[Analysis of causes for anemia in patients with multiple myeloma]. / Analiza przyczyn niedokrwistosci u chorych na szpiczaka mnogiego.

UNLABELLED: Pathogenetic mechanism of myeloma (MM) associated anaemia may involve: decreased level of erythropoietin (Epo) production, insufficient response to this hormone, bone marrow replacement by tumour cells, and cytokine mediated suppressive effect on erythropoiesis (ACD type of anaemia). We evaluated some possible causes of MM associated anaemia in a group of MM patients before treatment, using tests of in vitro culture of erythroid precursors and determination of the level of selected cytokines and evaluation of patient sera and media conditioned by patient cells for haematopoietic growth in vitro inhibitory/stimulatory activity. The study group included 15 patients with advanced MM at III clinical stage (according Durie and Salmon classification) prior treatment with a median age 61.8 women and 7 men. Diagnostic work-up included cytogenetics and serum Epo level as well as routine tests. We determined number of CFU-E, BFU-E and CFU-GM in the bone marrow of patients and healthy donors after mononuclear and T cell depletion in serum free culture under different conditions: 1) with conditioned medium (CM) by patients T cells, 2) CM by T cells of healthy donors and 3) without CM. IL-6, IL-1 alpha and TNF-alpha level in the serum and CM was determined. All patients were slightly anaemic--mean Hb 6 mmol/l (9.6 g/dl), transferrin level was increased--mean 1612 pmol/l (732 ng/ml) whereas iron level was normal. The average frequency of erythropoietic cells in myelogram was decreased (12%), however, the frequency of plasmocytes was increased (32%). Epo serum level was decreased in comparison with degree of anaemia (mean 22.2 U/ml). The average number of CFU-E/10(5) was slightly lower--212 and in the cultures containing CM by patient T cell and CM-by T cells of healthy donor decreased significantly to 138 and 183, accordingly. This phenomenon was not observed in cultures containing normal bone marrow cells. IL-6 level was increased in patients' serum and CM by patients T cells (27 ng/ml and 51 ng/ml, respectively). CONCLUSIONS: The results of this study support the notion on the multifactorial origin of anaemia in myeloma patients. The factors specified in this study include 1. defective response of Epo to the degree of anaemia 2. decreased number of committed erythroid cells in the marrow 3. suppression of erythropoiesis by IL-6.

[Lymphoma lymphoplasmocytoides: a case report]. / Chloniak limfoplazmocytoidalny--analiza kliniczna.

Clinical symptoms and haematological disorders in patients suffering from lymphoplasmatic/lymphoplasmocytoidal lymphoma were presented, 82 patients were examined (median age of 63), all of the in clinical stage IV (ANN Arbor scale). In all of the patients bone marrow was invaded. The most common symptom was enlargement of peripheral lymph nodes (86%) less often abdominal ones (21%). Splenomegalia was found in 55% and hepatomegalia in 49% of patients 35% of patients had anaemia and 38% thrombocytopenia. Close to 1/3 of patients dermatoses were found, in most cases allergic ones. In 7% another cancer was found.

[Erythropoietin in the pathogenesis of anemia in patients with multiple myeloma]. / Erytropoetyna w patogenezie niedokrwistosci u chorych na szpiczaka mnogiego.

UNLABELLED: Anemia is a common symptom in multiple myeloma (MM) patients but the pathogenesis of it is still unknown. The aim of the study was to explain the causes of anemia in MM patients. Peripheral blood count, bone marrow aspirate, iron and ferritin level, serum erythropoietin (EPO) level, T cell subsets and in vitro CFU-E count were analyzed in the group od 31 MM patients. Erythropoietin and iron deficiency in the study group were not observed. EPO serum level was not significantly different in patients with multiple myeloma and in comparison to patients with sideroblastic anemia with solid tumors. Absolute CD8 T lymphocyte count was not significantly increased in the study group. CFU-E colonies count in vitro was not decreased in these patients. CONCLUSIONS: In the study group of the MM patients anemia probably does not depend on EPO production. Diminished proliferative response of erythropoietic cells on normal serum level of EPO and abnormal iron utilisation probably occur in these patients. Replacement of normal erythropoiesis by tumor plasma cells is probably not decisive.

2-Chlorodeoxyadenosine (cladribine)-related eosinophilia in patients with lymphoproliferative diseases.

Eosinophilia and allergic skin reactions are uncommon events after 2-chlorodoxyadenosine (2-CdA, cladribine) administration. A multicentre retrospective analysis of eosinophilia in 360 patients treated with 2-CdA for lymphoid malignancies has been made. B-cell chronic lymphocytic leukaemia (B-CLL) was diagnosed in 153, hairy cell leukaemia (HCL) in 68, low-grade non-Hodgkin's lymphoma (LGNHL) in 119, high-grade NHL in 2 and Waldenstrom's macroglobulinaemia (WM) in 18 patients. 2-CdA was administered at a dose 0.12 mg/kg/d in 2-h intravenous infusion for 5 consecutive d. The courses were repeated monthly. Patients with HCL received 1 cycle of 2-CdA, with NHL 2-6 (mean 3.5) cycles and with B-CLL 3-6 (mean 5) cycles. Twenty patients (5.5%), including 5 with HCL, 6 with LGNHL, 7 with B-CLL and 2 with WM, developed peripheral blood eosinophilia. The mean values of absolute eosinophil count were 0.78x10(9)/l (0.58-1.06x10(9)/l), 0.71x10(9)/l (0.52-1.3x10(9)/l), 85 (0.56-1.82x10(9)/l) and 0.75 (0.74-0.76x10(9)/l), respectively. Eosinophilia occurred in 13 patients after 1 course, in 4 after 2 courses, and in 5 after > or =3 courses of the therapy. In 17 cases it resolved spontaneously. Allergic skin lesions with pruritus were noticed in 3 patients simultaneously with an increase in eosinophil count. All of them required antihistaminic drugs and/or corticosteroids. One patient with B-CLL experienced repeated episodes of eosinophilia. The highest incidence of 2-CdA-induced eosinophilia was noticed in patients with MW (11.1%) and HCL (7.4%) who received only 1 cycle of this drug and entered a complete remission. This side effect was less frequently observed in LGNHL and B-CLL, i.e. in 5.0% and 4.6% of cases, respectively. The mechanism of 2-CdA-induced eosinophilia is not clear. It has been postulated that massive tumour cell lysis may trigger a release of IL-5 and probably other cytokines. The allergic mechanism of 2-CdA-induced eosinophilia is also possible, especially in patients with simultaneous skin reactions.

Activity of 2-chlorodeoxyadenosine (Cladribine) in 2-hour intravenous infusion in 94 previously treated patients with low grade non-Hodgkin's lymphoma.

The purpose of our study was to determine the efficacy of 2-chlorodeoxyadenosine (2-CdA) administered in 2-hour intravenous infusions in previously treated patients with low grade non-Hodgkin's lymphoma (LGNHL). We treated 94 LGNHL patients with 2-CdA at a dosage of 0.12 mg/kg/24h in 2-hour intravenous infusion for 5 consecutive days. The treatment consisted of from 1 to 7 courses (median 3), repeated usually at monthly intervals. All patients were refractory to or relapsed after standard chemotherapy. Of these 94 patients 78 (83%) had clinical stage IV of the disease. Complete response (CR) was obtained in 12 (12.8%) and partial response (PR) in 36 (38.3%) giving an overall response rate of 51.1%. In 12 (12.8%) grade 4 thrombocytopenia with haemorrhagic diathesis was noted, grade 4 neutropenia was observed in 12 (12.8%) and infections complicated the course of treatment in 38 (40.4%) patients. 2-CdA treatment was the cause of death of 3 patients. The results of our study show that 2-CdA given in 2-hour infusions is an effective agent in advanced, heavily pretreated patients with LGNHL.

[Zinc protoporphyrin (ZPP) in diagnosis of anemia]. / Protoporfiryna cynkowa (ZPP) w diagnostyce niedokrwistosci.

In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and the ZPP concentration in erythrocytes increased (normal value < 2.3 micrograms ZPP/g Hb). The ZPP level and comparison with the other normally used tests in iron deficiency in the group of the patients with iron deficiency, ACD, MDS, AML, plasmocytoma was investigated. The ZPP level was determined by hematofluorometry in samples from 96 patients. Thirty five patients with iron depletion showed decreased both serum ferritin (median 5.9 ng/ml), and hemoglobin level (median 9.8 g/dl) with significantly increased ZPP level (median 8.5 micrograms/gHb). An increased level of ZPP (median 3.95 micrograms/gHb) with normal level of ferritin (median 24 ng/ml) and iron (median 50 (g/dl) in the serum of patients with ACD was determined. Measurement of ZPP level in the combination with ferritin and peripheral blood morphology allows to classify the degree of iron deficiency. The ZPP levels higher than 4.55 micrograms/gHb confirms iron deficiency in the group of anaemic patients.

[Nocturnal paroxysmal hemoglobinuria--case report]. / Nocna napadowa hemoglobinuria--opis dwóch przypadków.

Paroxysmal nocturnal hemoglobinuria (PNH)-a case report. We present clinical and postmortem findings in patient with PNH who developed cerebral thrombosis. The pathogenesis of the PNH is discussed.

2-chlorodeoxyadenosine (2-CdA) in 2-hour versus 24-hour intravenous infusion in the treatment of patients with hairy cell leukemia.

Forty one patients with hairy cell leukemia (HCL) were treated with 2-chloro-deoxyadenosine (2-CdA) administered in various schedules. Complete remission (CR) was achieved in 31 (76%) patients and partial remission (PR) in 9 (22%). The mean duration of remission (CR + PR) was 25.2 months (range 9-45 months). One patient did not respond to therapy. Twelve out of 16 patients (75%) achieved CR after 5-day intravenous infusions of 2-CdA and 19 out of 25 patients (76%) after 7-day courses. In 19 out of 23 patients (82.6%) CR was achieved after intermittent 2-hour infusions and in 12 out of 18 (66.7%) after continuous 24-hour infusion. The differences were not statistically significant. Side effects of 2-CdA were similar in both groups except for infections, which were less frequently observed in the group treated for 5 days. The results of our study suggest that 2-CdA can be effectively administered to patients with HCL using 5-day courses and a 2-hour daily infusion.

[Lymphoplasmacytoid lymphoma and the immune system in patients with this type of lymphoma]. / Chloniak limfoplazmocytoidalny a uklad odpornosciowy u chorych na ten typ chloniaka.

Among 82 patients with L-LP in clinical stage IV, 14% were found to have monoclonal gammapathy and 22% polyclonal gammapathy. The other classes of immunoglobulins were not affected. In 78%, cell immunity was impaired. Decrease in T cell count (CD2+ and CD3+) in blood was found. Particularly T helper cells (CD4+), to a lesser degree T suppressor cells (CD8+) were affected. The life time of patients varied from 3 to 120 months. 60% of deaths were caused by infection.

[Bone mineral disorders in patients with multiple myeloma]. / Zaburzenia mineralizacji kosci u chorych na szpiczaka mnogiego.

The aim of the study was to evaluate bone mineralization in the patients with multiple myeloma. The examinations were performed in 49 patients (25 men and 24 women). Seven patients were before chemotherapy and 42 patients were treated with chemotherapy. All of them received prednisone. The bone mineral density was measured by dual-energy X-ray absorptiometry with Lunar spine (L2-L4) in AP projection, femoral neck and total body were examined. There was a decrease of bone mineral density in 35 patients in at least one place (T-score more than 2 SD below normal of young healthy persons). There was no correlation between densitometric results and the duration of multiple myeloma, or chemotherapy. The decrease of bone mineral density (expressed es T-score) of lumbar spine (for the patients without spinal degenerative changes) was higher than that of femoral neck (p < 0.05). The decrease of bone mineral density (expressed as T-score) of lumbar spine and femoral neck was more pronounced than that of total body (p < 0.001). Bone densitometry, especially of lumbar spine and femoral neck and less of total body is indicated in the patients with multiple myeloma. The result of this examination may be considered as an independent parameter of disease intensity.

[Preliminary results of erythropoietin treatment of anemia in myelodysplastic syndromes and chronic lymphocytic leukemia]. / Wstepne wyniki leczenia erytropoetyna niedokrwistosci w zespolach mielodysplastycznych i przewleklej bialaczce limfatycznej.

Six patients with myelodysplastic syndromes (MDS) and two patients with chronic lymphocytic leukemia, all with severe anemia entered the study. Before treatment reasons of secondary anemia were excluded. Concentration of erythropoietin, iron, transferrin, ferritin were measured before, and in the second and the third month of the trial. A r-HuEpo dosage of 80 U/kg was administered intravenously three times weekly for a minimum of three months. Four patients finished the study. The increase in hemoglobin concentration by 6 g% was observed in one patient with MDS subtype RA. In three other patients who apart from r-HuEpo received chemotherapy transfusion requirements decreased by 90%. Together with increase in hemoglobin decrease in ferritin was observed. The correlation between r-HuEpo and endogenous erythropoietin and ferritin was defined.

[Perforation in the gastrointestinal tract as a complication of acute leukemia]. / Perforacja w obrebie przewodu pokarmowego jako powiklanie ostrej bialaczki.

Two cases of gastrointestinal perforation in patients with acute leukemia are reported. They were thrombocytopenic, but successfully surgically treated.

[Effect of calcitonin treatment on bone mineralization in patients with multiple myeloma]. / Wplyw leczenia kalcytonina na mineralizacje kosci u chorych na szpiczaka mnogiego.

The aim of the study was to evaluate the efficacy of half-year treatment of bone mineral disturbances with calcitonin in the patients with multiple myeloma. Thirty five patients (11 men and 24 women) were examined. They were treated among other with prednisone. Nineteen patients (15 patients with normal bone mineral density of lumbar spine and femoral neck and 4 with low bone mineral density who could not be treated with calcitonin) were treated only with chemotherapy. Other 16 patients with low bone mineral density have received also calcitonin (100 units subcutaneous daily) with vitamin D3 and calcium carbonate. Bone mineral density was evaluated with dual energy X-ray absorptiometry in lumbar spine and femoral neck. After treatment with calcitonin there was more pronounced influence on bone mineral density in lumbar spine and femoral neck than after treatment with chemotherapy only but the difference was not statistically significant. Because the bone mineral disturbances in the patients with multiple myeloma is the big problem there is a need for further and longer evaluation of the treatment of these disturbances.

[Detection of minimal residual disease in acute leukemias by immunophenotyping of bone marrow cells]. / Wykrywanie minimalnej choroby resztkowej w ostrych bialaczkach metoda immunofenotypowania komórek szpiku kostnego.

Minimal residual disease (MRD) can be detected only by sophisticated methods, e.g. immunologic. The purpose of the study was to detect MRD in leukemia patients (AL) being in hematological and clinical remission (CR) by immunophenotyping of bone marrow cells and to define the role of the immunologic method in the detection of MRD. Bone marrow samples from 31 patients with ALL and AML and from 18 volunteers were taken several times. Staining of the cells was performed by double color immunofluorescence (IF) and double color immunoenzyme assay (APAAP). The detection of MRD was done by the comparison of the percent of positive cells between AL and normal cases. Each pair of the antigens (CD) was estimated in its usefulness in MRD detection. The statistical analyses were evaluated with a t-Student's test.

[Clinical significance and prognostic detection of minimal residual disease in acute leukemias]. / Znaczenie kliniczne i prognostyczne wykrycia minimalnej choroby resztkowej w ostrych bialaczkach.

The term minimal residual disease (MRD) describes leukemia cells present in bone marrow at a level below that detectable by conventional methodology in patients being in complete hematological and clinical remission (CR). The purpose of the study was, the detection of MRD in leukemia patients (AL-MRD+), the correlation between AL-MRD+ and the chosen hematological and clinical parameters and the follow up, and the prognosis. Bone marrow samples from 31 patients with ALL and AML, and from 18 volunteers were taken several times. Staining of cells was performed by double color immunofluorescence (IF), using flow cytometer and double color immunoenzyme assay (APAAP). The statistical analysis were evaluated with a t-Student's test and chi-squared test.

[Anemia and erythropoietin level in some hematology malignancies]. / Niedokrwistosc a stezenie erytropoetyny w niektórych chorobach nowotworowych ukladu krwiotwórczego.

UNLABELLED: Pathogenesis of anemia in patients with myeloma, low grade lymphoma and acute leukaemia was the aim of the study. Erythropoietin (Epo) serum level was detected according to ELISA test. Significant increase of Epo serum level in 13 myeloma and 30 low grade lymphoma patients was found. In 21 acute leukemia cases the Epo serum level was significantly increased (disproportional to Hb concentration). CONCLUSION: in the studied myeloma and low grade lymphoma patients anemia did not depend on defective Epo secretion. Significant increase of Epo serum level in acute leukaemia, strongly suggested additional stimulation mechanism for hormone synthesis. Further studies of this mechanism are needed.