Serum Biomarkers Predict Relapse in Classical Hodgkin Lymphoma Patients
Undergoing Autologous Hematopoietic Cell Transplantation
1
Bryan Trottier MD, 2Holly Miller MD, 1Qing Cao MS, 1Jeffrey Miller MD, 1Michael
Verneris MD, 1Veronika Bachanova MD PhD, 1Daniel J Weisdorf MD, 2John E Levine
MD, 1Linda J Burns MD
From the Blood and Marrow Transplant Programs at the 1University of Minnesota and
2
University of Michigan
ABSTRACT
In the non-transplant setting, classical Hodgkin Lymphoma (cHL) serum
biomarkers, reflective of tumor burden and biology, may identify patients at increased
risk for relapse. We tested the prognostic value of selected cHL biomarkers in predicting
relapse among cHL patients undergoing autologous hematopoietic cell transplantation
(AHCT). Sixty-one cHL patients with prospectively collected serum samples received
AHCT at the University of Minnesota and the University of Michigan. Serum biomarkers
with established prognostic significance following initial treatment (IL-6, IL-10, sCD30,
sIL-2R, CCL-17, Galectin-1, sCD68 and sCD163) were analyzed. Optimal cutpoints,
distinguishing patients with early relapse (<2 years post-AHCT) from those remaining in
remission, were calculated using recursive partitioning. The majority (89%) of patients
were in complete remission (CR; 47%) or partial remission (PR; 42%) at the time of
transplant. Elevated concentrations of pre-AHCT IL-6 (RR 9.89 [2.25-43.41, 95% CI];
P<0.01) and CCL-17 (RR 6.42 [2.07-19.91]; P<0.01) were independently associated with
higher risks of 2-year disease relapse. Differences in relapse were significant only
among patients in PR pre-AHCT as relapse events were rare among patients in CR.
Optimal risk-stratification occurred by combining pre-AHCT and day +28 serum
biomarker measurements. Patients with elevated CCL-17 both pre-AHCT and at day+28
had higher 2-year relapse rates (69% [45-91%, 95% CI]) versus those with low levels at
both time points (0%; P<0.01). These data suggest that elevated pre-AHCT IL-6 and
CCL-17 predict for higher rates of 2-year relapse, particularly among patients in PR preAHCT. Combining pre-AHCT and day +28 biomarker measurements may better
discriminate those at highest risk who might benefit from further intervention, such as
post-AHCT maintenance therapies or novel alternative treatments.