Skip to main content

Advertisement

SpringerLink
Log in

Imatinib in myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB in chronic or blast phase

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20–80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×109/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0–13)​. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3–34) and 19 months (range 7–110), respectively. In patients with blast phase (myeloid, n = 2; lymphoid, n = 3), treatment included combinations of imatinib (n = 5), intensive chemotherapy (n = 3), and/or allogeneic stem cell transplantation (n = 3). All 3 transplanted patients (complex karyotype, n = 2) experienced early relapse. Initially, patients were treated with imatinib 400 mg/day (n = 15) or 100 mg/day (n = 7), the dose was reduced from 400 mg/day to 100 mg/day during follow-up in 9 patients. After a median treatment of 71 months (range 1–135), the 5-year survival rate was 83%; 4/22 (18%) patients died (chronic phase; n = 2; blast phase, n = 2) due to progression (n = 3) or comorbidity while in remission (n = 1). Of note, 3/4 patients had a complex karyotype. In summary, the most important characteristics of myeloid/lymphoid neoplasms with rearrangement of PDGFRB include (a) male predominance, (b) frequent lack of hypereosinophilia, (c) presentation in chronic or blast phase, (d) rapid responses and long-term remission on low-dose imatinib, and (e) possible adverse prognostic impact of a complex karyotype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Arber DA, Orazi A, Hasserjian R et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405

    Article  CAS  PubMed  Google Scholar 

  2. Cools J, DeAngelo DJ, Gotlib J et al (2003) A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 348(13):1201–1214

    Article  CAS  PubMed  Google Scholar 

  3. Naumann N, Schwaab J, Metzgeroth G et al (2015) Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia-associated myeloproliferative neoplasms. Genes Chromosomes Cancer 54(12):762–770

    Article  CAS  PubMed  Google Scholar 

  4. Gosenca D, Kellert B, Metzgeroth G et al (2014) Identification and functional characterization of imatinib-sensitive DTD1-PDGFRB and CCDC88C-PDGFRB fusion genes in eosinophilia-associated myeloid/lymphoid neoplasms. Genes Chromosomes Cancer 53(5):411–421

    Article  CAS  PubMed  Google Scholar 

  5. Maccaferri M, Pierini V, Di Giacomo D, et al. (2016) The importance of cytogenetic and molecular analyses in eosinophilia-associated myeloproliferative neoplasms: an unusual case with normal karyotype and TNIP1- PDGFRB rearrangement and overview of PDGFRB partner genes. Leuk Lymphoma; 1–5

  6. Reiter A, Gotlib J (2017) Myeloid neoplasms with eosinophilia. Blood 129(6):704–714

    Article  CAS  PubMed  Google Scholar 

  7. Cheah CY, Burbury K, Apperley JF et al (2014) Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood 123(23):3574–3577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. David M, Cross NC, Burgstaller S et al (2007) Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 109(1):61–64

    Article  CAS  PubMed  Google Scholar 

  9. Lierman E, Michaux L, Beullens E et al (2009) FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib. Leukemia 23(5):845–851

    Article  CAS  PubMed  Google Scholar 

  10. von Bubnoff N, Gorantla SP, Engh RA et al (2011) The low frequency of clinical resistance to PDGFR inhibitors in myeloid neoplasms with abnormalities of PDGFRA might be related to the limited repertoire of possible PDGFRA kinase domain mutations in vitro. Oncogene 30(8):933–943

    Article  Google Scholar 

  11. Byrgazov K, Kastner R, Gorna M et al (2017) NDEL1-PDGFRB fusion gene in a myeloid malignancy with eosinophilia associated with resistance to tyrosine kinase inhibitors. Leukemia 31(1):237–240

    Article  CAS  PubMed  Google Scholar 

  12. Walz C, Haferlach C, Hanel A et al (2009) Identification of a MYO18A-PDGFRB fusion gene in an eosinophilia-associated atypical myeloproliferative neoplasm with a t(5;17)(q33-34;q11.2). Genes Chromosomes Cancer 48(2):179–183

    Article  CAS  PubMed  Google Scholar 

  13. Walz C, Metzgeroth G, Haferlach C et al (2007) Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor beta gene. Haematologica 92(2):163–169

    Article  CAS  PubMed  Google Scholar 

  14. Erben P, Gosenca D, Muller MC et al (2010) Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis. Haematologica 95(5):738–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Baccarani M, Cilloni D, Rondoni M et al (2007) The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study. Haematologica 92(9):1173–1179

    Article  CAS  PubMed  Google Scholar 

  16. Breccia M, Cilloni D, Cannella L et al (2009) Isolated molecular relapse in FIP1L1-PDGFRalpha hypereosinophilic syndrome after discontinuation and single weekly dose of imatinib: need of quantitative molecular procedures to modulate imatinib dose. Cancer Chemother Pharmacol 63(6):1161–1163

    Article  CAS  PubMed  Google Scholar 

  17. Pardanani A, D'Souza A, Knudson RA et al (2012) Long-term follow-up of FIP1L1-PDGFRA-mutated patients with eosinophilia: survival and clinical outcome. Leukemia 26(11):2439–2441

    Article  CAS  PubMed  Google Scholar 

  18. Saussele S, Richter J, Hochhaus A, Mahon FX (2016) The concept of treatment-free remission in chronic myeloid leukemia. Leukemia 30(8):1638–1647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mahon FX, Rea D, Guilhot J et al (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11(11):1029–1035

    Article  CAS  PubMed  Google Scholar 

  20. Bastie JN, Garcia I, Terre C et al (2004) Lack of response to imatinib mesylate in a patient with accelerated phase myeloproliferative disorder with rearrangement of the platelet-derived growth factor receptor beta-gene. Haematologica 89(10):1263–1264

    PubMed  Google Scholar 

  21. Metzgeroth G, Schwaab J, Gosenca D et al (2013) Long-term follow-up of treatment with imatinib in eosinophilia-associated myeloid/lymphoid neoplasms with PDGFR rearrangements in blast phase. Leukemia 27(11):2254–2256

    Article  CAS  PubMed  Google Scholar 

  22. Metzgeroth G, Walz C, Score J et al (2007) Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma. Leukemia 21(6):1183–1188

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the ‘Deutsche José Carreras Leukämie-Stiftung e.V.’ (H11/03 and R13/05), Germany.

Author information

Author notes

  1. Andreas Reiter and Georgia Metzgeroth contributed equally to this study

Authors and Affiliations

  1. Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany

    Mohamad Jawhar, Nicole Naumann, Juliana Schwaab, Wolf-Karsten Hofmann, Alice Fabarius, Andreas Reiter & Georgia Metzgeroth

  2. Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany

    Mohamad Jawhar, Nicole Naumann, Juliana Schwaab, Wolf-Karsten Hofmann, Alice Fabarius, Andreas Reiter & Georgia Metzgeroth

  3. Department of Hematology and Oncology, HELIOS Clinic Berlin-Buch, Berlin, Germany

    Herrad Baurmann

  4. Department of Hematology and Oncology, University of Oldenburg, Oldenburg, Germany

    Jochen Casper

  5. Department of Hematology and Oncology, Clinic Darmstadt, Darmstadt, Germany

    Tu-Anh Dang

  6. Gemeinschaftspraxis für Hämatologie und Onkologie, Cologne, Germany

    Lutz Dietze

  7. Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany

    Konstanze Döhner

  8. Department of Hematology and Oncology, Clinic Chemnitz, Chemnitz, Germany

    Annette Hänel

  9. Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund, Germany

    Bernd Lathan

  10. Department of Hematology and Oncology, Westpfalz-Klinikum, Kaiserslautern, Germany

    Hartmut Link

  11. Gemeinschaftspraxis für Hämatologie und Onkologie, Pforzheim, Germany

    Sina Lotfi

  12. Gemeinschaftspraxis für Hämatologie und Onkologie, Ingolstadt, Germany

    Ole Maywald

  13. Center for Allogeneic Stem Cell Transplantation, Department of Medicine II, University of Wuerzburg Medical Center, Würzburg, Germany

    Stephan Mielke

  14. Gemeinschaftspraxis für Hämatologie und Onkologie, Leer, Germany

    Lothar Müller

  15. Department of Hematology and Oncology, University Hospital Carl Gustav Carus, Dresden, Germany

    Uwe Platzbecker

  16. Gemeinschaftspraxis für Hämatologie und Onkologie, Clinic Kempten, Kempten, Germany

    Otto Prümmer

  17. Department of Hematology and Oncology, Klinikum Bremen Mitte, Bremen, Germany

    Henrike Thomssen

  18. Department of Hematology and Oncology, University Hospital Cologne, Cologne, Germany

    Karin Töpelt

  19. Department of Oncology, Hematology, Hemostaseology and Stem Cell Transplantation, RWTH University Hospital Aachen, Aachen, Germany

    Jens Panse

  20. Department of Hematology and Oncology, University Medical Centre Schleswig-Holstein, Kiel, Germany

    Tom Vieler

  21. Munich Leukemia Laboratory, Munich, Germany

    Torsten Haferlach & Claudia Haferlach

  22. Klinik für Innere Medizin II, Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany

    Andreas Hochhaus

  23. Wessex Regional Genetics Laboratory, Salisbury, UK

    Nicholas C.P. Cross

  24. Faculty of Medicine, University of Southampton, Southampton, UK

    Nicholas C.P. Cross

Authors
  1. Mohamad Jawhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicole Naumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juliana Schwaab
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Herrad Baurmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jochen Casper
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tu-Anh Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lutz Dietze
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Konstanze Döhner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Annette Hänel
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bernd Lathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sina Lotfi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ole Maywald
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Stephan Mielke
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Lothar Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Uwe Platzbecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Otto Prümmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Henrike Thomssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Karin Töpelt
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Jens Panse
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Tom Vieler
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Wolf-Karsten Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Torsten Haferlach
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Claudia Haferlach
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Alice Fabarius
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Andreas Hochhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Nicholas C.P. Cross
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Andreas Reiter
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Georgia Metzgeroth
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MJ, NN, JS,CH, NCPC, AF, AR, GM performed the laboratory work for the study. MJ, NN, JS, HB, JC, TD, LF, KD, ANH, BL, HL, SL, OM, SM, LM, UP, OP, HT, KT, JP, TV, WKH, TH CH, AF, AH, NCPC, AR, and GM provided patient material and information. MJ, NN, JS, WKH, TH, CH, AF, AH, NCPC, AR and GM wrote the paper.

Corresponding author

Correspondence to Andreas Reiter.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jawhar, M., Naumann, N., Schwaab, J. et al. Imatinib in myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB in chronic or blast phase. Ann Hematol 96, 1463–1470 (2017). https://doi.org/10.1007/s00277-017-3067-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-017-3067-x

Keywords

Search

Navigation