No Utility of Routine Laboratory Testing during Surveillance in Detecting Relapse in Patients with Classic Hodgkin Lymphoma in First Remission

Background: Classic Hodgkin lymphoma (CHL) is currently highly curable. Surveillance guidelines have been extrapolated largely from an era where sophisticated staging techniques were lacking, radiotherapy alone was the mainstay of therapy, and cure rates were lower. While the lack of a role for surveillance imaging for patients (pts) in complete remission (CR) at end of therapy (EOT) is well established, there is paucity of data regarding role of laboratory testing. Current NCCN guidelines recommend complete blood counts (CBC), chemistry panels, and erythrocyte sedimentation rate (ESR) "as clinically indicated," while ESMO recommends testing be performed at each clinic visit. To assess the utility of surveillance laboratory testing in detecting relapse, we conducted a retrospective analysis.

Methods: Newly diagnosed CHL pts, uniformly treated with the Stanford V regimen from 1998-2014 and in CR for at least 3 months, were identified from our institutional lymphoma database. Post EOT, follow up included; a clinic visit and laboratory tests (CBC, metabolic panel, ESR) every 2-3 months for years 1-2 and at 6-12 month intervals thereafter for years 3-5. Data at surveillance visits were abstracted from electronic medical records for up to five years after EOT. Laboratory tests categorized by CTCAE v4.03 as Grade 2 or higher were considered abnormal. Values outside the normal range were considered abnormal for non-categorized tests. Primary analysis included sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of surveillance laboratory tests for predicting relapse in first three years after EOT. Secondary objectives included assessment of subsets of higher risk pts defined as early stage (ES) unfavorable [GHSG or EORTC criteria], early stage bulky disease, ESR > 30 mm/hr and advanced stage disease with an international prognostic score (IPS) 3-7.

Results: 235 pts were identified. Characteristics included median age 32 (range 18-82), 92 (39.1%) ES favorable, 66 (28.0%) ES unfavorable, and 61 (25.9%) advanced stage. 16 (6.8%) of ES pts could not be classified as favorable or unfavorable due to missing data. 24 (10.2%) pts relapsed at a median time from EOT of 8 months (range 3.4-80.5). In the first three years after EOT among 234 pts (one did not undergo laboratory testing), the mean number of surveillance blood draws per patient was 7.1, range (1-13). These 1661 surveillance blood draws included 4684 individual laboratory tests, comprising 1609 CBCs, 1578 metabolic panels, and 1497 ESRs. 180 (77%) of pts had at least one abnormal test result over five years. None of the biopsies confirming relapses were prompted by any abnormal laboratory finding. Relapses were detected on basis of surveillance imaging (n=15, 65.2%), patient symptoms and/or abnormal physical exam (n= 8, 34.8%). The sensitivity of any surveillance laboratory test for detecting relapse within 3 years of EOT was 72.7% (95% CI: 49.8-89.3%), specificity 22.6% (17.2%-28.9%), yielding a PPV of 8.9% (95% CI: 7.0%-11.3%) and NPV of 88.9% (79%-94%). Similar results were seen in higher risk subsets (Table 1).

Conclusion: Our study found no utility of routine surveillance laboratory testing in detecting relapse in pts with CR at EOT including higher risk subsets. Our results support modifications of current practice guidelines.

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