Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: an analysis of patients from LYSA centers.

Background: Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods: In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results: Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69-1.50 for PFS and HR = 1.08; 95% CI: 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions: The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.

Allogeneic stem cell transplantation for patients with mantle cell lymphoma who failed autologous stem cell transplantation: a national survey of the SFGM-TC.

Poly-chemotherapy plus rituximab followed by autologous stem cell transplantation (auto-SCT) is standard care for untreated young patients with mantle cell lymphoma (MCL). Despite this intensive treatment, transplant patients remain highly susceptible to relapse over time. The French SFGM-TC performed a national survey on reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) for fit relapsed/refractory patients who failed after auto-SCT (n=106). Median times of relapse after auto-SCT, and from auto-SCT to RIC-allo-SCT were 28 months and 3.6 years, respectively. Sixty per cent of patients received at least three lines of treatment before RIC-allo-SCT. Conditioning regimens for RIC-allo-SCT were heterogeneous. Twenty patients experienced grade III/IV aGvHD, extensive cGvHD was reported in 28 cases. Median follow-up after RIC-allo-SCT was 45 months. Median PFS after RIC-allo-SCT was 30.1 months and median overall survival was 62 months. Treatment-related mortality (TRM) at 1 year and 3 years were estimated at 28% and 32%, respectively. A total of 52 patients died; major causes of death were related to toxicity (n=34) and MCL (n=11). Patients in good response before RIC-allo-SCT experienced a better PFS and OS. Our work highlights the need for new RIC-allo-SCT MCL-tailored approaches to reduce TRM, and early and late relapse.

[Natural history of portal cavernoma without liver disease. A single centre retrospective study of 32 cases]. / Évolution naturelle des cavernomes portaux non liés à une hépatopathie. Étude rétrospective monocentrique de 32 observations.

PURPOSE: Portal cavernoma follows a chronic occlusion of the portal vein. The long-term consequences of portal cavernoma are not well known. The objective of this study was to report the aetiology of the portal cavernoma and its natural course after excluding liver diseases causes. METHODOLOGY: A single centre retrospective study based on the data collected from the radiology department of the Clermont-Ferrand hospital was conducted from 2000 to 2011. All the patients for whom an imagery found a portal cavernoma have been looked for excluding the patients having a liver disease whatever the aetiology and the Budd-Chiari syndrome. RESULTS: Thirty-two cases (18 women and 14 men) were selected. The mean age at diagnosis was 54.2 years and the mean follow-up period was 5.4 years. The discovery of a portal cavernoma was incidental for 8 cases. An aetiology was found for 24 cases: it was an haematological aetiology in 15 cases (10 myeloproliferative syndromes, 2 antiphospholid syndromes, 1 thalassemia major, 1 hyperhomocysteinemia, 1 prothrombin gene mutation), a general aetiology in 2 cases (1 coeliac disease, 1 pancreatic neoplasia), and a local inflammation in 7 cases. A dysmorphic aspect of the liver was noticed on medical imaging for 11 out of the 32 cases. A liver biopsy was performed in 4 patients and was normal for all of them. Sixteen patients developed oesophageal varices, 4 patients developed ascites, 3 developed asymptomatic biliary compression by the portal cavernoma, and the patient who had been followed for the longest time (15 years) developed an encephalopathy. CONCLUSION: In addition to its underlying etiology, the prognosis of portal is mainly related to the occurrence of oesophageal varices that may develop during the follow-up of the patients.

FDG-PET/CT findings in systemic mastocytosis: a French multicentre study.

INTRODUCTION: Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in mastocytosis has yet to be determined. METHODS: We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data. RESULTS: Our cohort included 19 adult patients, median age 65 years [range 58-74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM-AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47%), LN (6/19, 32%), spleen (12/19, 63%), or liver (1/19, 5%). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells. CONCLUSIONS: FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients.

[Intraocular lymphoma associated with primary malignant lymphoma of the central nervous system: Seven-year experience of a tertiary center]. / Lymphome intraoculaire associé au lymphome primitif non hodgkinien du système nerveux central : expérience d'un centre tertiaire sur une durée de sept ans.

INTRODUCTION: Primary intraocular lymphoma (PIOL), associated with primary central nervous system lymphoma (PCNSL), is a rare malignancy disease. By way of a seven-year experience of a tertiary center, we discuss the presentation and we review the diagnostic and therapeutic modalities. OBSERVATIONS: We report six cases of PIOL associated with PCNSL. For all patients, the clinical presentation was a vitreoretinal syndrome. The diagnosis was histologically confirmed by vitreal sample or brain biopsy. Five patients developed a diffuse large B-cell lymphoma. Only one patient developed a T-cell lymphoma. The treatment consisted of conformational radiation therapy, systemic chemotherapy and intravitreal injections of methotrexate. The median survival after the diagnosis was 24 months. DISCUSSION: PIOL, associated with PCNSL, is the most common type of ocular lymphoma. In most cases, ocular manifestations inaugurate the disease. PIOL is often fatal because of ultimate central nervous system presentation. The role of the ophthalmologist consists in early diagnosis. Typical clinical findings include vitroretinal tumor syndrome but can mascarade other eye pathologies. Diagnosis requires histology. The majority of PIOL is diffused large B-cell lymphoma. Decisions are made through multidisciplinary consultation. PIOL exhibits high responsiveness to methotrexate. CONCLUSION: Through a literature review and many illustrations, we discuss epidemiological, clinical, histological, radiological and treatment characteristics of PIOL associated with PCNSL.

90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas.

BACKGROUND: Patients with advanced B-cell non-Hodgkin's lymphoma (NHL) refractory to initial chemotherapy or relapsing after autologous stem-cell transplantation have a poor prognosis. Allogeneic stem-cell transplantation after reduced-intensity conditioning (RIC) regimen can be a therapeutic option. However, the high incidence of relapse remains a challenging issue. We speculated that the incorporation of (90)Y-Ibritumomab tiuxetan into a fludarabine-based RIC regimen would improve the lymphoma control without overwhelming toxicity. Our aim was to evaluate the safety of (90)Y-Ibritumomab tiuxetan in association with such a regimen in a prospective multicenter phase II trial. PATIENTS AND METHODS: Thirty-one patients with advanced lymphoma from five distinct institutions were included between February 2008 and October 2010. Thirty patients in complete or partial response after failure of a median of 3 (range, 2-4) previous chemotherapy regimens including autologous transplant in 29 were evaluable for nonrelapse mortality (NRM) at day 100 post-transplant that was the primary end point. RESULTS: With a median follow-up of 32 months (range, 29-60 months), the 2-year event-free and overall survivals of the whole study group were both 80% [95 confidence interval (CI) 60.8% to 90.5%). The 100-day and 2-year post-transplant cumulative incidences of NRM were 3.3% (95% CI 0.2% to 14.9%) and 13.3% (95% CI 5.4% to 33.2%), respectively. The 2-year cumulative incidence of relapse was 6.7% (95% CI 1.7% to 25.4%). The cumulative incidences of grade II-IV and extensive chronic graft-versus-host disease were 27% and 14%, respectively. CONCLUSIONS: For chemosensitive advanced high-risk B-cell lymphoma, the addition of (90)Y-Ibritumomab tiuxetan to a RIC regimen based on fludarabine, busulfan and antithymocyte globulin followed by allogeneic transplant is safe and highly effective. clinicaltrials.gov: NCT00607854.

Impact of uncontrolled freezing and long-term storage of peripheral blood stem cells at - 80 °C on haematopoietic recovery after autologous transplantation. Report from two centres.

Controlled-rate freezing and storage in vapour phase nitrogen are used by most transplantation teams for the cryopreservation and storage of peripheral blood haematopoietic stem cells (PBSC). In this study, we analysed 666 autologous PBSC transplants after uncontrolled freezing and storage of PBSC at -80 °C. Statistical analysis showed that neutrophil recovery was associated with both the infused CD34(+) cell dose (P=0.01) and the post transplantation use of growth factors (P<0.001) and that platelet recovery was associated with the infused CD34(+) cell dose (P<0.001) and with the diagnosis (P=0.02). We analysed three groups according to the duration of the cryopreservation period (less than 6 months, between 6 and 12 months or more than 1 year). Haematopoietic recovery was not found to be adversely affected by longer storage at -80 °C. The haematopoietic recoveries of 50 pairs of sequential transplantations from the same PBSC mobilization were analysed. Despite prolonged cryopreservation, there were no statistically significant differences in neutrophil (P=0.09) or platelet (P=0.22) recovery in the second compared with the first transplant. In conclusion, the long-term storage of PBSC at -80 °C after uncontrolled-rate freezing is an easy and comparatively inexpensive cryopreservation method that leads to successful haematopoietic recovery even after prolonged storage.

Reduced-intensity conditioning allogeneic stem cell transplantation for relapsed/refractory mantle cell lymphoma: a multicenter experience.

BACKGROUND: Despite therapeutic approach that combines rituximab-containing chemotherapy, followed or not by autologous stem cell transplantation (auto-SCT), mantle cell lymphoma (MCL) patients experience relapses. Reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) at time of relapse may represent an attractive strategy. PATIENTS AND METHODS: We report a multicenter retrospective analysis. Seventy MCL patients underwent RIC-allo-SCT in 12 centers. RESULTS: Median age at transplantation was 56 years and median time from diagnosis to transplantation was 44 months. The median number of previous therapies was 2 (range, 1-5) including autologous transplantation in 47 cases. At time of transplantation, 35 patients were in complete remission, 20 were in partial response and 15 in stable disease or progressive disease. The median follow-up for living patients was 24 months. The 2-year event-free survival (EFS) and overall survival (OS) rates were 50% and 53%, respectively. The 1- and 2-year transplant-related mortality rates were 22% and 32%, respectively. The statistical analysis demonstrated that disease status at transplantation was the only parameter influencing EFS and OS. CONCLUSIONS: These results suggest that RIC-allo-SCT may be an effective therapy in MCL patients with a chemo-sensitive disease at time of transplantation, irrespective of the number of lines of prior therapy. Studies are warranted to investigate the best type of RIC regimen.

Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS.

BACKGROUND: There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL. PATIENTS AND METHODS: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. RESULTS: Thirty-nine patients were enrolled. Median age was 72 years (65-80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity. CONCLUSION: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL.

[CT imaging features of colitis in neutropenic patients]. / Aspects tomodensitométriques des colites chez les patients neutropéniques.

Colitis in neutropenic patients presents with non-specific clinical findings including abdominal pain, fever, diarrhea and abnormal liver function tests. Four diagnoses are relatively more frequent: neutropenic enterocolitis, pseudomembranous colitis, intestinal GVHD and CMV colitis. Knowledge of their respective imaging features combined with epidemiological data frequently leads to the correct diagnosis. The purpose of this paper is to illustrate the imaging features of colitis in neutropenic patients.

[Analysis of a severe septic transfusion reaction with standard platelet concentrate]. / Analyse d'un incident bactérien grave transmis par transfusion d'un concentré plaquettaire.

We recently observed a near fatal case of transfusion-transmitted infection with standard platelet concentrate. Streptococcus dysgalactiae subspecies equisimilis was isolated both from donor, residual component container and cultures of the patient's blood. This should question the usefulness of systematic bacterial detection in platelet concentrates, however a lethal accident has occurred recently which escaped bacterial detection. This observation calls for implementation of pathogen inactivation procedures for platelets concentrates.

[Family members integration in patients' care in haematology units: a new application of proximology.]. / L'intégration des familles aux soins des patients hospitalisés en hématologie : une nouvelle application de proximologie.

Hospitalization per se is a stress for the family members of a loved one. While their role as informal caregivers is well known with at home patients, especially in oncology, they usually are only mere visitors at the hospital. Hence the integration of family members of in patients' care might improve both patients and families' quality of life. Such a supportive care concept has been previously investigated in pediatric, neurology and intensive care units, but there is not such data in hematology although the therapeutic in this field is marked by long-term stay in hospitals' rooms. Since 2001, we developed in Clermont-Ferrand University hospital such a project of integration. Put together, the literature data and our first results (opinion poll) show that the main risk of this approach is the exhaustion of family caregivers, their fear of miss conduct and the alteration of the relationship they previously had with the patient. Conversely this approach is likely beneficial in improving both patients and family member's experience during hospitalization in lowering both patients' affective social and may be cultural loneliness and family members' feeling of uselessly and guilt. In France the development of supportive care and therapeutic education in oncology is nowadays encouraged and of there is no legal basis to restrain the development of this concept. Whose concept, nevertheless should be carefully set up and studied and its benefit remain to be clearly demonstrated.