Myeloproliferative Syndrome und chronisch myeloische Leukämie beim alten und geriatrischen Patienten

  • Juliana Schwaab
  • Susanne Saußele
  • Georgia Metzgeroth
  • Andreas Reiter
Chapter
Part of the Springer Reference Medizin book series (SRM)

Zusammenfassung

Die Myeloproliferativen Neoplasien sind eine heterogene Gruppe von Stammzellerkrankungen mit Proliferation mindestens einer Zellreihe, die gehäuft beim älteren Menschen vorkommen. Klinisch manifestieren sich oft eine ausgeprägte B-Symptomatik, Juckreiz, Schmerzen im Bereich der Milz bei Splenomegalie und Mikrozirkulationsstörungen. In letzter Zeit wurden neben den bekannten genetischen Aberrationen (z. B. JAK2 V617F oder BCR-ABL1) weitere Mutationen identifiziert, welche z. T. prognostische Relevanz haben. Auch das Alter bei Diagnosestellung hat eine negativ prognostische Bedeutung. Mit Tyrosinkinaseinhibitoren und dem zytoreduktiv wirkenden Hydroxyurea stehen jedoch aufgrund der guten Verträglichkeit für alle Altersgruppen anwendbare medikamentöse Therapien zur Verfügung, die die Lebenserwartung z. T. signifikant verlängern (z. B. bei der chronischen myeloischen Leukämie). Die allogene Stammzelltransplantation dagegen, stellt eine Therapiealternative für eher jüngere Patienten dar.

Literatur

  1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405CrossRefPubMedGoogle Scholar
  2. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Muller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saussele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122(6):872–884CrossRefPubMedPubMedCentralGoogle Scholar
  3. Barbui T, Finazzi MC, Finazzi G (2012a) Front-line therapy in polycythemia vera and essential thrombocythemia. Blood Rev 26(5):205–211CrossRefPubMedGoogle Scholar
  4. Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Vannucchi AM, Tefferi A (2012b) Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 120(26):5128–5133; quiz 5252CrossRefPubMedGoogle Scholar
  5. Bonicelli G, Abdulkarim K, Mounier M, Johansson P, Rossi C, Jooste V, Andreasson B, Maynadie M, Girodon F (2013) Leucocytosis and thrombosis at diagnosis are associated with poor survival in polycythaemia vera: a population-based study of 327 patients. Br J Haematol 160(2):251–254CrossRefPubMedGoogle Scholar
  6. Bose P, Verstovsek S (2016) Prognosis of primary myelofibrosis in the genomic era. Clin Lymphoma Myeloma Leuk 16(Suppl):105–113CrossRefGoogle Scholar
  7. Cervantes F, Pereira A, Esteve J, Rafel M, Cobo F, Rozman C, Montserrat E (1997) Identification of ‚short-lived‘ and ‚long-lived‘ patients at presentation of idiopathic myelofibrosis. Br J Haematol 97(3):635–640CrossRefPubMedGoogle Scholar
  8. Deeg HJ, Bredeson C, Farnia S, Ballen K, Gupta V, Mesa RA, Popat U, Hari P, Saber W, Seftel M, Tamari R, Petersdorf EW (2015) Hematopoietic cell transplantation as curative therapy for patients with myelofibrosis: long-term success in all age groups. Biol Blood Marrow Transplant 21(11):1883–1887CrossRefPubMedPubMedCentralGoogle Scholar
  9. Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, Van Dyke D, Hanson C, Wu W, Pardanani A, Cervantes F, Passamonti F, Tefferi A (2011) DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 29(4):392–397CrossRefPubMedGoogle Scholar
  10. Guglielmelli P, Lasho TL, Rotunno G, Score J, Mannarelli C, Pancrazzi A, Biamonte F, Pardanani A, Zoi K, Reiter A, Duncombe A, Fanelli T, Pietra D, Rumi E, Finke C, Gangat N, Ketterling RP, Knudson RA, Hanson CA, Bosi A, Pereira A, Manfredini R, Cervantes F, Barosi G, Cazzola M, Cross NC, Vannucchi AM, Tefferi A (2014) The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia 28(9):1804–1810CrossRefPubMedGoogle Scholar
  11. Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, Alimena G, Steegmann JL, Ansari H (1998) A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst 90(11):850–858CrossRefPubMedGoogle Scholar
  12. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G, Guilhot F, Porkka K, Ossenkoppele G, Lindoerfer D, Simonsson B, Pfirrmann M, Hehlmann R (2011) Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 118(3):686–692CrossRefPubMedGoogle Scholar
  13. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant’Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schonegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R (2013) Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 369(25):2379–2390CrossRefPubMedGoogle Scholar
  14. Marchioli R, Finazzi G, Specchia G, Masciulli A, Mennitto MR, Barbui T (2011) The CYTO-PV: a large-scale trial testing the intensity of CYTOreductive therapy to prevent cardiovascular events in patients with polycythemia vera. Thrombosis 2011:794240CrossRefPubMedPubMedCentralGoogle Scholar
  15. Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T, CYTO-PV Collaborative Group (2013) Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 368(1):22–33CrossRefPubMedGoogle Scholar
  16. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Cazzola M, Tefferi A (2010) Dynamic International Prognostic Scoring System (DIPSS) predicts progression to acute myeloid leukemia in primary myelofibrosis. Blood 116(15):2857–2858CrossRefPubMedGoogle Scholar
  17. Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T, Callum J, Vannucchi AM, Sivgin S, Bensasson C, Khan M, Mounedji N, Saydam G (2017) Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol 18(1):88–99CrossRefPubMedGoogle Scholar
  18. Pfirrmann M, Baccarani M, Saussele S, Guilhot J, Cervantes F, Ossenkoppele G, Hoffmann VS, Castagnetti F, Hasford J, Hehlmann R, Simonsson B (2016) Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia. Leukemia 30(1):48–56CrossRefPubMedGoogle Scholar
  19. Proetel U, Pletsch N, Lauseker M, Muller MC, Hanfstein B, Krause SW, Kalmanti L, Schreiber A, Heim D, Baerlocher GM, Hofmann WK, Lange E, Einsele H, Wernli M, Kremers S, Schlag R, Muller L, Hanel M, Link H, Hertenstein B, Pfirrman M, Hochhaus A, Hasford J, Hehlmann R, Saussele S, German Chronic Myeloid Leukemia Study Group, Schweizerische Arbeitsgemeinschaft fur Klinische Krebsforschung (2014) Older patients with chronic myeloid leukemia (>/=65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV. Ann Hematol 93(7):1167–1176CrossRefPubMedPubMedCentralGoogle Scholar
  20. Saussele S, Krauss MP, Hehlmann R, Lauseker M, Proetel U, Kalmanti L, Hanfstein B, Fabarius A, Kraemer D, Berdel WE, Bentz M, Staib P, de Wit M, Wernli M, Zettl F, Hebart HF, Hahn M, Heymanns J, Schmidt-Wolf I, Schmitz N, Eckart MJ, Gassmann W, Bartholomaus A, Pezzutto A, Leibundgut EO, Heim D, Krause SW, Burchert A, Hofmann WK, Hasford J, Hochhaus A, Pfirrmann M, Muller MC, Schweizerische Arbeitsgemeinschaft fur Klinische Krebsforschung and German C. M. L. S. G (2015) Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV. Blood 126(1):42–49CrossRefPubMedPubMedCentralGoogle Scholar
  21. Saussele S, Richter J, Hochhaus A, Mahon FX (2016) The concept of treatment-free remission in chronic myeloid leukemia. Leukemia 30(8):1638–1647CrossRefPubMedPubMedCentralGoogle Scholar
  22. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, Tso CY, Braun TJ, Clarkson BD, Cervantes F et al (1984) Prognostic discrimination in „good-risk“ chronic granulocytic leukemia. Blood 63(4):789–799PubMedGoogle Scholar
  23. Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, Randi ML, Vaidya R, Cazzola M, Rambaldi A, Gisslinger B, Pieri L, Ruggeri M, Bertozzi I, Sulai NH, Casetti I, Carobbio A, Jeryczynski G, Larson DR, Mullauer L, Pardanani A, Thiele J, Passamonti F, Barbui T (2013) Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 27(9):1874–1881CrossRefPubMedPubMedCentralGoogle Scholar
  24. Vannucchi AM (2015) Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med 372(17):1670–1671CrossRefPubMedGoogle Scholar
  25. Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, Pardanani A, Pereira A, Finke C, Score J, Gangat N, Mannarelli C, Ketterling RP, Rotunno G, Knudson RA, Susini MC, Laborde RR, Spolverini A, Pancrazzi A, Pieri L, Manfredini R, Tagliafico E, Zini R, Jones A, Zoi K, Reiter A, Duncombe A, Pietra D, Rumi E, Cervantes F, Barosi G, Cazzola M, Cross NC, Tefferi A (2013) Mutations and prognosis in primary myelofibrosis. Leukemia 27(9):1861–1869CrossRefPubMedGoogle Scholar
  26. Vannucchi AM, Barbui T, Cervantes F, Harrison C, Kiladjian JJ, Kroger N, Thiele J, Buske C, ESMO Guidelines Committee (2015a) Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(Suppl 5):v85–v99CrossRefPubMedGoogle Scholar
  27. Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S, Investigators C (2015b) A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica 100(9):1139–1145CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2018

Authors and Affiliations

  • Juliana Schwaab
    • 1
  • Susanne Saußele
    • 1
  • Georgia Metzgeroth
    • 1
  • Andreas Reiter
    • 1
  1. 1.Hämatologie und Internistische Onkologie, III. Medizinische KlinikUniversitätsmedizin MannheimMannheimDeutschland

Section editors and affiliations

  • Ulrich Wedding
    • 1
  1. 1.Abteilung für PalliativmedizinUniversitätsklinikum Jena, Klinik für Innere Medizin IIJenaDeutschland

Personalised recommendations