[Heterogeneity of acute myeloid leukemia with the translocation t(8;21)(q22;q22)].

AIM: To characterize the clinical and hematological variability of acute myeloid leukemia (AML) with t(8;21) and to identify the signs associated with the likelihood of its relapse. SUBJECTS AND METHODS: The results of examining 44 patients aged 11 to 70 years were analyzed; the efficiency of treatment was evaluated in 36. Their karyotypes were studied using the standard GTG method. Polymerase chain reaction (PCR) was employed to assess the mutational status of the FLT3, NPM1, NRAS and c-Kit genes. Qualitative PCR was used to reveal the chimeric transcript RUNX1/RUNX1T1. RESULTS: The M2 variant was verified using the French-American-British classification in 82% of cases. One patient was diagnosed with secondary AML. Additional chromosomal aberrations were found in 50% of the patients. The most common breakages were loss of one of the sex chromosomes (34.1%) and damage of chromosome 9 (16.6%). Gene mutations were detected in single cases. Following 2 7+3 induction chemotherapy (CT) cycles, complete remission (CR) was achieved in 97% of cases (3 patients with cytopenia died). Eight (25%) patients developed a relapse mainly within the first 7 months after achieving CR. The characteristic signs of relapse cases were the inefficiency of the first cycle of remission induction (RI), the absence of high-dose consolidation, damage of chromosome 9, D816V mutation in exone 17 of the c-Kit gene. Antirecurrent CT was ineffective in 5 patients. The median overall survival (OS) in patients with early recurrence was 10 months. That in the patients who were recorded to have CR was not achieved; 5-year OS was 57.8%. Chromosome 9 aberration was ascertained to have a negative impact on OS parameters (p=0.003). CONCLUSION: Patients with AML with t(8;21) is a group heterogeneous with respect to age, the morphological nature of blast cells, the pattern of the disease, the presence and type of additional chromosomal aberrations, mutations in individual genes, and clinical course. Those who are unresponsive to the first RI cycle and have additional chromosome 9 damages should be regarded as potential candidates for allogeneic hematopoietic stem cell transplantation.

[Invasive mucormycosis in patients with hemoblastosis in St.-Petersburg].

Thirty four patients with mucormycosis in 10 hospitals of St. Petersburg were observed in 2004-2013. The most frequent underlying diseases of mucormycosis were acute leukoses (64%). In 100% of the patients mucormycosis developed as a nosocomial infection. The risk factors, etiology, basic clinical signs and strategy in the treatment of mucormycosis were analyzed.

[Invasive mycoses during hematopoietic stem cell transplantation].

AIM: To define the frequency, etiology, and risk factors of invasive mycoses (IM) in patients with allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (HSCT) and to evaluate the impact of IM on overall survival (OS). MATERIALS AND METHODS: Data on 356 patients after allo-HSCT (n = 237) and auto-HSCT (n = 119) from 2000 to 2010 were analyzed. The diagnosis of IM was established according to the EORTC/MSG 2008 criteria. RESULTS: The incidence of myocardial infarction (MI) was 19.1%; that was 23.2 and 10.9% in allo-HSCT and auto-HSCT recipients, respectively. The incidence of MI following allo-HSCT was significantly higher than that after auto-HSCT. Aspergillus spp. (82.3%), Candida spp. (11.8%), zygomycetes (Mucor spp., Rhizopus spp.) (4.4%), and Cryptococcus neoformans (1.5%) are involved in the etiology of MI. Its risk factors are acute lymphoblastic leukemia; non-myeloablative conditioning regimen; use of fludarabine and antilymphocyte globulin; peripheral blood stem cells as a source for grafting; long-term lymphopenia, neutropenia; use of granulocyte colony-stimulating factor (G-CSF); acute graft-versus-host reaction; grade 3-4 mucositis; infections, such as cytomegalovirus, sepsis. The development of MI in HSCT recipients did not significantly reduce one-year OS after allo-HSCT and auto-HSCT--53.6 and 55% and 86.7 and 90.3% (with and without MI, respectively). In patients with invasive aspergillosis, OS (12 weeks after IM being diagnosed) was significantly longer in those with other invasive mycoses (91.3 and 50%, respectively). CONCLUSION: The incidence of MI after allo-HSCT was higher than that after auto-HSCT. MI induced by the fungal genus Aspergillus spp. was most common. Along with known risk factors, there was a poor prognostic factor, such as G-CSF. The development of MI failed to affect one-year OS, which was indicative of the adequate quality of its early diagnosis and therapy. The prognosis was poor in patients with invasive candidiasis, zygomycosis, and cryptococcosis. Investigations need to be continued to specify the reasons for high morbidity rates and the factors provoking discussion by investigators worldwide.

[Toxicity of different treatment protocols for acute myeloid leukemias in adults: the results of four Russian multicenter studies].

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.

[The results of a multicenter randomized trial on the treatment of acute myeloid leukemia of adults].

AIM: Systematization of the results of 20-year multicenter randomized trial of the efficacy of treatment of acute myeloid leukemia (AML) of adults; presentation of the design of the study of the strategy of consolidation and maintenance therapy after high-dose consolidation initiated in 2007. MATERIAL AND METHODS: Treatment outcomes on the protocol AML-01.01 are presented for 354 AML patients from 29 hematological centers located in 22 towns of Russia and 2 towns of Ukraine. The patients were randomized into 3 groups by variant of therapy: 124 patients (62 males and 62 females; age median 42 years) received 4 courses of 7+3+VP-16 and 5 courses of maintenance therapy (7+3 with thioguanin); 130 patients (65 males and 65 females, age median 41 year) received 2 courses of 7+3+VP-16, 2 courses 7+3, maintenance--5 courses 7+3 with thioguanin; 126 patients (57 males and 68 females, age median 40 years) were given 2 courses of 7+3+VP-16, 2 HAD courses, treatment discontinuation. RESULTS: A complete remission after the first course of 7+3+VP-16 was achieved in 55% patients, after the second course--in 30% after the course 7+3+VP-16 or 7+3 with mitoxantron, in 70%--after NAM. Overall and recurrence-free survival were 18 and 35%; 30 and 20%; 36 and 30%, respectively. There was no significant difference in efficacy of the treatment scheme. CONCLUSION: The multivariate analysis has shown that a leading factor having impact on treatment results was the number of randomized patients: the less patients were randomized, the worse were the results.

[Preliminary results of a multicenter randomized study on the treatment of acute promyelocytic leukemias]. / Predvaritel'nye rezul'taty mnogotsentrovogo randomizirovannogo issledovaniia po lecheniiu ostrykh promielotsitarnykh leikozov.

AIM: To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial. MATERIAL AND METHODS: The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5-day courses of cytostatic drugs which alternated or did not alternate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (65%)--bcr 3 variant. RESULTS: 65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also similar. Overall 2.5 year survival for all the patients was 77%, recurrence-free--80%. The survival analysis in patients with leukocytosis higher and lower 10 x 10(9)/l found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 x 10(9)/l (25% vs 5.3%, p = 0.03). CONCLUSION: The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%.