Prediction of interferon therapy efficacy in chronic myeloid leukemia according to histomorphological evidence

Abstract

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.

References

  1. 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.
  2. 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.
  3. 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.
  4. Хорошко Н. Д. Интенсификация терапия хронического миелолейкоза с учетом факторов прогнозирования болезни. Тер. арх. 1993; 7: 23-28.
  5. Sokal J. Е., Сох Е. В., Baccarani M. et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood 1984; 63: 789-799.
  6. Кумас Сотирис Морфи. Оценка эффективности интерферонотерапии при хроническом миелолейкозе по данным гистоморфологического исследования: Дис. ... канд. мед. наук. М.; 2002.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.

Copyright (c) 2004 Khoroshko N.D., Turkina A.G., Kumas S.M., Zhurarlev V.S., Kuznetsov S.V., Sokolova M.A., Semenova E.A., Kaplanskaya I.В., Frank G.A., Korolev А.V., Scherbinina L.A., Zakharova A.V., Domracheva E.V., Zingermam B.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies