Capture-based targeted sequencing using a T-cell control in myeloid malignancies and idiopathic cytopenias.

We report on a study of next-generation sequencing in 257 patients undergoing investigations for cytopenias. We sequenced bone marrow aspirates using a target enrichment panel comprising 82 genes and used T cells from paired blood as a control. One hundred and sixty patients had idiopathic cytopenias, 81 had myeloid malignancies and 16 had lymphoid malignancies or other diagnoses. Forty-seven of the 160 patients with idiopathic cytopenias had evidence of somatic pathogenic variants consistent with clonal cytopenias. Only 39 genes of the 82 tested were mutated in the 241 patients with either idiopathic cytopenias or myeloid neoplasms. We confirm that T cells can be used as a control to distinguish between germline and somatic variants. The use of paired analysis with a T-cell control significantly reduced the time molecular scientists spent reporting compared to unpaired analysis. We identified somatic variants of uncertain significance (VUS) in a higher proportion (24%) of patients with myeloid malignancies or clonal cytopenias compared to less than 2% of patients with non-clonal cytopenias. This suggests that somatic VUS are indicators of a clonal process. Lastly, we show that blood depleted of lymphocytes can be used in place of bone marrow as a source of material for sequencing.

Outcome for patients with relapsed/refractory aggressive lymphoma treated with gemcitabine and oxaliplatin with or without rituximab; a retrospective, multicentre study.

The treatment of relapsed aggressive lymphoma remains a challenge. Platinum-containing chemotherapy is standard of care. Gemcitabine/oxaliplatin (Gem-Ox) with or without rituximab (R) is an outpatient regimen with a favorable toxicity profile. This retrospective 'real world' study reports outcomes for 44 unselected patients with relapsed/refractory aggressive lymphoma treated with Gem-Ox ± R. 41% had primary refractory disease. The overall response rate (ORR) was 43% with a complete response (CR) of 30%. Response to the prior treatment regimen significantly affected the ORR with only 8% achieving CR if prior remission was <12 months. Grade 3-4 hematological toxicity was common and 22% had febrile neutropenia. Eight patients proceeded to stem cell transplant. Overall, outcomes remain poor with a median overall survival of 8 months. In this high-risk group of patients, Gem-Ox ± R results in similar responses to other more toxic, inpatient regimens and should therefore be considered as second line therapy in relapsed lymphoma.