Significant efficacy of 2-chlorodeoxyadenosine{+/-} rituximab in the treatment of splenic marginal zone lymphoma (SMZL): extended follow-up.

BACKGROUND: Splenic marginal zone lymphoma with or without villous lymphocytes (SLVL/SMZL) is an indolent lymphoma that typically affects elderly patients and that has a median survival >10 years. It presents with marked splenomegaly. Treatment is required in symptomatic cases. Splenectomy remains one of the first-line options in patients fit for surgery. The best pharmacological strategy has not yet been identified for poor surgical risk cases. Among different possible chemotherapeutic approaches, purine analogs, alone or in association with Rituximab, seem to be a valid therapeutic choice. PATIENTS AND METHODS: Fifty SMZL patients were treated with Cladribine ± anti-CD20 monoclonal antibody. RESULTS: Forty-seven of 50 patients were evaluable for response. ORR was 87%: 24 of 47 patients (51%) achieved a complete hematological response (CR), 17 of 47 (36%) a partial response (PR) and 6 (13%) resulted unresponsive. Interestingly, 15 of 24 cases (62%) in CR achieved also a molecular remission. After a median follow-up of 48 months, 7 of 41 responsive cases relapsed and the 5-year PFS was 80%. CONCLUSIONS: These data confirm the efficacy of this schedule emphasizing the impact of minimal residual disease even in the outcome of SMZL patients.

Significant efficacy of 2-CdA with or without rituximab in the treatment of splenic marginal zone lymphoma (SMZL).

BACKGROUND: Splenic marginal zone lymphoma (SMZL) with or without villous lymphocytes is an indolent lymphoma that typically affects elderly patients. Treatment is required in symptomatic cases. Splenectomy remains one of the first-line options in patients fit for surgery. The best therapeutic strategy has not yet been identified. Among different possible chemotherapeutic approaches, purine analogues, alone or in association with rituximab, seem to be a valid therapeutic choice. PATIENTS AND METHODS: Fifty SMZL patients were treated with cladribine with or without anti-CD20 mAb. RESULTS: Forty-six of 50 patients were assessable for response. Overall response rate was 87%: 24 of 46 patients (52%) achieved a complete hematological response (CR), 16 of 46 (35%) a partial response and 6 (13%) were unresponsive. Interestingly, 15 of 24 cases (62%) in CR also achieved a molecular remission. CONCLUSIONS: The present results indicate that this schedule is a valid therapeutic approach in SMZL. Addition of rituximab significantly improved quality of response and consequently the outcome of the disease.

Role of low-dose 2-CdA in refractory or resistant lymphoplasmocytic lymphoma.

Cladribrine (2-CdA), a purine analogue active on both dividing and resting lymphocytes, plays an important role in the treatment of indolent lymphoproliferative malignancies such as Hairy Cell Leukemia (HCL), Chronic Lymphocytic Leukemia (CLL), Lymphoplasmocytic Lymphoma (LPL), Waldenström's Macroglobulinemia (WM). With the aim of evaluating the efficacy and toxicity of low dose 2-CdA, 15 lymphoplasmocytic lymphoma patients, not eligible for more aggressive or standard therapies, because of age or poor performance status, were treated with the drug at a dose of 5 mg/m2, once a week for six total courses. All patients showed disease progression. Fourteen patients were valuable for response. In eleven out of these 14 (85.7%) disease progression stopped, with 21% having good hematological responses (one CR and two PR). The treatment was generally well tolerated, without serious infectious events. This schedule may be appropriate for the management of patients where the aim of the treatment is control of disease progression.

Low dose 2-CdA schedule activity in splenic marginal zone lymphomas.

Splenic Marginal Zone Lymphoma (SMZL) is a rare clinicopathological entity among marginal zone lymphomas. SMZL is an indolent lymphoma usually treated by splenectomy. A subset of patients is characterized by a more aggressive clinical course and poor prognosis. Treatment of these cases and second-line therapy for relapsed patients have not been yet identified. We report 10 cases treated with cladribrine (5 mg/m(2)/week) for six courses. Six patients (60%) achieved partial response, two patients (20%) achieved a complete response and the two remaining patients did not respond and died as a result of progression of the disease. The treatment was well tolerated. A total of 60% of the patients had an overall survival rate of 48 months and 24 months progression-free-survival was achieved by 37% with a median time of progression-free-survival of 17 months. Interestingly, in addition to a relevant percentage of hematological remission, some patients also experienced a molecular remission. We conclude that this treatment is safe and well tolerated and is able to induce a substantial number of responses. Our results suggest that this schedule is well tolerated and could be an useful alternative to splenectomy.

[Blood coagulation monitoring during liver transplantation: Sonoclot analysis and laboratory tests]. / Monitorizzazione della coagulazione in corso di trapianto di fegato: validazione dell'analisi tromboelastografica "Sonoclot" attraverso le indagini di laboratorio.

BACKGROUND: Aim of this paper is to validate blood coagulation data obtained using the Sonoclot thromboelastographic analyser (Sienco Inc., Morrison, USA) by means of standard laboratory tests during orthotopic liver transplantation (OLT). DESIGN: comparative study between laboratory data and Sonoclot analysis on simultaneously collected blood samples. SETTING: National Health System Liver Transplantation Center. PATIENTS: fifty-one patients, both males and females, affected by terminal hepatic disease submitted to OLT were enrolled in the study. DATA COLLECTION: simultaneous blood samples were collected during the pre-anhepatic, anhepatic and post-reperfusion phases of OLT; coagulation status was assessed by means of either standard Laboratory tests (INR, aPTT, Fibrinogen, PLT, D-Dimer) and Sonoclot analyser data (SonACT, Rate, Time to Peak, Downward Deflection); a statistical analysis was performed (Pearson s chi(2) test). RESULTS: A statistically significative correlation between the analysed data was found. The Sonoclot analyser was useful in identifying platelets dysfunction and was more sensitive to detect fibrinolysis. CONCLUSIONS: The Sonoclot thromboelastographic analyser is a reliable device for monitoring coagulation during OLT.

[The behaviour of plasma triglycerides and cholesterol in HIV positive haemophiliacs] / Il comportamento dei trigliceridi e del colesterolo plasmatici in emofilici HIV positivi.

Hypertriglyceridemia has frequently been found both in subjects with AIDS and in asymptomatic HIV-positive ones. In order to evaluate the importance of hyperlipemia as an index of the clinical evolution of HIV infection, the levels of triglycerides, total cholesterol and CD4 lymphocytes were determined over a period of 2 years in 8 haemophiliacs with AIDS, 13 asymptomatic HIV-positive and 45 HIV-negative haemophiliacs attending the Operative Unit of Coagulation Disorders of the University of Pisa. The mean concentration of triglycerides and incidence of hypertriglyceridemia were significantly higher in haemophiliacs with AIDS, compared with HIV-negative subjects (p<0.0001), while the triglycerides values of asymptomatic HIV-positives fell between those of the other groups. Cholesterol levels were lower in HIV-positive haemophiliacs and in those with AIDS compared with HIV-negatives. No correlation was found between triglyceride levels and those of CD4 lymphocytes.

Serological reactivity and viral genotypes in hepatitis C virus infection.

Patients infected with hepatitis C virus (HCV) were examined with four commercial HCV immunoblotting assays and for anti-GOR antibody to ascertain whether serological findings varied with the genotype of the infecting virus. The results indicate that patients infected with different HCV genotypes tend to show different immunoblotting profiles, mainly due to a low prevalence of antibodies to the viral region NS4 in patients infected with genotypes III and IV. Differences were more evident with second- than with third-generation assays. Patients infected with genotype IV exhibited a lower prevalence of anti-GOR antibody than patients infected with other genotypes.

Long-term follow-up of liver function in Italian haemophilic patients.

A 14-year follow-up of 153 haemophilic patients treated with clotted factor concentrates was made to assess liver function. Investigations included measurement of alanine amino transferase (ALT), immunoglobulins, HIV antibody, HBsAg, antibody to HBs and HBc antigens, antibodies to HCV (assayed by ELISA-2 and by RIBA-2) and HCV viraemia assessed by PCR. Assessment of liver function also included liver ultrasound scan and oesophageal X-ray. A positive correlation was found between abnormal liver function and age, HIV infection, HBV infection, HCV infection and hepatomegaly. However, there was no correlation between abnormal liver function and annual clotting factor concentrate use. The increasing incidence of liver insufficiency with increasing age is likely to result in substantial morbidity and mortality amongst haemophilic patients.

Hepatitis C virus serological and polymerase chain reactions in human immunodeficiency virus-positive and -negative patients.

BACKGROUND: Polytransfused patients may be dually infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). OBJECTIVES: To assess the correlation of antibodies to HCV with viral RNA in serum as determined by polymerase chain reaction (PCR) in anti HIV-positive and -negative haemophiliacs. STUDY DESIGN: Serum from 150 Patients with or without HIV infection were examined for anti-HCV by second generation enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblotting assay (RIBA). A sample was also tested in a nested-reverse transcription PCR for a conserved sequence of the 5' untranslated region of HCV. PCR-positive specimens were titrated and a type-specific PCR using viral core gene sequences was used to determine distribution of HCV viral types. RESULTS: Eighty-seven percent of the patients were positive in ELISA. All the positives but 2 were either positive of indeterminate in RIBA. The frequency of indeterminate RIBA results was 33% among HIV-positive subjects and less than 1% among HIV-negative ones. PCR was positive in 68% of 73 RIBA-positive or -indeterminate individuals and negative in all HCV-seronegative individuals examined. No significant differences were observed in HCV viral type, prevalence or titers of viraemia between HIV-positive or -negative patients. CONCLUSIONS: The majority (68%) of anti-HCV-positive haemophiliacs examined in this study had HCV RNA in their sera and anti-HCV profile determined by RIBA had no apparent influence on viraemia. The presence of HIV infection in these patients had no significant impact on HCV RNA prevalence, titer or HCV type distribution.

Prevalence of hepatitis C virus genotypes in Italy.

Hepatitis C viruses (HCV) present in 110 Italian patients were characterized by genotype-specific PCRs. Among the 65 cases of community-acquired hepatitis, HCV genotype II was dominant (60%), followed by genotypes IV (15%), III (11%), and I (3%). Among the 45 hemophilia-associated cases, the distribution of the four HCV genotypes was markedly different: genotype I was the most prevalent (61%), followed by genotypes II (25%), III (4%), and IV (2%). Double infections were observed in eight patients. Two HCV remained unclassified. For the 45 community-acquired cases from which a liver biopsy was available, genotype II was associated with more severe liver damage than the other types.

Hepatitis C virus seroprevalence in Italian haemophiliacs injected with virus-inactivated concentrates: five year follow-up and correlation with antibodies to other viruses.

The overall prevalence of anti-HCV antibody in a group of 125 haemophiliacs was 62%. Four patients who had never received replacement therapy were anti-HCV negative. Of the 121 patients injected regularly with commercial concentrates, 76 were already anti-HCV seropositive in 1985 and remained so throughout the follow-up. Two patients seroconverted in 1987 without obvious signs or symptoms of hepatitis. Our patients were treated with dry heat-treated concentrates since 1985 and with wet heat- or solvent/detergent-treated concentrates since 1988. The absence of further seroconversions and of symptoms of acute post-transfusion non-A, non-B hepatitis since 1988 suggest that present virucidal treatments of concentrates are effective in preventing HCV transmission. Anti-HCV positivity appeared to be unrelated to the type and degree of haemophilia as well as to the presence of antibodies to hepatitis B virus, human immunodeficiency virus type 1, and human herpesvirus type 6.

Pirenzepine versus ranitidine in gastroprotection during antiblastic chemotherapy: a double-blind study.

Corticosteroids and cytostatic drugs possess a documented lesive action on upper digestive mucosa, making epigastric pain and/or pyrosis common complaints among patients on antitumor treatment. The selective antimuscarinic pirenzepine and the H2-receptor antagonist ranitidine were tested against the ulcerogenic action of antiblastic chemotherapy. Thirty-eight patients affected with malignant lymphoproliferative disorders were endoscopically examined and the endoscopic pictures were quantified by using an arbitrary score. According to a double-blind randomized sequence, 19 out of the 38 patients received pirenzepine 100 mg/die/p.o. and the other 19 received ranitidine 300 mg/die/p.o. along with antitumoral therapy for periods of 3-6 months. Seven patients died of hematologic complications before ending the treatment. In the 31 surviving patients (13 pirenzepine- and 18 ranitidine-treated) a second endoscopic examination was performed at the end of the treatment and the lesion score repeated. No significant difference was found between initial and final scores in both groups. The antisecretive action of the two drugs may account for their effectiveness, but other mechanisms such as cytoprotection cannot be ruled out.

Severe pancytopenia due to copper deficiency. Case report.

A patient with copper deficiency and renal failure was suffering from pancytopenia. Marrow examination showed cytoplasmic and nuclear vacuolizations of the erythroid and myeloid series. These abnormalities disappeared after oral copper therapy. Possible mechanisms causing the pancytopenia are discussed. Copper supplementation is needed for patients receiving dietary changes.

Use of antisecretory drugs for gastroprotection during antiblastic chemotherapy.

Both prednisone and cytostatic drugs have an ulcerogenic effect on digestive mucosa. The protective action of the antisecretory drugs pirenzepine and ranitidine are compared against gastroduodenal lesions induced by antiblastic therapy. Twenty patients affected with lymphoproliferative disorders were endoscopically examined: none of them suffered from gastric or duodenal peptic ulcers or erosions. Ten out of the 20 patients received pirenzepine 100 mg/die/p.o. and the other 10 received ranitidine 300 mg/die/p.o. The study was performed according to a double-blind, randomized sequence. The antisecretory medication was administered together with antitumoral therapy for periods of 3-6 months. Four patients died of haematological complications before the course of treatment was completed. A further endoscopic examination was performed at the end of treatment: no patient showed evidence of gastric or duodenal peptic ulcers or erosions. Among the pirenzepine-treated cases, 1 out of the 7 evaluable patients showed a histological worsening of a pre-existing gastritis, while a slight duodenitis was observed in 1 out of the 9 ranitidine-treated patients. The comparable effectiveness of the two drugs is probably related to their antisecretory action, but cytoprotective mechanisms cannot be excluded.