A randomized, double blind comparative study of prophylactic parenteral nutritional support with or without glutamine in autologous stem cell transplantation for hematological malignancies -- three years' follow-up.

Forty-four adult autologous transplant patients with hematological malignancies were randomized to receive either prophylactic parenteral nutrition PN (P group), or PN given ad hoc (C group). In each group, they were further randomized to receive standard PN (B group), or PN with 0.5 g glutamine/kg as L-Ala-L-Gln (A group). The overall survival (OS), disease-free survival (DFS) and event-free survival (EFS) in groups C vs. P and A vs. B were compared during follow-up with median 38 months. The final outcome rates in C/P/A/B groups, respectively (OS 65/81/63/85%, EFS 45/53/33/65% and DFS 56/50/35/77%), were not significantly different, apart from A < B in DFS rate (p=0.03, Fisher's exact test). Also in survival analysis (logrank test), no significant difference between groups C and P was found but generally worse parameters were observed for A vs. B group: for DFS (p=0.04) and EFS (p=0.01) the difference was significant, and for OS (p=0.09) it was borderline. In the three years' follow-up, no clinically useful benefit of prophylactic PN in autologous transplant patients was proven. Also, glutamine supplementation was not helpful, and was even connected with apparently worse long-term outcome.

[Importance of selected laboratory indicators in the differential diagnosis and monitoring of multiple myeloma]. / Význam vybraných laboratorních ukazatelu pro diferenciální diagnostiku a sledování aktivity mnohocetného myelomu.

Multiple myeloma is one of the most common haematologic malignancies. Currently there are numerous studies looking for new prognostic markers in multiple myeloma. The most important of them are the markers related to proliferative activity of neoplastic cells or to size of tumor mass. The subject of this paper are the results obtained from investigation of some such laboratory markers in a group of patients with monoclonal gammopathies diagnosed at our department in the last 3 years. We analyzed blood and bone marrow samples from 51 patients with new diagnosed monoclonal gammopathies, 14 of them were patients with monoclonal gammopathy of undetermined significance and 37 patients had multiple myeloma. 17 patients with multiple myeloma were treated by high-dose chemotherapy regimen. We assessed significance of selected laboratory markers for differential diagnosis of monoclonal gammopathies and for monitoring of activity of multiple myeloma. Among the investigated parameters, we verified the significance of cell cycle analysis of bone marrow plasmatic population and of the determination of the number of circulating myeloma cells in differential diagnosis of monoclonal gammopathies. In our opinion, the determination of soluble CD138, beta 2-microglobulin and neopterin serum levels can be also recommended as helpful markers for a solution of this problem. Except of beta 2-microglobulin serum level we did not find statistically significant correlation with activity of multiple myeloma in any of the investigated parameters.

[Comparison of the effectiveness of idarubicin (Zavedos) and mitoxantrone (Refador) in induction therapy of acute myeloid leukemia in elderly patients (55-75) (a prospective multicenter randomized study conducted 1998-2000]. / Srovnání úcinnosti idarubicinu (Zavedos) a mitoxantronu (Refador) v indukcní lécbe akutní myeloidní leukémie nemocných seniorského veku (55-75 let) (prospektivní multicentrická randomizovaná studie 1998-2000).

The presented study compares the efficacy and the toxicity of idarubicine and mitoxantrone in combination with cytosar (3 + 7) in induction treatment of the patients with AML aged 55-75. 31 patients at the age of 55-75 (median 62) were evaluated in the arm with idarubicine and 29 patients at the age of 57-74 (median 64) in the arm with mithoxantrone. Complete haematological remission was achieved in 13 patients (41.9%) in the arm with idarubicine and 15 patients (51.7%) in the arm with mitoxantrone. The medians of overall survival time (OS) and disease free survival time (DFS) were 22 and 44 weeks in the idarubicine arm and 35 and 40 weeks in the mitoxantrone arm, respectively. Statistical analysis did not prove any significant difference in the complete remission rates, in the number of deaths during cytopenia, in the OS or DFS, in the duration of hospitalisation, severe neutropenia and thrombopenia, in the number of days with febrile neutropenia, or in the consumption of platelets and erythrocytes transfusion units between both arms. Despite the fact that these results are not statistically significant in favour of any treatment arm, which is probably influenced also by the small number of evaluated patients, more favourable results were achieved in the arm with mithoxantrone with the respect to the evaluated parameters. From the point of view of cost-effectiveness, the difference could be observed when considering the price of both intercalating cytostatics. The use of mitoxantrone (Refador, Lachema) is 15x times cheaper per course of treatment than the use of idarubicine (Zavedos, Pharmacia). Autologous peripheral blood stem cells transplantation (APBSC) was carried out only in 4 patients younger than 60. No one of them was cured by APBSC but the median of OS of these patients was longer than the median in the other patients of the group. The results achieved are comparable with those of other trials conducted by various foreign groups. The possible causes of our unfavourable treatment results in this high-risk category of aged patients and the ways how to individualize the treatment with the use of prognostic factors analysis and how to improve the quality of life of the patients has been discussed.

[The treatment of multiple myeloma with an allogeneic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen]. / Lécba mnohocetného myelomu alogenní transplantací periferních kmenových bunek po nemyeloablativním prípravném rezimu.

Between November 1998 and October 1999 authors treated five multiple myeloma patients with an allogeneic peripheral blood stem cell transplantation from HLA-identical sibling using a non-myeloablative conditioning regimen. The median age at the time of transplantation was 58 (range: 47-65) years. In all patients one (n = 3) or two (n = 2) autologous peripheral blood stem cell transplantations were already performed. Conditioning was performed with fludarabine, oral busulfan and anti-T-lymphocyte globulin. All patients engrafted from 13 to 18 (median: 17) days from transplantation. The duration of neutropenia (absolute neutrophiles count < 500/microl) and thrombocytopenia (platelets < 20,000/microl) ranged between 4 and 19 (median: 18) and between 13 and 18 (median: 17) days, respectively. In the period of posttransplant pancytopenia two patients developed mild gastrointestinal mucositis and two pulmonary complications (bronchopneumonia and dyspnoe of unknown etiology). Two patients had grade III-IV acute graft-versus-host disease (GvHD), none had extensive chronic GvHD. Two patients received prophylactic donor-lymphocytes infusions 200 and 225 days from transplantation. One of them developed grade III acute GvHD. All patients responded. One achieved complete and four partial remission of the disease. One patient died 111 days from transplantation due to bronchopneumonia, four are alive and well, in the stable disease, 35, 36, 51 and 52 weeks after transplantation. It can be concluded that allogenic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen is an effective way of the multiple myeloma treatment with an acceptable toxicity.

[A decision-support system for hematology]. / Systém pro podporu rozhodování v hematologii.

Thrombocytopenia and following bleeding at the treatment of hematological malignancies is a dangerous complication. The indication of thrombocyte transfusion is the key point for the therapy and proylaxy of bleeding. The all problem is divided into two parts. Evaluation of the risk of bleeding (80% of decision), estimation of the risk of aloimunization and risk of connected with the transfusion (20% decision). For now we are concentrated to the evaluation of the risk of bleeding. In the first stage we are concentrated to statistical evaluation of values to define factors possibly highering the risk of bleeding. Factors were determined with help of two test, GUHA method and using literature. For recognized factors were trained 3 layer neuron nets with a non-linear method pack propagation. After that an application was developed to determine the risk of bleeding for a routine use in clinical practice.

[Bleeding time in incisions in patients with thrombocyte transfusion]. / Vysetrení krvácivosti v rezu u nemocných s prevody trombocytu.

The authors used the Simplate test (Organon Teknika) to examine the bleeding time from an incision in 15 healthy blood donors and found normal values of 3.45 +/- 0.90 min. The authors proved a close correlation between the improvement of the number of platelets in 10 patients with thrombocytopenia, treated with thrombocyte infusions and the improvement of the bleeding time when using the Simplate R test after one hour and after 24 hours following thrombocyte administration. Examination of the bleeding time by means of the Simplate R test (Organon Teknika) was well tolerated by the authors' patients and the test does not produce any side-effects.

[Treatment of the leukostasis syndrome in chronic lymphadenosis using leukapheresis]. / Syndrom leukostázy pri chronické lymfadenóze, lécený leukaferézou.

The authors draw attention to the leukostasis syndrome which develops in haematological patients in case of enormous leucocyte proliferation. It occurs most frequently in chronic myelosis but may occur also in other types of leukaemia. The diagnosis is not easy. Most frequently disorders of the microcirculation develop in the lungs and brain. These are frequently very urgent clinical situations which can be resolved by leukapheresis. The authors described a patient where during chronic lymphadenosis proliferation of lymphocytes occurred to values of 1432 x 10(9)/l. After leukapheresis and cytostatic treatment rapid improvement of the condition occurred and the leucocyte values were approximately 30 x 10(9)/l. The patient's condition improved for a long period of time and became stabilized.