[Liposomal cytarabine in prophylaxis of the central nervous system involvement in rare aggresive lymphomas]. / Liposomalna cytarabina w profilaktyce zajEcia centralnego systemu nerwowego w rzadkich chloniakach agresywnych.

UNLABELLED: The involvement of central nervous system in the course of lymphoma is an adverse prognostic factor, therefore primary prevention is a standard of care of aggressive lymphoma subtypes. The aim of the paper is the safety and efficiency, retrospective analysis of liposomal cytarabine used profilactically in patients with rare aggressive lymphomas. MATERIALS AND METHODS: In the analysis we included 19 patients with aggressive lymphomas: LBL (lymphoblastic lymphoma), BL (Burkitt lymphoma) and PTCL (peripheral T- cell lymphoma) from three PLRG (Polish Lymphoma Research Group) centers, who received liposomal cytarabine as primary prevention of central nervous system involvement. All the included patients had a high risk of CNS due to histological subtype (10 patients with LBL, 4 patients with BL), the specific location of the disease (N=3) or the presence of at least 2 risk factors for CNS involvement (elevated LDH, IPI 3-5 or involvement of at least 2 extranodal sites, N = 16). In this group, 18 patients were subjected to prophylaxis during the 1-st line therapy and one after relapse. None of the patients had symptoms of central nervous system involvement at the time of diagnosis. The median age was 43 years (the range of 20-60 years). In this group there were 14 males (73.68%) and 5 females (26.32%). The patients were treated with liposomal cytarabine every 2 to 4 weeks during the systemic chemotherapy. The median number of cytarabine doses was 2 (the range of 1-5). RESULTS: Liposomal cytarabine was well-tolerated. 63.1% of patients had transient side effects (nausea, vomiting, fever, dizziness) in grade 1-2, 5.2% of patients experienced a more severe headache (grade 3). During the average follow-up of 18 months, 50% of patients died and 27.7% of systemic recurrences were noted. Only one patient had a relapse in the CSN con comitant with a systemic recurrence. CONCLUSIONS: Lipo somal cytarabine is well-tolerated and effective medicine used in the prevention of CNS relapse in patients with ag gressive lymphoma subtypes.

Liposomal cytarabine in the prophylaxis and treatment of CNS lymphoma: toxicity analysis in a retrospective case series study conducted at Polish Lymphoma Research Group Centers.

Lymphomas with primary or secondary involvement of central nervous system (CNS) have poor prognosis despite specific treatment protocols which include whole brain radiotherapy and high-dose systemic and/or intrathecal chemotherapy. Toxicity of intrathecal liposomal cytarabine-based regimens collected between November 2006 and January 2012 was assessed retrospectively. Data from 120 adult lymphoma patients with, or at high risk of CNS involvement who received intrathecal liposomal cytarabine-based regimens at six Polish Lymphoma Research Group centres between November 2006 and January 2012 were assessed retrospectively. Patients were divided into three cohorts: A (high risk of CNS disease, n = 88), B (cerebrospinal fluid pleocytosis without neurological symptoms or pathological imaging findings, n = 7), and C (CNS disease/neurological involvement; n = 25). In all examined groups, toxicity of treatment was found to be acceptable (including the prophylactic setting). None of the patients in cohorts A or B who took intrathecal liposomal cytarabine 50 mg, repeated every 2-4 weeks (mean 3.8 doses) had experienced a CNS relapse at a median follow-up time of 3 years. Patients in cohort C had a 76 % overall neurological response rate (including a 40 % complete response rate) and median overall survival of 4.8 years. Regimens incorporating liposomal cytarabine seem to be safe and effective treatments for lymphomas with CNS involvement.

Central nervous system prophylaxis with intrathecal liposomal cytarabine in diffuse large B-cell lymphomas.

INTRODUCTION:  Central nervous system (CNS) involvement is a serious and potentially fatal complication in patients with lymphoma because it is associated with a particularly poor prognosis (median progression­free survival [PFS] of 4-6 months). Although CNS prophylaxis is considered necessary, there are no clear guidelines on identifying high­risk patients or selecting treatment regimen.  OBJECTIVES:  The aim of the study was to assess the safety and efficacy of CNS prophylaxis with intrathecal liposomal cytarabine. PATIENTS AND METHODS:  We analyzed the data of 79 patients (46 men and 33 women; median age, 48.5 years [20-79]) with diffuse large B­cell lymphoma (83.5% of the patients) and primary mediastinal large B­cell lymphoma (16.5%). Patients were treated in the departments of hematology in Kraków and Wroclaw, Poland, between the years 2009-2012. They were considered to be at a high risk of developing CNS involvement associated with a lymphoma. RESULTS:  Adverse reactions after intrathecal liposomal cytarabine were reported in 59 patients (74.7%); in 7 cases, the reactions were severe. The most common side effect was headache (67.1%). During antilymphoma therapy and prophylaxis, the functional status assessed by the Karnofsky score improved in 56 patients (70.9%) and remained unchanged in the remaining cases. A median follow­up time did not exceed 28 months (range, 1.4-52.1); during follow­up, neither median overall survival (OS) nor PFS were reached (projected OS and PFS at 48 months are 86.1% and 90.1%, respectively).  CONCLUSIONS:  Our results encourage the use of intrathecal liposomal cytarabine in CNS prophylaxis in patients with lymphoma.

Severe bleeding and miscarriages in a hypofibrinogenemic woman heterozygous for the gamma Ala82Gly mutation.

We report a case of hypofibrinogenemia caused by heterozygosity for gamma Ala82Gly in a 69-year-old Polish woman with severe bleeding tendency and a history of six miscarriages. She suffered from frequent mucocutaneous bleedings, epistaxes requiring therapeutic interventions, prolonged bleedings after tooth extractions and surgical interventions. Her mother and sister had bleeding tendency. Fibrinogen levels ranged from 0.93 to 2.0 g/l (von Clauss method). Fibrinogen antigen levels determined by immunonephelometry were about 2 g/l. No other coagulation, platelet or liver function tests yielded abnormal results. Antiphospholipid syndrome was excluded. This report suggests that the fibrinogen gamma Ala82Gly mutation could have variable clinical presentation.