[Patients older than 80 years with de novo acute myeloid leukemias without erythroblastic and/or megakaryocytic dysplasia achieve complete remission and longer survival after classical chemotherapy 3 + 7]. / Nemocní starsí 80 let s de novo akutními myeloidními leukemiemi bez dysplazie v erytroblastické 8/nebo megakaryocytární rade dosahují kompletní remise a delsího prezlití po klasické chemoterapii 3+7.

Chemotherapy in most patients with AML over 80 years of age is not recommended because their median survival is about 1 month. The aim of our study was to identify patients in this age group who might achieve complete remission with standard dose chemotherapy. We report 9 consecutive patients with de novo AML diagnosed and treated in 1992-2008. All bone marrow samples were hypercellular, classified as FAB types M2 in 2 cases, M4 in 6, and M5 in one case. Three patients opted for supportive or palliative therapy and survived 1-4 months. Six patients received standard dose chemotherapy. Two patients with a normal karyotype had resistant AML and survived 1.0 and 2.7 months; one patient with a complex karyotype died of septic shock on the 10th day of therapy. All these three patients exhibited erythroblastic and/or megakaryocytic dysplasia (EMD) at presentation (two in more than 26% erythroblasts, all three in a half or more of megakaryocytes). Three remaining patients with AML M4, a normal karyotype but without EMD, achieved complete remission in spite of co-morbidities and a poor performance status. Two of them survived 18.6 and 28 months on maintenance therapy, the third 16.5 months without it. Very elderly AML patients without EMD appear to represent a favorable prognostic biological category (single-lineage AML) that show a good response to standard dose chemotherapy.

CD87 (urokinase-type plasminogen activator receptor), function and pathology in hematological disorders: a review.

The analysis of CD87 (urokinase-type plasminogen activator receptor - uPAR) expression has a potential role in the diagnostic or prognostic work-up of several hematological malignancies, particularly acute leukemia and multiple myeloma. The distribution of CD87 in acute myeloid leukemia (AML) varies according to the FAB subtype (highest expression in M5 and lowest in M0). Functionally, it is conceivable that the expression of CD87 could contribute to the invasive properties of the leukemic cells towards the skin and mucosal tissues as reflected by the clinical behavior of CD87 high cases. The lack of or weaker expression of CD87 on blast cells from ALL patients supports the concept that CD87 investigation might help in the distinction of AMLs from lymphoid malignancies. Among lymphoproliferative disorders, the expression of CD87 is exclusively found in pathological plasma cells. Since plasma cells also coexpress some adhesion molecules such as CD138 and CD56, this observation is consistent with the capacity of these cells to home in the bone compartment. High levels of soluble uPAR appear to represent an independent factor predicting worse prognosis and extramedullary involvement in multiple myeloma.

Chemotherapy for acute myeloid leukemias with cytosine arabinoside, daunorubicin, etoposide, and mitoxantrone may cause permanent oligoasthenozoospermia or amenorrhea in middle-aged patients.

The aim was to follow-up gonadal functions in long-term survivors of acute myeloid leukemias (AML) after intensive chemotherapy based on high-doses of cytosine arabinoside (Ara-C) and anthracyclines in the study UHKT-911. Adult patients were treated with at least 3 cycles of chemotherapy including 1-3 courses of Ara-C 10 x 2000 mg/m2/12 h and daunorubicin (DNR) 2 x 45 mg/m2/d. Spermiologic examinations were performed in 7 men by the classic microscopic method and results were evaluated according to the WHOcriteria. Two patients (42- and 47-year-old) after DNR and Ara-C chemotherapy had nearly normal spermiologic findings. The semen of a 49-year-old patient contained normal numbers of spermatozoa with decreased velocity when examined 1 year after chemotherapy but 4 years later exhibited oligoasthenozoospermia. The patient received 4 cycles of Ara-C and DNR plus one cycle with etoposide 350 mg/m2 and mitoxantrone 30 mg/m2. Semen examination of two patients 55- and 59-year-old showed permanent oligoasthenozoospermia with only sporadic progressively motile spermatozoa which might not be compatible with fertilization by sexual intercourse. They received the same chemotherapy including cumulative doses of etoposide 500 mg/m2 and mitoxantrone 36 mg/m2. Semen of two patients after allogeneic bone marrow transplantation exhibited severe oligoasthenozoospermia with no motile spermatozoa. Permanent amenorrhea developed in two women (42- and 46-year-old) during chemotherapy with DNR, Ara-C, etoposide, and mitoxantrone which was not the case in three women (29-40 years old) treated without etoposide and mitoxantrone. Intensive chemotherapy with high-doses of Ara-C and DNR plus one cycle of etoposide and mitoxantrone may cause permanent gonadal dysfunction in middle-aged patients with AML.

Efficacy of dexrazoxane as a cardioprotective agent in patients receiving mitoxantrone- and daunorubicin-based chemotherapy.

Dexrazoxane (DEX) selectively blocks the development of irreversible diffuse myocardial toxicity induced by anthracyclines and related antitumor agents, such as mitoxantrone (MTX). Therefore, daunorubicin (DNR) should not be administered to patients with cumulative DNR doses higher than 550 to 700 mg/m2, which we used for remission induction and consolidation therapy in patients with acute myeloid leukemia (AML). To administer further doses of anthracyclines without risks in seven relapsed AML patients and in one patient with impaired heart functions receiving consolidation therapy, we used DEX as a cardioprotective agent. Patients received DEX 30 minutes before DNR 45 mg/m2 or MTX 10 mg/m2 in doses eight to 13 times higher (DNR) or 30 to 60 times higher (MTX) in the treatment cycle with 10 high doses (2,000 mg/m2/12 hr) of cytosine arabinoside plus two doses of DNR or MTX on the fourth and fifth day. When this cycle was used as reinduction therapy, complete remission was achieved in all five cases. A cycle of MTX and etoposide was given three times with DEX as consolidation. Myelotoxicity of the treatment cycles with DEX was similar to the cycles without it. Two patients received cumulative anthracyclines doses corresponding to more than 1,300 and 1,000 mg/m2 of DNR, respectively; the remaining five relapsed patients received 550 to 850 mg/m2 of DNR, all without signs of cardiac toxicity. Delayed administration of DEX after cumulative doses of DNR 500 mg/m2 in AML patients at relapse provides cardioprotection against DNR or MTX in combination with high doses of cytosine arabinoside. This type of chemotherapy seems to be effective for remission induction in relapsed, heavily pretreated AML patients or in patients with impaired heart functions.

Erythroblastic and/or megakaryocytic dysplasia in de novo acute myeloid leukemias M0-M5 show relation to myelodysplastic syndromes and delimit two main categories.

Erythroblastic and/or megakaryocytic dysplasia (EMD) was evaluated in diagnostic bone marrow smears of 43 consecutively treated patients under 65 years with de novo acute myeloid leukemia (AML) M0-M5 according to FAB criteria. The evaluation was possible in 39 (91%) patients, i.e. in 32 of 34 patients with non-M3 AML treated in the study UHKT-911 and seven of nine cases with AML M3 treated in other studies. Among non-M3 AML 15 patients were categorized without EMD and 17 cases with EMD. Cytogenetic abnormalities of chromosome 5, 7, 3 or a complex karyotype were found in eight of 17 patients with EMD and in one of 15 cases without EMD (P = 0.018). Seven patients in each category exhibited a normal karyotype. Classical induction therapy with three to four doses of daunorubicin 45 mg/m2 and standard doses of cytosine arabinoside (AraC) for 7 days lead to complete remission in 11 of 14 (78.6%) cases without EMD but only in four of 14 (28.6%) cases with EMD (P = 0.021). High doses (2000 mg/m2 per 12-h x 10) of AraC plus daunorubicin induced complete remission in seven of 10 patients with EMD. Patients with EMD showed significantly worse overall survival (P = 0.03) with a median 13.5 months, while the median survival was estimated to 68.7 months in cases without EMD. The dysplastic features of EMD, karyotypes typical for myelodysplastic syndromes (MDS), poor response to classical therapy and survival show a relation of AML with EMD to MDS. AML without EMD may represent a different biological favorable category.

Three cases of near-tetraploid acute myeloid leukemias originating in pluripotent myeloid progenitors.

We report three cases of acute myeloid leukemia (AML) with a near-tetraploid karyotype in most metaphases while lacking chromosomal abnormalities typical for AML. All patients, 63, 72 and 81 years old, were female. In two cases, AML was diagnosed 5-7 months after a cytopenic period while the third patient had a secondary AML after therapy for a pleural tumor. Leukemic blasts were classified as AML M0, AML M1 and AML without further specification. Two patients died on the 18th and 52nd day after the start of cytotoxic chemotherapy, the third patient refused chemotherapy and died 22 days after the diagnosis. The three patients may represent a distinct AML category with the following features: (1) the near-tetraploid karyotype in most bone marrow metaphases examined at diagnosis of AML; (2) the presence of very large myeloid blasts in the bone marrow and dysplastic changes in erythroid and/or megakaryocytic lineages pointing to the origin of AML in pluripotent myeloid progenitor cells; (3) the expression of the CD34 antigen; (4) the low growth of granulocyte-macrophage colony forming cells in culture; and (5) the presence of a preleukemic phase, a higher age and a poor prognosis.

Near-tetraploid poorly differentiated acute myeloid leukemia M0 diagnosed by short-term cultures with a phorbol ester TPA.

Leukemic blasts of two patients with acute leukemia exhibited similar characteristics. They were heterogeneous in size with a diameter of 14-30 microns in smears and unclassifiable by morphological, cytochemical, immunophenotypic and ultrastructural examinations. Cytogenetic examinations of both revealed a near-tetraploid karyotype. Blasts from both patients differentiated into macrophages in cultures with 10 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA) which is a feature specific for myeloid blasts and the cases were thus classified as poorly differentiated acute myeloid leukemias (AML M0). Near-tetraploid poorly differentiated acute myeloid leukemias M0 seem to be a special category of AML in the morphologic, immunologic and cytogenetic (MIC) classification. The presence of very large blasts in the heterogeneous blast population in acute unclassified leukemias could be a morphological sign of near-tetraploid leukemias AML M0.

Derivative (6)t(1;6)(q22;p21) revealed in bone marrow cells by FISH 9 months before diagnosis of acute T-lymphoblastic leukemia.

A chromosomal clone with unbalanced translocation resulting in partial trisomy of segment 1q22-qter and partial monosomy of segment 6p21-pter was revealed by fluorescence in situ hybridization (FISH) using a panel of different whole chromosome painting probes. The pathologic clone appeared after sequential chemotherapy treatment for AML-M5 when the patient was in complete remission before development of T-ALL. However, this clone was present during the whole period of treatment for T-ALL. The clone remained the only chromosomal aberration found. Breakpoints were detected more easily and more precisely with the use of the FISH technique than with G-banding only.

Significance of lineage specific differentiation markers for complex classification of acute leukemias. I. Acute myeloid leukemias.

Acute leukemias are clonal malignant neoplastic diseases which do not originate from the transformation of totipotent hematopoietic stem cells but of progenitors committed to the myeloid, T-lymphatic or B-lymphatic differentiation lineage. The transforming event seems to be associated with a nonrandom aberrant DNA rearrangement. Although a leukemic population is clonal, originating from a single cell, it exhibits phenotypic, and sometimes even karyotypic, heterogeneity. Leukemic cells are allocated to a particular differentiation cell lineage on the basis of a positive finding of the lineage specific differentiation marker (LSDM) in the presented classification of acute leukemias. Criteria for common types of acute myeloid leukemias are described and the possible existence of several other types is discussed.

Significance of lineage specific differentiation markers for complex classification of acute leukemias. II. Acute lymphoblastic leukemias.

Acute lymphoblastic leukemias originate from cells committed either to the T-lineage (T-ALL) or B-lineage (nonT-ALL). Leukemic cells are allocated to these lineages according to the expression of lineage specific differentiation markers (LSDM), which are T-cell antigen receptors for the T-cell lineage and immunoglobulins for the B-cell lineage. T-ALL seem to be one type of disease, among nonT-ALL it is possible to distinguish several types of diseases according to the immunoglobulin expression and clinical findings. The specificity of monoclonal antibodies and other markers is discussed with regard to the classification of ALL and "hybrid acute leukemias" (hAL), the latter with cells differentiating into myeloid and lymphoid lineages. The existence of a single hAL has not yet been reliably proved with the use of LSDM. Short-term cultures of leukemic cells represent useful diagnostic tools particularly for acute unclassifiable leukemias. Present knowledge of karyotype findings in acute leukemias classified according to LSDM is reviewed and the necessity to introduce a complex classification on this basis stressed.

Protective effects of cardioxane against anthracycline-induced cardiotoxicity in relapsed acute myeloid leukemias.

The clinical use of anthracyclines and related antitumor agents is limited by their cumulative dose-related cardiac toxicity. Cardioxane (ICRF-187) is an agent that has been recommended to block selectively this toxicity which e.g. limits the use of daunorubicin (DNR) in doses higher than 550-700 mg/m2. We decided to use cardioxane in patients with relapsed acute myeloid leukemias (AML) who have previously been treated with DNR doses above 500 mg/m2. Seven patients with relapsed AML received cardioxane 30 min before DNR or mitozantrone (MTZ) in doses 8-13x higher than DNR or 40-60x higher than MTZ. Two patients received anthracyclines cumulative doses corresponding to more than 1300 mg/m2 and 1000 mg/m2 of DNR, respectively, without any signs of cardiac toxicity. The other 5AML patients in relapse received 1-3 chemotherapy cycles with cardioxane. Their total cumulative doses of DNR were 550-750 mg/m2 and their left ventricular ejection fraction remained above 50% as were their pretreatment values. Cardioxane seems to be a useful cardioprotective agent in relapsed AML which enables further treatment with anthracyclines.

Do de novo acute myeloid leukemias with normal cytogenetics involve two main prognostic categories distinguished by the presence of erythroblastic and/or megakaryocytic dysplasia?

De novo acute myeloid leukemias (AML) patients with normal cytogenetics represent a standard risk cytogenetic group. Erythroblastic and/or megakaryocytic dysplasia (EMD) in diagnostic bone marrow smears of 28 consecutive AML patients with a normal karyotype was studied. Twelve patients 21-85 (median 48) years old were categorized without EMD, 14 patients 34-90 (median 58) years old with EMD, and 2 patients were not evaluable for EMD. One cycle of induction therapy 4 + 7, with 4 doses of daunorubicin 45 mg/m2/d and standard doses of cytosine arabinoside for 7 days induced 10 complete and 2 partial remissions in 12 cases without EMD but lead to only one complete remission, 6 non-responses and 3 induction deaths in 10 cases with EMD (p = 0.002). However, high doses of cytosine arabinoside plus daunorubicin induced complete remission in 6 of 7 patients with EMD. In patients under 66 years treated by intensive consolidations the estimate of median survival was 50.6 months in 10 cases without EMD, significantly higher than 8.0 months in 11 cases with EMD (p = 0.043). De novo AML with normal cytogenetics might be divided into two biological categories, the first favorable-risk category without EMD and the second poor-risk category with EMD.

Differentiation of human myeloid leukemia cell line ML-1 induced by retinoic acid and 1,25-dihydroxyvitamin D3.

Human myeloblastic leukemia cell line ML-1 was induced to differentiate by 1 mumol/l all-trans-retinoic acid (RA) or by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). After 4-6 days of the induction several differentiation-associated characteristics were observed: (1) Ability to stimulate respiration burst in the ML-1 induced cells as detected by nitroblue tetrazolium (NBT) test or by chemiluminescence (CL). (The percentage of the NBT-positive cells was up to 99% in the RA-induced cells and up to 85% in the 1,25(OH)2D3-induced cells.) (2) Substantially higher phagocytosis of colloid iron, latex or Staphylococcus particles was found in the induced cells. (3) The 1,25(OH)2D3-induced ML-1 cells expressed the monocytic enzyme NaF-inhibitable alpha-naphthyl butyrate esterase and the surface monocytic antigen CD-14. (4) A majority of the induced cells lost the morphological features of blast cells; while the 1,25(OH)2D3-treated cells acquired certain features of monocyte-macrophage differentiation, the RA-treated cells displayed several granulocytic characteristics. (5) Cytofluorometric DNA assay after treatment of the cells with colcemid showed that the decline observed in the growth rate of the induced cells was connected with their arrest in G1/G0 phase of the cell cycle. The obtained results indicate granulocytic differentiation of the RA-induced ML-1 cells and monocyto/macrophage differentiation of the 1,25-(OH)2-D3 induced cells.

To the incidence of nucleoli in circulating myeloblasts of patients suffering from acute myeloblastic, promyelocytic and myelomonocytic leukemias.

Nucleoli were studied in circulating myeloblasts of myeloblastic (FAB M1, M2), promyelocytic (FAB M3) and myelomonocytic (FAB M4) acute myeloid leukemias (AMLs) using a cytochemical procedure for the demonstration of RNA. In patients untreated with cytostatic chemotherapy, myeloblasts of myeloblastic acute leukemias possessed less frequently "active large" nucleoli and more frequently "inactive" micronucleoli in comparison with other investigated types of AMLs. When myeloblasts were classified according to the presence of functionally dominant nucleoli, the higher percentage of "terminal" myeloblasts containing only micronucleoli in this type of AML was significantly reduced in patients treated with the cytostatic chemotherapy. In patients suffering from promyelocytic leukemia treated with cytostatic chemotherapy, the decreased percentage of myeloblasts containing functionally dominant active large nucleoli was accompanied by the increased incidence of myeloblasts with functionally dominant "resting" ring shaped nucleoli. In myelomonocytic AML no significant differences were noted between patients untreated or treated with the cytostatic chemotherapy in the incidence of main nucleolar types in myeloblasts and myeloblasts classified according to the presence of functionally dominant nucleoli. Thus a further biological specificity might exist among leukemic blasts in various types of AMLs which should be considered for a rational approach to the therapy of these malignancies. In addition, the cytostatic chemotherapy did not influence incidence of the nucleolar asynchrony in myeloblasts of all investigated types of AML.

Human placental conditioned medium (from different phase of pregnancy) as a source of colony-stimulating activity for cultures of human and mouse. granulocyte-macrophage colony-forming cells in semisolid agar.

We have investigated the effect of conditioned medium derived from cultures of human placental tissue from different phases of pregnancy on in vitro growth of human and mouse granulocyte-macrophage colony forming cells in semisolid agar. We have confirmed that the colony-stimulating activity of human placental conditioned (normal delivery) medium was equivalent to the activity of peripheral blood leucocyte underlayers when medium was added at a 5%-20% concentration to the semisolid agar. Placentas from the 12th amd 10th week of gestation were found not convenient for preparation of medium with high CSA; the activity of media prepared from their cultures was not significantly higher than the autostimulating activity of bone marrow alone. Human placental conditioned medium proved inconvenient for cultures of mouse GM-CFC in semisolid agar containing foetal calf serum.

[The importance of prognostic signs in malignant diseases]. / Význam prognostických znaku u zhoubných chorob.

The paper deals with the general importance of prognostic signs in malignant tumours. The author defines basic terms such as disease, illness, sign etc. Diagrams describe individual stages and the complexity of the diagnostic and therapeutic procedure and the main factors which influence its result, the patient's recovery. From the aspect of assessment of the accurate diagnosis signs assembled during the diagnostic process are divided into three prognostic groups as the correct diagnosis is the prerequisite of rational therapy and thus can influence the prognosis of the disease. In the first group are only signs associated with the aetiopathogenesis of the disease, in the second group signs associated with the patient's general condition and in the third group signs of the patient's normal phenotype. The signs in each of these groups have as a rule a different prognostic value. The author emphasizes the great dependence of prognostic signs on the type of applied treatment as well as the fact that with improving treatment the majority of signs lose their prognostic importance.

[A female patient with near-tetraploid acute myeloid M4 leukemia]. / Nemocná s témer tetraploidní akutní myeloidní leukémií M4.

BACKGROUND: Acute myeloid leukemias (AML) are a heterogeneous group of diseases, several types of them are well characterized by typical morphologic, immunologic and cytogenetic features of their leukemic blasts in the MIC classification. We have recently described 2 patients with a new AML type--poorly differentiated near-tetraploid AML L0. The occurrence of very large blasts in a heterogeneous blast population seemed to be a morphological sign of this new type of AML. RESULTS: The same morphologic characteristics were observed by us when we studied blasts of another 80-year-old patient with a near-tetraploid karyotype. However, 34% of blasts were positive for myeloperoxidase and they exhibited in 24-33% surface myelomonocytic markers CD11b, CD13, CD15 and CD14. The illness was classified as acute myelomonoblastic leukemia M4 without significant dysplastic changes in erythroid and megakaryocytic lineages. The growth of granulocyte-macrophage bone marrow progenitors CFU-GM was low. The patient refused cytotoxic chemotherapy and expired 3 months later on supportive treatment. CONCLUSIONS: The finding of very large blasts is a typical sign in cases of near-tetraploid AML. Precise classification of leukemia type is essential for successful therapy.

[Occurrence of cells with ring-shaped nuclei in hairy cell leukemia]. / Výskyt bunek s prstencitými jádry u leukémií s vlasatými bunkami.

We reviewed smears of 102 bone marrow aspirates and 3 spleen punctures of 30 patients with hairy cell leukaemia (HCL) to find the occurrence of hairy cells with ring-shaped nuclei. No such cells were found in 18 bone marrow aspirates designated as non-evaluable, because of the poor smears quality or low numbers of hairy cells (under 500). Hairy cells with ring-shaped nuclei were found in 4 bone marrow aspirates of two patients with a frequency of 1.5% and 1.0% of hairy cells in the first patient and 0.3% and 0.1% in the second one. It seems that if cells with ring-shaped nuclei occur more frequently than in 0.1%, it is possible to find them in all other aspirates of such a patient. Besides these 4 aspirates with hairy cells with ring-shaped nuclei we found one or two such hairy cells in 5 other bone marrow aspirates and in one puncture from the spleen of another patient but with a low frequency between 2/5000 and 1/16,000. We found hairy cells with ring-shaped nuclei in all aspirates from 2 of 30 patients (7%) while at least one such cell was found in 8 patients (27%) with HCL. Neutrophil bands with a bent nucleus and its overlapping ends, simulating ring-shaped nuclei but with easily recognizable edges of overlapping ends, were found with a frequency of about 1 per mille of all nucleated bone marrow cells in 18 aspirates of 11 patients with HCL.

[Poor response in patients with de novo acute myeloid leukemia and erythroblastic or megakaryocytic dysplasia to treatment with standard doses of cytosine arabinoside and daunorubicin]. / Spatná odpoved nemocných s de novo akutními myeloidními leukémiemi s erytroblastickou ci megakaryocytární dysplazií na lécbu standardními dávkami cytosin-arabinosidu a daunorubicinu.

Erythroid and/or megakaryocytic dysplasia (EMD) was evaluated in diagnostic bone marrow smears of 37 consecutively treated cases with de novo acute myeloid leukemia (AML) M0-M2 and M4-M5 types and three newly diagnosed cases of refractory anaemia with excess of blasts in transformation. This evaluation was possible in 38 of 40 (95%) patients and 17 cases were categorized without EMD and 21 cases with EMD. One or two cycles with 3-4 doses of daunorubicin 45 mg/m2/d and cytosine arabinoside 200 mg/m2/12 h x 14 lead to complete remission in 13 of 16 cases without EMD but only in 4 of 16 cases with EMD (p = 0.004). However, 10 of 13 patients with EMD reached complete remission with 2000 mg/m2/12 h x 10 of cytosine arabinoside plus daunorubicin. After intensive consolidations 20 patients under 65 years with EMD showed significantly worse overall survival (p = 0.017) with a median 11.5 months, while the median survival was estimated 66.8 months in 15 cases under 65 years without EMD. The proposed categorization of de novo AML patients according to the EMD seems to be useful for selection of optimal induction therapy, clinically relevant for survival and might reflect two biologic groups of AML arising in two different stages of differentiation.

[Long-term results of the UHKT-911 study of adult patients under 65 years of age with de novo acute myeloid leukemias without favorable karyotypes]. / Dlouhodobé výsledky lécby dospelých nemocných do 65 let s de novo akutními myeloidními leukémiemi bez príznivých karyotypu ve studii UHKT-911.

Between February 1991 and April 1994 induction chemotherapy of 32 adult consecutive patients under 65 years with de novo acute myeloid leukemias (AML) was started in the study UHKT-911. They were 19 women and 13 men, aged 18-63 (median 44) years. Their AML were classified according to the FAB classification: 3 M0, 3 M1, 9 M2, 14 M4, 3 M5. Induction chemotherapy consisted of 1-2 cycles with 3-4 doses of daunorubicin (DNR) 45 mg/m2/d i.v. and 14 doses of cytosine arabinoside (Ara-C) 200 mg/m2 per 3-h infusion every 12 hours. After the treatment patients, not being in complete remission, got the HD cycle with 10 high-doses of Ara-C 2000 mg/m2 per 3-h infusion every 12 hours i.v. and DNR 45 mg/m2/d i.v. on days 4 and 5, then the EMi cycle composed of etoposide 100 mg/m2/d i.v. for 5 days and mitozantrone 10-12 mg/m2/d i.v. on days 1, 3 and 5. Complete remission (CR) was achieved in 25 of 32 (78%) patients after 1-3 cycles. Five patients died between days 5 and 24 of treatment of infections, two patients were resistant to 4 cycles of induction therapy and survived 8.4 and 13.5 months. Three patients chose allogeneic bone marrow transplantation in their 1st CR from their relatives. Two of them have been living in CR for 115 a 110 months since diagnosis, the third died of sepsis on the day 52 after transplantation. Two patients in CR died of infections after their 2nd. consolidation cycle. Twenty patients in CR completed 2-4 consolidation cycles (1-3 HD, 1 EMi). Median of their CR duration was 17.8 (2-117) months. Relapse appeared in 12 cases after 4.4-34.8 (median 12.5) months, 8 patients (6 women and 2 men, aged 29-63 years) have remained longer than 5 years in their 1st. CR. Cytogenetic examination of their bone marrow showed a normal karyotype in 4 cases, 1x 46,XX,del(1)(p32p34), 1x 46,XX,16p+, 1x 47,XX,+mar, 1x 46,XX,del(5)(q22q33). After 62 months in CR a pancytopenia with dysplastic bone marrow changes developed in one of them, probably a secondary myelodysplastic syndrome, lasting for further 33 months. Event-free survival at 5 years was 27.5% (8/29 patients), significantly better (p = 0.046) against 7.5% (3/40) patients treated without HD cycles in the years 1982-1987. The same difference was observed in 7.5-year overall survival (p = 0.036) between the two studies, when 3 of 6 patients 60-64 years old remain in their 1. CR.