[Practical aspects and clinical value of t(14;18) monitoring in peripheral blood of the follicular lymphoma patients]. / Praktické aspekty a reálný klinický význam sledování t(14;18) v periferní krvi pacientu s folikuláirním lymfomem.

BACKGROUND: Evaluation of practical value of monitoring t(14:18) in peripheral blood in follicular lymphoma. METHODS AND RESULTS: t(14;18) was tested in 115 follicular lymphoma patients by methods: FISH, nested and multiplex PCR of blood, bone marrow and lymph node specimens. We tested the patients with rearrangement MBR quantitatively by real-time PCR. Testing intervals of t(14;18) in peripheral blood were 1 month during treatment, 2-3 months during the first year after the end of treatment, then every 4 to 6 months. Patients were clinically examined in the same intervals and regular restaging was done by CT/PET. Each patient was evaluatee separately. Total detection of t(14;18) was 97% regardless tissue and methods of detection, FISH was superior to PCR (95% vs. 72%). The higher number of copies were observed in lymph nodes in comparison to bone marrow (p = 0.036) and peripheral blood (p = 0.016); 46/115 (40%) patients were positive for MBR, we followed up behaviour of t(14;18) in peripheral blood in 33 of them in long intervals (>6 months, med. 33 months). Molecular and clinical courses correlated in 20/33 (61%) patients, 7/33 (21%) clinically relapsed in lasting molecular remission. We found very short interval to clinical relaps in 7 cases of molecular relapses (0-5 months, median 3 months). We could not define "threshold quantity" of clinically important molecular relaps. Lasting molecular remission was associated with clinical in about 60% cases; lasting molecular activity corresponded with clinical relaps in 86% patients. CONCLUSIONS: t(14;18) is highly associated with follicular lymphoma. In practice, monitoring of t(14;18) is feasible only in part of patients. Even if there is some correlation of clinical and molecular course, monitoring of t(14;18) in blood bears only limited prognostic value for the concrete patient. The treatment of patient can not be accomplished on the basis of these results only.

[Evaluation of the clinical effectivity and toxicity of the FDN regimen (fludarabin, mitoxantron, dexamethason) in patients with follicular lymphoma]. / Hodnocení klinické ucinnosti a toxicity rezimu FND (fludarabin, mitoxantron, dexamethason) u pacientu s folikulárním lymfomem.

BACKGROUND: One of the perspective therapeutic possibilities in follicular lymphomas (FL) is the fludarabine-based regimen FND (fludarabine, mitoxantron, dexamethason). However serious signs of myelotoxicity and significant immunosuppression with appearance of the opportunistic infections were described after the fludarabine treatment. METHODS AND RESULTS: Follicular lymphoma patients with advanced disease grade I-II were treated with FND (6-8 cycles). The immunotoxicity was evaluated by measuring of immunoglobuline levels (IgA, IgG, IgM) and that of lymphocytes subpopulations (CD3+, CD4+, CD8+, CD20+, CD56+) in peripheral blood. The myelotoxicity was evaluated by cultures of progenitor cells (CFC and LTC-IC). Totally 34 patients (median age 55.5 years) were evaluated, the overall response was 72% (CR 61%, PR 11%, progression 28%). 73% patients of 11 after 6-8 FND show persisting CR (27% relapsed) with median follow-up about 15 months. The dominating toxicity was myelotoxicity. The leucopenia grade III-IV occurred in about 30% cycles. Because of toxicity it was necessary to reduce doses of FND in 10% cycles and this treatment had to be finished ahead of schedule in 29% patients. The significant immunotoxicity was found only in the decrease of whole lymphocyte population (p < 0.05) and of IgG level (p < 0.05). The decrease of lymphocyte subpopulations did not reach any statistical significance. The long-term myelotoxicity caused the decrease of LTC-IC that had a clinical correlation with the very difficult mobilization of PBSC. CONCLUSIONS: FND is efficient in treatment of follicular lymphoma. However myelotoxicity seems to be limiting. Myelotoxicity doesn't allow administering scheduled dose of FND in substantial amount of patients, long-term myelotoxicity complicates PBSC-mobilization. Lymphotoxicity is apparent, but seems not to be clinically important.

[Hemophagocytic syndrome (case report and literature review)]. / Hemofagocytární syndrom (Kazuistika a review literatury).

The haemophagocytic syndrome (HPS) is clinically characterized by fever, pancytopenia and hepatosplenomegaly. Usually it takes an acute course with a high mortality. The pathogenetic basis is inadequate activation of the immune system--in particular Th1-lymphocytes with subsequent overproduction of cytokines and extreme activation of macrophages with haemophagocytosis. The activated cells infiltrate organs, cause tissue damage and clinical manifestations of the syndrome. From the etiological aspect two forms exist: primary (familial) with autosomal recessive inheritance and the secondary form which forms a heterogeneous sub-group, caused as a rule by infection and/or a tumour. The prognosis seems somewhat more favourable in secondary forms. In treatment which is essentially the same for both forms, chemotherapy combined with immunosuppression proves useful, in more aggressive forms chemotherapy as used in the treatment of non-Hodgkin lymphomas. The only curative method is transplantation of haematopoietic stem cells which is also the treatment of first choice in the familial form of haemophagocytosis. In the submitted paper the authors present a review of contemporary knowledge on this treacherous and relatively rare entity. The haemopgagocytic syndrome should be always taken into account in the differential diagnosis of fever with an obscure etiology. The authors assume that the haemophagocytic syndrome is rarely considered in practice and therefore is usually inadequately diagnosed and thus not treated in time. In the conclusion the authors describe the case-records of a 26-year-old female patient with haemophagocytic syndrome which developed during pregnancy.

[Treatment of acute lymphoblastic leukemia in adults with seven-drug induction therapy and intensive consolidation with or without autologous stem cell transplantation followed by maintenance therapy. Experience of a single center]. / Terapie akutní lymfoblastické leukémie dospelých kombinací sedmi chemoterapeutik v indukcní lécbe, intenzivní konzolidací s autologní transplantací kmenových bunek krvetvorby nebo bez ní a s následnou udrzovací lécbou. Zkusenosti jednoho centra.

BACKGROUND: During the last few years, improvement in prognosis of the adult acute lymphoblastic leukaemia (ALL) has been modest. The probability of leukemia-free survival is 20-40%. Philadelphia-chromosome positive (BCR-ABL positive) ALL has the worse prognosis. A single centre experience with treatment of ALL in adults is reported. METHODS AND RESULTS: Between April 1997 and July 2000, 15 consecutive patients with de novo adult ALL (7 T-lineage ALL, 7 B-lineage ALL, 1 null ALL) begin their treatment with the seven-drug induction regimen (in phase I, daunorubicin, vincristine, L-asparaginase, i.v., and prednisone, p.o.; in phase II, 6-mercaptopurine, p.o., cytosine arabinoside and cyclophosphamide, i.v.) and central nervous system (CNS) prophylaxis (methotrexate and CNS irradiation in patients without total body irradiation in conditioning regimen), with intensive consolidation (three times high-dose methotrexate and high-dose-cytarabine, i.v.), and with/out autologous peripheral blood stem cell transplantation (PBSCT) followed by maintenance chemotherapy (6-mercaptopurine and methotrexate, p.o.). Seven patients received autologous PBSCT. Median patient age was 30 years. Three patients were BCR-ABL positive at diagnosis. With median follow-up 14 month (range 0.1-46 month), seven (4 T-lineage ALL, 2 B-lineage ALL, 1 null ALL) out of 15 patients are alive in remission (four of them receiving autologous PBSCT). Causes of death were relapse (n = 3), chemotherapy related toxicity (n = 2), infection (n = 1), and acute myeloid leukaemia developed 10 months after autologous PBSCT (n = 1). All BCR-ABL positive patients died. CONCLUSIONS: Chemotherapy alone and autologous PBSCT with maintenance therapy may be curative for adult patients with ALL. We can recommend these treatment options for patients without risk factors in particular.

[Who was Mr. McBean and what resulted from his death?]. / Kdo byl pan McBean a co následovalo po jeho smrti.

Authors present a historical overview of multiple myeloma. The first well-known case of multiple myeloma was that of Mr. McBean described in 1846, 1847, and 1850 by John Darlympe, Henry Bence Jones, and William MacIntyre. The term multiple myeloma dates from 1873, and was introduced by von Rusitzky. In 1889, Otto Kahler published the case report about Dr. Loos, his patient with multiple myeloma. In 1895, Marschalkó described the essential characteristics of plasma cells. Authors present other interesting early cases of multiple myeloma and diagnostic advances in this disease.

[Schnitzler's syndrome]. / Schnitzleruv syndrom.

The authors describe the development of disease in a patient with monoclonal immunoglobulin IgM, urticarial morphoeae and intensive pain in the region of the pelvic bones due to osteolysis and osteosclerosis. The combination of these symptoms corresponds with the so-called Schnitzler syndrome which is analyzed in detail in the discussion. The urticarial manifestations diminish only temporarily during corticoid treatment, other drugs have no effect. 2-chlorodeoxyadenosine, the most effective drug in treatment of m. Waldenström, suppressed the skin manifestations temporarily. However, the concentration of monoclonal IgM did not decline even after two cycles and therefore the authors did not proceed with it during subsequent cycles. The severity of urticaria called for a permanent daily dose of Prednisone. The second symptom, bone pain, was however influenced by the administration of pamidronate (Aredia), using an initial dose of 120 mg per month. Now the patient takes a maintenance dose of 60 mg/month. The authors describe the case to draw attention to a rare cause of urticaria and the possibility to treat bone pain with bisphosphonates.