[Prognostic significance of cytogenetic changes in patients with acute myeloid leukemia (AML). (Analysis of results in 105 patients treated at the Hemato-oncology Clinic of the University Hospital in Olomouc from 1997 to 2000]. / Prognostický význam cytogenetických zmen u nemocných s akutní myeloidní leukémií (AML). (Analýza výsledku 105 nemocných lécených v letech 1997-2000 na Hemato-onkologické klinice FN a LF UP v Olomouci).

Chromosomal aberrations are one of the most important prognostic factors in patients with acute myeloid leukemia (AML). This work present analysis of conventional cytogenetic results completed by fluorescence in situ hybridization (FISH) obtained from 105 patients in the time of diagnosis of AML. The median age of patients was 51 years (range 19-79 years), with slight predominance of women (female to male ratio 1.2:1). The evaluated group involved all patients with AML diagnosis, treated by intensive induction chemotherapy in the Department of Hematology-oncology, University Hospital, Olomouc during last 4 years with assessable cytogenetic results. Chromosomal changes were found in 63 (60%) patients. The most often affected chromosomes in succession of frequency were 8, 17, 7, 5, 11, 15, 16 a 21. Based on found specific and frequent chromosomal changes the patients were divided into 3 prognostic subgroups and the significance of chromosomal aberrations was evaluated. The subgroup of 17 patients with good prognosis consisted of a patients with acute promyelocytic leukemia with translocation t(15;17), 4 patients with t(8;21) and 4 patients with inv(16). 14 patients of 17 live in complete remission, median of overall survival (OS) is 63 weeks. The subgroup of intermediate prognosis was formed by 60 patients, 42 had normal karyotype and 18 patients had other chromosomal abnormalities. Median OS of this group was 35 weeks. The third subgroup with poor prognosis consisted of 28 patients with changes of chromosomes 3, 5, 7, 11 and complex karyotype. 64.3% of patients received complete remission and median OS was 35 weeks. Statistical evaluation of OS showed significant difference (p = 0.002) in subgroup with good prognosis versus subgroup with poor prognosis and in subgroup with good prognosis versus subgroup with intermediate prognosis (p = 0.014). Statistical significance of OS in subgroup with intermediate prognosis versus subgroup with poor prognosis was not proved (p = 0.34), but fit appeared in evaluation of both groups in patients under 55 years. It seems that in patients in age 55 and more the age is independent poor prognostic factor and findings of chromosomal aberrations do not significantly influence prognosis.

[Mantle cell lymphoma as a diagnostic and therapeutic problem]. / Mantle cell lymfom jako diagnostický a lécebný problém.

The authors present the characteristics of a group of 23 patients with mantle cell lymphoma. In the group only a slight predominance of men over women was found (1.1:1), the median age was 63 years. Twenty-one (91%) of the patients were diagnosed in stage IV (Ann Arbor). In all these patients the bone marrow was affected. In 19 of them immunoflowcytometric analysis revealed the typical clone of B lymphocytes (CD5 positive)/CD 23 negative). The majority of patients had at the time of diagnosis a large tumourous mass with massive splenomegaly (61%), hepatomegaly (57%) and bulky disease (52%). The node was excised in 17 patients, but in four patients (24%) during the first session the diagnosis was not assessed correctly. In the laboratory findings an inclination to anaemia, thrombocytopenia, lymphocytosis and in particular to high levels of serological indicators of activity of the disease dominated--lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase. All patients were treated by chemotherapy. Complete remission was achieved by the date of evaluation in one patient (4%), partial remission in seven patients (30%) but 48% patients did not respond to first line treatment. Nine patients of the group died, their median of survival was 14 months (0-24), the median of the follow up of the remaining patients was 133 months (2-31). Two female patients had large-dose treatment with subsequent administration of autologous stem cells. The first one is after 370 days of treatment in complete remission, the second one developed a relapse 100 days after the procedure. From the results and analysis of the literature ensues that mantle cell lymphoma is one of the aggressive malignant B-lymphoproliferations with a very adverse prognosis and it deserves therefore special diagnostic and intense therapeutic attention.

[Interferon-alpha in the treatment of patients with chronic myeloid leukemia]. / Interferon alfa v lécbe nemocných s chronickou myeloidní leukémií.

A retrospective analysis of the treatment with Interferon alpha in 18 patients with Ph positive chronic myeloid leukaemia is presented and compared with the results of peroral chemotherapy with Hydroxyurea or Busulphan in 20 patients. Patients treated with Interferon were significantly younger than the control group (median age 40.5 versus 55.5) (p = 0.01) and were followed-up for shorter period of time (median 10.5 months versus 36.5 months) ( p = 0.002), but did not differ in other parameters. Despite the shorter period of observation and treatment, significantly more complete haematological remissions were achieved with Interferon (86%) than with peroral chemotherapy (25%) (p = 0.03). 6 major and 2 minor (44%) cytogenetic responses were observed after Interferon, despite the fact that 8 patients had been treated for less than one year. Interferon was not the optimal therapy in the patients with additional or complex cytogenetic abnormalities at the time of diagnosis, which were the most significant negative prognostic factor. In general, our short-term results confirm the importance and effectiveness of Interferon in the patient with CML providing the therapy was started early, with an effective dose and with simultaneous cytogenetic monitoring. Longer observation of the patients is needed to confirm the impact of Interferon on the survival of patients.

[Fludarabine monophosphate in the treatment of patients with advanced stages of chronic B-cell lymphatic leukemia resistant to conventional chemotherapy]. / Fludarabin monofosfát v lécbe nemocných s pokrocilým stupnem B-chronické lymfatické leukémie rezistentní ke konvencní chemoterapii.

The authors evaluated retrospectively a group of 12 patients with B-chronic lymphatic leukaemia to whom fludarabine was administered. All patients had been treated in the past by combined chemotherapy (1-4 regimes, median 3). Fludarabine was administered in amounts of 30 mg/m2/day for 5 days to 4 patients and for 3 days to patients. The median of the number of administered cycles was 3. Only two patients achieved partial remission of the disease, the reminder did not respond to therapy. All patients had complications which very probably were associated with the administered treatment. A total of 21 episodes were recorded in the course of 36 cycles, 1 complication per 1.7 cycles. The most frequent complications were infections, a total of 14 episodes, incl. 3 invasive aspergilloses. Infections were more frequent in patients with a 5-day cycle, the majority was recorded after the first two cycles. Eight patients (67%) died from complications which developed in the course of treatment or after its termination. The author's experience with the administration of fludarabine in intensively pretreated patients with advanced forms of B-chronic lymphatic leukaemia indicates that this treatment is associated with a large number of serious complications, which are not compensated by a corresponding therapeutic effect.

[Cytogenetic findings in patients with primary myelodysplastic syndrome and their prognostic significance. (Analysis of results in 65 patients)]. / Cytogenetické nálezy u nemocných s primárním myelodysplastickým syndromem a jejich prognostický význam. (Rozbor výsledku 65 nemocných).

Cytogenetic examination of 65 patients with primary MDS revealed cytogenetic changes in 39 (60%) of the patients. The most frequently affected chromosomes were chromosomes 5, 7, 11, 17 and 20. Deletion of 5q only found in 9 (23%) of the patients with chromosomal changes occurred similarly as simple chromosomal changes most frequently in the prognostically more favourable group MDS-RA. Prognostically adverse monosomy of chromosome 7 was found in 3 patients in group RAEB and RAEB-t but only as part of complex chromosomal changes. The latter were encountered most frequently in patients of groups RAEB and RAEB-t, similarly as trisomy of chromosome 8. Patients in these groups had also a significantly shorter survival time (RAEB 17.7 and RAEB-t 14.2 months) than patients in group MDS-RA (31.5 months). Evaluation of survival according to Kaplan-Meyer's curve revealed significantly longer survival of patients without cytogenetic changes. Laboratory, cytogenetic and clinical findings in four patients with CMML differed from findings of the remaining patients with MDS. This supports the view that this sub-group is rather a myoproliferative conditions than MDS. Transformation to AL was proved in 19 patients. 14 of them (74%) had a chromosomal change at the time of diagnosis.

Compound heterozygosity for a beta zero-thalassemia (frameshift codons 38/39; -C) and a nondeletional Swiss type of HPFH (A----C at NT -110, G gamma) in a Czechoslovakian family.

We have analyzed the levels and composition of the fetal hemoglobin (Hb F) in several members of a Czechoslovakian family with a heterozygosity for a newly discovered beta zero-thalassemia (codons 38/39; -C), or for a newly detected nondeletional hereditary persistence of fetal hemoglobin (a form of Swiss-HPFH with an A----C mutation at nucleotide -100 5' to the Cap site of G gamma), or with a compound heterozygosity for these two conditions. The Hb F level in the beta zero-thalassemia heterozygotes averaged approximately 0.3% with low G gamma values (approximately 28%) and relatively high A gamma T values (approximately 50%), that in the two Swiss-HPFH heterozygotes averaged 0.8% with approximately 95% G gamma, while that of the compound heterozygote was 3.1% with approximately 95% G gamma. The low Hb F levels were determined with a recently published cation exchange high-performance liquid chromatography (HPLC) procedure that is accurate at the 0.1%-0.2% Hb F level. This method, together with a reversed-phase HPLC procedure, made it possible to detect this unusual type of nondeletional G gamma-HPFH and provided the data indicating that the increased Hb F in the compound heterozygote was derived mainly from the chromosome with the HPFH determinant.