AIM:To analyze the efficiency of the ALL-2009 protocol (ClinicalTrials.gov NCT01 193933) in patients with T-cell leukemias, particularly the role of autologous hematopoietic stem cell transplantation (auto-HSCT) after non-myeloablative BEAM conditioning, followed by maintenance therapy.SUBJECTS AND METHODS:Since 2009, the ALL-2009 study has enrolled 90 patients with T-cell acute lymphoblastic leukemia (T-ALL), the treatment results were assessed in 86 patients: 6 and 28 patients underwent allogeneic HSCT and auto-HSCT, respectively. A landmark analysis was used to compare survival rates in patients who had undergone auto-HSCT and in those who had not. For this, the median time from complete remission to the date of auto-HSCT was determined (the median was 6 months). Then to compare with the auto-HSCT group, only 27 patients who had been in complete remission for 6 months or more were included in a chemotherapy group.RESULTS:The achievement of complete remission in patients with thymic T-ALL (100%) was significantly higher than in those with early (85.7%) or mature (70%) variants. The patients with early and mature T-ALL as compared to those with thymic T-ALL showed high death rates in the remission induction (7.4 and 10% versus 0) and the patients with mature T-ALL had a.higher proportion of refractory forms (20% versus 0). The 5-year overall and relapse-free survival rates in all the T-ALL patients were 66 and 76%, respectively. After auto-HSCT, the risk of recurrence was 0% versus 21% after chemotherapy (p=0.03). The relapse-free survival rates significantly differed in the auto-HSCT and non-auto-HSCT groups: 100 and 66%, respectively (p=0.047).CONCLUSION:The long-term survival rates obtained during this multicenter study in the T-ALL patients treated according to the ALL-2009 protocol, the basis for which is the principle of continuity of cytostatic effects, are exclusively optimistic. Late consolidation with auto-HSCT following non-myeloablative BEAM conditioning, followed by maintenance therapy, considerably reduces the risk of recurrence.

The purpose of this trial was to evaluate the role of high doses Ara-C consolidation, maintenance chemotherapy, bone marrow transplantation (BMT) by assessing the long-term results of adult patients (pts) with acute myeloid leukemia (AML) according to AML-06.06 treatment protocol. During the period 2006-2009, 216 AML pts (except M3 and secondary AML) were included in this study. 143 of them were randomized in 2 groups. Chemotherapy consisted of conventional dose Ara-C + daunorubicin as the first induction course «7+3», High dose Ara-C + Mitoxantrone (HAM) as the second induction/consolidation course, HAM as the third course was applied if no complete remission (CR) after the first course has been achieved or High dose Ara-C (HiDAC) as the third course if CR was obtained after the first course, the fourth and the fifth courses with HiDAC, and two randomized arms of maintenance: «5+2» (AraC + Mercaptopurine) versus stop chemotherapy (randomization was performed before the treatment start). BMT was performed after 3, or 4, or 5 consolidation courses (26 AlloBMT, 10 AutoBMT). CR was obtained in 155 pts (72 %). If CR was obtained during the first 60 days of treatment then 5-year leukemia-free survival (LFS) was 38 %, if later 18 % (p = 0,0244). OS was similar. 5-year LFS in cytogenetic low and intermediate risk groups was 37 %, and in high risk groups 8 % (p = 0,0044). In cytogenetic low risk group 5-year overall survival was 100 % in inv(16) pts and 20 % in t(8;21) pts (p = 0736). If lactate dehydrogenase (LDH) activity was 1500 U/l and higher, 5-year LFS was 8 %, if lower 23 %, p = 0,0011). 5-year LFS in AutoBMT pts was 40 %, in AlloBMT pts 32 %, in chemotherapy pts 25 % (p = 0,4464). Relapse probability was 83 % in no-maintenance randomization group and 50 % in maintenance group (p = 0,0667). Dose intensification and maintenance chemotherapy have shown high antileukemic efficacy in limited groups of AML pts (low LDH, inv(16), WBC < 40 x 10 9/l). High LDH activity at the diagnosis, high risk cytogenetic group should be managed with other treatment approaches. Introducing BMT technologies may provide some benefit in some groups of AML pts. We have to emphasize that there were some differences in the results in t(8;21) pts comparing with published data.

Aim. To give the preliminary results of the AML-01.10 Russian multicenter randomized trial to treat adult acute myeloid leukemia (AML), the basic principle of which is to use high-dose anthracycline antibiotics in induction/consolidation.Subjects and methods. By December 2011, 145 patients with AML had been randomized from 18 hematology centers of 15 cities and towns of the Russian Federation; the median age of all the patients was 44 years. Seventy-one patients were analyzed in August 2011 (a 1.5-year follow-up).Results. The efficiency of 2 courses 7+3 using high-dose daunorubicin (60 mg/m(2) per administration) and continuous infusion of cytarabine during the second course was high and comparable with that in the use of a high-dose HAM protocol as a second induction course and can achieve a complete remission in 74.6%. The protocol toxicity evaluated from its early mortality (11.3%) and its death in complete remission (16.6%) was permissible, particularly by taking into consideration the multicenter pattern of the trial. At the completion of analysis, 53 (68.8%) out of the 77 patients on whom the data on their vital status were available were alive. In this follow-up period, the frequency of recurrences was 19.2% (10/52). Only 3 (4.2%) patients out of the 71 patients in whom the efficiency of the protocol had been completely evaluated underwent allogeneic bone marrow transplantation.Conclusion. The total high dose (720 mg/m(2)) of anthracycline antibiotics, which is used in the period of induction and consolidation, determines the long periods of myelosuppression and intercourse intervals. Protocol deviations (no course of consolidation therapy, lower-dose idarubicin during consolidation therapy, a course of low-dose cytarabine between the courses of induction and consolidation chemotherapy, and very long intercourse intervals) were recorded in a total of 20 (28%) patients.

AIM:To comparatively analyze the toxicity of 4 treatment protocols in patients with acute myeloid leukemia (AML), which were used in the Russian multicenter center in 1992 to 2009.MATERIALS AND METHODS:The information obtained in 4 Russian multicenter studies conducted in 33 hematology departments of 26 cities and towns of the Russian Federation in 1992 to 2009 was analyzed. Randomization was made in 243 patients with AML (median age 38 years) in 1992-1995, 396 patients (median age 39 years) in 1995-1999, 392 patients (median age 39 years) in 2001-2006, and 137 patients (median age 40 years) in 2006-2009. The analysis excluded patients with acute promyelocytic leukemias who were recruited in the AML-92 and AML-95 studies. These patients' statutory forms adequately filled in were 60-70% therefore toxicity was analyzed on the basis of the data of 631 patients.RESULTS:The baseline clinical and laboratory parameters in the patients enrolled in the studies in different years slightly differ in the count of leukocytes at the onset of the disease and in the level of lactate dehydrogenase (LDH): the recent studies revealed a larger number of high-risk group patients (leukocytes more than 30 10(9)(/l; LDH more than 500 units) possibly due to the later diagnosis of AML. During the studies, the number of complete remissions remained as before (55%) after the first course and increased from 65 to 78% after the second course using cytosine arabinoside in high doses. Despite treatment intensification, mortality in the induction period remained as before (19-21%). Remission mortality decreased from 18 to 10-13%. The long-term results of using the aggressive therapy did not differ from those obtained during the standard treatment protocols. The duration of leucopenia after standard induction courses during the all studies remained equal (17-19 days); the exclusion was a HAM course as the second induction course after which the duration of neutropenia was much more than that of the standard course (17 and 10 days, respectively). During the study years, there was an increase in platelet transfusion volumes (from 20 to 53 doses during the first course and from 7 to 28 doses during the second course) and a reduction in the percentage of severe hemorrhagic complications. The incidence of pneumonias remained at the same level (40-50%) during the induction courses and that of septic complications and necrotic enteropathy considerably decreased from 40-46 to 17-19%. The incidence of invasive aspergillosis during the current programs from AML treatment was 10% (two induction courses), that of invasive candidiasis was 4.7% (two induction courses). CONCLUSION; The long-term results of treatment for AML were virtually unchanged regardless significant therapy intensification. Mortality remained high during induction treatment and in the postremission period. Its cause is severe infectious complications developing during myelotoxic agranulocytosis. The results of the analysis provide the basis for developing a new AML treatment protocol that should take into account all the merits and demerits of the previous protocols and provide a toxicity-treatment efficiency balance.

Results of the Second Russian Multi-Center Study of Acute Promyelocytic Leukemia (APL) Treatment are summed up. Overall 5-year survival of 102 APL patients treated by the 7 + 3 protocol (rubomycin dose 60 mg/m(2)) in combination with ATRA, two similar consolidation courses, and 2 years of maintenance therapy was 68.3%, relapse-free survival 77.4%, probability of complete remission prolongation 89.5%. High early mortality (15%) and mortality during complete remission (10%) reduced significantly the total efficiency of APL treatment. Experience gained in accompanying therapy of APL patients largely determined the remote results of treatment: overall and relapse-free survival of APL patients in centers, which included more than 10 patients in the study, was 89 and 95%, respectively, vs. just 58 and 69% in centers with groups of I to 8 patients. Relapse-free survival and probability of prolongation of complete remission did not differ much in patients receiving maintenance therapy by different protocols (cytostatic alone or alternation of ATRA and chemotherapy courses), but the incidence of relapses was somewhat higher (p = 0. 16) in patients receiving reduced cytostatic loading. Leukocyte count (more or less than 10 x 10(9)/L is not a factor determining the remote results of treatment - relapse-free survival (82 and 84% respectively) and probability of complete remission prolongation (90 and 91% respectively), but early mortality of patients with leukocyte counts of more than 10 x 10(9)/L was significantly higher than that of patients with lower leukocyte counts (30 and 9.4% respectively).

Aim. Assessment of high-dose dexamethasone efficacy in combination with standard drugs (adriablastin, vincristin, alpha-asparaginase) in patients with refractory acute lymphoblastic leukemia (ALL).Material and methods. A pilot multicenter trial with participation of hematological departments of Hematological Research Center (Moscow), municipal hospital N 1 (Krasnoyarsk), municipal hospital N 8 (Yaroslavl), Research Institute of Hematology and Blood Transfusion (Kirov) included 34 patients (10 patients with late recurrences, 24 - with primary resistant forms, early and secondary recurrences).Results. In patients with late ALL recurrences a complete remission (CR) was achieved in 70% cases, the median being 10 months. In patients with primary resistant ALL, early and secondary recurrences CR reached 37.5%, the median was 14 months.Conclusion. The program HiDexa is highly effective : overall complete remission rate reached 47916, median of complete remission duration was 10 months. Dexamethasone in high doses must be used only intravenously.

Aim. Comparison of effectiveness of induction regimens varying in intensity and maintenance variants in patients with acute myeloid leukemia (AML) included in a randomised multicenter trial. Materials and methods. Clinical trial 1 enrolled 185 AML patients. Vepezide-free induction was used in 85 patients (group 1), induction with vepezide - in 99 patients (group 2). 223 AML patients enter ed trial 2. Of them 37 patients were treated for 3 years 7+3 with daumorubicin in the dose 45 mg/m(2) in the induction phase (group 1), 85 and 101 patients received 7+3 with daunorubicin for a year in the dose 45 mg/m(2) and 60 mg/m(2), respectively, (group 2 and 3). Results. For group 1 in trial 1 the, remission rate, early lethality, resistance were, respectively, 60, 20 and 20%, respectively. For group 2 in trial 1 - 66, 22 and 12%, respectively. 5-year recurrence-free survival reached 32 and 37% for group 1 and 2 respectively. For trial 2 relevant figures made up 75.5, 16.2, 8.1% for group 1; 60, 17.6 and 22.4% for group 2; 63, 20.8 and 16% for group 3, respectively. The 3.5-year recurrence-free survival in groups 1, 2 and 3, was 16, 46 and 50%, respectively. For both trials, the differences between the groups were insignificant. Conclusion. The results evidence that the treatment can be shorter (not 3 but 1 year or even 6 months), the induction more intensive (the dose of anthracycline antibiotics can be elevated up to 60 mg/m(2) without a rise in early lethality).