Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 2/2005

01.02.2005 | Original Paper

Serum-soluble interleukin-2 receptor (sIL-2R) level determines clinical outcome in patients with aggressive non-Hodgkin’s lymphoma: in combination with the International Prognostic Index

verfasst von: Hideko Goto, Hisashi Tsurumi, Masao Takemura, Yoriko Ino-Shimomura, Senji Kasahara, Michio Sawada, Toshiki Yamada, Takeshi Hara, Kenji Fukuno, Naoe Goto, Masataka Okuno, Tsuyoshi Takami, Mitsuru Seishima, Hisataka Moriwaki

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2005

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The aim of the present study was to assess the prognostic significance of serum soluble interleukin-2 receptor (sIL-2R) in aggressive non-Hodgkin’s lymphoma (NHL).

Methods

One hundred and thirteen consecutive patients with previously untreated aggressive NHL (diffuse large B-cell lymphoma, 96; peripheral T-cell lymphoma, 17) prospectively participated in this study between 1995 and 2001. The patients were treated with 6–8 cycles of a CHOP or THP (pirarubicin)-COP regimen.

Results

A high serum sIL-2R level (2,000 U/ml and over) at onset was associated with a low complete remission rate. Patients with high sIL-2R had significantly lower survival rates (5-year, 24%) than those with low sIL-2R (under 2,000 U/ml) (74%) (P<0.01). Multivariate analysis employing sIL-2R levels and conventional prognostic factors demonstrated that high sIL-2R, presence of B-symptoms, and advanced age (60 years and older) were significantly unfavorable variables for overall survival. In addition, we attempted to use sIL-2R in combination with the International Prognostic Index (IPI). The patients in the high (H) risk group and those with high sIL-2R in the low-intermediate (LI)/high-intermediate (HI) risk group had significantly lower survival rates than the patients in the low (L) risk group and those with low sIL-2R in the LI/HI risk group (P<0.001).

Conclusion

The results suggest that a high serum sIL-2R level predicts a poor prognosis in aggressive NHL and may be a useful biomarker for selecting appropriate treatment when used in combination with the IPI.
Literatur
Zurück zum Zitat Adida C, Haioun C, Gaulard P, Lepage E, Morel P, Briere J, Dombret H, Reyes F, Diebold J, Gisselbrecht C, Salles G, Altieri DC, Molina TJ (2000) Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood 96:1921–1925PubMed Adida C, Haioun C, Gaulard P, Lepage E, Morel P, Briere J, Dombret H, Reyes F, Diebold J, Gisselbrecht C, Salles G, Altieri DC, Molina TJ (2000) Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood 96:1921–1925PubMed
Zurück zum Zitat Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson Jr J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511CrossRefPubMed Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson Jr J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511CrossRefPubMed
Zurück zum Zitat Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin’s disease staging classification. Cancer Res 31:1860–1861PubMed Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the committee on Hodgkin’s disease staging classification. Cancer Res 31:1860–1861PubMed
Zurück zum Zitat Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Kippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an International Workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol 17:1244–1253PubMed Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Kippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an International Workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol 17:1244–1253PubMed
Zurück zum Zitat Cox DR (1972) Regression models and life-tables (with discussions). J R Stat Soc (Series B) 34:187–220 Cox DR (1972) Regression models and life-tables (with discussions). J R Stat Soc (Series B) 34:187–220
Zurück zum Zitat Haioun C, Lepage E, Gisselbrecht C, Bastion Y, Coiffier B, Brice P, Bosly A, Dupriez B, Nouvel C, Tilly H, Lederlin P, Biron P, Briere J, Gaulard P, Reyes F for the Group d’Etude des Lymphomes de I’Adulte (1997) Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin’s lymphoma: updated results of the prospective study LNH87–2. J Clin Oncol 15:1131–1137PubMed Haioun C, Lepage E, Gisselbrecht C, Bastion Y, Coiffier B, Brice P, Bosly A, Dupriez B, Nouvel C, Tilly H, Lederlin P, Biron P, Briere J, Gaulard P, Reyes F for the Group d’Etude des Lymphomes de I’Adulte (1997) Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin’s lymphoma: updated results of the prospective study LNH87–2. J Clin Oncol 15:1131–1137PubMed
Zurück zum Zitat Hara T, Tsurumi H, Takemura M, Goto H, Yamada T, Sawada M, Takahashi T, Moriwaki H (2000) Serum-soluble Fas level determines clinical symptoms and outcome of patients with aggressive non-Hodgkin’s lymphoma. Am J Hematol 64:257–261CrossRefPubMed Hara T, Tsurumi H, Takemura M, Goto H, Yamada T, Sawada M, Takahashi T, Moriwaki H (2000) Serum-soluble Fas level determines clinical symptoms and outcome of patients with aggressive non-Hodgkin’s lymphoma. Am J Hematol 64:257–261CrossRefPubMed
Zurück zum Zitat Ichikawa A, Kinoshita T, Watanabe T, Kato H, Nagai H, Tsushita K, Saito H, Hotta T (1997) Mutation of the p53 gene as a prognostic factor in aggressive B-cell lymphoma. N Engl J Med 337:529–534CrossRefPubMed Ichikawa A, Kinoshita T, Watanabe T, Kato H, Nagai H, Tsushita K, Saito H, Hotta T (1997) Mutation of the p53 gene as a prognostic factor in aggressive B-cell lymphoma. N Engl J Med 337:529–534CrossRefPubMed
Zurück zum Zitat The International Non-Hodgkin’s Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329:987–994CrossRefPubMed The International Non-Hodgkin’s Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329:987–994CrossRefPubMed
Zurück zum Zitat Jaffe ES, Harris NL, Stein H, Vardiman JW, eds (2001) World health organization classification of tumors, pathology and genetics tumors of haematopoietic and lymphoid tissues. IARC, Lyon, 109–236 Jaffe ES, Harris NL, Stein H, Vardiman JW, eds (2001) World health organization classification of tumors, pathology and genetics tumors of haematopoietic and lymphoid tissues. IARC, Lyon, 109–236
Zurück zum Zitat Kaplan EL, Meier P (1958) Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457–481 Kaplan EL, Meier P (1958) Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457–481
Zurück zum Zitat Kitamura K, Takaku F (1990) Pirarubicin, a novel derivative of doxorubicin. THP-COP therapy for non-Hodgkin’s lymphoma in the elderly. Am J Clin Oncol 13 [Suppl 1]:S15-S19 Kitamura K, Takaku F (1990) Pirarubicin, a novel derivative of doxorubicin. THP-COP therapy for non-Hodgkin’s lymphoma in the elderly. Am J Clin Oncol 13 [Suppl 1]:S15-S19
Zurück zum Zitat Kono N, Kanda Y, Yamamoto R, Chizuka A, Suguro M, Hamaki T, Arai C, Matsuyama T, Takezako N, Miwa A, Togawa A (2000) Prognostic significance of serum soluble interleukin-2 receptor level in non-Hodgkin’s lymphoma: a single center study in Japan. Leuk Lymphoma 37:151–156PubMed Kono N, Kanda Y, Yamamoto R, Chizuka A, Suguro M, Hamaki T, Arai C, Matsuyama T, Takezako N, Miwa A, Togawa A (2000) Prognostic significance of serum soluble interleukin-2 receptor level in non-Hodgkin’s lymphoma: a single center study in Japan. Leuk Lymphoma 37:151–156PubMed
Zurück zum Zitat Miller AA, Salewski E (1994) Prospects for pirarubicin. Med Pediatr Oncol 22:261–268PubMed Miller AA, Salewski E (1994) Prospects for pirarubicin. Med Pediatr Oncol 22:261–268PubMed
Zurück zum Zitat Nicolaides C, Dimou S, Pavlidis N (1998) Prognostic factors in aggressive non-Hodgkin’s lymphomas. Oncologist 3:189–197PubMed Nicolaides C, Dimou S, Pavlidis N (1998) Prognostic factors in aggressive non-Hodgkin’s lymphomas. Oncologist 3:189–197PubMed
Zurück zum Zitat Niitsu N, Okabe-Kado J, Kasukabe T, Yamamoto-Yamaguchi Y, Umeda M, Honma Y (1999) Prognostic implications of the differentiation inhibitory factor nm23-H1 protein in the plasma of aggressive non-Hodgkin’s lymphoma. Blood 94:3541–3550PubMed Niitsu N, Okabe-Kado J, Kasukabe T, Yamamoto-Yamaguchi Y, Umeda M, Honma Y (1999) Prognostic implications of the differentiation inhibitory factor nm23-H1 protein in the plasma of aggressive non-Hodgkin’s lymphoma. Blood 94:3541–3550PubMed
Zurück zum Zitat Niitsu N, Iijima K, Chizuka A (2001) A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin’s lymphoma. Eur J Haematol 66:24–30CrossRefPubMed Niitsu N, Iijima K, Chizuka A (2001) A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin’s lymphoma. Eur J Haematol 66:24–30CrossRefPubMed
Zurück zum Zitat The non-Hodgkin’s lymphoma pathologic classification project (1982) National Cancer Institute-sponsored study of classifications of non-Hodgkin’s lymphomas. Summary and description of a working formulation for clinical usage. Cancer 49:2112–2135 The non-Hodgkin’s lymphoma pathologic classification project (1982) National Cancer Institute-sponsored study of classifications of non-Hodgkin’s lymphomas. Summary and description of a working formulation for clinical usage. Cancer 49:2112–2135
Zurück zum Zitat Ogata K, Yokose N, An E, Kamikubo K, Tamura H, Dan K, Sakamaki H, Onozawa Y, Hamaguchi H, Nomura T (1996) Plasma soluble interleukin-2 receptor level in patients with primary myelodysplastic syndrome: a relationship with disease subtype and clinical outcome. Brit J Haematol 93:45–52CrossRef Ogata K, Yokose N, An E, Kamikubo K, Tamura H, Dan K, Sakamaki H, Onozawa Y, Hamaguchi H, Nomura T (1996) Plasma soluble interleukin-2 receptor level in patients with primary myelodysplastic syndrome: a relationship with disease subtype and clinical outcome. Brit J Haematol 93:45–52CrossRef
Zurück zum Zitat Preti HA, Cabanillas F, Talpaz M, Tucker SL, Seymour JF, Kurzrock R (1997) Prognostic value of serum interleukin-6 in diffuse large-cell lymphoma. Ann Intern Med 127:186–194PubMed Preti HA, Cabanillas F, Talpaz M, Tucker SL, Seymour JF, Kurzrock R (1997) Prognostic value of serum interleukin-6 in diffuse large-cell lymphoma. Ann Intern Med 127:186–194PubMed
Zurück zum Zitat Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL (1985) Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 135:3172–3177PubMed Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL (1985) Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 135:3172–3177PubMed
Zurück zum Zitat Rubin LA, Nelson DL (1990) The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med 113:619–627PubMed Rubin LA, Nelson DL (1990) The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med 113:619–627PubMed
Zurück zum Zitat Salven P, Teerenhovi L, Joensuu H (1999) A high pretreatment serum basic fibroblast growth factor concentration is an independent predictor of poor prognosis in non-Hodgkin’s lymphoma. Blood 94:3334–3339PubMed Salven P, Teerenhovi L, Joensuu H (1999) A high pretreatment serum basic fibroblast growth factor concentration is an independent predictor of poor prognosis in non-Hodgkin’s lymphoma. Blood 94:3334–3339PubMed
Zurück zum Zitat Sasaki K, Niitsu N (2000) Elevated serum levels of soluble CD44 variant 6 are correlated with shorter survival in aggressive non-Hodgkin’s lymphoma. Eur J Haematol 65:195–202CrossRefPubMed Sasaki K, Niitsu N (2000) Elevated serum levels of soluble CD44 variant 6 are correlated with shorter survival in aggressive non-Hodgkin’s lymphoma. Eur J Haematol 65:195–202CrossRefPubMed
Zurück zum Zitat Sawada M, Tsurumi H, Yamada T, Hara T, Fukuno K, Goto H, Shimizu M, Kasahara S, Yoshikawa T, Kanemura N, Oyama M, Takami T, Moriwaki H (2002) A prospective study of P-IMVP-16/CBDCA: a novel salvage chemotherapy for patients with aggressive non-Hodgkin’s lymphoma who previously received CHOP therapy as first-line chemotherapy. Eur J Haematol 68:354–361CrossRefPubMed Sawada M, Tsurumi H, Yamada T, Hara T, Fukuno K, Goto H, Shimizu M, Kasahara S, Yoshikawa T, Kanemura N, Oyama M, Takami T, Moriwaki H (2002) A prospective study of P-IMVP-16/CBDCA: a novel salvage chemotherapy for patients with aggressive non-Hodgkin’s lymphoma who previously received CHOP therapy as first-line chemotherapy. Eur J Haematol 68:354–361CrossRefPubMed
Zurück zum Zitat Semenzato G, Foa R, Agostini C, Zambello R, Trentin L, Vinante F, Benedetti F, Chilosi M, Pizzolo G (1987) High serum levels of soluble interleukin-2 receptor in patients with B chronic lymphocytic leukemia. Blood 70:396–400PubMed Semenzato G, Foa R, Agostini C, Zambello R, Trentin L, Vinante F, Benedetti F, Chilosi M, Pizzolo G (1987) High serum levels of soluble interleukin-2 receptor in patients with B chronic lymphocytic leukemia. Blood 70:396–400PubMed
Zurück zum Zitat Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M, Montserrat E, Radford JA, Salles G, Schmitz N, Symann M, Armitage JO, Philip T, Coiffier B (1999) International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin’s lymphoma: Report of the July. J Clin Oncol 17:423–429PubMed Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M, Montserrat E, Radford JA, Salles G, Schmitz N, Symann M, Armitage JO, Philip T, Coiffier B (1999) International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin’s lymphoma: Report of the July. J Clin Oncol 17:423–429PubMed
Zurück zum Zitat Stasi R, Zinzani PL, Galieni P, Lauta VM, Damasio E, Dispensa E, Dammacco F, Papa G, Tura S (1994) Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin’s lymphoma. Brit J Haematol 88:770–777 Stasi R, Zinzani PL, Galieni P, Lauta VM, Damasio E, Dispensa E, Dammacco F, Papa G, Tura S (1994) Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin’s lymphoma. Brit J Haematol 88:770–777
Zurück zum Zitat Takagi T, Oguro M (1987) (2”-R)-4’-o-Tetrahydropyranyladriamycin, a new anthracyclin derivative; its effectiveness in lymphoid malignancies. Cancer Chemother Pharmacol 20:151–154PubMed Takagi T, Oguro M (1987) (2”-R)-4’-o-Tetrahydropyranyladriamycin, a new anthracyclin derivative; its effectiveness in lymphoid malignancies. Cancer Chemother Pharmacol 20:151–154PubMed
Zurück zum Zitat Tsurumi H, Yamada T, Sawada M, Kasahara S, Kanemura N, Kojima Y, Fukuno K, Hara T, Saio M, Takahashi T, Oyama M, Ozawa K, Takami T, Moriwaki H (2004) Biweekly CHOP or biweekly THP-COP regimens in the treatment of aggressive non-Hodgkin’s lymphoma: a comparison of doxorubicin and pirarubicin: a randomized phase II study. J Cancer Res Clin Oncol 130:107–113CrossRefPubMed Tsurumi H, Yamada T, Sawada M, Kasahara S, Kanemura N, Kojima Y, Fukuno K, Hara T, Saio M, Takahashi T, Oyama M, Ozawa K, Takami T, Moriwaki H (2004) Biweekly CHOP or biweekly THP-COP regimens in the treatment of aggressive non-Hodgkin’s lymphoma: a comparison of doxorubicin and pirarubicin: a randomized phase II study. J Cancer Res Clin Oncol 130:107–113CrossRefPubMed
Zurück zum Zitat Viviani S, Camerini E, Bonfante V, Santoro A, Balzarotti M, Fornier M, Devizzi L, Verderio P, Valagussa P, Bonadonna G (1998) Soluble interleukin-2 receptors (sIL-2R) in Hodgkin’s disease: outcome and clinical implications. Brit J Cancer 77: 992–997PubMed Viviani S, Camerini E, Bonfante V, Santoro A, Balzarotti M, Fornier M, Devizzi L, Verderio P, Valagussa P, Bonadonna G (1998) Soluble interleukin-2 receptors (sIL-2R) in Hodgkin’s disease: outcome and clinical implications. Brit J Cancer 77: 992–997PubMed
Zurück zum Zitat Wagner DK, Kiwanuka J, Edwards BK, Rubin LA, Nelson DL, Magrath IT (1987) Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival. J Clin Oncol 5:1262–1274PubMed Wagner DK, Kiwanuka J, Edwards BK, Rubin LA, Nelson DL, Magrath IT (1987) Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival. J Clin Oncol 5:1262–1274PubMed
Zurück zum Zitat Yasuda N, Lai PK, Ip SH, Kung PC, Hinuma Y, Matsuoka M, Hattori T, Takatsuki K, Purtilo DT (1988) Soluble interleukin-2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease. Blood 71:1021–1026PubMed Yasuda N, Lai PK, Ip SH, Kung PC, Hinuma Y, Matsuoka M, Hattori T, Takatsuki K, Purtilo DT (1988) Soluble interleukin-2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease. Blood 71:1021–1026PubMed
Metadaten
Titel
Serum-soluble interleukin-2 receptor (sIL-2R) level determines clinical outcome in patients with aggressive non-Hodgkin’s lymphoma: in combination with the International Prognostic Index
verfasst von
Hideko Goto
Hisashi Tsurumi
Masao Takemura
Yoriko Ino-Shimomura
Senji Kasahara
Michio Sawada
Toshiki Yamada
Takeshi Hara
Kenji Fukuno
Naoe Goto
Masataka Okuno
Tsuyoshi Takami
Mitsuru Seishima
Hisataka Moriwaki
Publikationsdatum
01.02.2005
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2005
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-004-0600-9

Weitere Artikel der Ausgabe 2/2005

Journal of Cancer Research and Clinical Oncology 2/2005 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.