Summary. Limited data are available concerning treatment and outcome of primary lymphoma of the breast (PLB), especially after CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, prednisone) chemotherapy. We retrospectively reviewed 20 consecutive cases of localized PLB seen at our institution over a 20 year period. All PLB were of B-cell origin: treatment was CHOP or a CHOP-like regimen in all patients. Sixteen of the 20 patients achieved complete remission (CR) and two achieved partial remission (. 75% tumour regression). Two patients had progressive disease on therapy. With a median follow-up of 54 months, six patients relapsed after 8±66 months. Two of the relapses involved the central nervous system (CNS) (isolated in one case, associated with other sites of relapse in the other). The two patients who achieved partial remission also had progression in the CNS, 4 and 8 months after the end of CHOP chemotherapy. All four patients have died as a result of their disease 3, 6, 10 and 13 months after CNS relapse. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), three had CNS disease at relapse. We also observed three (15%) controlateral breast relapses. Thirteen of the initial 20 patients are alive in CR, six patients have died as a result of their lymphoma and one of unrelated disease. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB.

Summary:Infectious complications after autologous peripheral blood progenitor cell transplantation (PBPCT) have been reported in a few studies including small patient numbers. The present study was performed to assess the incidence, types, outcome and factors affecting early and late infections in 150 patients aged 18 to 68 years (median 46.5) who underwent high-dose therapy, with G-CSF. Patients were kept in reverse isolation rooms and received antimicrobial chemoprophylaxis with oral quinolone and fluconazole. One hundred and fifteen patients (76.7%) developed fever (median 3 days, range 1-29); 20 patients (55.5%) had Gram-positive and 13 (36.2%) Gram-negative bacterial infections. There were no fungal infections or infection-related deaths. Mucositis grade II-IV (P ‫؍‬ 0.0001; odds ratio 3.4) and Ͼ5 days on ANC Ͻ100/ l (P ‫؍‬ 0.0001; odds ratio 2.3) correlated with development of infection. Only days with ANC Ͻ100/ l affected infection outcome (P ‫؍‬ 0.0024) whereas the antibiotic regimen did not. After day ؉30 there were four cases of bacterial pneumonitis (2.7%), one case of fatal CMV pneumonia (0.8%) and 20 of localized VZV infection (13.3%). Reduction of neutropenia duration with PBPCT and G-CSF is not enough to prevent early infectious complications since only a few days of severe neutropenia and mucositis are related to development of early infections. However, no infection-related deaths were seen. Although Grampositive organisms were the major cause of bacteremia, a glycopeptide in the empirical antibiotic regimen did not affect infection outcome. In PBPCT recipients, early and late opportunistic infections were notably absent, which was at variance with what was seen with bone marrow recipients. Efforts should be made to prevent mucositis and neutropenia and identify new strategies of antibacterial prophylaxis.

Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including L-asparaginase (L-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m 2 ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three L-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with L-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P 5 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned L-ASP infusions without recurrence of CNS thrombotic whereas L-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P 5 0.4).

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Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP). Antithrombin (AT) replacement has been suggested to prevent VTE and thus might increase exposure to ASP. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Between 2006 and 2014, 784 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 16% with 69% of them occurring during induction therapy. Most patients received AT supplementation (87%). After excluding patients who did not receive L-ASP or developed thrombosis before L-ASP, AT supplementation did not have a significant impact on VTE (8% versus 14%, OR: 0.6, p=0.1). Fibrinogen concentrates administration was associated with an increased risk of VTE (17% versus 9%, OR 2.2, p=0.02) whereas transfusion of fresh-frozen plasma had no effect. Heparin prophylaxis was associated with an increased risk of VTE (13% versus 7%, OR 1.9, p=0.04). Prophylactic measures were not associated with an increased risk of grade 3-4 bleeding complications. The rate of VTE recurrence after L-ASP reintroduction was 3% (1/34). In ALL patients receiving L-ASP therapy, the use of fibrinogen concentrates may increase the risk of thrombosis and should be restricted to rare patients with hypofibrinogenemia-induced hemorrhage. Patients developed VTE despite extensive AT supplementation which advocates for additional prophylactic measures. While this large descriptive study was not powered to demonstrate the efficacy of these prophylactic measures, it provides important insight to guide future trial design. NCT00327678.