No abstract

Patients with mycosis fungoides (MF), the most common subtype of primary cutaneous T-cell lymphoma, have an increased risk of developing secondary malignancies. We herein report two rare cases of MF concurring with diffuse large B cell lymphoma (B lymphoid lineage) and acute myeloid leukemia (myeloid lineage) in two otherwise healthy elderly patients. Potential etiologic factors, including the impact of the therapy-associated inflammatory response on the development of secondary tumors in patients with MF, are discussed. Further clinical, experimental and genetic studies are needed to elucidate possible physiopathogenic associations among the three concurrent malignancies occurring in the cases presented here.

Background: Several clinical risk stratification models have been proposed to predict the clinical outcomes of follicular lymphoma (FL) cases, however, few reports are available to predict prognosis of FL cases receiving bendamustine-based regimens. We previously examined the utility of rituximab-bendamustine (RB) treatment for newly diagnosed advanced FL, who showed non-optimal responses to two cycles of R-CHOP therapy. Methods: In this study, we explored the biomarkers that could influence outcomes for the RB-treated FL cases in the context of the prospective cohort by target capture and sanger sequencing, and gene-expression profiling analyses using 50 diagnostic biopsies.Results: We first examined the mutational status of 410 genes in tumor specimens derived from RB-treated cases. As reported before, CREBBP, KMT2D, MEF2B, BCL2, EZH2, CARD11, TNFRSF14, EP300, and APC were recurrently mutated, however, none of which was predictive for progression-free survival (PFS) in RB-treated cases. Similarly, the m7-FLIPI did not correlate with PFS or progression of disease within 24 months (POD24). A gene expression analysis using a panel of 770 genes associated with carcinogenesis and/or immune response showed that the expression of CD8+ T-cell markers (GZMM, FLT3LG, CD8A, CD8B, GZMK) and half of the genes regulating Th1 and Th2 responses were significantly lower in the POD24 group than in the noPOD24 group. Finally, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and dichotomized RB-treated cases into immune infiltrationhigh (infilhigh) and infiltrationlow (infillow) clusters. The 3-years PFS rate was lower in the infillow cluster than in the infilhigh cluster (50.0% [95% CI: 27.1–69.2%] vs. 84.2% [95% CI: 58.7–94.6%], p=0.0237). Of note, the proportion of cases with peripheral lymphopenia (<869/mL) at diagnosis was higher in the infillow cluster than in the infilhigh cluster (38.5% vs. 9.09%, OR: 6.25 [95%CI, 1.20-32.7], p=0.0235). Conclusion: These results suggest that the T-cell-associated immune markers could be useful to predict prognosis in RB-treated FL cases.Trial registration: This trial was retrospectively registered in UMIN on April. 24, 2014 (UMIN000013795; http://www.umin.ac.jp/icdr/index-j.html).