Vol 81, No 7 (2009)

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).

Aim. To determine surface and intracellular expression of ACE antigen and Bip shaperon on leukemic dendritic cells (LDC); to study expression of ACE genes and Bip, Calnexin, calreticulin shaperons in LDC at diagnosis of acute myeloid leukemia (AML) under standard and stress cultivation. Material and methods. Expression of ACE antigens and Bip was studied with immunophenotyping and flow cytometry using monoclonal antibodies to shaperon Bip and to CD143), expression of genes of ACE and shaperons Bip, Calnexin, Calreticulin - with polymerase chain reaction (RT-PCR). Dendritic cells (DC) were obtained by culturing of a monoclonal fraction of donor peripheral blood and AML patients in the presence of 180 ng/ml calcium ionophor A23187 (Sigma) for 4 days in parallel at 37°C and 33°C in the atmosphere of 5% CO2. The trial included 9 patients (5 males and 4 females) aged 39-53 years (median 43 years). The control group consisted of 8 healthy donors. Results. Lowering of cultivation temperature did not increase ACE expression. Intracellular shaperon Bip rose insignificantly (1.3-fold) in DC of the controls. ACE and Bip shaperon expression on LDC membrane increased 15- and 11-fold, respectively, while the level of intracellular ACE and Bip decreased 11- and 2-fold, respectively. Expression of the genes was investigated in cultivation temperature lowering from 37 to 33°C and was presented as a logarithmic scale. Changes in expression of the genes Bip, Calnexin, Calreticulin in LDc and DC of the controls were insignificant. ACE expression in LDC significantly differed from ACE gene expression in DC (p = 0.05). Conclusion. LCD and DC of healthy donors are cells which differ by genetic and functional characteristics. Therefore, LDC may response inadequately in development of antitumor immune response. The phenomenon of ACE antigen expression normalization on cell membrane in stress open new opportunities for regulating functional activity of LDC.

Aim. To ascertain individual sensitivity to veikeid in patients with resistant and recurrent multiple myeloma (MM) by determination of free light chains (FLC) of serum immunoglobulins. Material and methods. Forteen patients with MM stage III (Gcappa-5, Glambda-2, Acappa-3, Alambda-1, BJcappa-3) aged 52-75 years with documented resistance to treatment or recurrence received second-line monotherapy with velkeid. The drug was injected intravenously (jet) in a dose 1.3 mg/m2 on the treatment day 1, 4, 8 and 11. Free light chains concentration was examined with antibodies to their latent determinants (Binding Site, UK) on nephelometer (Hitathi-911, Japan) on velkeid treatment day 1, 2, 3, 5, 9 and 12. Results. Nine patients showed lowering of FLC concentration and responded to treatment by Durie criteria. Conclusion. Dynamic follow-up of FLC concentration of the tumor clone in resistant and recurrent MM evaluates pharmacodynamics of the drug. The method provides prognosis of late clinical results.

Aim. To characterize clinical and epidemiological features of adult Berkitt's lymphoma (BL). Material and methods. The trial enrolled 72 patients (51 males and 21 females, age 14-69, mean age 27 years) treated in 1995-2008. Results. Stage I BL (by S.B. Murphy) was diagnosed in 5 patients, stage II - in 9, stage III - in 25, IV - in 14 patients, B-cell acute lymphoblastic leukemia (ALL) (L3) - in 19 patients. Intoxication was seen in 56(78%) patients, 38% patients had severe cachexia. Elevated concentration of lactatedehydrogenase (LDG) was detected in 57(79%) patients. In all the cases clinical symptoms developed for 1-3 months, median 6 weeks. Bone marrow involvement was diagnosed in 22 (31%) patients, CNS was affected in 17(24%) patients, of them 14 were males. Fifty two (72%) patients had abdominal, retroperitoneal and/or small pelvis tumors. Intestinal, hepatic, renal and gastric tumors occurred most frequently. Specific ascitis was detected in 25(48%), tumor pleuritis - in 11(15%) patients. BL of the facial skeleton, Waldeyer's ring, oro- and nasopharynx was in 12(17%) patients. Seven patients had concomitant involvement of the CNS. Eight (38%) and 2(10%) women had tumors of the ovaries and uterus, respectively. Conclusion. BL is characterized by the following clinical features: young age of the patients, most of them are males, B-symptoms, short history, generalized stages, extranodal lesions, frequent involvement of the bone marrow and CNS.

Aim. To define complex of parameters characterizing transformation of skin T-cell tumors in lymphosarcoma; to show specific treatment of patients with this transformation. Material and methods. Of 57 patients with primary T-cell lymphomas of the skin (mycosis fungoides, Sezary's disease), we studied 12 patients with transformation of the process into lymphosarcoma by clinical, histological, moleculobiological and immunophenotypical parameters. Results. We found that transformation of T-cell lymphoma into lymphosarcoma occurred in different time from the disease onset (2-12 years). In patients with mycosis fungoides (MF) the transformation was local while in those with Sezary's disease (SD) transformation of the tumor clone was determined by appearance of peripheral blood tumor cells rejuvenation. Morphological alterations were accompanied with immunomorphological parameters of progression. Most significant of them were high expression of the proliferative activity marker Ki-67 (10-70%), enhancement of activation (CD30, CD25), loss of some linear T-cell markers. Treatment of lymphosarcoma arising on the background of lingering MF or SD may combine two types of antitumor treatment - intensive and supporting because of coexistence of different clones of one tumor. Conclusion. Verification of skin T-cell lymphoma diagnosis and its transformation into lymphosarcoma must be based on the evidence from a number of examinations: histological, immunophenotyping, moleculobiological and clinical. Among criteria of the transformation, markers of lymphoproliferative activation are of great importance.

Aim. To examine ability of mesenchymal stromal cells (MSC) of the bone marrow (BM) for differentiation in adipogenic and osteogenic differentiation in donors and patients with aplastic anemia (AA). Material and methods. We obtained MSC cultures from BM cells of donors and AA patients and induced differentiation of mesenchymal cells with use of relevant reagents. Morphological changes in MSC were studied with light microscopy. A relative level of expression of differentiation marker genes in MSC cultures before and after induction of differentiation was analysed with reverse transcription-polymerase chain reaction. Results. By morphological characteristics, MSC cultures in AA patients before and after differentiation induction do not differ from donor cultures, but relative expression of the genes of differentiation markers demonstrated that expression was different in male and female donors; MSC before and after induction of differentiation differ in donors and AA patients. Conclusion. Further studies are needed for detection of functional changes in precursors of stromal microenvironment and understanding of the disease pathogenesis.

Literature gives only few reports of hyaline-vascular variant of Kastleman's disease associated with tumor from dendritic cells. A case of simultaneous detection of these diseases in the tumor located in the retroperitoneal space and successfully removed surgically is reported.

The article demonstrates objective difficulties and subjective mistakes in assessment of a clinical picture in a patient with subleukemic myelosis and thrombosis of the portal system. A careful examination of such patients is necessary to reveal latent disorders (in this case - a complete selective IgA deficiency) influencing treatment policy.

Matrix metalloproteinases and their inhibitors play an essential role in invasion and dissemination of malignant tumors. The study of expression of MMP and their inhibitors in solid and blood cancer may appear a key study giving assessment of antitumor response.