Late myelotoxicity of high-dose chemotherapy according to the modified NHL-BFM-90 program in adult patients with diffuse large B-cell lymphoma

Abstract


Aim. To evaluate late myelotoxicity (MT) relate to high-dose chemotherapy (CT) according to the modified NHL-BFM-90 (mNHL-BFM-90) program in adult patients with diffuse large B-cell lymphoma (DLBCL). Subjects and methods. The results of a complex clinical, laboratory, and instrumental examination, including cytologic, histologic, and routine cytogenetic studies of the bone marrow (BM), were analyzed in 40 DLBCL patients treated according to the mNHL-BFM-90 program in the National Research Center for Hematology (NRCH), Ministry of Health of the Russian Federation (MHRF), in 2002 to 2009; among them, there were 20 men and 20 women (median age, 57 years). A comparison group consisted of 19 patients who had received high-dose СНОР/R-СНОР-21 CT in HRC, MHRF, in the same period of time; out of them, there were 8 men and 11 women (median age, 70 years). The median posttherapy follow-up period was 6 years. The results of BM studies were analyzed before and 5-10 years after treatment in complete remission. The cytological and histological studies of BM determined its cellularity, the sizes of erythroid, granulocytic, and megakaryocytic lineages, their ratios, the signs of dysplasia, and stromal dysplastic changes. Routine BM cytogenetic study was conducted to identify karyological problems. Only myelopoietic changes that had been revealed for the first time 5-10 years after completion of CT were kept in mind as late MT. Cases of baseline and post-CT changes and those of baseline and no post-CT changes were not taken into account. Results. Cytopenic syndromes (having no signs of myelopoietic lineage dysplasia or needing no blood component replacement transfusions) were revealed in 52% of the patients in the high-dose CT; thrombocytopenia amounted to 46%. In the late follow-up period, the patient group after high-dose mNHL-BFM-90 CT were found to have BM hypocellularity in 15 (38%) cases, a narrowing of erythroid and megakaryocytic lineages in 13 (33%) and 19 (48%) cases, respectively, and obvious secondary stromal changes in 17 (43%). The first 6 patients underwent routine BM cytogenetic study; all the patients were ascertained to have a normal karyotype; in this connection further BM study was stopped. Conclusion. The late MT of high-dose mNHL-BFM 90 CT is statistically significantly higher than that of the standard CHOP/R-CHOP-21 therapy. However, signs of myelodysplastic syndromes and those of cytopenia requiring blood component transfusions were observed in none patient.

References

  1. Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller A, Rudolph C, Reiser M, Hossfeld D, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M, and the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL). Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004;104:626-633. doi: 10.1182/blood-2003-06-2094
  2. Магомедова А.У. Диффузная В-крупноклеточная лимфосаркома лимфоидных органов: клинические формы и лечение: Дис. … д-ра мед. наук. М.; 2008.
  3. Récher C, Coiffier B, Haioun C, Molina T, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais J, Salles G, Tilly H. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomized phase 3 trial. Lancet. 2011;378:1858-1867. doi: 10.1016/s0140-6736(11)61040-4
  4. Wilson WH, Jung S-H, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Zelenetz AD, Cheson BD, His ED. A Cancer and Leukemi Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcomeby molecular subtype. Haematologica. 2012;97:758-765. doi: 10.3324/haematol.2011.056531
  5. Магомедова А.У., Кравченко С.К., Кременецкая А.М., Звонков Е.А., Барях Е.А., Мангасарова Я.К., Воробьев А.И. Девятилетний опыт лечения больных диффузной В-крупноклеточной лимфосаркомой. Терапевтический архив. 2011;7:5-10.
  6. Smith C. Hematopoietic stem cells and hematopoiesis. Cancer Control. 2003;10(1):9-16.
  7. Gale R. Antineoplastic chemotherapy myelosuppression: Mechanisms and new approaches (Keynote address). Exp Hematol. 1985;13:3-7.
  8. Neben S, Hellman S, Montgomery M, Ferrara J, Mauch P, Hemman S. Hematopoietic stem cell deficit of transplanted bone marrow previously exposed to cytotoxic agents. Exp Hematol. 1993;21(1):156-162.
  9. Minderman H, Linssen P, van der Lely N, Wessels J, Boezeman J, de Witte T, Haanen C. Toxicity of idarubicin and doxorubicin towards normal and leukemic human bone marrow progenitors in relation to their proliferative state. Leukemia. 1994;8(3):382-387.
  10. Schein PS, Winokur SH. Immunosuppressive and cytotoxic chemotherapy: long-term complications. Ann Intern Med. 1975; 82(1):84-95.
  11. Trainor KJ, Seshadri RS, Morley AA. Residual marrow injury following cytotoxic drugs. Leuk Res. 1979;3(4):205-210.
  12. Lohrmann HP. The problem of permanent bone marrow damage after cytotoxic drug treatment. Oncology. 1984;41(3):180-184.
  13. Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst. 1999;91(19): 1616-1634.
  14. Ludwig H, Van Belle S, Barrett-Lee P, Birgegård G, Bokemeyer C, Gascón P, Kosmidis P, Krzakowski M, Nortier J, Olmi P, Schneider M, Schrijvers D. The European Cancer Anaemia survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer. 2004;40(15):2293-2306. doi: 10.1016/j.ejca.2004.06.019
  15. Parameswaran R, Lunning M, Mantha S, Devlin S, Hamilton A, Schwartz G, Soff G. Romiplostim for management of chemotherapy-induced thrombocytopenia. Support Care Cancer. 2014;22(5): 1217-1222. doi: 10.1007/s00520-013-2074-2
  16. Shen Y, Nilsson SK. Bone, microenvironment and hematopoiesis. CurrOpin Hematol. 2012;19(4):250-255. doi: 10.1097/moh.0b013e328353c714
  17. Dale DC. Understanding neutropenia. Curr Opin Hematol. 2014;21(1):1-2. doi: 10.1097/moh.0000000000000012
  18. Грибанова Е.О. Кроветворение после аллогенной и аутологичной трансплантации костного мозга: Дис. … канд. мед. наук. М.; 2003.
  19. Грибанова Е.О., Гласко Е.Н., Любимова Л.С., Капланская И.Б., Петров А.Н., Лебедев Э.А. Гистологическая картина костного мозга у больных острыми лейкозами в разные сроки после трансплантации костного мозга. Проблемы гематологии и переливания крови. 2002;4:13-20.
  20. O´Flaherty E, Sparrow R, Szer J. Bone marrow stromal function from patients after bone marrow transplantation. Bone Marrow Transplant. 1995;15:207-212.
  21. Chinello M, Naviglio S, Shardlow A, Severino A, Ventura A, Locasciulli A. Dysplastic bone marrow changes during maintenance therapy for acute leukemia. J Pediatr Hematol Oncol. 2015;37(2): 156-157. doi: 10.1097/mph.0000000000000295
  22. Schmitz LL, McClure JS, Litz CE, Dayton V, Weisdorf DJ, Parkin JL, Brunning RD. Morphologic and quantitave changes in blood and marrow cells following growth factor therapy. Am О Сlin Pathol. 1994;101:67-75.
  23. Гайдамака Н.В., Паровичникова Е.Н., Завалишина Л.Э., Гармаева Т.Ц., Гапонова Т.В., Троицкая В.В. Длительные аплазии костного мозга после химиотерапии у больных острыми лейкозами. Терапевтический архив. 2010;7:12-18.
  24. Гармаева Т.Ц., Куликов С.М., Карякин А.В. и другие. Мониторирование факторов риска и индикаторов инфицированности вирусами гепатитов В и С гематологических больных. Гематология и трансфузиология. 2006;1:23-27.
  25. Долгих Т.Ю. Клинико-патоморфологическое исследование эритрона и костномозгового микроокружения при агрессивных и индолентных неходжкинских лимфомах: Автореферат дис. … канд. мед. наук. Новосибирск; 2011.
  26. Ширин А.Д., Френкель М.А. Современная диагностика миелодиспластических синдромов взрослых. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2010;3:3.

Statistics

Views

Abstract - 83

PDF (Russian) - 25

Cited-By


Article Metrics

Metrics Loading ...

Refbacks

  • There are currently no refbacks.

Copyright (c) 2020 Dorokhina E.I., Magomedova A.U., Dvirnyk V.N., Galtseva I.V., Glinkina S.A., Kulikov S.M., Obukhova T.N., Kravchenko S.K.

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

Address of the Editorial Office:

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

Correspondence address:

  • Novoslobodskaya str 31c4., Moscow, 127005, Russian Federation

Managing Editor:

 

© 2018 "Consilium Medicum" Publishing house


This website uses cookies

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

About Cookies