PRIMARY PROPHYLAXIS OF VENOUS THROMBOEMBOLISM IN PATIENTS AFFECTED BY HAEMATOLOGICAL MALIGNANCIES (LYMPHOMA, MULTIPLE MYELOMA, ACUTE LEUKAEMIA): GUIDELINES FORM THE ITALIAN SOCIETY OF HAEMATOLOGY

Several risk factors are involved in the pathogenesis of venous thromboembolism (VTE) in patients affected by cancer, these include cancer type, central venous catheters placement, chemotherapy, radiotherapy, immunomodulatory drugs. The management of VTE may be quite complex in patients with cancer, this is mainly due to an increased risk of recurrent VTE, haemorrhages, morbidity, and hospital admissions. With reference to haematological malignancies, a high intrinsic risk of VTE is related to several disease-specific factors (high blood viscosity, JAK-2 hyper activation, nephrotic syndrome and elevated cytokines levels) and treatment related factors (immunomodulatory drugs and asparaginase). VTE occurrence may negatively affect treatment of the underlying blood cancer and expose patients to a higher risk of death. Furthermore, patients affected by haematological malignancies have a particularly higher risk of bleeding because of thrombocytopenia and hyperfibrinolysis. Defining the clinical indication to prophylaxis of VTE is quite challenging, based on the varying risks of VTE and bleeding complications across different haematological malignancies and their specific treatments. Options for the treatment and prevention of cancer associated VTE, previously mainly based on low-molecular- weight heparin (LMWH), have recently been enriched by direct oral anticoagulants (DOACs). These agents have shown a good risk/benefit profile, however they require an accurate patient-based evaluation for their potential interactions with other treatments and bleeding risks. Up-to-date, studies on the treatment of VTE in patients affected by acute leukaemia are scant and specific guidelines on prophylaxis of VTE in patients affected by leukaemia and lymphoma are not available, while single consensus documents have been developed for patients affected by multiple myeloma and chronic myeloproliferative neoplasm (MPN) with several limits; guidelines on the prevention of VTE in patients with cancer have been recently updated by several scientific societies, and one National Society (AIOM 2020). These recommendations, however, have not been specifically conceived for patients with haematological malignancies, thus the Società Italiana di Ematologia (SIE) has recently developed the first national evidence-based clinical practice guidelines on the administration of pharmacological primary prophylaxis of VTE in patients affected by haematological malignancies. The SIE guidelines have used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and adopted as reference international guideline, the last updated guidelines from ITAC. The primary aim of these guidelines was to define the primary prophylaxis of VTE schedule in patients affected by haematological malignancies, managed in national structures, including available options, approved for this indication in Italy and published evidences. The target population of these guidelines includes patients affected by acute leukemia, lymphoma and multiple myeloma, not under chronic anticoagulant treatments. The SIE guideline working group (WG) involved Italian haematologists expert in this field (AF, VdS ,MM, AV), three methodology experts (MM,MP, PB) one coordinator (MN), volunteer representatives from scientific societies (MdN, AT,PT,GL) and patients (AP). Guidelines were peer reviewed by 3 external academic clinicians (SS, FR, RS). During the first WG teleconference encounter, recommendations from ITAC guidelines were selected for their further analysis. The following benchmarks were selected: Patients were deemed at high risk of VTE for an estimated VTE risk of more than 5% at 6 months; A pharmacological prophylaxis of VTE was judged acceptable for a ratio of the number needed to treat (NNT) for symptomatic VTE prevention and the number needed to harm (NNH) for major bleeding complications of more than 3; The availability of oral pharmacological prophylaxis of VTE was deemed relevant for patients’ quality of life.PICO questions and recommendations are summarised in Table 1 and 2. Further studies in this field will allow to improve the intricate management of VTE in haematological malignancies.