[Trisomy of chromosome 8 in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia treated with inhibitors of BCR-ABL tyrosine kinases].

AIM: To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK). MATERIAL AND METHODS: A total of 386 patients with CML (chronic phase--288, acceleration phase--77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib). This study included 8 CML patients (7 in a chronic phase, 1 in acceleration phase) treated with BCR-ABL ITK inhibitors of the first (imatinib) and the second line (ITK-II). The standard cytogenetic examination, on demand--investigation of the interphase nuclei with FISH, in some cases morphological, cytochemical and histological examinations of the bone marrow were made. RESULTS: The existence of a Ph-negative clone with trisomy of chromosome 8 had no negative effect on the course of the disease. The patients showed a stable hematological and cytogenetic response and no need in changing treatment policy. In long-term follow-up Ph-negative clone with trisomy of the chromosome 8 persisted without a clear trend to rise in most patients. CONCLUSION: Detection of a Ph-negative clone with chromosome 8 trisomy at early stages suggests parallel existence of Ph-positive and Ph-negative clones. None of the patients had myelodisplasia.

[Dasatinib treatment of imatinib-resistant and imatinib-intolerant patients with chronic myeloid leukemia in a chronic phase].

AIM: To analyse resistance to imatinib therapy, efficacy and safety of dasatinib. MATERIAL AND METHODS: A total of 18 patients with chronic myeloid leukemia (CML) in a chronic stage received dasatinib for 9-30 months (median 30 months) to September 2008. RESULTS: Lethal outcomes during dasatinib treatment were absent. To September 2008, 16 (89%) patients were alive, 2 (11%) patients died of the disease progression after dasatinib discontinuation. A complete clinicohematological response was observed in all the patients. Major cytogenetic, complete cytogenetic, major molecular, complete molecular responses were achieved in 12 (67%), 10 (55%), 7 (39%) and 5 (28%) patients, respectively. Hematological and non-hematological toxicity occurred in 9 (50%) patients. Now 12 (67%) patients continue dasatinib treatment, in 6 (33%) patients the drug was discontinued. CONCLUSION: The results from trials in Russian Hematological Research Center are the same as in the international study. Dasatinib is effective and well tolerated therapeutic option for imatinib-resistant patients with a chronic phase of CML.

[Prognosis factors in imatinib mesilate therapy in patients with a chronic phase of Ph-positive chronic myeloid leukemia: data from a multicenter non-randomized trial in Russia].

AIM: To reveal prognostically significant factors affecting efficacy of glivek therapy in untreated (duration of the disease < or = 6 months) and pretreated (duration of the disease > 6 months) patients with chronic myeloid leukemia (CML) in a chronic phase. MATERIAL AND METHODS: A total of 338 patients (64 untreated and 274 pretreated) with a chronic-phase CML on glivek therapy entered the trial. RESULTS: Five-year survival on glivek was high (89, 98 and 88% in untreated and pretreated patients, respectively). Incidence of transformation in the acceleration phase and blast crisis was low both in untreated and pretreated patients (1.6 and 11%, respectively) and correlated with the rate of a complete cytogenetic response (CCR). Untreated patients had no factors affecting treatment efficacy negatively, CCR probability was 96%. Blastemia, thrombocytosis and splenomegaly reduced CCR probability significantly in pretreated patients. Slow reduction of the tumor mass, late achievement of a complete hematological response and a cytogenetic response decreased probability of CCR. CONCLUSION: Glivek is a drug of choice for patients with chronic-phase CML. High probability of CCR both in untreated and pretreated patients lowers the risk of the disease transformation into the phase of acceleration/blast crisis and raises overall survival in both groups.

[Cytogenetic response as a marker of efficacy of chronic myeloid leukemia therapy with a BCR-ABL thyrosine kinase inhibitor glivek].

AIM: Clinical practice with the drug glivek (imatinibe mesilate, ST1571) blocking activity of oncoprotein p210 shows that a cytogenetic response can be reached in 50-60% of patients with chronic myeloid leukemia (CML), in a late chronic phase (CP) in resistance to or intolerance of interferon alpha (IF-alpha) and in 24-43% of patients in the acceleration phase (AP). This study aimed at assessment of the rate and stability of a cytogenetic response (CR) and long-term results of survival in CML patients on glivek. MATERIAL AND METHODS: Glivek was given to 195 CML patients (median of the treatment duration was 42 months, 1-156 months, of the patients' age--46 years). 79 patients were in CP, 116--in AP. The doses were 400 mg/day and 116 mg/day, respectively. Karyotype was studied before the treatment and later after each 6 months. RESULTS: A considerable CR was achieved in 57% patients in CP and 44%--in AP. Of them complete CR was obtained in 48 and 35%, respectively. Marked CR is a favourable prognostic factor. Survival of patients with marked CR in CP (97% 0 and AP (89%) was significantly higher than without CR (58 and 47%, respectively, p < 0.05). Marked CR persisted in 95% cases in both phases of CML. In complete CR, a repeated study of karyotype revealed residual number of Ph+ cells both in CP and AP in 86% patients. This demonstrates necessity to take glivek continuously in achievement of a complete CR by karyotypic test. Glivek inhibits the disease progression, lowers annual lethality. 42-month (median of glivek treatment duration) overall survival reached 91 and 59% in CP and AP, respectively. CONCLUSION: CR is an integral index prognosticating CML course. Survival rose significantly in patients with marked CR both in CP and AP of CML. Marked CR is persistent in continuous glivek therapy. The rate of a CR depends much on the disease stage.

[Experience with using aclarubicin in the treatment of acute leukemia and blast crisis of chronic myeloid leukemia]. / Opyt primeneniia aklarubitsina v terapii ostrykh leikozov i blastnogo kriza khronicheskogo mieloleikoza.

The clinical efficacy of aclarubicin, an anthracycline antibiotic, was studied in 48 patients with leukemia. The antibiotic was used in the following combinations with cytarabine: "7 + 7", "5 + 5" and "7 & 3". A complete remission was stated in 14 (42.4 per cent) out of 33 patients with acute nonlymphoid leukemia, 6 (43 per cent) out of the 14 patients having relapses. The combined therapy was effective in 4 out of 5 pre-resistant patients. The "7 + 3" scheme was the most beneficial. The most common adverse reactions were nausea and vomiting.

[The prognostic significance of parameters of bone marrow blast cell proliferation in patients with acute leukemia]. / Prognosticheskoe znachenie parametrov proliferatsii blastnykh kletok kostnogo mozga u bol'nykh ostrym leikozom.

Percentage of bone marrow blasts in S-phase (S%) in acute leukemia patients was evaluated by 3H-thymidine autoradiography or Feulgen cytophotometry at the initial acute period before chemotherapy. In acute lymphoid leukemia (ALL) patients who showed complete remission (CR) S% was 8.6 +/- 1.8% versus 2.1 +/- 0.4% in cases without CR (p less than 0.001). In acute non-lymphoid leukemia (ANLL) the corresponding values were 11.4 +/- 1.4% and 8.3 +/- 1.8%, p greater than 0.05. A negative correlation was observed between S% and the duration of CR in ALL: S% was 13.0 +/- 0.7% in CR, more than 12 months, and 6.9 +/- 1.1% in CR less than 12 months (p less than 0.01). The duration of life also correlated negatively with S%. In ALL S% was 9.5 +/- 1.5% for patients with survival less than 12 months versus 6.2 +/- 0.6% for patients with survival more than 12 months (p less than 0.05). In ANLL the difference (10.3 +/- 1.6% and 6.8 +/- 1.2, respectively) was not significant (p greater than 0.05). Thus in ALL the correlations between S% and the probability to achieve CR is positive, while the correlations between S% and survival and remission duration are negative. In ANLL these correlations are statistically insignificant.

[Standardization of the treatment of acute leukemia]. / Standartizatsiia terapii ostrykh leikozov.

The causes of the lagging as to the survival of patients suffering from acute leukemias in this country are analyzed. The principles of the current therapy of acute leukemias are discussed. The unified programmed treatment is offered as basis for the therapeutic policy.

[Bacteriotherapy of intestinal dysbacteriosis in patients with acute leukemia]. / Bakterioterapiia disbakterioza kishechnika u bol'nykh ostrymi leikozami.

The results have been presented of correcting intestinal microflora in 127 patients with acute leukemia by preparations containing Bacillus bifidus and acidophilus: dried and milk bifidum-bacterin, biofructolact, acidophilic milk.

[Low doses of cytarabine in the treatment of acute non-lymphoblastic leukemia in adults]. / Malye dozy tsitozara v lechenii ostrykh nelimfoblastnykh leikozov vzroslykh.

Low doses of cytarabine were used in the therapy of 33 adult patients with non-lymphoblastic leukemia. A total of 37.5% of complete remissions were recorded in the group of primary patients, and 36% of complete remissions--in the group of resistant patients and in those with relapses. Indications have been determined, and an opinion on the mechanism of action of low doses of cytarabine has been expressed.