DLBCL is the most frequent lymphoid malignancy in the adult population and the one with
the highest risk of thrombotic events. The indications for thromboprophylaxis are,
however, debated.
For such reason, risk scores (i.e., the Khorana, Throly and the recently published Model
IX score), have been developed to identify patients bearing a high thrombotic risk at
diagnosis. These models, however, were developed considering not only aggressive
lymphomas, but also indolent lymphomas, characterized by a markedly lower risk of VTE
when compared to DLBCL.
The performance of the Khorana, Throly and Model IX score has never been evaluated and
compared in the sole DLBCL population. Such understanding in a cohort of "real world"
patients could aid clinicians in deciding whether to initiate thromboprophylaxis and may
direct randomised controlled trials on the use of prophylactic heparin in the future.
Moreover, the aforementioned scores assess independent variables at diagnosis, not taking
into account the possible occurrence of risk factors that may arise over the course of
DLBCL treatment or in case of placement of a central venous catheter (CVC).
Assessing the impact of thrombotic risk factors at diagnosis and during the disease, in a
cohort of sole DLBCL patients, could allow the development of a new predictive model of
thrombotic risk adapted to DLBCL.
- OBJECTIVES AND ENDPOINTS OBJECTIVES Primary objective
- To assess the impact of thrombotic risk factors on the development of VTE in
patients with Diffuse Large B-cell Lymphoma (DLBCL): real-life comparison of models
predictive of thrombotic risk (Khorana, Throly and Model IX scores).
Secondary objectives
To evaluate the statistical performance of the aforementioned predictive models in
the subgroup of patients who did not have a thrombotic event at diagnosis
To assess the impact of dynamic risk factors (i.e., not present at diagnosis) on
thrombotic risk
To evaluate the impact of risk factors at diagnosis which are not included in the
published predictive models
To evaluate overall survival and VTE-free survival
Creation of a predictive model of thrombotic risk adapted to DLBCL
ENDPOINTS Primary endpoints
Measurement of thrombotic risk factors present in the Khorana, Throly and Model IX
scores: previous arterial or venous thrombotic event, ECOG, weight, extra nodal
and/or mediastinal localization of disease, leukocytes, neutrophils, haemoglobin,
platelet count, albumin, bulky mass
Occurrence of arterial and venous thrombotic events, type of event, time to event
after diagnosis and during disease
Secondary endpoints
Data collection of static thrombotic risk factors at diagnosis and not included in
the already published scores:
de novo or secondary DLBCL status
Neutrophil/lymphocyte ratio (ANC/ALC ratio)
Cardio aspirin
R-IPI
Immunohistochemistry: Ki67, Myc, CD10, BCL-6, BCL-2
Correlation between static risk factors at diagnosis and relative risk of thrombotic
events
Data collection of dynamic risk factors (as both categorical-dichotomous and
temporal variable) present from diagnosis to expected event, death or lost at
follow-up:
Central venous catheter placement
Therapy: radiotherapy, chemotherapy, anthracycline therapy, number of
therapeutic lines, autologous haematopoietic stem cell transplantation
LDH, haemoglobin < 10 g/dl if > than 10 at diagnosis, venous compression at CT
scan, extra nodal localisation if not present at diagnosis, albumin < 3.5 g/dl
if greater at diagnosis
ANC/ALC ratio at the time of thrombotic event
Correlation between acquisition of dynamic risk factors and relative risk of
thrombotic event
Date of thrombotic event, death or lost to follow-up to determine overall survival
and VTE free survival
Creation and validation of a predictive model adapted to DLBCL based on the Hazard
Ratios of the independent variables