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Prognostic Value of Serum Interleukin-6 in Diffuse Large-cell Lymphoma

H. Alejandro Preti, MD; Fernando Cabanillas, MD; Moshe Talpaz, MD; Susan L. Tucker, PhD; John F. Seymour, MB, BS; and Razelle Kurzrock, MD
[+] Article and Author Information

From The University of Texas M.D. Anderson Cancer Center, Houston, Texas; and Royal Melbourne Hospital, Melbourne, Australia. Requests for Reprints: Razelle Kurzrock, MD, Department of Bioimmunotherapy, Box 302, The M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Current Author Addresses: Dr. Preti: San Martin de Tours 2980, 1425 Capital Federal, Buenos Aires, Argentina.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;127(3):186-194. doi:10.7326/0003-4819-127-3-199708010-00002
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Background: Interleukin-6 has important lymphoid bioregulatory effects, and serum levels of interleukin-6 are often elevated in patients with lymphoma.

Objective: To determine the relation between serum levels of interleukin-6 before treatment and outcome in patients with diffuse large-cell lymphoma.

Design: Retrospective cohort analysis with multivariate analysis.

Setting: Tertiary referral center.

Participants: 118 untreated patients with diffuse large-cell lymphoma who were enrolled in frontline chemotherapy protocols and 45 healthy controls.

Measurements: Serum levels of interleukin-6 were measured by using a sensitive enzyme-linked immunosorbent assay. Levels below the upper limit of the range for controls were considered normal. Outcomes were complete response, failure-free survival, and overall survival.

Results: Serum levels of interleukin-6 were higher in patients with lymphoma (median, 4.6 pg/mL [range, undetectable to 224 pg/mL]) than in controls (median, undetectable [range, undetectable to 4.3 pg/mL]) (P = 0.009). The complete response rate was 95% for persons with normal interleukin-6 levels and 66% for persons with high interleukin-6 levels (P = 0.001). Patients with high interleukin-6 levels had inferior failure-free and overall survival rates (P < 0.001 for both comparisons). The actuarial 4-year failure-free and overall survival rates were 72% and 85%, respectively, for persons with normal interleukin-6 levels and 37% and 46%, respectively, for persons with high interleukin-6 levels. In multivariate analysis, interleukin-6 was selected as the most significant predictor of complete response and failure-free survival. Failure-free and overall survival of patients stratified according to International Prognostic Index score could be further stratified by interleukin-6 level (P ≤ 0.03 for all comparisons).

Conclusion: In patients with diffuse large-cell lymphoma, serum interleukin-6 levels are an independent prognostic factor for complete response and failure-free survival.

Figures

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Figure 1.
Failure-free survival of participants with high and low interleukin-6 levels.P

Data were analyzed by using the Kaplan-Meier method. Tick marks indicate the point of last follow-up for one or more participants who did not have treatment failure. Low = an interleukin-6 level of 4.3 pg/mL or less (56 participants had such a level, and 11 of them had treatment failure); high = an interleukin-6 level greater than 4.3 pg/mL (62 patients had such a level, and 35 of them had treatment failure) ( < 0.001, log-rank test).

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Figure 2.
Failure-free survival of participants with favorable and unfavorable prognosis.Top.PBottom.P

Data were analyzed by using the Kaplan-Meier method. Tick marks indicate the point of last follow-up for one or more patients who did not have treatment failure. Low = an interleukin-6 level of 4.3 pg/mL or less; high = an interleukin-6 level greater than 4.3 pg/mL. Participants with favorable prognosis (treated with the CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone]-based regimen). Forty-one participants had low interleukin-6 levels, and 6 of them had treatment failure; 17 participants had high interleukin-6 levels, and 7 of them had treatment failure ( = 0.007, log-rank test). Participants with unfavorable prognosis (treated with the alternating triple therapy regimen). Fifteen participants had low interleukin-6 levels, and 5 of them had treatment failure; 45 participants had high interleukin-6 levels, and 28 of them had treatment failure ( = 0.02, log-rank test).

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Figure 3.
Overall survival of participants with high and low interleukin-6 levels.P

Data were analyzed by using the Kaplan-Meier method. Tick marks indicate points at which one or more participants were alive. Low = an interleukin-6 level of 4.3 pg/mL or less (56 participants had such levels, and 6 of them died); high = an interleukin-6 level greater than 4.3 pg/mL (62 participants had such levels, and 28 of them died) ( < 0.001, log-rank test).

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Figure 4.
Failure-free survival of participants with good and poor prognosis stratified according to interleukin-6 levels.Top.PBottom.P

Data were analyzed by using the Kaplan-Meier method. Tick marks indicate the point of last follow-up for one or more participants who did not have treatment failure. Low = an interleukin-6 level of 4.3 pg/mL or less; high = an interleukin-6 level greater than 4.3 pg/mL. Participants with good prognosis (International Prognostic Index score <2). Forty-four participants had low interleukin-6 levels, and 8 of them had treatment failure; 21 participants had high interleukin-6 levels, and 10 of them had treatment failure ( = 0.009, log-rank test). Participants with poor prognosis (International Prognostic Index score ≥ 2). Twelve participants had low interleukin-6 levels, and 3 of them had treatment failure; 41 participants had high interleukin-6 levels, and 25 of them had treatment failure ( = 0.01, log-rank test).

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