Onco-haematological Research Team

NEW THERAPEUTIC APPROACH IN LYMPHOMA

Numerous clinical trials are currently underway at the Institute for patients with aggressive or indolent lymphomas. The aim of these studies includes both the identification of new prognostic factors and treatment strategies but also testing new anticancer agents.

Marginal lymphoma or Waldenstrom macroglobulinemia are the subjects of a large prospective multicenter study, which aims to better outline the outcome and prognostic molecular factors.

T-cell lymphomas are also the subject of a large international multicentre study, which aims to identify the biological prognostic factors of these rare diseases. Particular attention has been paid to the relationship between some lymphoma histotypes and HCV infection. This allowed highlighting the etiological and therapeutic relationships between marginal lymphoma or diffuse large cell lymphomas and HCV. Similar assessments are underway in mantle cell lymphomas.

Our Institute also deals with clinical research in immunocompromised patients after solid organ transplantation affected by lymphoproliferative neoplasms and is the Regional referral hospital for high dose chemotherapy and peripheral blood stem cell transplantation in patients with relapsed/refractory germ cell tumors.

DIFFUSE LARGE B CELL LYMPHOMA IN ELDERLY PATIENTS

Our research activity is mainly addressed to elderly patients, rarely included in clinical trials and with different therapeutic approach according to local practice. A pre-treatment evaluation based on Performance Status (PS) or comorbidity index is not sufficient to identify patients suitable for treatment with curative intent. We therefore tried to develop prognostic scores at diagnosis that would allow us to stratify patients and direct them to the most suitable therapeutic choice.

Together with the determination of prognostic factors, our research is directed, in collaboration with Fondazione Italiana Linfomi (FIL), to the development of specific therapeutic approaches for the most fragile categories of patients. A first protocol involves the use of a chemo free strategy (Rituximab and Lenalidomide) with the aim of optimizing efficacy and reducing side effects.

Similar considerations led to the development of an immunochemotherapy study with administration of Rituximab, Bendamustine and Copanlisib, aimed at patients with relapsed DLBCL who are not candidates for intensive approaches such as transplant procedures.

MOLECULAR PROGNOSTIC FACTORS IN DIFFUSE LARGE B CELL LYMPHOMA

DLBCL are classified according to gene expression profiling (GEP) into three distinct molecular cell-of origin (COO) subtypes: germinal center B-cell (GCB), activated B-cell (ABC) and unclassified or primary mediastinal B-cell lymphoma (PMBL). The three COO subtypes are associated with very different prognoses (worst for ABC-subtype). The microarray-based GEP technique was originally described using RNA extracted from frozen tissue, even if its limited access.

We propose a novel approach, which is to study protein levels rather than mRNA transcript levels focusing on proteins which represent the translational products of transcripts implicated in DLBCL pathobiology such as those implicated in cell-of origin, oncogenes and drug targetable targets. This analysis was associated with clinical data and allowed us to determine the presence of correlations with overall survival.