Thrombosis as a Treatment Complication in Hodgkin Lymphoma Patients

A Comprehensive Analysis of Three Prospective Randomized German Hodgkin Study Group (GHSG) Trials

S. Borchmann; H. Müller; I. Hude; M. Fuchs; P. Borchmann; A. Engert

Disclosures

Ann Oncol. 2019;30(8):1329-1334. 

In This Article

Abstract and Introduction

Abstract

Background: The prognosis of Hodgkin lymphoma (HL) is excellent rendering research into treatment complications highly important. An important complication of cancer and its treatment is thrombosis. Thrombotic events are regularly observed in HL patients but precise information on incidence and risk factors is lacking and the value of prophylactic anticoagulation unclear.

Patients and methods: Thus, we comprehensively studied thrombotic events in 5773 patients from the German Hodgkin Study Group (GHSG) HD13–15 trials in early-favorable, intermediate and advanced HL. We estimated the incidence of and identified risk factors for thrombotic events. Additionally, we provide detailed data on the time course and characteristics of thrombotic events.

Results: A total of 193 thrombotic events occurred for an incidence of 3.3%. Out of these, 175 (90.7%) were venous thromboses, 3 (1.5%) newly emerging post-thrombotic syndromes and 15 (7.8%) arterial thromboses. There were 11 (0.7%) events in early-favorable, 27 (1.3%) in early-unfavorable and 155 (7.3%) in advanced patients, the latter incidence being significantly higher (P < 0.001). The most common locations were deep vein thrombosis of the arm (46.3%) and leg (24.6%). Most venous thrombotic events occurred during chemotherapy (78.9%). We observed 59 (30.6%) catheter-associated events and a descriptively increased risk of venous thrombotic events in patients with oral contraception use during treatment (6.8% versus 3.9%). In advanced HL, the incidence of venous thrombotic events was increased upon treatment with BEACOPP-14 (9.4%, P = 0.0079) compared with 5.1% with 6×BEACOPPesc and 5.7% with 8×BEACOPPesc. Among commonly applied risk factors, including the Khorana score, only age and smoking were prognostic.

Conclusions: The incidence of thrombotic events in advanced stage HL is comparable to other high-risk cancer patients, especially if treated with dose-dense regimens. Additional risk factors are higher age and smoking. Selected HL patients could benefit from prophylactic anticoagulation, however, further interventional studies are needed before general recommendations can be made.

Introduction

The prognosis of Hodgkin lymphoma (HL) is excellent and most patients can be cured with stage and risk factor adapted first line treatment[1,2] rendering treatment complications with potential long-term effects highly relevant for this group of patients. An important complication of cancer and its treatment is thrombosis.[3] Many factors contribute to this risk. Cancer itself and the host's inflammatory response can cause a hypercoagulable state. Furthermore, cancer patients are often less mobile, need to undergo surgery or other invasive measures, have intravenous access devices and receive treatments, such as chemotherapy, that increase the risk of thrombotic events.[4–6]

Thrombosis in cancer patients is associated with severe consequences, including increased mortality, and is thus of particularly high relevance for patients with a highly curable cancer, such as HL.[7–9] Prophylactic anticoagulation can prevent thrombotic events in cancer patients, but can in turn be associated with an increased risk of bleeding.[10] Additionally, patients with HL regularly receive aggressive chemotherapy that can be associated with an increased risk of thrombocytopenia and potential subsequent bleeding itself.[11] For ambulatory cancer patients treated with chemotherapy, current ESMO guidelines recommend the consideration of prophylactic anticoagulation only for patients with a high risk of thrombosis.[10] Various scores have been developed to identify patients at high risk for thrombosis with the Khorana score being the most widely used.[12] However, it is not known whether scores developed in ambulatory solid tumor patients can be used in lymphoma patients in general and in HL patients in particular. Previous studies investigated the incidence of thrombosis in lymphoma patients and reported incidence rates of between 1.5% and 13%,[13–20] but high-quality data on HL patients is still lacking. Therefore, there is a clear medical need to identify HL patients at increased risk for cancer-associated thrombosis for whom, on balance, the benefits of prophylactic anticoagulation outweigh associated risks.

Here, we studied the incidence, type and timing of thrombotic events in the largest prospectively treated HL cohort to date. Additionally, we aim to evaluate potential risk factors that define a subset of the HL population at increased risk of thrombotic events.

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