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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Terapevticheskii arkhiv</journal-id><journal-title-group><journal-title xml:lang="en">Terapevticheskii arkhiv</journal-title><trans-title-group xml:lang="ru"><trans-title>Терапевтический архив</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0040-3660</issn><issn publication-format="electronic">2309-5342</issn><publisher><publisher-name xml:lang="en">LLC Obyedinennaya Redaktsiya</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">29994</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Editorial article</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Передовая статья</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Prediction of interferon therapy efficacy in chronic myeloid leukemia according to histomorphological evidence</article-title><trans-title-group xml:lang="ru"><trans-title>Прогнозирование эффективности интерферонотерапии при хроническом миелолейкозе по данным гистоморфологического исследования</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Khoroshko</surname><given-names>N D</given-names></name><name xml:lang="ru"><surname>Хорошко</surname><given-names>Н Д</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Turkina</surname><given-names>A G</given-names></name><name xml:lang="ru"><surname>Туркина</surname><given-names>А Г</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kumas</surname><given-names>S M</given-names></name><name xml:lang="ru"><surname>Кумас</surname><given-names>С М</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Zhurarlev</surname><given-names>V S</given-names></name><name xml:lang="ru"><surname>Журавлев</surname><given-names>В С</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kuznetsov</surname><given-names>S V</given-names></name><name xml:lang="ru"><surname>Кузнецов</surname><given-names>С В</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Sokolova</surname><given-names>M A</given-names></name><name xml:lang="ru"><surname>Соколова</surname><given-names>М А</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Semenova</surname><given-names>E A</given-names></name><name xml:lang="ru"><surname>Семенова</surname><given-names>Е А</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kaplanskaya</surname><given-names>I В</given-names></name><name xml:lang="ru"><surname>Капланская</surname><given-names>И Б</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Frank</surname><given-names>G A</given-names></name><name xml:lang="ru"><surname>Франк</surname><given-names>Г А</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Korolev</surname><given-names>А V</given-names></name><name xml:lang="ru"><surname>Королев</surname><given-names>А В</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Scherbinina</surname><given-names>L A</given-names></name><name xml:lang="ru"><surname>Щербинина</surname><given-names>Л А</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Zakharova</surname><given-names>A V</given-names></name><name xml:lang="ru"><surname>Захарова</surname><given-names>А В</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Domracheva</surname><given-names>E V</given-names></name><name xml:lang="ru"><surname>Домрачева</surname><given-names>Е В</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Zingermam</surname><given-names>B V</given-names></name><name xml:lang="ru"><surname>Зингерман</surname><given-names>Б А</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва; ГНЦ РАМН</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en"></institution></aff><aff><institution xml:lang="ru">ГНЦ РАМН</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2004-07-15" publication-format="electronic"><day>15</day><month>07</month><year>2004</year></pub-date><volume>79</volume><issue>7</issue><issue-title xml:lang="en">NO7 (2004)</issue-title><issue-title xml:lang="ru">ТОМ 79, №7 (2004)</issue-title><fpage>44</fpage><lpage>50</lpage><history><date date-type="received" iso-8601-date="2020-04-09"><day>09</day><month>04</month><year>2020</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2004, Consilium Medicum</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2004, ООО "Консилиум Медикум"</copyright-statement><copyright-year>2004</copyright-year><copyright-holder xml:lang="en">Consilium Medicum</copyright-holder><copyright-holder xml:lang="ru">ООО "Консилиум Медикум"</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-sa/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://ter-arkhiv.ru/0040-3660/article/view/29994">https://ter-arkhiv.ru/0040-3660/article/view/29994</self-uri><abstract xml:lang="en"><p>Aim. To investigate factors determining prognosis and efficacy of induction therapy including interferon-alpha-2b (intron-A, Schehng Plough) in patients at an early chronic stage of Ph-positive chronic myeloid leukemia (CML) as shown by histomorphological examination.
Material and methods. The analysis covered 52 CML patients treated at an early chronic phase with intron-A in a standard daily dose 5 IU/m2 in combination with low-dose cytosinearabinoside (10 mg/m2, s.c. , daily for 10 days of each month). The treatment efficacy was assessed by the international criteria of complete and partial hematological remission and cytogenetic response. The cytogenetic study employed the direct method, even and G-differential staining, fluorescent hybridization in situ (FISH). The sections were stained with hematoxilin-eosine by Gomori, van Gieson. Histological samples were examined with histomorphometry. Immunohistochemical examination was made on paraffin sections using a panel of monoclonal antibodies CD3, CD4, CDS, CD20, NK, PCNA, Ki-67 (Dako, Denmark).
Results. Repeated assessment of histomorphological parameters such as erythroid lineage, degree of myelofibrosis and reduction of leukemic population indicate the treatment efficacy. Estimation of the level of leukemic population proliferation in trephine biopsies from CML patients with monoclonal antibodies PCNA and Ki-67 before the treatment is prognostically significant as it further correlates with the cytogenetic response (r = 0.821, p = 0.000000).
Conclusion. It is valid to study histomorphological picture of CML to prognosticate and assess treatment efficacy with standard doses of interferon-alpha with high probability.</p></abstract><trans-abstract xml:lang="ru"><p>Цель исследования. Выявление факторов, определяющих прогноз и эффективность индукционной терапии больных в ранней хронической стадии Ph '-положительного хронического миелолейкоза (ХМЛ), включающей интерферон-а-2р - ИФ-а (интрон-А, Schering Plough) no данным гистоморфологического исследования.
Материалы и методы. В анализ были включены 52 больных ХМЛ, леченных в ранней хронической фазе ИФ-а в стандартных дозах (5 МЕ/м2/сут, ежедневно) в сочетании с малыми дозами цитозинарабинозида (10 мг/м2, ежедневно, подкожно, 10 дней каждого месяца). Для оценки эффективности терапии использованы международные критерии, характеризующие полную и частичную гематологическую ремиссию и степень цитогенетического ответа. Цитогенетическое исследование включало использование прямого метода, равномерной и G-дифференцированной окраски, определение наличия слитного гена bcr/abl (метод флюоресцентной гибридизации in situ). Срезы биоптатов костного мозга окрашивали гематоксилин-эозином по Гомори, по Ван-Гизону. Комплексная оценка гистологических препаратов включала метод гистоморфометрии. Иммуногистохимическое исследование проводилось на парафиновых срезах с помощью панели моноклональных антител: CD3, CD4, CD8, CD20, NK, PCNA, Ki-67 ("Dako", Дания).
Результаты. Повторное определение гистоморфологических параметров, таких, как состояние эритроидного ростка, степень миелофиброза и редукция лейкозной популяции, позволяет оценить эффективность терапии. Определение уровня пролиферации лейкозной популяции в трепанобиоптатах больных ХМЛ с помощью моноклональных антител PCNA и Ki-67 до лечения обладает прогностической ценностью, так как этот показатель в последующем коррелирует со степенью цитогенетического ответа (г = 0,821, р = 0,000000).
Заключение. Показана целесообразность комплексного изучения гистоморфологической картины ХМЛ с целью прогнозирования и оценки эффективности терапии стандартными дозами ИФ-а с высокой долей вероятности.</p></trans-abstract><kwd-group xml:lang="en"><kwd>chronic myeloid leukemia</kwd><kwd>interferon-alpha</kwd><kwd>cytogenetic response</kwd><kwd>histomorphological examination of the bone marrow hemopoiesis</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>хронический миелолейкоз</kwd><kwd>интерферон-а</kwd><kwd>цитогенетический ответ</kwd><kwd>гистоморфологическое исследование костно-мозгового кроветворения</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Allan N. С., Richards S. M., Shepherd Р. С. UK Medical Research Council randomized, multicentre trial of interferon-alpha nl for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. The UK Medical Research Councils Working Parties for Therapeutic Trials in Adult Leukaemia. Lancet 1995; 345: 1392-1397.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Hasford J., Pfirrmann M., Hehlmann R. et al. A new prognostic score for the survival of patients with chronic myeloid leukemia treated with interferon a. J. Natl. Cancer Inst. 1998; 90: 850-858.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>The Italian Cooperative Study Group on Chronic Myeloid Leukemia. Long-term follow-up of the Italian trial of interferon-a versus conventional chemotherapv in chronic myelogenous leukemia. Blood 1998; 92: 1541-1548.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Хорошко Н. Д. Интенсификация терапия хронического миелолейкоза с учетом факторов прогнозирования болезни. Тер. арх. 1993; 7: 23-28.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Sokal J. Е., Сох Е. В., Baccarani M. et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood 1984; 63: 789-799.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Кумас Сотирис Морфи. Оценка эффективности интерферонотерапии при хроническом миелолейкозе по данным гистоморфологического исследования: Дис. ... канд. мед. наук. М.; 2002.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Семенова Е. А., Хохлова М. П., Хорошко Н. Д. и др. Гистологические варианты хронического миелолейкоза и их клиническое значение. Гематол. и трансфузиол. 1988; 3: 24-28.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Thiele J., Kantarjian H. M., Niederle N. et al. Clinical and histological features retain their prognostic impact under interferon therapy of CML: a pilot study. Am. J. Hematol. 1995; 50: 30-39.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Lambertenghi-Deliliers G., Pozzoli E., Benazzi E. et al. Bone marrow biopsy in chronic myeloid leukemia: significance of some histological parameters. Haematologica 1986; 1 (2): 113-116.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Lazzarino M., Mozza E., Castello A. et al. Myelofibrosis in cyronic granulocytic leukemia: clinicopathologic correlations and prognostic significance. Br. J. Haematol. 1986; 1 (2): 227- 240.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Thiele J., Wienhold S., Zankovich R., Fischer R. A histomorphometric analysis of trephine biopsies of bone marrow from 65 patients with chronic myeloid leukemia. Classification of patients into subgroups with different survival patterns. Analyt. Quant. Cytol. Histol. 1990; 12: 103-116.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Straetmans N., Ma D. D., Nevell D. F. et al. Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy. Hematopathol. Mol. Hematol. 1996; 10 (4): 213-222.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Thiele J., Zirbes T. K., Kvasnicka H. M. et al. Effect of interferon therapy on bone marrow morphology in chronic myeloid leukemia: a cytochemical and immunohistochemical study of trephine biopsies. J. Interferon Cytokine Res. 1996; 16 (3): 217-224.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Thiele J., Kvasnicka H. M., Schmitt-Graeff A. et al. Effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukemia: a comparative retrospective multicentre histological and clinical study. Br. J. Haematol. 2000; 108: 64-71.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Wilhem M., Bueso-Ramos C., O'Brien S. et al. Effect of interferon-alpha therapy on bone marrow fibrosis in chronic myelogenous leukemia. Leukemia 1998; 12 (1): 65-70.</mixed-citation></ref></ref-list></back></article>
