Top

Published in:

01-09-2019 | Hodgkin Lymphoma | Original Article

Predictive value of soluble interlukin-2 receptor level at diagnosis on the outcome for patients with classical Hodgkin lymphoma treated with ABVD with or without radiotherapy

Authors: Kento Umino, Shin-ichiro Fujiwara, Takashi Ikeda, Shin-ichiro Kawaguchi, Yumiko Toda, Shoko Ito, Shin-ichi Ochi, Takashi Nagayama, Kiyomi Mashima, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Kaoru Morita, Yasufumi Kawasaki, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda

Published in: Annals of Hematology | Issue 9/2019

Abstract

We retrospectively analyzed 70 patients with classical Hodgkin lymphoma (cHL) who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiotherapy to assess the influence of the soluble interleukin-2 receptor (sIL-2R) level at diagnosis on the clinical outcome. Receiver operating characteristic analyses determined that the optimal cutoff value of the sIL-2R level for progression-free survival (PFS) was 2490 U/mL. Using this cutoff value, patients were classified into low (n = 46) and high (n = 24) sIL-2R groups. The patients in the high sIL-2R group exhibited a significantly inferior PFS (44.1% vs. 90.4% at 5 years, P < 0.001) and overall survival (OS) (67.6% vs. 94.7% at 5 years, P = 0.001) compared with those in the low sIL-2R group. Multivariate analysis showed that a high sIL-2R level was an independent prognostic factor for PFS after adjusting for stage, white blood cell, hemoglobin, and B symptoms, and also OS after adjusting for age and stage (hazard ratio (HR) 6.49, P < 0.001 and HR 5.98, P = 0.009, respectively). In patients with advanced-stage cHL, a high sIL-2R level predicted 5-year PFS even after adjustment for international prognostic score > 4 (HR 6.00, P = 0.007). These results demonstrate that the sIL-2R level can be a useful prognostic factor in patients with cHL treated with ABVD with or without radiotherapy.

Ansell SM (2018) Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol 93(5):704–715. https://doi.org/10.1002/ajh.25071 CrossRefPubMed

Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–2390. https://doi.org/10.1182/blood-2016-01-643569 CrossRefPubMedPubMedCentral

Eich HT, Diehl V, Gorgen H, Pabst T, Markova J, Debus J, Ho A, Dorken B, Rank A, Grosu AL, Wiegel T, Karstens JH, Greil R, Willich N, Schmidberger H, Dohner H, Borchmann P, Muller-Hermelink HK, Muller RP, Engert A (2010) Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol Off J Am Soc Clin Oncol 28(27):4199–4206. https://doi.org/10.1200/jco.2010.29.8018 CrossRef

Behringer K, Goergen H, Hitz F, Zijlstra JM, Greil R, Markova J, Sasse S, Fuchs M, Topp MS, Soekler M, Mathas S, Meissner J, Wilhelm M, Koch P, Lindemann HW, Schalk E, Semrau R, Kriz J, Vieler T, Bentz M, Lange E, Mahlberg R, Hassler A, Vogelhuber M, Hahn D, Mezger J, Krause SW, Skoetz N, Boll B, von Tresckow B, Diehl V, Hallek M, Borchmann P, Stein H, Eich H, Engert A (2015) Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet 385(9976):1418–1427. https://doi.org/10.1016/s0140-6736(14)61469-0 CrossRefPubMed

Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA (1992) Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 327(21):1478–1484. https://doi.org/10.1056/nejm199211193272102 CrossRefPubMed

Merli F, Luminari S, Gobbi PG, Cascavilla N, Mammi C, Ilariucci F, Stelitano C, Musso M, Baldini L, Galimberti S, Angrilli F, Polimeno G, Scalzulli PR, Ferrari A, Marcheselli L, Federico M (2016) Long-term results of the HD2000 trial comparing ABVD versus BEACOPP versus COPP-EBV-CAD in untreated patients with advanced Hodgkin lymphoma: a study by Fondazione Italiana Linfomi. J Clin Oncol Off J Am Soc Clin Oncol 34(11):1175–1181. https://doi.org/10.1200/jco.2015.62.4817 CrossRef

Skoetz N, Trelle S, Rancea M, Haverkamp H, Diehl V, Engert A, Borchmann P (2013) Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin’s lymphoma: a systematic review and network meta-analysis. Lancet Oncol 14(10):943–952. https://doi.org/10.1016/s1470-2045(13)70341-3 CrossRefPubMed

Smith KA (1988) Interleukin-2: inception, impact, and implications. Science (New York, NY) 240(4856):1169–1176CrossRef

Kawaguchi Y, Nakamaki T, Abe M, Baba Y, Murai S, Watanuki M, Arai N, Fujiwara S, Kabasawa N, Tsukamoto H, Uto Y, Ariizumi H, Yanagisawa K, Hattori N, Harada H, Saito B (2018) Association of soluble interleukin-2 receptor and C-reactive protein with the efficacy of bendamustine salvage treatment for indolent lymphomas and mantle cell lymphoma. Acta Haematol 139(1):12–18. https://doi.org/10.1159/000484711 CrossRefPubMed

10.

Kusano Y, Yokoyama M, Terui Y, Inoue N, Takahashi A, Yamauchi H, Tsuyama N, Nishimura N, Mishima Y, Takeuchi K, Hatake K (2017) High pretreatment level of soluble interleukin-2 receptor is a robust prognostic factor in patients with follicular lymphoma treated with R-CHOP-like therapy. Blood Cancer J 7(9):e614. https://doi.org/10.1038/bcj.2017.96 CrossRefPubMedPubMedCentral

11.

Umino K, Fujiwara SI, Ikeda T, Toda Y, Ito S, Mashima K, Minakata D, Nakano H, Yamasaki R, Kawasaki Y, Sugimoto M, Yamamoto C, Ashizawa M, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Kanda Y (2017) Prognostic value of the soluble interleukin-2 receptor level after patients with follicular lymphoma achieve a response to R-CHOP. Hematology 22(9):521–526. https://doi.org/10.1080/10245332.2017.1312204 CrossRefPubMed

12.

Tomita N, Suzuki T, Miyashita K, Yamamoto W, Motohashi K, Tachibana T, Takasaki H, Kawasaki R, Hagihara M, Hashimoto C, Takemura S, Koharazawa H, Yamazaki E, Taguchi J, Fujimaki K, Fujita H, Sakai R, Fujisawa S, Motomura S, Kawamoto K, Sone H, Takizawa J (2016) The SIL index is a simple and objective prognostic indicator in diffuse large B-cell lymphoma. Leuk Lymphoma 57(12):2763–2770. https://doi.org/10.1080/10428194.2016.1195498 CrossRefPubMed

13.

Umino K, Fujiwara SI, Ito S, Mashima K, Minakata D, Nakano H, Yamasaki R, Kawasaki Y, Sugimoto M, Ashizawa M, Hatano K, Okazuka K, Sato K, Oh I, Ohmine K, Suzuki T, Muroi K, Kanda Y (2017) Serum soluble interleukin-2 receptor level at diagnosis predicts transformation in patients with follicular lymphoma. Leuk Lymphoma 58(2):316–323. https://doi.org/10.1080/10428194.2016.1190975 CrossRefPubMed

14.

Shiratori S, Kosugi-Kanaya M, Shigematsu A, Kobayashi H, Yamamoto S, Kobayashi N, Iwasaki H, Mori A, Kunieda Y, Yutaka T, Kurosawa M, Kakinoki Y, Endo T, Kondo T, Hashino S, Teshima T (2015) Ultra-high level of serum soluble interleukin-2 receptor at diagnosis predicts poor outcome for angioimmunoblastic T-cell lymphoma. Leuk Lymphoma 56(9):2592–2597. https://doi.org/10.3109/10428194.2014.1001985 CrossRefPubMed

15.

Ennishi D, Yokoyama M, Terui Y, Asai H, Sakajiri S, Mishima Y, Takahashi S, Komatsu H, Ikeda K, Takeuchi K, Tanimoto M, Hatake K (2009) Soluble interleukin-2 receptor retains prognostic value in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP (RCHOP) therapy. Ann Oncol 20(3):526–533. https://doi.org/10.1093/annonc/mdn677 CrossRefPubMed

16.

Umino K, Fujiwara SI, Minakata D, Yamamoto C, Meguro A, Matsuyama T, Sato K, Ohmine K, Izumi T, Muroi K, Kanda Y (2018) Prognostic impact of serum soluble interleukin-2 receptor level at diagnosis in elderly patients with diffuse large B-cell lymphoma treated with R-CHOP. Leuk Lymphoma 60:1–8. https://doi.org/10.1080/10428194.2018.1504939 CrossRef

17.

Marri PR, Hodge LS, Maurer MJ, Ziesmer SC, Slager SL, Habermann TM, Link BK, Cerhan JR, Novak AJ, Ansell SM (2013) Prognostic significance of pretreatment serum cytokines in classical Hodgkin lymphoma. Clin Cancer Res 19(24):6812–6819. https://doi.org/10.1158/1078-0432.ccr-13-1879 CrossRefPubMed

18.

Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V (2007) Revised response criteria for malignant lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 25(5):579–586. https://doi.org/10.1200/jco.2006.09.2403 CrossRef

19.

Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–458. https://doi.org/10.1038/bmt.2012.244 CrossRef

20.

Javanmardi F, Saki-Malehi A, Ahmadzadeh A, Rahim F (2018) Assessing prognostic factors in Hodgkin’s lymphoma: multistate illness-death model. Int J Hematol Oncol Stem Cell Res 12(1):57–64PubMedPubMedCentral

21.

Ahmadzadeh A, Yekaninejad MS, Jalili MH, Bahadoram M, Efazat M, Seghatoleslami M, Yazdi F, Mahdipour M, Valizadeh A, Saki N (2014) Evaluating the survival rate and the secondary malignancies after treating Hodgkin’s lymphoma patients with chemotherapy regimens. Int J Hematol Oncol Stem Cell Res 8(2):21–26PubMedPubMedCentral

22.

Gaudio F, Pedote P, Asabella AN, Perrone T, Laddaga FE, Sindaco P, Cimmino A, D'Abbicco D, Pezzolla A, Rubini G, Specchia G (2018) Extralymphatic disease is an independent prognostic factor in Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 18(6):e261–e266. https://doi.org/10.1016/j.clml.2018.04.001 CrossRefPubMed

23.

Pizzolo G, Chilosi M, Vinante F, Dazzi F, Lestani M, Perona G, Benedetti F, Todeschini G, Vincenzi C, Trentin L, Semenzato G (1987) Soluble interleukin-2 receptors in the serum of patients with Hodgkin’s disease. Br J Cancer 55(4):427–428CrossRefPubMedPubMedCentral

24.

Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J (2018) Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med 378(4):331–344. https://doi.org/10.1056/NEJMoa1708984 CrossRefPubMed

25.

Borchmann P, Goergen H, Kobe C, Lohri A, Greil R, Eichenauer DA, Zijlstra JM, Markova J, Meissner J, Feuring-Buske M, Huttmann A, Dierlamm J, Soekler M, Beck HJ, Willenbacher W, Ludwig WD, Pabst T, Topp MS, Hitz F, Bentz M, Keller UB, Kuhnhardt D, Ostermann H, Schmitz N, Hertenstein B, Aulitzky W, Maschmeyer G, Vieler T, Eich H, Baues C, Stein H, Fuchs M, Kuhnert G, Diehl V, Dietlein M, Engert A (2018) PET-guided treatment in patients with advanced-stage Hodgkin’s lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet 390(10114):2790–2802. https://doi.org/10.1016/s0140-6736(17)32134-7 CrossRef

26.

Yamauchi T, Matsuda Y, Takai M, Tasaki T, Tai K, Hosono N, Negoro E, Ikegaya S, Takagi K, Kishi S, Yoshida A, Urasaki Y, Iwasaki H, Ueda T (2012) Early relapse is associated with high serum soluble interleukin-2 receptor after the sixth cycle of R-CHOP chemotherapy in patients with advanced diffuse large B-cell lymphoma. Anticancer Res 32(11):5051–5057PubMed

27.

Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M, Patti C, Loft A, Di Raimondo F, D'Amore F, Biggi A, Vitolo U, Stelitano C, Sancetta R, Trentin L, Luminari S, Iannitto E, Viviani S, Pierri I, Levis A (2007) Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin’s lymphoma: a report from a joint Italian-Danish study. J Clin Oncol Off J Am Soc Clin Oncol 25(24):3746–3752. https://doi.org/10.1200/jco.2007.11.6525 CrossRef

Title: Predictive value of soluble interlukin-2 receptor level at diagnosis on the outcome for patients with classical Hodgkin lymphoma treated with ABVD with or without radiotherapy
Authors: Kento Umino
Shin-ichiro Fujiwara
Takashi Ikeda
Shin-ichiro Kawaguchi
Yumiko Toda
Shoko Ito
Shin-ichi Ochi
Takashi Nagayama
Kiyomi Mashima
Daisuke Minakata
Hirofumi Nakano
Ryoko Yamasaki
Kaoru Morita
Yasufumi Kawasaki
Chihiro Yamamoto
Masahiro Ashizawa
Kaoru Hatano
Kazuya Sato
Iekuni Oh
Ken Ohmine
Kazuo Muroi
Yoshinobu Kanda
Publication date: 01-09-2019
Publisher: Springer Berlin Heidelberg
Keywords: Hodgkin Lymphoma
Radiotherapy
Published in: Annals of Hematology / Issue 9/2019
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-019-03738-3

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Predictive value of soluble interlukin-2 receptor level at diagnosis on the outcome for patients with classical Hodgkin lymphoma treated with ABVD with or without radiotherapy

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2019

Bronchoscopic features, associations, and outcomes of organizing pneumonia following allogeneic hematopoietic stem cell transplantation

Pixantrone beyond monotherapy: a review

Prolonged severe neutropenia after the first daratumumab administration for multiple myeloma with baseline neutropenia

Effect of allogeneic hematopoietic cell transplantation for patients with T-prolymphocytic leukemia: a retrospective study from the Adult Lymphoma Working Group of the Japan Society for hematopoietic cell transplantation

Outcomes of autologous stem cell transplantation in Waldenström’s macroglobulinemia

Low-dose nivolumab induced durable complete response in relapsed primary central nervous system diffuse large B cell lymphoma

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page