Clinical and histological study of follicular helper T-cell lymphomas with indolent evolution.

INTRODUCTION: Follicular helper T-cell lymphomas (TFHL) have an aggressive course with a poor outcome. European and US guidelines recommend anthracycline-based chemotherapy as a first-line treatment, but the 5-year overall survival rate is still approximately 30%. We describe here the features of a cohort of TFHL patients who experienced prolonged survival despite the absence of specific treatment or the initiation of steroid-based therapy. PATIENTS AND METHODS: In our study, we describe 15 adult patients who suffered from TFHL and had not received intensive chemotherapy at diagnosis for any reason. Biopsies of these cases were centrally reviewed, and the mutational pattern was determined using next-generation sequencing. RESULTS: These 15 patients had the classic clinical, biological and pathological features of TFHL, angioimmunoblastic-type. TET2 mutations were found in 83% of patients; RHOA G17V, IDH2 R172 and DNMT3A mutations were found in 67%, 42% and 33% of the patients, respectively. Among the 15 patients, 8 did not receive any treatment, and 7 received steroid-based treatment. Ten patients had progression (5 in each group). Four patients died (3 of them from the progression of their lymphoma). The median follow-up in our cohort was 53 months. The 5-year OS was 66%, 100% for untreated patients and 29% for the others. In those 2 groups, the median time to treatment initiation was 22 months from diagnosis. CONCLUSION: We described a series of 15 well-characterized TFHL patients with an indolent outcome, suggesting that a watch-and-wait approach can be proposed in selected patients. Identifying factors predicting such evolution is warranted.

Ibrutinib as a treatment of hematologic autoimmune disorders in patients with indolent B-cell lymphoma.

BACKGROUND: Autoimmune conditions in B-cell lymphomas are frequent. Steroids are standard of care, but many patients require other immunosuppressive agents. Ibrutinib is a Bruton Tyrosine Kinase inhibitor that is approved for B-cell indolent lymphoma treatment. We evaluated the use of ibrutinib in previously treated hematologic immune manifestations associated with B-cell lymphomas. RESULTS: We conducted a retrospective multicentric observational study. Patients presenting with active, relapsed/refractory B-cell lymphoma associated hematological immune manifestation (autoimmune cytopenia, acquired immune-mediated bleeding disorders) were included. Twenty-five patients were identified. Median age at ibrutinib introduction was 69 years (range 44-84) and median number of previous treatment lines before ibrutinib was 2 (1-7). Twenty-two patients (88%) were on concomitant stable treatment at inclusion. Within a median exposure of 8 months (2-35), overall response rate to ibrutinib on immune manifestations was 76% (95% CI, 54.9-90.6); complete response rate 44%. Fourteen patients (63%) were able to be weaned from concomitant treatments. Fourteen patients (56%) presented treatment-related adverse events, mostly Grade 1 or 2. CONCLUSIONS: Ibrutinib in this setting provides good efficacy and safety profile. Clinical trials are needed to define subgroups of patients who will benefit from this strategy and establish its place in the therapeutic arsenal.

Splenectomy before allogeneic hematopoietic cell transplantation for myelofibrosis: A French nationwide study.

The value of pretransplant splenectomy in patients with myelofibrosis (MF) is subject to debate, since the procedure may preclude subsequent allogeneic hematopoietic cell transplantation (allo-HCT). To determine the impact of pretransplant splenectomy on the incidence of allo-HCT, we conducted a comprehensive retrospective study of all patients with MF for whom an unrelated donor search had been initiated via the French bone marrow transplantation registry (RFGM) between 1 January 2008 and 1 January 2017. Additional data were collected from the patients' medical files and a database held by the French-Language Society for Bone Marrow Transplantation and Cell Therapy (SFGM-TC). We used a multistate model with four states ("RFGM registration"; "splenectomy"; "death before allo-HCT", and "allo-HCT") to evaluate the association between splenectomy and the incidence of allo-HCT. The study included 530 patients from 57 centers. With a median follow-up time of 6 years, we observed 81 splenectomies, 99 deaths before allo-HCT (90 without splenectomy and nine after), and 333 allo-HCTs (268 without splenectomy and 65 after). In a bivariable analysis, the hazard ratio [95% confidence interval (CI)] for the association of splenectomy with allo-HCT was 7.2 [5.1-10.3] in the first 4 months and 1.18 [0.69-2.03] thereafter. The hazard ratio [95% CI] for death associated with splenectomy was 1.58 [0.79-3.14]. These reassuring results suggest that splenectomy does not preclude allo-HCT in patients with MF.

Discontinuation of antimicrobial therapy in adult neutropenic haematology patients: A prospective cohort.

OBJECTIVES: Antibiotics for febrile neutropenia (FN) in acute myeloid leukaemia (AML) patients undergoing intensive chemotherapy are usually maintained until neutropenia resolution, because of the risk of uncontrolled sepsis in this vulnerable population. This leads to unnecessarily prolonged antimicrobial therapy. METHODS: Based on ECIL-4 recommendations, we modified our management strategy and discontinued antibiotics after a pre-established duration in patients treated for a first episode of FN between August 2014 and October 2017. RESULTS: Antibiotics were stopped during 62 FN episodes, and maintained in the control group (n = 13). Median age of patients was 54 years. A total of 39 (63%) patients received induction and 23 (37%) consolidation chemotherapy; 36 (58%) patients had fever of unknown origin. Median neutropenia length was 26 days (IQR 24-30). Antibiotics were started at day 9 (IQR 5-13). Most patients received piperacillin-tazobactam (56%) or cefepime (32%). Antimicrobial therapy was longer in the control group than in the policy compliant group, 10 (IQR 7-16) vs. 19 days (IQR 15-23), P = 0.0001. After antibiotics discontinuation, 20% patients experienced fever recurrence, within 5.5 days (IQR 3-7.5). None of these febrile episodes were severe and 80% patients remained afebrile, with neutrophil recovery occurring within 5 days (IQR 2-8.5). Overall, 287 antibiotics days were spared; this represents 49% of all days with antibiotics. No patient had died at day 30 from intervention; six died during late follow-up, two from graft-versus-host disease and four from relapsed or refractory leukaemia. CONCLUSIONS: Discontinuing antibiotics in neutropenic AML patients treated for a first episode of FN is safe, and results in significant antibiotic sparing.

Disproportionality Analysis for the Assessment of Abuse and Dependence Potential of Pregabalin in the French Pharmacovigilance Database.

BACKGROUND AND OBJECTIVE: Pregabalin abuse and dependence has been increasingly described; however, it is not described in France. Our study aimed to investigate the abuse and dependence potential of pregabalin by a disproportionality analysis, in the French Pharmacovigilance Database (FPVD), in comparison with amitriptyline and clonazepam. METHODS: We performed a case/noncase study in the FPVD. Between January, 1 2010 and December, 31 2015, we identified cases of abuse and or dependence (excluding isolated withdrawal syndromes) using MedDRA (Medical Dictionary for Regular Activities) terms. Exposure to pregabalin was defined as the mention of pregabalin in the report. Clonazepam was used as positive control and amitriptyline as negative control. RESULTS: Among the 184,310 reports in the database, 521 were abuse or dependence cases. Exposure to pregabalin was found in eight (1.5 %) of them. We did not find any significant association between exposure to pregabalin and drug abuse or dependence: reporting odds ratio (ROR) = 1.1 95 % confidence interval (CI) (0.6-2.3). ROR for clonazepam was 5.7 95 % CI (3.5-9.2). No case of an amitriptyline-related abuse or dependence was recorded in the FPVD. CONCLUSIONS: The first cases of pregabalin-related abuse or dependence reported in France occurred later than in other European countries, since none had been described before 2010. This analysis in the FPVD did not find a higher proportion of abuse/dependence with pregabalin in comparison with other drugs. Considering evidence of pregabalin abuse worldwide, this analysis underlines the limitations of spontaneous reporting system in the field of addictovigilance.