An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma.

The aim of this study was to assess the prognostic value of pretreatment clinical and laboratory parameters in refractory or relapsed multiple myeloma (MM) patients who have a long-term response to thalidomide (THAL), lasting at least 18 months. The study was carried out on 234 patients who received THAL for relapsed/refractory myeloma. Out of the 234 patients, 129 patients (55.1%) responded to THAL with a mean response duration of 11.9 months (ranging from 1 to 48) and an overall survival rate of 20.3 months (ranging 1-55 months). In 64 patients (27.4% of the whole group), the response to THAL lasted > or =18 months with a mean response lasting 24 months. Statistical analysis of the group of nonresponders and patients with long-term response to THAL showed a significantly higher serum albumin level (P=0.0003) and haemoglobin level (P=0.05), as well as a lower beta2 microglobulin (beta2M) (P=0.022), LDH (P=0.045) serum level in patients with long-term response. In this study, the LDH and serum albumin level were predictors for response to THAL therapy. The beta2M serum level was not a predictor for response to THAL. The albumin serum level was the best parameter distinguishing the group of patients with long-term response to THAL from the entire responding group (P=0.02).

Outcome and prognostic factors in advanced Hodgkin's disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients.

BACKGROUND: The reported probability of survival of patients with Hodgkin's disease (HD) following high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT) is 35-65% at 5 years. The Polish Lymphoma Research Group investigated retrospectively prognostic factors for overall survival (OS) and event-free survival (EFS), and the risk of secondary malignancies in a large series of patients who underwent HDC/ASCT. PATIENTS AND METHODS: The data of 341 consecutive patients treated in 10 centers from 1990 to 2002 were collected and analyzed. RESULTS: The actuarial 5-year OS and EFS were 64% [95% confidence interval (CI) 57% to 71%] and 45% (95% CI 39% to 51%), respectively. In the multivariate model, unfavorable prognostic factors for EFS were less than partial response at the time of ASCT [relative risk (RR), 2.92 (95% CI 1.68-5.08); P<0.001] and three or more previous chemotherapy lines (RR, 2.16; 95% CI 1.42-3.30; P<0.001). These two factors were also associated with unfavorable OS (RR, 3.32; 95% CI 1.90-5.79; P<0.001 and RR, 2.34, 95% CI 1.51-3.64; P<0.001). Five-year cumulative risk of secondary malignancy was 8.4% (95% CI 2% to 13%) and the only identified risk factor was splenectomy (P=0.02). CONCLUSIONS: HDC/ASCT should be considered early in the course of disease for patients with a response after standard therapy.

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.

Second malignancies and Richter's syndrome in patients with chronic lymphocytic leukaemia treated with cladribine.

The increased frequency of second malignancies in chronic lymphocytic leukaemia (CLL) is well known. Moreover, antineoplastic therapy additionally increases the risk of secondary cancers. In this study, we analysed whether treatment with cladribine (2-chlorodeoxyadenosine, 2-CdA) during the course of CLL had an impact on the subsequent occurrence of either secondary solid tumours or Richter's syndrome. There were 1487 eligible patients, 251 treated with 2-CdA alone, 913 treated with alkylating agents (AA)-based regimens alone and 323 treated with both 2-CdA and AA. Median time from the start of CLL treatment to the diagnosis of secondary malignancy was 1.9 years (0.5-5.1 years) for the 2-CdA group, 1.8 years (0.3-7.9 years) for the AA group and 3.9 years (0.3-8.4 years) for the 2-CdA+AA group. A total of 68 malignancies were reported in 65 patients. Ten events were non-melanotic skin cancers and were excluded from the analysis, leaving 58 events in 58 patients. In the group of patients treated with 2-CdA alone, there were 15 (6.0%) cases, in the group of patients treated with AA alone there were 26 (2.8%) cases, and in the group treated with 2-CdA+AA there were 17 (5.3%) cases of secondary malignancies. The differences between the frequency of secondary malignancies in the 2-CdA and 2-CdA+AA versus AA alone groups were not significant (P=0.05 and P=0.06, respectively). Only lung cancers occurred significantly more frequently in the 2-CdA (2.8%) and 2-CdA+AA (2.2%) treated groups compared with the AA patients (0.3%) (P<0.001 and P<0.01, respectively). In conclusion, 2-CdA in CLL patients does not seem to increase the risk of secondary malignancies except for lung cancers. However, further studies are necessary to establish the real risk of lung cancer in CLL patients treated with 2-CdA.

High-dose chemotherapy with autologous stem cell transplantation is an effective treatment of primary refractory Hodgkin's disease. Retrospective study of the Polish Lymphoma Research Group.

We analysed the treatment outcome of primary refractory HD patients managed with high-dose chemotherapy and haematopoietic cell transplantation. Data of 65 adult patients who underwent HDC/ASCT in nine Polish centres for primary resistant Hodgkin's disease between June 1991 and July 2000 were collected retrospectively. Response rate to HDC/ASC: CR, 54%; PR, 20%; less than PR, 15%; early deaths, 11%. Actuarial 3-year OS and PFS were 55% and 36%, respectively. In multivariate analysis, lack of bulky lymph nodes and use of immunotherapy were favourable factors for both OS and PFS. IPF <3 at the time of transplantation was predictive for PFS. However, the prognostic impact of immunotherapy should be interpreted with caution since this group included more patients who achieved CR after HDC/ASCT. The results of HDC/ASCT are encouraging and confirm earlier findings. The role of immunotherapy should be further investigated in prospective trials.

First cases of acute human granulocytic ehrlichiosis in Poland.

The first three cases of acute human granulocytic ehrlichiosis in Poland are described. Blood samples were tested by an indirect immunofluorescence method to detect specific serum antibodies, and the polymerase chain reaction was used to detect ehrlichial DNA. Additionally, peripheral blood smears were examined for the presence of morulae. According to criteria of the Centers for Disease Control and Prevention, all three cases can be classified as confirmed granulocytic ehrlichiosis. Using the criteria recommended by a consensus group, however, two cases can be classified as confirmed granulocytic ehrlichiosis and one case as probable granulocytic ehrlichiosis.

[Evaluation of nephrologic "risk" in a newly diagnosed case of plasma cell dyscrasias from personal material (1994-2000)]. / Ocena "ryzyka" nerkowego w swiezo wykrytych przypadkach dyskrazji komórek plazmatycznych w materiale wlasnym (lata 1994-2000).

UNLABELLED: Among 149 patients with recently recognized plasma cell dyscrasia (PCD) in years 1994-2000 72 persons with serologically and nephrologically documented diagnostic profile were selected. In this group of pts we assessed dependence between degree of reduced glomerular filtration rate (GFR), evaluated by serum creatinine concentration and calculated with Barasckay's formula and hypercalcemia, hyperuricemia as well as type of monoclonal protein in urine. RESULTS: We revealed statistically significant higher values of calcium (p = 0.005), uric acid (p = 0.000001) concentrations and higher occurrence of Bence-Jones proteinuria (mainly kappa) in 22 patients with serum creatinine > 1.5 mg/dl in comparison with 50 patients with serum creatinine < or = 1.5 mg/dl. Among 72 patients, GFR > 90 ml/min, calculated with Barasckay's formula, was stated only in 9 patients (12.5%). There was no difference in nephrotoxity between kappa and lambda light chains with reference to serum creatinine concentration and GFR. The group of 12 patients with light chain dyscrasia (LCD) had higher degree of nephrotoxicity in comparison with other forms of PCD. On the basis of our study we concluded that patients with clinical suspicion of PCD, especially those with LCD are referred to a special Protein Laboratory too late, it means at the time of significant nephrological risk in the form of low glomerular filtration rate, hypercalcemia and hyperuricemia.

Impaired skin microcirculation and blood rheology in patients with monoclonal gammapathy.

Hemorheological disturbances in patients with monoclonal gammapathies are widely known, but there is little information about microcirculation in these patients. The following study was performed to examine skin microcirculation and its relationship with blood rheology. We analysed both haematological and hemorheological parameters (blood and plasma viscosity, aggregation index and filterability of 1 ml of whole blood) and skin microcirculation in 46 patients with monoclonal gammapathy and 22 healthy controls. Microcirculation on dorsal aspect of the hand was examined with laser Doppler flowmeter. We measured resting flow and biological zero and maximal flow during postischemic hyperaemic reaction after one minute occlusion on the arm. The same parameters were estimated for CMBC (concentration of moving blood cells). Patients with monoclonal gammapathy are characterised by statistically higher whole blood and plasma viscosities and other hemorheological parameters and disturbed skin microcirculation expressed as statistically significant lower resting flux and impaired reaction for temporary occlusion.

[Diagnosis of the increase of lymph nodes in the abdominal cavity]. / Diagnostyka powiekszenia wezlów chlonnych jamy brzusznej.

Isolated abdominal lymphadenopathy is not such a common but a real diagnostic problem. Widespread prevalence of ultrasonography in routine diagnostics has been contributed to its greater recognition. In the first part of the article examinations which lead to the diagnosis (such as: microbiological examination, ultrasonography, CT, MRI, lymphography, histopathological examination) are discussed basing on the literature. The potential etiology of abdominal lymphadenopathy is described in the second part of the article. The characteristic changes are discussed for mentioned disease entities.

[Examination of skin microcirculation with laser-Doppler flowmetry in patients with essential hypertension]. / Wykorzystanie wlosniczkowej przeplywometrii laserowej do oceny stanu mikrokrazenia skórnego u chorych na nadcisnienie tetnicze samoistne.

The estimation of microcirculatory parameters in patients with essential hypertension and in normotensic control group was the aim of this study. The study group consisted of 14 patients with essential hypertension confirmed by 24-hours ABP. 10 healthy patients served as control group. The flow in the skin microcirculation was measured by laser-Doppler flowmeter (PF-3, PERIMED) on dorsal part of the palm. Microcirculatory indices were registered in resting conditions, during one-minute occlusion reaction and during reactive hyperemia. The following indices were calculated: resting flow, biological zero, maximal flow, time to maximal flow, ratio of maximal to resting flow, ratio of resting flow to biological zero and ratio of maximal flow to biological zero. Skin microcirculation was highly disturbed in patients with essential hypertension. It was expressed by significantly higher biological zero and longer time to maximal flow.

[Five cases of acquired pure red cell aplasia]. / Piec przypadków nabytej wybiórczej aplazji ukladu czerwonokrwinkowego.

Acquired pure red cell aplasia is rare disorder of hematopoiesis. Because of the variety of reasons for PRCA optimal treatment is based on highly specialistic diagnostics. Both humoral and cellular mechanisms are involved in the pathogenesis of PRCA. Corticosteroids, cyclosporin A, high-dose intravenous immunoglobulin therapy are recommended in PRCA. Treatment failures may be successfully managed with antihuman thymocyte globulin, cyclophosphamide or azathioprine. We describe also the lots of five patients with this disorder.

[Changes in the quality of life influenced by treatment of primary arterial hypertension]. / Zmiany jakosci zycia pod wplywem leczenia pierwotnego nadcisnienia tetniczego.

The quality of life (QL) in 90 male patients (age 41.2 +/- 41) suffering from Ist IInd hemodynamic WHO-stage of essential arterial hypertension has been studied during 3 months therapy. The patients have been divided into 3 groups treated with enalapril, atenolol and verapamil respectively. The Sickness Impact Profile, Bulpitt's test and Spitzer's test were used for evaluation of QL. Significant reduction in diastolic arterial blood pressure has been achieved during the treatment period. In the same time improvement in QL indices was observed, most evident in group of enalapril, moderate in group of verapamil and the minor in atenolol group. It is concluded that these three QL test (SIP, Bulpit, Spitzer) are very useful in monitoring of treatment of the essential arterial hypertension.

[Anxiety and depression during chemotherapy for lymphoproliferative diseases]. / Lek i depresja w przebiegu chemioterapii chorób limfoproliferacyjnych.

In order to analyse anxiety and depression states observed during the treatment of lymphoproliferative diseases, a group of 23 patients were studied. For assessment of the variables the following was used: history taking, psychological observation and psychometric techniques. The obtained results point to various dynamics of anxiety and depression. The intensity of anxiety states decreases during single as well as successive courses of chemotherapy. Depression states intensify during one course with a tendency for mood lowering with prolonged treatment duration. Therapeutic conclusions: 1. It is necessary to minimize anxiety attitudes, particularly during the first phase of the treatment (cognitive psychotherapy). 2. In deep depression it is indicated to use antidepressants and supportive psychotherapy.

[Laser Doppler flowmetry--a new promising technique for assessment of the microcirculation]. / Wlosniczkowa przeplywometria laserowa--nowa obiecujaca metoda badania mikrokrazeniowa.

The laser Doppler flowmetry is a new technique for evaluating microcirculation. It is based on the Doppler phenomenon-reflected light changes its frequency when it interacts with moving objects such as red blood cells. The source of light is 2 mW He-Ne laser. The light penetrates into the tissue to the depth of 1 mm, and measures microvascular blood flow throughout it. This technique is objective, harmless even during prolonged exposition, repeatable, and very sensitive even to small changes in the blood flow. Because of difficulties with determination of the perfusion normal values and several factors disturbing microcirculation, the most objective results are obtained with dynamic tests. They measure a response of microcirculation to local ischemia, cooling or given medicines. A disadvantage is its high sensitivity to motion-produced disturbances. Laser Doppler flowmetry may be used not only in scientific investigations. It is of diagnostic value in plastic surgery, vascular surgery, dermatology, internal medicine, dentistry, and neurology.

[Psychological aspects of bone marrow marrow transplantation]. / Psychologiczne aspekty przeszczepiania szpiku kostnego.

Bone marrow transplantation is connected with many psychological problems of the patient determined mainly by the procedure itself. In individual phases of bone marrow transplantation (qualification of patients for operation, peritransplantation and post-transplantation periods, and final phase) different disturbances and difficulties are seen. Own observations as well as the literature data indicate the need of full diagnosis and psychotherapy, and sometimes even of psychiatric intervention during that method of treatment.

[Effect of erythropoietin on some rheological and biochemical properties of blood in dialysed patients with irreversible kidney failure. Preliminary results]. / Wplyw erytropoetyny na wybrane parametry reologiczne i biochemiczne krwi chorych z nieodwracalna niewydolnoscia nerek leczonych powtarzanymi dializami. Doswiadczenia wstepne.

6 patients with symptomatic renal anaemia treated with haemodialysis (3F, 3M, aged 41 +/- 17 years) were given r-Hu EPO in initial dose of 50 U/kg, modified during the treatment, according to the Hkt, and Hgb values. Some biochemical and rheological properties of blood taken before treatment showed: normochromic and normocytic anemia with Hkt 22.7 +/- 1.7% Hgb 6.81 +/- 1.6 g% and normal reticulocytosis: significant (p less than 0.001) decrease of whole blood viscosity (WBV) at low shear rate (2.25 x sec-1) and high shear rate (225 x sec-1) related to Hkt values, and significant increase of red celles aggregation (RCA) (p less than 0.02) in comparison to healthy persons. Plasma viscosity (PV), serum fibrinogen, protein and albumin were normal. In 4 patients treated with r-Hu EPO for 12 weeks at least, we observed an increase Hkt to 36.7 +/- 2% and Hgb to 11.2 +/- 1.2 g% and a significant increase of WBV at high shear rate (p less than 0.05), normalization of RCA and improvement of the filtrability of whole blood. No side effects were observed, especially insufficient control of blood pressure. Our preliminary results indicate that our treatment of renal anemia with r-Hu EPO was clinically effective, safe and had positive influence on blood rheology.

[Our first experience with allogeneic and autologous transplantation of hematopoietic stem cells]. / Pierwsze wlasne doswiadczenia z allo- i autotransplantacja krwiotwórczych komórek macierzystych.

The main problems and difficulties in transplantation of haematogenous stem cells are discussed. The problems include: organization of a team of specialists and bone marrow transplantation centre, preparation of the recipient (patient) complications connected with preparation for transplantation, graft taking, graft versus host disease, recurrence of the underlying disease. In the analysis only those patients (8 cases) are included who had received marrow transplantation after chemotherapeutic-radiotherapeutic preparation (3 patients are alive). The first experiences are described also with three autotransplantations of haematogenous stem cells obtained by means of cell separator from peripheral blood. These experiences indicate that it is possible in our country to carry out this highly sophisticated method which requires, however, further improvements and ensuring of adequate personnel and equipment.