The use of all-trans retinoic acid (ATRA) drastically improved the results of therapy for acute promyelocytic leukeimia (APL). The high efficiency of the Russian protocol APL-93—98 applied to 62 children and adolescents with APL (event-free and overall survival (EFS and OS) were 84±5% respectively with a relapse rate of 7%) was achieved, by administering the high cumulative dose of daunoruicin (495 mg/m2) and single doses of АТRА (45 mg/m2). In this connection, the APL-2003 protocol attempted to reduce both acute and chronic toxicity of the therapy, by decreasing the cumulative dose of daunorubicin to 405 mg/m2 and the single dose of АТRА to 25 mg/m2 under regular control of minimal residual disease via molecular monitoring of the specific transcript PML/RARα. Analysis of the results of treatment in 61 patients aged 1.3 to 17 years (median 11.3) showed that despite of the reduced protocol intensity, the efficiency of therapy did not generally reduce — EFS and OS were 79±6 and 93±3%, respectively. The likelihood of the development of a relapse was significantly affected by molecular resistance, i.e. the retention of the transcript PML/RARα before a phase of maintenance therapy: the recurrence risk in this group was 57% whereas there were no differences in all cure rates between the patients depending on baseline leukocytosis. All 6 patients with relapses were treated with arsenic trioxide, resulting in not only clinical and hematological, but also molecular remissions; thereafter the patients received myeloablative therapy and autologous hemopoietic stem cell transplantation. The second remission lasted 3 to 24 months. Thus, reducing the cumulative dose of anthracyclines and the dose of АТRА did not make the results of the therapy for APL worse. The monitoring of minimal residual disease before and during maintenance therapy is a mandatory component of successful treatment in APL patients. Arsenic trioxide is an effective agent for the treatment of APL relapses.

The retrospective study of clinical data, risk factors, and results of treatment of a large group of patients with primary systemic anaplastic large-cell lymphoma (ALCL) (n = 42) with the Т-/О phenotype is presented. Primary systemic ALCL occurred in young persons aged less than 30 years. A group of patients with its poor course (with complete remission (CR) being achieved) showed a trend for the prevalence of the signs that were a part of the standard (International Prognostic Index — IPI) factors and ones of poor prognosis, which were additionally analyzed by the authors. Significant differences in a group of patients with a good prognosis (with CR being achieved) were obtained only in the following indices: ALK protein expression (substantiating the further division and study of a homogenous group of patients), the stage of the disease, evaluation of the patients’ general condition by the ECOG scale, and the presence of B-symptoms.
According to the data available in the literature, ALK-positive ALCL has a better prognosis than ALK-negative ALCL. The results given in this communication additionally confirm and extend these observations. There is evidence that, by using the IPI and the baseline prevalence of the disease, one may predict an outcome in the homogenous group of patients without CR being achieved after first-line therapy. Analysis of the findings has established no clinical risk factors associated with the baseline site of a tumor process, which influence long-term results, but this matter should be studied in further prospective investigations, by keeping in mind the location zones characteristic of ALCL.

The paper presents the results of a multicenter randomized study of two-dose COLI-ASP regimens in therapy of consolidation of standard risk-group (SRG) children and adolescents with acute lymphoblastic leukemia (ALL) treated by the ALL-MB-2002 protocol. The principal aim of the study was to elucidate whether the dose of COLI-ASP might be reduced without losing the efficiency of therapy. The analysis covered primary ALL patients notified at 36 clinics of Russia and Belarus, enrolled for the study in the period of May 1, 2002, to October 10, 2006. Out of 819 patients to be examined, 414 received COLI-ASP in a dose of 10,000 U/m2 (a control group), and 405 children took it in a dose of 5,000 U/m2 (a study group). No statistically significant differences were found between the patients in gender, age, baseline leukocytosis, and spleen size. The study showed no statistically and clinically significant differences in event-free, overall, and relapse-free survival (EFS, OS, and RFS, respectively) and relapse rates with the use of two-dose COLI-ASP regimens. However, in the control group, the death rate in remission was twice greater than that in the study group (p = 0.02). Detailed analysis of the outcomes of therapy in some subgroups revealed no differences between the control and study groups. The Cox multiple regression analysis has indicated that the factors influencing EFS and RFS are the baseline sizes of the spleen, baseline leukocytosis, age, and a response to treatment in the period of induction, rather than the dose of E. coli asparaginase. The authors have also found that among the SRG patients, there is a subgroup of patients without risk factors, in whom the reduction in the COLI-ASP dose may substantially increase survival rates, by lowering toxicity and mortality in remission.

To obtain a sufficient number of hemopoietic progenitor cells (HPCs) for a rapid and stable recovery of hematopoiesis is one of the major conditions for safe high-dose chemotherapy. The paper analyses the current approaches to mobilizing and collecting HPCs, as well as the factors influencing their efficiency. By using their own large material (264 patients who had undergone mobilizing procedures), the authors have shown that none of predictors (age, a history of multiple courses of chemotherapy, peripheral blood levels of CD34+ cells at sampling, etc.) may identify patients in whom peripheral blood HPCs cannot be certainly ineffectively collected. At the same time, combined mobilization with myelostimulating factors (granulocyte, granulocytemacrophage colony-stimulating factors) and cytostatics (high-dose cyclophosphamide) yield the greatest quantities of HPCs from peripheral blood in patients with solid tumors and multiple myeloma.

A graft versus host disease (GVHD) is one of the most serious complications occurring after allogeneic marrow cell transplantation. The investigation of the immune mechanisms responsible for the development of an acute GVHD has revealed a critical role of the regulatory T cells CD4+CD25+Foxp3+ that are responsible for the suppression of the function of effector rejection mechanisms, including the inhibition of the cytotoxic T lymphocytes CD8+, Т- helper cells CD4+CD25, natural killer cells and others that damage the host cells. Animal experiments have indicated the leading role of regulatory T cells in the initiation of GVHD. A number of human studies have analysed a correlation between the levels of the regulatory T cells CD4+CD25+Foxp3+ in the graft and/or blood of a recipient and the further occurrence of acute or chronic GVHD. The severity of an allogeneic GVHD is inversely related to the low expression of Foxp3.
Besides regulatory T cells, mesenchymal stem cells (MSCs) have a significant immunosuppressive effect that has been demonstrated in the animal experiments and in the clinical trials in patients. MSCs do not only prevent the development of a GVHD, but may be used for the treatment of a just incipient process. In the opinion of a number of authors, MSCs prevent the development of a GVHD by directly affecting the induction of regulatory T cells in vivo.

The characteristics of peripheral neuropathy (PN), its incidence and a possibility of relieving in multiple myeloma (MM) patients receiving bortezomib are presented. A hundred and twenty-four patients with recurrent/refractory MM and 14 primary patients were followed up. PN more commonly occurred after 3—5 cycles of bortezomib therapy. Grade > 2 PN was observed in 29% of the patients. The cumulative dose of bortezomib was 15.6 to 26 mg/m2. After 6—8 cycles the incidence of PN was also high. There was a correlation between the cumulative dose of bortezomib and the incidence of PN (R = 0.927; p < 0.0009). A correlation was also found between the incidence of PN and prior vincristine-containing treatment regimens (VAD scheme). Overall, PN was identified in 54% of the patients. Treatment of PN with gabapentin, pregabalin, vitamins B, and α-lipoic acid was effective. PN resolved to the baseline levels or the patients’ condition improved in 72% of the patients, the median time taken for resolution or improvement being 114 days. It is necessary to reduce the dose of bortezomib or to discontinue the drug temporarily in order to relieve the symptoms of neuropathy.

The theoretical rationale for intensification of chemotherapy (CT) has become a basis for using of high-dose chemotherapy and for reducing of intervals between courses. At the same time, the toxic effect of cytostatics on bone marrow is one of the most critical deferent to the intensification of CT. The use of dose-intensive regimens, without supporting granulocyte colony-stimulating factor (G-CSF) preparations, inevitably results in the occurrence of severe neuropenia in most patients and the development of serious infectious complications.
This paper presents the results of the prospective clinical study of the safety and efficiency of intensive-dose CT programs for breast cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, conducted at Moscow City Cancer Hospital Sixty-Two in the period of April to November 2007. The study included 56 patients aged 18 to 72 years who received different intensive-dose CT, including 21 patients with breast cancer, 30 with Hodgkin’s lymphoma, and 5 with non-Hodgkin’s lymphoma. For hemopoietic stimulation, the Russian recombinant G-CSF preparation Leukostim® was subcutaneously injected for all the patients. According to results of this study, intensive-dose CT regimens are effective in treating a number of malignancies and the administration of Leukostim® substantially enhances the accessibility of current treatment for malignancies in a wide circle of Russian patients. The capacities of intensedose CT require meticulous investigation and the method itself deserves further development and Russian oncologists’ scrupulous attention.

The paper deals with the treatment policy, including erythropoiesis-stimulating drugs (ESD), in anemic patients with malignancies. The use of ESD remains the basic recommended treatment option for anemia in cancer patients treated with cytostatics if the causes of anemia, which are eliminable by other means, are absent. Introduction of darbepoetin α makes ESD therapy more convenient for patients and medical staff.