Diagnosis and Treatment of Clonal Myeloproliferative Neoplasms with Eosinophilia

Irina Semenovna Nemchenko, N.N. Tsyba, A.G. Turkina, E.Yu. Chelysheva, O.A. Shukhov, A.M. Kovrigina, T.N. Obukhova,

DOI:

https://doi.org/10.21320/2500-2139-2020-13-2-161-169

Aim. Based on our own materials to characterize the clinical manifestations of hypereosinophilic states distinguishing between reactive eosinophilia (RE), clonal myeloproliferative neoplasms with eosinophilia (MPN-eo), and myeloproliferative variant of hypereosinophilic syndrome (MP-HES); to evaluate treatment results.

Materials & Methods. The trial included 188 patients with primary HES (132 men and 56 women, aged 19–72 years) having been followed-up at the National Research Center for Hematology since 2001. The main entry criteria were blood eosinophilia ≥ 1.5 × 109/L and clinical symptoms resulting sometimes from hypereosinophilia. All patients received complete physical examination, immunomorphological, standard cytogenetic, and molecular genetic testing. Treatment was provided to 73 patients (63 men and 10 women) including those with MPN-eo PDGFRA+ (n = 39), PDGFRB+ (n = 2), FGFR1+ (n = 1), chronic eosinophilic leukemia not otherwise specified (n = 8), systemic mastocytosis (n = 1), and MP-HES (n = 22). Complete hematological response (CHR) was the criterion for treatment efficacy. In the MPN-eo PDGFRA+ and PDGFRB+ groups molecular response (MR) rate was also estimated in cases of imatinib treatment. MR was considered as no expression of the FIP1L1-PDGFRA and ETV6-PDGFRB transcripts in RT-PCR.

Results. The trial yielded the cause of eosinophilia in 117 (62.2 %) out of 188 patients. RE was diagnosed in 60 (32 %) out of 117 patients, various types of clonal MPNs were reported in 57 (30 %) patients. In 71 (38 %) out of 188 patients HES was still present at the first trial stages. Later within this group MP-HES was identified in 22 (30.9 %) out of 71 patients. Among imatinib recipients CHR was achieved in 37 (90 %) out of 41 patients within 1–3 months: in 36 patients with MPN-eo FIP1L1-PDGFRA+ and in 1 patient with MPN-eo ETV6-PDGFRB+. MR was achieved in 88 % of cases. In the absence of molecular markers characteristic of MPN-eo CHR was achieved in 26 % of cases. Among the recipients of treatments other than imatinib nobody achieved CHR.

Conclusion. The diagnosis approach in patients with HES should be complex and individualized. Development and enhancement of molecular genetic diagnostic techniques are regarded as ones of the highest priority areas in modern hematology. The use of imatinib mesylate in MPN-eo therapy commonly results in long-term hematological and molecular remissions. On achieving CHR to imatinib treatment of patients without molecular markers characteristic of MPN-eo early use of this drug (or other tyrosine kinase inhibitors) can be recommended in acute forms of HES.

  • Irina Semenovna Nemchenko National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 ; ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167
  • N.N. Tsyba National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 ; ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167
  • A.G. Turkina National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 ; ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167
  • E.Yu. Chelysheva National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 ; ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167
  • O.A. Shukhov National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 ; ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167
  • A.M. Kovrigina National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 ; ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167
  • T.N. Obukhova National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 ; ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167
  1. Hardy WR, Anderson RE. The hypereosinophilic syndromes. Ann Intern Med. 1968;68(6):1220–9. doi: 10.7326/0003-4819-68-6-1220. DOI: https://doi.org/10.7326/0003-4819-68-6-1220
  2. Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore). 1975;54(1):1–27. DOI: https://doi.org/10.1097/00005792-197501000-00001
  3. Gotlib J, Cools J. Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias. Leukemia. 2008;22(11):1999–2010. doi: 1038/leu.2008.287. DOI: https://doi.org/10.1038/leu.2008.287
  4. Abruzzo LV, Jaffe ES, Cotelingam JD, et al. T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol. 1992;16(3):236–45. doi: 1097/00000478-199203000-00003. DOI: https://doi.org/10.1097/00000478-199203000-00003
  5. Golub TR, Barker GF, Lovett M, et al. Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell. 1994;77(2):307–16. doi: 1016/0092-8674(94)90322-0. DOI: https://doi.org/10.1016/0092-8674(94)90322-0
  6. Cools J, DeAngelo DJ, Gotlib J, et al. 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. 2003;348(13):1201–14. doi: 1056/NEJMoa025217.
  7. Reiter A, Gotlib J. Myeloid neoplasms with eosinophilia. Blood. 2017;129(6):704–14. doi: 1182/blood-2016-10-695973. DOI: https://doi.org/10.1182/blood-2016-10-695973
  8. Capovilla M, Cayuela JM, Bilhou-Nabera C, et al. Synchronous FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma: a bilineal clonal malignancy. Eur J Haematol. 2008;80(1):81–6. doi: 1111/j.1600-0609.2007.00973.x. DOI: https://doi.org/10.1111/j.1600-0609.2007.00973.x
  9. Metzgeroth G, Walz C, Score J, et al. Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma. Leukemia. 2007;21(6):1183–8. doi: 1038/sj.leu.2404662. DOI: https://doi.org/10.1038/sj.leu.2404662
  10. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008;22(1):14–22. doi: 10.1038/sj.leu.2404955. DOI: https://doi.org/10.1038/sj.leu.2404955
  11. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405. doi: 10.1182/blood-2016-03-643544. DOI: https://doi.org/10.1182/blood-2016-03-643544
  12. Bain BJ, Gilliland DG, Horny H-P., et al. Chronic eosinophilic leukaemia, not otherwise specified. In: Swerdlow S, Harris NL, Stein H, et al. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2008. рр. 51–3.
  13. Valent Mastocytosis: a paradigmatic example of a rare disease with complex biology and pathology. Am J Cancer Res. 2013;3(2):159–72.
  14. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood. 1994;83(10):2759–79. doi: 10.1182/blood.v83.10.2759.2759. DOI: https://doi.org/10.1182/blood.V83.10.2759.2759
  15. Bain BJ. Cytogenetic and molecular genetic aspects of eosinophilic leukaemias. Br J Haemat. 2003;122(2):173–9. doi: 10.1046/j.1365-2141.2003.04458.x. DOI: https://doi.org/10.1046/j.1365-2141.2003.04458.x
  16. Klion AD, Robyn J, Akin C, et al. Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Blood. 2004;103(2):473–8. doi: 10.1182/blood-2003-08-2798. DOI: https://doi.org/10.1182/blood-2003-08-2798
  17. Klion Recent Advances in the Diagnosis and Treatment of Hypereosinophilic Syndrome. Hematology. 2005;2005(1):209–14. doi: 10.1182/asheducation-2005.1.209. DOI: https://doi.org/10.1182/asheducation-2005.1.209
  18. NMPN Study Group. Guidelines for the diagnosis and treatment of eosinophilia. 2nd version, September 2012. Available from: https://ru.scribd.com/document/264225330/Nordic-Eos-Guideline-Revised-Sept-2012 (accessed 9.01.2020).
  19. Andersen CL, Siersma VD, Hasselbalch HC, et al. Association of the blood eosinophil count with hematological malignancies and mortality. Am J Hematol. 2015;90(3):225–9. doi: 10.1002/ajh.23916. DOI: https://doi.org/10.1002/ajh.23916
  20. Crane MM, Chang CM, Kobayashi MG, et al. Incidence of myeloproliferative hypereosinophilic syndrome in the Unites States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin Immunol. 2010;126(1):179–81. doi: 10.1016/j.jaci.2010.03.035. DOI: https://doi.org/10.1016/j.jaci.2010.03.035
  21. Pardanani A, Ketterling RP, Li CY, et al. FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature. Leuk Res. 2006;30(8):965–70. doi: 10.1016/j.leukres.2005.11.011. DOI: https://doi.org/10.1016/j.leukres.2005.11.011
  22. Jovanovic JV, Score J, Waghorn K, et al. Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood. 2007;109(11):4635–40. doi: 10.1182/blood-2006-10-050054. DOI: https://doi.org/10.1182/blood-2006-10-050054
  23. 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. 2017;96(9):1463–70. doi: 1007/s00277-017-3067-x. DOI: https://doi.org/10.1007/s00277-017-3067-x
  24. Zhou J, Papenhausen P, Shao H. Therapy-related acute myeloid leukemia with eosinophilia, basophilia, t(4;14)(q12;q24) and PDGFRA rearrangement: a case report and review of the literature. Int J Clin Exp Pathol. 2015;8(5):5812–20.
  25. Shomali W, Gotlib J. World Health Organization eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management. Am J Hematol. 2019;94(10):149–67. doi: 1002/ajh.25617. DOI: https://doi.org/10.1002/ajh.25617
  26. Bain BJ. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. Haematologica. 2010;95(5):696–8. doi: 3324/haematol.2009.021675. DOI: https://doi.org/10.3324/haematol.2009.021675
  27. Legrand F, Renneville A, Macintyre E, et al. The spectrum of FIP1L1-PDGFRA-associated chronic eosinophilic leukemia: new insights based on a survey of 44 cases. Medicine (Baltimore). 2013;92(5):e1–e9. doi: 10.1097/MD.0b013e3182a71eba. DOI: https://doi.org/10.1097/MD.0b013e3182a71eba
  28. Ogbogu PU, Bochner BS, Butterfield JH, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009;124(6):1319–25. doi: 10.1016/j.jaci.2009.09.022. DOI: https://doi.org/10.1016/j.jaci.2009.09.022
  29. Metzgeroth G, Schwaab J, Gosenca D, et al. Long-term follow-up of treatment with imatinib in eosinophilia-associated myeloid/lymphoid neoplasms with PDGFR rearrangements in blast phase. 2013;27(11):2254–6. doi: 10.1038/leu.2013.129. DOI: https://doi.org/10.1038/leu.2013.129
  30. Baccarani M, Cilloni D, Rondoni M, et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRα-positive hypereosinophilic syndrome. Results of a multicenter prospective study. Haematologica. 2007;92(9):1173–9. doi: 3324/haematol.11420. DOI: https://doi.org/10.3324/haematol.11420
  31. Helbig G, Moskwa A, Hus M, et al. Clinical characteristics of patients with chronic eosinophilic leukaemia (CEL) harbouring FIP1L1-PDGFRA fusion transcript-results of Polish multicentre study. Hematol Oncol. 2010;28(2):93–7. doi: 10.1002/hon.919. DOI: https://doi.org/10.1002/hon.919
  32. Klion AD. Recent Advances in the Diagnosis and Treatment of Hypereosinophilic Syndromes. Hematology. 2005;2005(1):209–14. doi: 10.1182/asheducation-2005.1.209. DOI: https://doi.org/10.1182/asheducation-2005.1.209
  33. Helbig G, Moskwa A, Hus M, et al. Durable remission after treatment with very low of imatinib for FIP1L1-PDGFRα-positive chronic eosinophilic leukemia. Cancer Chemother Pharmacol. 2011;67(4):967–9. doi: 1007/s00280-011-1582-3. DOI: https://doi.org/10.1007/s00280-011-1582-3
  34. Pardanani A, D’Souza A, Knudson RA, et al. Long-term follow-up of FIP1L1-PDGFRA-mutated patients with eosinophilia: survival and clinical outcome. Leukemia. 2012;26(11):2439–41. doi:1038/leu.2012.162. DOI: https://doi.org/10.1038/leu.2012.162
  35. von Bubnoff N, Sandherr M, Schlimok G, et al. Myeloid blast crisis evolving during imatinib treatment of an FIP1L1-PDGFR alpha-positive chronic myeloproliferative disease with prominent eosinophilia. 2005;19(2):286–7. doi: 10.1038/sj.leu.2403600. DOI: https://doi.org/10.1038/sj.leu.2403600
  36. Ohnishi H, Kandabashi K, Maeda Y, et al. Chronic eosinophilic leukaemia with FIP1L1-PDGFRA fusion and T6741 mutation that evolved from Langerhans cell histiocytosis with eosinophilia after chemotherapy. Br J Haematol. 2006;134(5):547–9. doi: 10.1111/j.1365-2141.2006.06221.x. DOI: https://doi.org/10.1111/j.1365-2141.2006.06221.x
  37. Lierman E, Michaux L, Beullens E, et al. FIP1L1-PDGFRα D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRα T674I eosinophilic leukemia with single agent sorafenib. 2009;23(5):845–51. doi: 10.1038/leu.2009.2. DOI: https://doi.org/10.1038/leu.2009.2
  38. Bradeen HA, Eide CA, O’Hare T, et al. Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations. 2006;108(7):2332–8. doi: 10.1182/blood-2006-02-004580. DOI: https://doi.org/10.1182/blood-2006-02-004580
  39. Helbig G, Hus M, Halasz M, et al. Imatinib mesylate may induce long-term clinical response in FIP1L1-PDGFRα-negative hypereosinophilic syndrome. Med Oncol. 2012;29 (2):1073–6. doi:1007/s12032-011-9831-1. DOI: https://doi.org/10.1007/s12032-011-9831-1
  40. Butt NM, Lambert J, Ali S, et al. Guideline for the investigation and management of eosinophilia. Br J Haematol. 2017;176(4):553–72. doi: 10.1111/bjh.14488. DOI: https://doi.org/10.1111/bjh.14488
  41. Butterfield JH. Success of short-term, higher-dose imatinib mesylate to induce clinical response in FIP1L1-PDGFRα-negative hypereosinophilic syndrome. Leuk Res. 2009;33(8):1127–9. doi: 10.1016/j.leukres.2008.12.001. DOI: https://doi.org/10.1016/j.leukres.2008.12.001
  42. Klion AD, Robyn J, Maric I, et al. Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing. Blood. 2007;110(10):3552–6. doi: 10.1182/blood-2007-07-100164. DOI: https://doi.org/10.1182/blood-2007-07-100164

Keywords:

eosinophilia, hypereosinophilic syndrome, myeloproliferative neoplasm, PDGFRA, PDGFRВ, FGFR1, imatinib

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01.04.2020

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Vol. 13 No. 2 (2020)
MYELOID TUMORS

How to Cite

Nemchenko I.S., Tsyba N.N., Turkina A.G., et al. Diagnosis and Treatment of Clonal Myeloproliferative Neoplasms with Eosinophilia. Clinical Oncohematology. Basic Research and Clinical Practice. 2020;13(2):161–169. doi:10.21320/2500-2139-2020-13-2-161-169.

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