[First results of Ph-negative acute lymphoblastic leukemia therapy of adults according to the protocol of Research Group of Russian Hematological Centers ALL-2009].

AIM: To review results of 2-year experience in execution of the protocol on the treatment of adult acute Ph-negative lymphoblastic leukemia ALL-2009. MATERIAL AND METHODS: Of 111 patients registered in the study from November 2008 to December 2010 the analysis covered 96 patients from 23 hematological centers in 18 towns of the RF. RESULTS: Treatment according to the Protocol ALL-2009 resulted in achievement of a complete remission in 91.2% patients with low early lethality of 5.5%. Postremission lethality fell to 3.7% versus previous studies (22%). Overall 2-year survival and recurrence-free survival reached 77.6 and 78.4%, respectively. Detection of any chromosomic aberrations significantly affected recurrence-free survival: 74 vs 100% in patients with normal karyotype. CONCLUSION: Protocol All-2009 demonstrates high efficacy in moderate toxicity and good reproducibility in any hematologic center.

[Results of the treatment of adult acute lymphoblastic leukemia according to ALL-2005 protocol as a basis for new trials].

AIM: To analyse the results of the treatment according to ALL-2005 protocol for adult patients with acute lymphoblastic leukemia (ALL); on the basis of the summarized evidence on ALL treatment to propose principles for development of a new program of ALL treatment in 15-55-year-old patients. MATERIAL AND METHODS: Five hematological centers (in Moscow, Saransk, Volgograd, Tambov, Kirov) participated in ALL-2005 protocol trial initiated in 2005. A total of 71 adult patients with ALL (age median 27 years) were treated. The results of the MB-2002 study with participation of 16 patients aged 16-23 years performed in the State Hematological Research Center (SHRC) were reviewed RESULTS: The results of the induction therapy according to ALL-2005 protocol conducted in Moscow SHRC were good: a complete remission was achieved in 90% patients, early lethality was 6%, resistance was observed in 4%. In regional centers lethality in remission was higher, 5-year overall survival was 28% (in SHRC it was 56%), recurrence-free survival in regional center was 22% versus 51%, respectively. Long-term response by ALL-2005 and MB-2002 in patients aged 19-23 was the same, but toxicity of ALL-2005 treatment was higher (no lethality and 5, 4% in induction and remission, respectively). CONCLUSION: The decision was made on design of a new protocol of treatment of Ph-negative ALL for patients aged from 15 to 55 years the main principles of which are the following: continuous treatment with modification of cytostatic drugs doses depending on myelosuppression severity; assessment of tumor cells sensitivity to prednisolone and its replacement for dexametasone throughout the treatment; prolongation of L-asparaginase treatment with elevation of its total dose; monitoring of minimal residual disease (MRD) for decision on late intensification in patients with MRD at late treatment stages (5 months).

[Clonal chromosomal aberrations in patients with aplastic anemia at the disease onset and transformation].

AIM: To estimate detectability and characteristic features of chromosomal aberrations in bone marrow cells of patients with aplastic anemia (AA). MATERIAL AND METHODS: The trial covered 155 AA patients admitted to the Hematological Research Center in 1987-2002. Cytogenetic study by G-differential staining was performed in 58 patients with AA and 5 patients with AA transforming into myelodysplastic syndrome (MDS) or acute leukemia (AL). Cytogenetic and morphological specimens of the latter's bone marrow were studied retrospectively using fluorescent in situ hybridization (FISH) with DNA probes for detection of monosomia 7 and deletion 7q. RESULTS: Clonal chromosomal aberrations were detected in 4 out of 28 patients. Further examinations revealed no aberrations. Clonal diseases developed in 7 (4.5%) of 155 patients. In 2 patients the disease transformed into paroxysmal nocturnal hemoglobinuria, 5 (3.2%) patients developed variants of MDS and AL. Monosomia 7 or deletion 7q were diagnosed in 3 cases of MDS/AL. In retrospective study of bone marrow specimens of patients with transformation in MDS/AL with monosomia 7, FISH recognized a small elevation over control values in 2 cases. CONCLUSION: Stable clonal chromosomal aberrations are not characteristic of AA. Some AA patients with subsequent MDS/AL may have minor neoplastic clone in the disease onset.