courses were administered at 28-day intervals or longer if myelosuppression developed. The therapy was finished if complete response (CR) was achieved. Of 229 available patients 126 received 2-CdA+P and 103 received Chl+P as a first-line treatment. CR and overall response rates were significantly higher in the patients treated with 2-CdA+P (47% and 87%, respectively) than in the patients treated with Chl+P (12% and 57%, respectively) (P = .001). Progression-free survival was significantly longer in the 2-CdA-treated group (P = .01), but event-free survival was not statistically different. Thirteen percent of patients were refractory to 2-CdA+P and 43% to Chl+P (P = .001). Drug-induced neutropenia was more frequently observed during 2-CdA+P (23%) than Chl+P therapy (11%) (P = .02), but thrombocytopenia occurred with similar frequency in both groups (36% and 27%, respectively). Infections were seen more frequently in the 2-CdA+P-treated group (56%) than in the Chl+P-treated group (40%; P = .02). Death rates have so far been similar in patients treated with 2-CdA (20%) and with Chl (17%). The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups (78% and 82%, respectively). (Blood. 2000;96:2723-2729)

Adult↗
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↗
PubMed2000

[History of Kraków hematology].

The development of the studies of the blood diseases at the IIIrd Department of Internal Medicine and later at the Department of Hematology of the Medical Academy and subsequently the Collegium Medicum at the Jagiellonian University in the years 1950 to 2000 are presented here. The Cracow Hematological Center, headed by professor Julian Aleksandrowicz from 1950 to 1979, by professor Julian Blicharski from 1979 to 1989, by ass. professor Jerzy Lisiewicz from 1990 to 1993, and presently by Aleksander B. Skotnicki--has drawn many brilliant hematologists who have initiated, developed and verified new concepts of pathogenesis as well as new methods of diagnosis and therapy of haematological diseases. The Polish Haematological Society was founded in 1949 in Cracow where the first Conference took place in May 1950. The first specialistic haematological journal--Haematologica Cracoviensia later retitled as Haematologica Polonica was first published in Cracow in 1957. Finally here, in Cracow, one of the first syngeneic bone marrow transplantation was performed in 1958. Presently the Chair and Department of Haematology of the Collegium Medicum at the Jagiellonian University is a modern and well facilitated center of research and didactics (both pre and post graduate studies); the modern cytological, immunophenotype, cytogenetic and molecular diagnostic methods are used in haematological patients from the Macroregion of South-Eastern Poland (inhabited by approximately 8 million people). The offered treatment includes chemo- and radiotherapy, immunotherapy and autologous and allogeneic bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1999

2-Chlorodeoxyadenosine (Cladribine) in the treatment of patients with chronic lymphocytic leukemia 55 years old and younger.

The aim of the study was to determine the effectiveness of 2-chlorodeoxyadenosine (2-CdA) administered in 2-h i.v. infusions in the treatment of B cell chronic lymphocytic leukemia (B-CLL) in patients 55 years old and younger. One hundred and thirteen patients received three to 10 courses of 2-CdA administered at a dose of 0.12 mg/kg daily for 5 consecutive days. Sixty-seven patients were previously treated with chlorambucil and prednisone, COP and some of them also with CHOP, and 46 were untreated. Complete remission (CR) was achieved in 21 (18.6%) (19 in untreated and two in previously treated) patients and partial response (PR) in 38 (33.6%) (23 and 15, respectively) giving an overall response rate in 52.2%. The differences in CR and overall response rate between previously treated and untreated patients were statistically significant (P = 0.001). Surface immunophenotyping by flow cytometry using dual-color staining on the peripheral blood and/or bone marrow was performed in 38 patients who responded to 2-CdA therapy. Residual disease had been demonstrated in five out of 17 (29.4%) patients who were in CR and in all 21 investigated PR patients. 2-CdA-induced thrombocytopenia occurred in 24 (35.8%) of previously treated and in 13 (28.3%) previously untreated patients (P = NS). Neutropenia was observed in eight (11.9%) and in five (10.9%) patients, respectively (P = NS). Severe infections, including pneumonia and sepsis, occurred more often in previously treated (44.8%) than untreated patients (26.1%) (P < 0.05). Twenty-seven (23.9%) patients died, 11 because of infections, five because of drug-related thrombocytopenia and hemorrhage, one because of second malignancy and eight because of disease progression. In conclusion, our results indicate that 2-CdA is an effective agent in younger patients with B-CLL, especially used as a first line therapy.

Adult↗
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↗
PubMed1999

[Rationale and methods for high dose chemotherapy in oncology].

Waiting for a new, highly effective cytotoxic drugs it is necessary to improve antineoplastic treatment using presently existing drugs and methods. Chemosensitive tumors should be treated with intensive, short-lasting courses of the induction as well as of the adjuvant chemotherapy. Chemotherapy delay, dose reduction, unproper therapy regimen increases risk of the development of drug-resistance and treatment failure. Autologous hemopoietic cell transplantation allows cytostatics dose escalation (high-dose chemotherapy, HDCT) with an acceptable non-hematological toxicity. HDCT with autologous peripheral blood stem cell transplantation (auto-PBSCT) is increasingly used. Auto-PBSCT has the same efficacy as autologous bone marrow transplantation (ABMT), but it is a safer procedure, allows more rapid hemopoietic recovery and shorter hospitalization.

Animals↗
PubMed1999

[General characteristics, basis and procedures for high dose chemotherapy procedures supported by hemopoietic stem cell transplantation].

Indications for autologous and allogeneic bone marrow transplantation in hematological malignancies and solid tumours are summarised. AML treatment protocol including induction and consolidation chemotherapy followed by conventional maintenance chemotherapy or high dose chemotherapy with subsequent autologous or allogeneic stem cell transplant are presented. We compared elements and targets of autologous and allogeneic procedures pointing out the major differences regarding transplant related mortality, disease free survival and relapse rates.

Antineoplastic Combined Chemotherapy Protocols↗