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The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high-dose methotrexate (≥1 g/m2 ) for haematological malignancy and to identify the impact of interacting drugs, especially proton-pump inhibitors (PPIs) and ranitidine. All patients treated with high-dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton-pump inhibitors were co-administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety-three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delayed methotrexate elimination in 20.5%, 21.9%, and 19.4% of cycles (P = .89). Impaired baseline creatinine clearance showed significant association in univariate analysis. Fifteen patients showed grade 1 acute kidney injury, 1 grade 2, 2 grade 3, and none grade 4. For half of these cases, delayed methotrexate elimination was observed and the 2 grade 3 events appeared in patients treated with PPIs. This retrospective study suggests that there is no association between concomitant use of proton-pump inhibitors (pantoprazole and esomeprazole) or ranitidine and delayed methotrexate elimination.

International audience; Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone-High dose aracytine (cis)platin (DHAP), dexamethasone-High dose aracytine carboplatin (DHAC), or dexamethasone-High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin-based regimen (50.0% versus 12.0%, P \\textless .05) and female (44.6% versus 29.7%, P \\textless .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P \\textless .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I-II and 15 grade III-IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I-II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens

In July 1999, a 26-year-old Caucasian woman was diagnosed with a vertebral plasmacytoma revealed by neuralgia. A bone marrow biopsy showed diffuse infiltration of atypical plasma cells, and protein...

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is common in developed countries. Neoplastic CLL infiltration has been found in the skin, lungs and kidneys. However, cen...

We report the case of an immunocompetent 23-year-old Caucasian woman, with symptoms including rectal bleeding, tenesmus and epreint, 6 months after an anal sexual trauma. The rectal examination showed a hardened, inflammatory and painful anal margin, associated with stenosis of the anal canal, suggesting abscess. The neurological examination showed numbing of the chin. Pelvic MRI and CT scan confirmed a bulky posterior tissular pelvic mass more than 7 cm in diameter, infiltrating the rectum and the anal canal. Final diagnosis confirmed by biopsy performed during rectosigmoidoscopy was an Epstein-Barr Virus-Associated Burkitt's lymphoma. Chemotherapy resulted in rapid regression of the tumoral mass.

Background: Less than 20% of patients with follicular lymphoma (FL) present with Ann Arbor Stage I or II disease at diagnosis. Numerous therapeutic options exist, however radiation therapy is considered the standard of care for early-stage disease based on single-institution or retrospective series. Our aim was to revisit the outcome of patients with localized FL in the rituximab era. Patients and Methods. We analyzed the characteristics and outcomes of 145 early-stage FL patients, who were retrospectively divided into six groups according to their initial treatment: watchful waiting (WW), chemotherapy alone (CT), radiotherapy alone (RT), combined radiotherapy and chemotherapy (RT-CT), rituximab alone (Ri), and immunochemotherapy (Ri-CT). Results: Of the 145 patients, 84 (57.9%) had stage I disease and 61 (42.1%) stage II. The complete response (CR) rate varied from 57% for the Ri group to 95% for the RT-CT group. Overall survival (OS) at 7.5 y of patients treated after 2000 was better than that of those treated prior to 2000. OS did not significantly differ from one treatment to another. In contrast, a significant difference was found for progression-free survival (PFS) at 7.5 y, which favored Ri-CT (60%) therapy versus the others (p=0.00135). Conclusion: Delayed therapy initiation was associated with a similar OS than that observed in patients receiving immediate intervention. The "watchful waiting" strategy may thus be proposed as first-line therapy, similar to stage III and IV FL patients with a low tumor burden. However, when treatment is required, immunochemotherapy appears to be the best option. © 2013 Michallet et al.; licensee BioMed Central Ltd.

Described for the first time by Adachi et al. in 1994 [1], CD4+/CD56+ hematodermic neoplasm was thought to be of natural killer (NK) lineage due to expression of the NK-cell marker CD56 by the tumo...

The role of rituximab retreatment in relapsed B-cell lymphoma is not well known. We undertook a single center retrospective cohort study to investigate the efficacy of retreatment with rituximab with or without chemotherapy in patients with relapsed and refractory B-cell lymphomas. We only included patients treated first-line and in first progression; 178 patients were included in the study, of whom 29% had diffuse large B-cell lymphoma (DLBCL) and 28% had follicular lymphoma (FL). The overall response rate for the first treatment was 81% and for the second treatment was 66%. The median progression-free survival (PFS) for all patients from diagnosis was 13.2 months and from relapse was 12.5 months (not statistically different). For DLBCL the median PFS from diagnosis was 9.6 months and from relapse was 8.4 months, and for FL the median PFS from diagnosis was 26.4 months and from relapse was 19.2 months (not statistically different). The 5-year overall survival was 57%. In a historical comparison with rituximab-naive patients, rituximab-retreated patients had a shorter time to initial relapse than control patients, but there was no difference between the two groups for PFS from relapse. In conclusion, retreatment with rituximab, with or without chemotherapy, yields a high overall response rate in patients with relapsed and refractory B-cell lymphomas. Relapse occurring after rituximab-containing therapy appears to be more aggressive than that occurring after chemotherapy alone. The outcome of retreatment, in terms of progression-free survival, is similar to that of primary treatment.

BACKGROUND The authors evaluated the efficacy of chemotherapy combined with rituximab followed by high-dose therapy (HDT) plus autologous stem cell transplantation in patients with mantle cell lymphoma (MCL). METHODS This was a retrospective analysis of 34 patients who were treated in 2 departments of hematology, including 29 patients (85%) who received first-line treatment. Rituximab was administered as 4 injections just before harvest in 25 patients (73%) or simultaneously with chemotherapy in 9 patients (27%). HDT included total body irradiation in 26 patients (77%). RESULTS After induction therapy, all patients except one reached a response: There were 14 (41%) complete responses (CR) and 19 (56%) partial responses (PR). Stem cell harvest was successful in all patients but 2, with a median number of 5.9 CD34-positive cells per 106/kg. Three months after transplantation, 24 patients (71%) were in CR, and 7 patients (21%) were in PR. At 3 years from the day of transplantation, the estimated overall survival was 87%. With a median follow-up at 2.6 years, the estimated median time to disease progression was 3.4 years. Rituximab treatment before harvest did not delay hematopoietic reconstitution: The median time it took patients to recover absolute neutrophil count to > 0.5 G/L was 10 days. CONCLUSIONS Chemotherapy combined with rituximab followed by HDT improved the overall survival and progression-free survival in patients MCL without adding toxicities. Cancer 2005. © 2005 American Cancer Society.

Background: Rituximab has demonstrated significant clinical efficacy in the treatment of NHL, particularly in combination with chemotherapy, and its use has dramatically changed the treatment and outcome of both indolent and aggressive B-cell NHL over the past decade. Furthermore, consistent toxicity data have been obtained with a safe and tolerable profile in a large majority of patients. Aim: The objective of this retrospective study is to evaluate the long-term efficacy of rituximab monotherapy (4 weekly infusion at induction followed by 4 infusion every 2 months as consolidation) used for patients with relapsed indolent NHL. Results: From May 1998 through January 2011, Among 919 patients with indolent NHL treated in our department, 488 (53%) relapsed and were treated with rituximab alone (first and later relapse). 126 (26%) responded and were still in response 2 years later. These 126 patients (68 (54%) males and 58 (46%) females with a median age of 61 y; range: 17-94) are the subject of our analysis. 24% were over 70 years old, 45% were in first relapsed and 25% in later relapsed. Only 16% of the population have more than one co-morbidities (cardiac and or renal respectively); 79% a normal PS (0-1) with only 4 patients having a PS >2; 80% no bulky disease but 72% a disseminated disease (73% stage III and IV). In this study, 60 (48%) patients had a follicular lymphoma with 50% at an intermediate risk group according to the FLIPI score ; 20 (16%) a marginal zone lymphoma, and 43 (34%) a small lymphocytic or lymphoplasmacytic lymphoma and 3 patients other characteristics of lymphoproliferative disorders. After rituximab monotherapy, 55% of the entire cohort was in complete response (CR) and 31% in CRu or partial response and 5% in stable disease. Among these 126 patients, 74% progressed later than 3 years (38% later than 5 years). With a median follow-up of 6.5 years, 4-year and 8-year PFS were 70% and 30%, respectively. 18% had transformation into Richter syndrome and 12 patients have died. Conclusion: Rituximab monotherapy is an effective therapy in selected relapsed indolent NHL and allows long-term response. This strategy could be used as “spare of chemotherapy” which is an important question today, especially in indolent not curable disease. Disclosures No relevant conflicts of interest to declare.

Abstract 2722 Introduction Follicular lymphoma (FL) is the commonest type of indolent lymphomas and is considered as an incurable malignancy with a relapsing and remitting course. Most patients are diagnosed with FL when they have an advanced stage of disease, only less than 20% presenting with stage I or II. Initial management of early stage (Ann Arbor stage I or II) FL remains undefined. Numerous options exist but radiotherapy appeared to be the standard of care for early stage disease based on single institution or retrospective series. Our aim was to revisit the outcome of patients with localized FL in the era of rituximab. Patients and Methods We analyzed 145 patients treated in our institution with early stage (I or II) FL between January 01/1967 and 01/2011. Patients were retrospectively divided into six groups according to their initial treatment: watch and wait (WW), chemotherapy alone (CT), radiotherapy alone (RT), combination of radiotherapy and chemotherapy (RT-CT), Rituximab alone (Ri) and immuno-chemotherapy (Ri-CT). Results Of the 145 patients (79 females and 66 males), 84 (57.9%) patients had stage I disease and 61 (42.1%) a stage II. Median age was 55 years (20% of patients > 65 years). Only 22 (15.2%) of them had a bulky disease (> 7cm). FLIPI score was 0–1 in 116 pts, 2 in 29 pts and none had a score >2. The management of patients significantly varied over the different time (period I: Patients characteristics were similar in terms of age between the 6 groups but differed in term of stage and prognostic factors, essentially more stage II (61%) and bulky disease (42%) in the Ri-CT group compared to the others. The CR rate varied from 57% for the Ri group to 95% for the RT-CT group with 69% for CT, 75% for Ri-CT and 81% for RT alone. As expected, the proportion of PR was higher in the Ri group (43%). With a median follow-up of 7 years, the relapse rate was significantly lower in the Ri-CT group (40% versus 90.5% RT, 84% RT-CT, 69% CT and 58% WW respectively). According to the modifications of management over time, OS and PFS are analyzed according to two period of time: < year 2000 and ≥ 2000. OS at 7.5 years for the patients managed after >2000 was better (75%) than for those managed Conclusion Within the inherent limits of this retrospective study, delayed start of therapy was associated with a similar OS than the one observed in patients receiving immediate intervention, and PFS was not different between WW versus RT or RT-CT. Thus, the “watch and wait” strategy could be proposed as first line therapy, like it is in stage III and IV follicular lymphoma patients with a low tumor burden. However, when a treatment is required, the combination of immunochemotherapy seems to be the best option. Legends: R-CT: Ri CT or immunochemotherapy Others regimens: WW, RT, RT+CT, CT Disclosures: No relevant conflicts of interest to declare.