Eighty-one patients treated with high-dose therapy and autologous stem cell transplantation (ASCT) as part of salvage therapy after a frontline ASCT were included in a retrospective analysis. The median time between the first and the salvage ASCT was 47 months. After salvage ASCT, 75 patients (93%) achieved at least a partial response, including 67% very good partial responses, and no toxic death was reported. Sixteen patients (20%) underwent consolidation therapy, whereas 30 patients (37%) underwent some form of maintenance therapy after salvage ASCT. For all patients, the median overall survival (OS) was 10 years from diagnosis and 4 years from salvage ASCT. The median progression-free survival (PFS) from the date of the first ASCT to the date of the first relapse was 40 months, and the median PFS from the date of salvage ASCT to the date of subsequent progression was 18 months. In the multivariate analysis of prognostic factors, three independent factors unfavorably affected PFS: a short duration of response to the first ASCT (cut-off value of 24 months), a response less than a very good partial response after salvage therapy, and no maintenance treatment after salvage ASCT. Age over 60 years and a short duration of response after the first ASCT were the two factors adversely affecting OS from the time of diagnosis and OS from the time of salvage ASCT. Our data show that salvage ASCT is a feasible option that should be routinely considered at the time of relapse for patients with a response duration of more than 2 years to frontline high-dose therapy.

CDs160/200 were associated with markers of the gold standard 'Matutes score' and could be useful markers to differentiate atypical CLL from other B-cell neoplasms in the absence of available biopsies or cytogenetics and molecular studies.

BACKGROUND: Lenalidomide in combination with dexamethasone (Len=Dex) is indicated for patients with recurrent=refractory multiple myeloma (RRMM) who were treated with 1 prior therapy until evidence of disease progression. The objective of the current study was to determine the efficacy and safety profile of long-term exposure to Len=Dex. METHODS: A total of 50 patients with RRMM who were treated with long-term Len for 2 years from 2 Intergroupe Francophone du My elome (IFM) centers (Lille and Nancy) were included in the current study. RESULTS: The median age of the patients was 58 years, with 30% of the patients aged > 65 years, 49% having an International Staging System stage of 2 and 3, 12% having severe renal insufficiency, and 8% demonstrating an adverse result on fluorescence in situ hybridization. Approximately 56% of the patients received treatment with Len=Dex for 3 years. The median duration of treatment with Len=Dex was 3 years (range, 2 years-7 years). The response rates for partial response or better and very good partial response or better for the overall cohort were 96% and 74%, respectively, which is similar to patients exposed to Len for 3 years. With a median follow-up of 4 years, 19 (38%) patients had stopped treatment with Len=Dex. The time to disease progression rate at 37 months was 78% and 91%, respectively, in patients exposed to Len for 2 years to < 3 years and for 3 years (P 5 025). The safety profile was manageable, similar to that of Len when administered for a shorter period of time; 16% of patients had grade 3 to 4 neutropenia, 6% had thrombopenia, 6% had anemia, and 20% experienced thromboembolic events, all of venous type. The annual incidence rate of second primary malignancy was 1.96% in the current series. CONCLUSIONS: The results of the current study confirmed that the Len=Dex combination is feasible for long-term use in patients with RRMM, with a significant benefit noted in terms of time to disease progression for prolonged treatment with Len=Dex. Cancer 2013;119:3680-6.

Introduction:Adult T-cell leukemia/lymphoma (ATL) is a lymphoid neoplasm of CD4+ T lymphocytes caused by the human T-cell leukemia virus type I (HTLV-1), which is classified into 4 clinical subtypes (ie, smoldering, chronic, acute, and lymphoma). Natural killer receptors (NKRs) were previously identified on T-cell lymphoma.Methods: NKRs expression was assessed by flow-cytometry and immunohistochemistry on peripheral blood samples (n = 55) and biopsies (n = 21) obtained from 50 ATL patients. Array-based analysis of genomic DNA methylation patterns of KIR3DL2 promoter was assessed. To explore the role of HTLV-1 on KIR3DL2 expression, KIR3DL2 and TAX mRNA expressions were assessed on primary ATL cells and on activated CD4+ T cells that were infected with HTLV-1 in-vitro. Ex-vivo autologous antibody dependent cell cytotoxicity (ADCC) was performed on sorted primary ATL cells with IPH4102, a monoclonal anti-KIR3DL2 antibody that has shown robust clinical activity in Phase I in patients with relapsed Sézary Syndrome (NCT02593045).Results: KIR3DL2 was the only detected NKR, mainly expressed on acute-compared to lymphoma-and chronic-types ATL (28/30 vs. 2/8 and 2/12 respectively; p = 0.001). KIR3DL2 expression correlated with the demethylation status in its promoter, and treatment by 5-Aza increased its expression from a positive basal state. TAX mRNA and KIR3DL2 expressions were correlated on primary ATL cells. HTLV-1 infection triggered KIR3DL2 protein expression by CD4+cells. However, Tax alone is not sufficient to induce KIR3DL2 mRNA expression. Treatment with IPH4102 can selectively kill human KIR3DL2+ primary ATL cells ex-vivothrough ADCC with autologous NK cells.Conclusion: KIR3DL2 expression is mainly associated with acute-type ATL, the most frequent subtype with the poorest prognosis. Induction of KIR3DL2 gene transcription may be triggered by HTLV-1 infection followed by transcription maintenance due to DNA hypomethylation of the gene promoter. The benefit of targeting KIR3DL2 by IPH4102 should be further investigated in ATL patients. Introduction: Extranodal Natural killer/T-cell lymphoma, nasal type (ENKTCL) is a rare and aggressive subtype of peripheral T cell lymphoma strongly associated with Epstein-Barr virus. The use of Asparaginase in the last ten years has significantly improved the prognosis of this lymphoma. Although 60% of these patients are now cured with this regimen even while relapsing, some are however primary refractory or relapse early. NK/T lymphomagenesis is characterized by immune resistance with inefficient immune response directed against EBV-positive tumor cells. The PD-1 (programmed cell death protein 1) / PD-L1 (programmed cell death protein ligand 1) axis is thought to play a role in this process by averting effector T-cell targeting. PD-1/PD-L1 blockade represents therefore a relevant therapeutic strategy in relapsed/ refractory ENKTCL patients and has already demonstrated efficacy in very few cases. Methods: We report here the outcome of 13 ENKTCL patients treated with PD-1 inhibit...

warfarin therapy with a supratherapeutic INR (ibrutinib was dose reduced to once every 3 days, and warfarin was discontinued and not restarted prior to the patient expiring) and one patient had a spontaneous subdural hematoma while on concomitant rivaroxaban and aspirin therapy (ibrutinib, anticoagulation, and antiplatelet agents were discontinued permanently). In the 13 patients with minor bleeding events, the site of bleeding was: 6 genitourinary, 4 skin, 1 soft tissue, 1 tympanic, and 1 GI. Anticoagulation was discontinued permanently in 7 pts, continued at the same dose in 5 pts, and held for one month in 1 pt. Ibrutinib was discontinued permanently in 1 pt, continued at the same dose in 8 pts, held temporarily in 2 pts, and dose reduced in 2 pts. Anticoagulation therapy was effective for patients who received it given that no patient experienced a thrombotic stroke or subsequent venous thromboembolism while on anticoagulation therapy.