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Outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with adult T cell leukemia/lymphoma (ATL) are not satisfactory, particularly in patients in non-complete remission at transplantation (Pt-non-CR). We conducted a regional retrospective study in the ATL endemic area of Okinawa, Japan. Of 62 ATL patients, 21 received allo-HSCT in CR and 41 in non-CR. The 3-year overall survival (3yOS) rate and median survival time for the whole cohort was 25.6% and 7.7 months, respectively. The 3yOS of Pt-non-CR was significantly lower than that of patients in CR (Pt-CR) (16.8% vs. 43.6%, P = 0.005). Transplant-related mortality (TRM) was significantly higher in Pt-non-CR than in Pt-CR (46.3% vs. 15.7%, P = 0.025), while there was no significant difference in disease-associated mortality (DAM) between Pt-non-CR and Pt-CR. Multivariable analysis for Pt-non-CR revealed that poor performance status (poor-PS) and higher sIL-2R level (high sIL-2R) adversely affected OS. Poor-PS was associated with higher TRM, but not with higher DAM in Pt-non-CR. High sIL-2R did not affect TRM or DAM in Pt-non-CR. Overall, high TRM rates rather than DAM contribute to the poor outcomes of Pt-non-CR, suggesting that not only disease control but also management of transplant-related complications is required for allo-HSCT in ATL patients.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Although the HLA class II locus is the strongest genetic risk factor for rheumatoid arthritis, the relationship between HLA class II alleles and lymphocyte activation remains unclear. We performed immunophenotyping of peripheral blood mononuclear cells on 91 HLA-DRB1-genotyped RA patients and 110 healthy donors. The frequency of memory CXCR4(+)CD4(+) T cells, and not Th1 and Th17 cells, was significantly associated with disease severity by multiple linear regression analysis. RA patients with one or more susceptible HLA-DR haplotypes (shared epitope: SE) displayed a significantly higher frequency of memory CXCR4(+)CD4(+) T cells. Moreover, the frequency of memory CXCR4(+)CD4(+) T cells significantly correlated with the expression level of HLA-DR on B cells, which was elevated in RA patients with SE. In vitro analysis and transcriptomic pathway analysis suggested that the interaction between HLA-DR and T cell receptors is an important regulator of memory CXCR4(+)CD4(+) T cells. Clinically, a higher frequency of memory CXCR4(+)CD4(+) T cells predicted a better response to CTLA4-Ig. Memory CXCR4(+)CD4(+) T cells may serve as a powerful biomarker for unraveling the linkage between HLA-DRB1 genotype and disease activity in RA.