Introduction of the immunophenotyping in 70-ties and 80-ties of the past century has led to significant revision of conception of hematological malignancies. A new era in developement of medicine and oncology in particular is related to functional genomics. This field of molecular biology attempts to make use of the vast wealth of data produced by genomic projects for studying gene functions and interactions. Functional genomics focus on the dynamic aspects such as gene transcription, mRNA translation, and protein-protein interactions, as opposed to the static aspects of the genomic information such as DNA sequence or structure. Several genomic technologies have been developed to study gene expression. Gene expression profiling on DNA microarrays has been particularly useful in analyzing expression of thousands genes in parallel. Modern microarrays contain comprehensive probe sets which are able to measure the majority of genes encoded in human genome. Here we focus on microarray technology, discuss its clinical applications and briefly review some results obtained by this method in researches of hematological malignancies.

Cytogenetic changes in bone marrow cells and their influence on clinical course of the disease were analyzed in 106 patients with acute non-lymphoblastic leukemia (ANLL). According to rearrangements of chromosomes the patients were divided into three groups. The first group consisted of patients with anomalies of karyotype typical for particular variants of ANLL. The second group comprised patients with chromosome anomalies, which are not associated with any special variant of disease. The third group included patients with unique rearrangements of chromosomes characterized by special mechanism of formation of karyotype changes. Overall, three patients with complex karyotype anomalies formed the third group: first patient with 46, Y,t(2;15)(q37;p13),+12,add(13)(q14),add(13)(21), second patient with 42, XX, -4, t(6;17)(p25;q25), -8, -15, i(17q),-18, +mar/ 44, XX, -4, t(6;17)(p25;q25), -15, i(17q),-18, ++mar[2]/ 44, XX, -4, t(6;17)(p25;q25), -15, i(17q),-18, +mar, + min/ 46, XX, -4, t(6;17)(p25;q25), del(8)(q21), -15, i(17q), -18, +mar[4]/44, XX, -3, t(6;17)(p25;q25), -15, i(17q),-18,+ mar, + min, and third patient with 51, XY, t(12;18)(p13;p11.3), +8, +10,-14, der17,+ mar[5]. Among peculiar features of - t(2;15)(q37;p13), t(6;17)(p25;q25), t(12;18) rearrangements were the primary character of translocations between these chromosomes, and participation of whole chromosomes, but not their fragments, in the formation of translocations.

Clinical efficacy of DAL-HD-90m protocol in the treatment of adolescent and young patients with Hodgkin's lymphomas was analyzed. From November 1997 to April 2007, 97 patients (38 males and 59 females) aged from 15 to 45 years with first diagnosed Hodgkin's lymphomas were enrolled to trial. Patients with IA, IB and IIA stages (therapeutic group (TG) 1) were treated by 2 cycles of ODPA regimen (vincristine, procarbasine, prednisolone, adriamycin) for females and 2 cycles of OEPA regimen (vincristine, ethoposide, prednisolone, adriamycin) for males. Patients with IIB, IIIA, IE A, IE B, IIE A stages (TG 2) received additional two cycles of multi-agent chemotherapy with COPD regimen (cyclophosphamide, vincristine, prednisolone, adriamycin). Patients of TG 3 (stages IIIB, IVA, IVB, IIE B, IIIE A, IIIE B) were treated with 2 cycles of ODPA and 4 cycles of COPD regimens irrespective of the patient's sex. Radiotherapy was carried out to all patients: targets included regional lymph nodes (total local dose of 30 Gy) and additionally the residual tumor (total dose of 6-10 Gy). Complete response was achieved in 91 % patients from TG 1, 94% patients from TG 2 and 89% from TG 3 group. Six-year overall survival was 0,91±0,09; 0,88±0,08 and 0,76±0,08, respectively. The absence of CR/CRu after 2 courses of OPPA/OEPA (0,60 versus 0,93; p=0,006), initial tumors of larger volumes than 50 cm3 (0,66 versus 0,91, p=0,017) and the International Prognostic Index no lower than 4 points (0,44 versus 0,82; p=0,039) were unfavorable prognostic factors for TG3 patients in this study.

Acute graft-versus-host disease (GFHD) and graft rejection reaction (GRR) early in the post-transplantation period are main complications of allogeneic transplantation of hematopoietic stem cells. We analyzed the incidence of principal early complications in 109 patients with various oncohematologic diseases who underwent 112 allogeneic transplantations of hematopoietic stem cells from related and unrelated donors with myeloablative and non-myeloablative regimens of conditioning with and without use of anti-monocyte globulin. Application of anti-monocyte globulin provides effective control of acute GFHD without increment of disease relapsing risk and lowers the incidence of GRR to 7%. So, results of our study showed that usage of anti-monocyte globulin with conditioning regimens for patients who habe undergone allogeneic transplantation of hematopoietic stem cells, allows to effectively decrease the incidence of early posttransplantation complications. Consequently, that increases the 4-year overall survival of these patients as compared with patients who did not undergo the use of anti-monocyte globulin.

In spite of striking successes achieved in the treatment of chronic leukemia with Gleevec, some patients remain resistant to the drug. Risk for development of resistance to Gleevec increases with the duration of chronic phase of disease and, more evidently, with onset of acceleration phase and blast crisis. Besides, other patients can not tolerate Gleevec. Nilotinib (tasigna, Novartis Pharma) which is a new highly selective inhibitor of bcr/abl tyrosine-kinase has been introduced into clinical practice after the mechanisms of resistance to drug became clear. Clinical trials of phase I and II demonstrated high activity of Nilotinib in patients with resistance to Gleevec, low toxicity profile and absence of cross toxicity with Gleevec. The clinical case of successful therapy with Nilotinib in patient with cytogenetically proved resistance to Gleevec is reported in the article. The major cytogenetic response was achieved after a short period of time (6 months) with acceptable tolerability of treatment.

Prognosis of patients with juvenile myelomonocytic leukemia not undergoing allogeneic hematopoietic cells transplantation (SCT) is dismal and not affected by any cytotoxic chemotherapy. Differentiating therapy is an attractive approach in JMML, due to ability of JMML cells to differentiate and die under influence of treatment with various agents in vitro. We report results of first-line treatment of 14 patients with JMML with 13-cis retinoic acid (RA) 100 mg/m2 daily peroral intake and low dose Ara-C - 25 mg/m2 daily for 10 days monthly. Complete remission (CR) or hematological improvement (HI) was obtained in 7 patients (50%). Four patients (median age at disease manifestation 5 months, median level of HbF —6,2%) achieved CR after a median of 9 cycles of therapy; in 3 patients the best response was HI (age at disease manifestation - 5; 7 and 46 months, HbF — 4,2; 8,0 and 51,7%) after 2; 3 and 5 cycles. Three out of 4 patients with CR are alive and have been in CR for 10; 17 and 30 months after start of therapy, acute lymphoblastic leukemia developed in one patient after 84 months of CR. Two patients with HI are still receiving treatment and have been in stable condition for 10 months after the initiating therapy, while 1 patient died after 8 months of therapy from catheter-related sepsis. The progression of the disease despite the treatment was registered in 7 patients (median age at disease manifestation 16,3 months, median HbF — 35,4%). We conclude that 13-cis RA in combination with low dose AraC may be useful in the treatment of patients younger than 1 year with low level of HbF, although the general paradigm of treatment of JMML with SCT remains unchanged.

Preclinical studies showed synergic anti-tumor activity of Rituximab and Fludarabin. Comparison of efficacy of FC with FCR regimens administered in first line therapy and their influence on disease-free and overall survival in patients with B-cell lymphocytic leukemia were the main goals of this retrospective study. It has been demonstrated that inclusion of Rituximab into the FC regimen improves outcome of patients with B-cell lymphocytic leukemia without significant increase of toxicity.

Some recommendations of Infectious Diseases Society of America for diagnosis and treatment of invasive aspergillosis with lung involvement, which is the most frequent clinical manifestation of aspergillar infection.
Full version of recommendations was published in one of the editions of journal “Clinical microbiology and antibacterial chemotherapy” (2008. Т. 10. №2). Fungi of Aspergillus kin is the main etiologic cause of life-threatening infections in immunocompromised patients, such as patients with prolonged neutropenia, advanced stages of HIV infection, hereditary immunodeficiency states and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and/or lung transplantation. This version of recommendations for treatment of invasive aspergillosis from IDSA (Infectious Diseases Society of America) substituted the former recommendations published in 2000. The level of evidence of treatment data is given in according with standard scheme used in the IDSA guidance.

Multiple myeloma frequently leads to bone complications characterized by the presence of lytic defects with high incidence of pathologic fractures, hypercalcemia and osteoporosis. The basic cause of this effect lies in the ability of malignant plasmatic cells to stimulate osteoclasts which are cells participating in the process of resorption of osseous tissue. Increased resorption of osseous matrix by means of osteoclasts activation runs concurrently with the process of decrease of activity of osteoblasts which are cells synthesizing osseous matrix of the bones. It has been a long time since the efforts to cope with consequences of unfavorable influence of myeloma cells on osseous tissue has been under way mainly by symptomatic means: local radiotherapy, surgical reconstruction of the bone, especially in cases of vertebral involvement, and anesthesia. Recently new weapon has been added to the arsenal for treatment of bone complications: bisphosphonates which are agents inhibiting the activity of osteoclasts and thus promoting the consolidation of the bones. Results of controlled clinical trials showed that such a medications as clodronate, pamidronate and zoledronate considerably decrease the incidence of bone complications in patients with multiple myelomas. Pamidronate and xoledronate turned out to be more active, at the same time long term usage of zoledronic acid can lead to development of such an adverse complication as osteonecrosis of jaw. The ASCO recommendations indicates the appropriateness of long term use of pamidronate or zoledronate in patients with multiple myelomas and bone complications.

For past decades there have been substantial changes in the therapy of oncohematologic diseases in children. Today, the treatment of this subset of patients is impossible without close cooperation between pediatric oncology/hematology professionals and general pediatricians. Authors underline the following critical steps in the management of oncohematologic patients necessarily requiring participation of general pediatricians: early diagnosis of malignancies, management of patients during their anti-tumor treatment, observation of patients in complete remissions after effective anti-tumor treatment, management of patents receiving palliative care, organization of hospices. Issues regarding prophylaxis and treatment of infectious complications in oncohematologic patients, use of growth factors, substitutive treatment with blood components and vaccination are reviewed.