Vol 9, No 3 (2014)

Cover Page

Full Issue

HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE

Interim results of the Ph-negative acute lymphoblastic leukemia treatment in adult patients (results of Russian research group of ALL treatment (RALL))

Parovichnikova E.N., Troitskaya V.V., Sokolov A.N., Akhmerzaeva Z.K., Kuzmina L.A., Mendeleeva L.P., Klyasova G.A., Kravchenko S.K., Gribanova Y.O., Bondarenko S.N., Baranova O.Y., Kaporskaya T.S., Ryltsova T.V., Nizamutdinova A.S., Zagoskina T.P., Zinina Y.Y., Samoylova O.S., Klimovich A.V., Karyakina Y.A., Yelufer’eva A.S., Gavrilova L.V., Konstantinova T.S., Toropova I.Y., Pristupa A.S., Vopilina N.A., Tikunova T.S., Skamorina O.P., Kaplanov K.D., Obukhova T.N., Galtseva I.V., Rusinov M.A., Kulikov S.M., Savchenko V.G.

Abstract

An interim analysis of long-term treatment results for 202 patients with acute lymphoblastic leukemia (ALL), aged 15–60 years, received therapy according protocol ALL-2009 was shown. The basic principle of ALL-2009 was non-aggressive, but continued cytostatic exposure, as well as the reproducibility in a regional hematology centers. Long-term treatment results of ALL-2009 are 2 times higher than the previously obtained in adult ALL patients within the Russian clinical multicenter studies of adult ALL. The 5‑year overall survival of patients younger than 30 years was 73.6 %, relapse-free survival (RFS) – 71.5 %, compared with 52.7 % and 61.8 % in patients aged 30 years and older, respectively. In patients with B-precursor ALL with normal karyotype of blast cells significantly higher 5‑year RFS (82.1 %) compared to patients with abnormal karyotype (58.8 %) was registered. For T-ALL cytogenetic characteristics of blast cells had no prognostic significance. For patients with T-ALL important to perform autologous stem cell transplantation as a later consolidation, as this significantly reduce
relapse rate (from 33 to 0 %).

Oncohematology. 2014;9(3):6-15
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Pharmacoeconomic modeling of target therapy of chronic myeloid leukemia in remission

Shuvaev V.A., Abdulkadyrov K.M., Martynkevich I.S., Fominykh M.S.

Abstract

The article presents example of modeling for pharmacoeconomical-founded choice of chronic myelogenous leukemia treatment strategy related to therapeutic efficacy and economical rationality. The economic model of chronic myelogenous leukemia diagnosis and treatment with Markov chain approach was constructed, based on modern national and international clinical guidelines. Pharmacoeconomical comparison of chronic myelogenous leukemia target therapy using first and second-generation tyrosine kinase inhibitors was performed. The average direct cost for one patient and total budget impact in twenty years were calculated. Analysis was made based on costs of original imatinib and generics. We used the imatinib generics’ substitution experience as a scenario for the second generation TKIs. Under these conditions, more frequent therapy cessation with second generation TKIs resulted in nilotinib first line is cost saving over imatinib. We should note that the
results of our analysis were strongly dependent on the input parameters values. The Pharmacoeconomic modelling can forecast the budget burden and its future dynamics on the individual and national level. The results of such modelling could be of value in decision-making in national guidelines development and discussion with healthcare authorities.

Oncohematology. 2014;9(3):16-24
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HEMATOPOIETIC STEM CELL TRANSPLANTATION

Analysis of the results of allogeneic hematopoietic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair

Kuzmich Y.V., Alyanskiy A.I., Ivanova N.Y., Vitrischak A.A., Vladovskaya M.D., Morozova Y.V., Bondarenko S.N., Semenova Y.V., Zubarovskaya L.S., Afanasyev B.V.

Abstract

HLA matching of the donor / recipient pair is a major factor associated with the outcome of allogeneic stem cell transplantation. In the present
study we analyzed the risk of severe acute graft-versus-host disease, graft failure, 2.year overall survival of the patients after allogeneic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair.

Oncohematology. 2014;9(3):25-31
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The optimal time for hematopoietic stem cell translantation for Hodgkin's lymphoma. International guidelines and real practic in Russia and former USSSR countries (Part II)

Zhukov N.V., Uss A.L., Milanovich N.F., Ptushkin V.V., Afanasiev B.V., Mikhaylova N.B., Larionova V.B., Demina Y.A., Tyurina N.G., Vernyuk M.A., Karamanesht Y.Y., Rumyantsev A.G.

Abstract

The influence of previous antitumor therapy the efficacy and tolerability of high-dose chemotherapy with autologous hematopoietic progenitor cells transplantation (HCST) in 369 patients with Hodgkin, s lymphoma in the clinics of Russia and CIS countries was analyzed. Longterm treatment results of patients who have received 1 or 2 therapy lines before deciding about HCST were comparable (5‑year overall survival (OS) – 67 ± 3.8 % and 71 ± 5.0 %; freedom from treatment failure survival (FFTF) – 52.6 ± 3.9 % and 61 ± 5.0 %, respectively). The worst results (p < 0.05) are in patients who have received > 2 lines of therapy prior HSCT (5‑year OS – 46 ± 9.7 %, FFTF – 38.4 ± 9.0 %). The negative impact of previous treatment on the efficiency of hematopoietic material collection and hematopoiesis reconstitution as well observed in patients who received > 2 lines of therapy. Therefore, if the delay of HSCT in patients who achieved remission on secondline therapy was caused by organizational problems, for optimum results is necessary to conduct HSCT not later than second relapse while maintaining tumor chemosensitivity (third disease remission). However, when remission is not achieved after second-line therapy, is necessary to change the treatment regimen and performing HSCT only at confirmation of tumor chemosensitivity, because regardless of prior therapy line number, this approach leads to better results than earlier performing HSCT without remission.

Oncohematology. 2014;9(3):32-40
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PHARMACOTHERAPY

Role of biosimilars in neutropenia prevention in cancer patients

Ptushkin V.V.

Abstract

Oncohematology. 2014;9(3):41-46
pages 41-46 views

Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy

Kuter D.J., Bussel J.B., Newland A., Baker R.I., Lyons R.M., Wasser J., Viallard J., Macik G., Rummel M., Nie K., Jun S.

Abstract

Romiplostim was effective, safe, and well-tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP). This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin / fibrosis), platelet response (platelet count >50 × 109 per litre), and the proportion of patients requiring rescue treatments. Treatment – related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5 % of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintained
with stable doses of romiplostim (mean 5–8 μg / kg; generally self-administered at home) throughout the study. A platelet response was achieved at least once by 95 % of patients, with a platelet response maintained by all patients on a median 92 % of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and welltolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.

Oncohematology. 2014;9(3):47-62
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EDUCATIONAL LECTURES, REVIEWS

Programmed cell death of platelets during their overactivation

Artemenko E.O., Sveshnikova A.N., Panteleev M.A.

Abstract

Programmed cell death – it is a cell death by a strictly defined mechanism with possible impact on him and, due to this, the death control, including using of pharmacological agents. Currently known many different types of cell death, but only two basic types of cell death are adequately characterized: apoptosis and programmed necrosis. Platelets are one of the key components of the blood clotting process. A group of platelets, exposing phosphatidylserine (PS), with the programmed cell death characteristics appears at their critical agonist-induced activation. This overactivation of platelets accompanied by subsequent cell death is not completely characterized cellular processes. We view the platelets overactivation in comparison with the main known types of cell death because the platelets group exposing PS is important for blood
coagulation processes, accelerating by several orders the plasma coagulation, and important for the thrombus formation.

Oncohematology. 2014;9(3):63-66
pages 63-66 views

Basic mechanisms of iron metabolism regulation and their clinical significance

Meshсheryakova L.M., Levina A.A., Tsybulskaya M.M., Sokolova T.V.

Abstract

This article is а composition of literature and experimental data of iron metabolism. There were studied the level of DMT-1, ferroportin, hepcidin at different stages of anemia and hemochromatosis. It is clear that the level of DMT-1 regulates by the hepcidin. Increaseing of the hepcidin concentration and decreasing DMT-1 level in patients with hemochromatosis explained good results of treatment.

Oncohematology. 2014;9(3):67-71
pages 67-71 views