No abstract

Clinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective antiviral agents, BK virus–specific T cells are emerging as a potential therapy for BK virus disease, but the immune response to BK virus after allogeneic HCT has not been well characterized. Our study describes reconstitution of BK virus–specific T-cell immunity in 77 adult patients after HCT. All patients had urinary symptoms, and urine was tested for BK virus replication; 33 patients were positive for BK virus (cases), and 44 were negative (controls). In BK virus cases, the median time to first positive test was 75 days (range, 2-511). BK virus cases had lower CD4 T-cell counts 3 to 9 months after transplant, but CD8 T-cell counts were similar in cases and controls. BK virus–specific T cells were identified by cytokine flow cytometry in cryopreserved samples collected prospectively. BK virus–specific CD4 T cells producing T helper 1 (Th1) cytokines recovered quickly after HCT. BK virus–specific T cells were detected more frequently in patients with BK virus reactivation at most time points, and CD4 T cells producing Th1 cytokines were more frequent than BK virus–specific cytolytic CD8 T cells. Early detection of interferon-γ+ and cytolytic BK virus–specific CD4 T cells was associated with lower rates of hematuria among cases. Overall, our study describes recovery of BK virus–specific T cells after HCT and the distinct roles for BK virus–specific T cells in the development and resolution of clinical symptoms.

Introduction MM is a B cell malignancy characterized by the presence of a monoclonal immunoglobulin (Ig) in the serum and/or urine produced by clonal plasma cells. MM has a variable outcome depending on age, stage and cytogenetic abnormalities. FLCr is a readily available laboratory test and has independent prognostic significance in all the plasma cell disease entities, helping to clarify International Staging System (ISS), namely the heterogeneous stage II. In the era of new therapeutic agents trending to personalized therapy, its prognostic value needs to be proved. Purpose To evaluate the prognostic value of baseline serum FLCr on outcome of patients with newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib based regimens. Methods This is a retrospective study, from January 2005 to December 2012. We analyzed the relationship of baseline FLCr with outcome and its contribution to clarify the prognostic value of ISS. Serum FLC levels were measured in frozen sera drew at diagnosis before treatment, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK) on a Beckman Coulter nephelometric analyzer. FLCr was calculated as k/λ (reference range: 0,26-1,65). Abnormal FLCr was defined of <0,03 or >32,00 and standard FLCr of 0,03-32. Patients have been staged by ISS and Mayo Clinic stratification. All patients received at least two cycles of a bortezomib based regimen (64,7%), with doxorubicin and dexamethasone (PAD) in 55 patients (53,9%), with cyclophosphamide and dexamethasone (Cy-Bor-D) in 11 patients (10,8%) or thalidomide, doxorubicin and dexamethasone (TAD) in 36 patients (35,3%). Median follow-up from diagnosis was 30 months. Follow-up was through the review of each patient’s complete medical records at our center. Statistical analysis was performed with SPSS 20 ®. Results We reviewed 102 patients treated with thalidomide or bortezomib based-regimens eligible for HDM. Fifty one percent of patients were male and median age was 52 years (22-70y). The Ig type was IgG in 62,7%, IgA in 14,7%, IgD in 3,9%, light chains MM in 17,7% and non-secretory MM in 1,0% of patients. The median Hb level was 9,8 g/dL (5,3-16,7mg/L) and median serum albumin was 31,5 g/L (22,3-48,3g/L). Creatinine clearance <30ml/mn occurred in 18,6% of patients, 34,3% had elevated LDH and median β2-microglobulin was 6,61 mg/L (1,06-45,77mg/L). According to ISS, 39,2%% of patients were on stage I, 25,5%% on stage II and 35,3% on stage III. Clonal k light chain present in 58,8% of patients: 64,7% had abnormal FLCr (<0,03 or >32,00). Cytogenetic FISH analysis was performed in 86,3% of patients: 32,4% presented high-risk features. We observed a significant difference on overall survival (OS) and progression free survival (PFS) according to Mayo Clinic risk-factors: 0, not reached (NR), 1, NR, 2, 49 months and 3, 71 months for OS (P=0,000) and 0, 68 months, 1, 55 months, 2, 16 months and 3, 24 months for PFS (P=0,000). According the FLCr there was a significant advantage on OS for standard FLCr: NR vs 71 months (P=0,035). A trend to a better OS (P=0,061) was observed in stage II patients with standard FLCr but no significant difference at any stage. Conclusions Baseline serum FLCr associated to others risk-factors like serum β2-microglobuline and albumin is a powerful prognostic factor for survival in newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib-based therapies. We fail to fully demonstrate FLCr prognostic value on ISS stage II patients, only a trend for better outcome with standard FLCr. Disclosures: Esteves: Janssen-Cylag and Celgene. Consultancy on the area of multiple myeloma and acute myeloid leukaemia: Consultancy. Raposo:Roche; lymphoproliferative diseases: Consultancy. Guerra:Novartis, Bristol-Myers Squibb and Amgen. Advisory bord meetings. Areas involved: Myeloproliferative neoplasms and acute leukaemia: Consultancy.