Objectives
High grade B-cell lymphoma (HGBL) with rearrangement of MYC and BCL2 and/or BCL6 are a rare subgroup of Diffuse Large B-cell Lymphoma (DLBCL) as defined by the 2016 WHO classification.
Methods	
With this case we want to illustrate the aggressive behaviour of high grade B-cell lymphoma and the need to define better treatment regimens.
Results
A 64-year old man was diagnosed with polycythemia vera in 2014, for which Ruxolitinib was started in 2016.  In September 2017 he presented with malaise and bleeding. Lab results showed an extremely elevated Lactate Dehydrogenase, deep anaemia and thrombopenia. Peripheral blastosis of 20% suggested transformation to acute myeloid leukemia (AML). Immunophenotyping showed aberrant mature B-lymphocytes with blastoid appearance but no evidence for AML. Eventually FISH analysis on bone marrow biopsy showed rearrangement of MYC/8q24 and BCL2/18q21, confirming the diagnosis of a “double hit lymphoma”. After treatment with 6 cycles R-CHOEP (+ 2 Rituximab) and CNS prophylaxis PET-CT showed a complete metabolic response. The patient relapsed four months later. We stopped Ruxolitinib and started a second line chemotherapy with Gemcitabine-Oxaliplatin. Patient reached partial metabolic response (Deauville 4) after 2 cycles but showed progression a few weeks later. He currently receives Bendamustine and Cytarabine as rescue therapy.
Conclusion
HGBL are an aggressive subgroup of DLBCL with a poor response to chemoimmunotherapy. 20% to 30% of patients have primary refractory disease despite receiving intensive induction regimens. Due to the rarity of the disease prospective data are lacking and there is no standard treatment regimen. Enrolment in clinical trials should be considered for eligible patients.
There is an emerging concern about risk of development of high grade DLBCL in patients receiving JAK-inhibitors, possibly due to the transformation of a pre-existing B-cell clone. Until conclusive data arise, Ruxolitinib should be discontinued in patients developing a new lymphoproliferative disorder.

Occurrence of high grade B-cell lymphoma with rearrangement of MYC and BCL2 and/or BCL6 under Ruxolitinib: a case report