Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts

The outcome of children and adults with acute lymphoblastic leukemia is markedly different. Since there is limited information on the distribution of clinico-biological variables in different age cohorts, we analyzed 5202 patients with acute lymphoblastic leukemia enrolled in the Italian multicenter AIEOP and GIMEMA protocols and stratified them in nine age cohorts. The highest prevalence of acute lymphoblastic leukemia was observed in children, although a second peak was recorded from the 4^th decade onwards. Interestingly, the lowest incidence was found in females between 14–40 years. Immunophenotypic characterization showed a B-lineage in 85.8% of patients: a pro-B stage, associated with MLL/AF4 positivity, was more frequent in patients between 10–50 years. T-lineage leukemia (14.2%) was rare among small children and increased in patients aged 10–40 years. The prevalence of the BCR/ABL1 rearrangement increased progressively with age starting from the cohort of patients 10–14 years old and was present in 52.7% of cases in the 6th decade. Similarly, the MLL/AF4 rearrangement constantly increased up to the 5^th decade, while the ETV6/RUNX1 rearrangement disappeared from the age of 30 onwards. This study shows that acute lymphoblastic leukemia in adolescents and young adults is characterized by a male prevalence, higher percentage of T-lineage cases, an increase of poor prognostic molecular markers with aging compared to cases in children, and conclusively quantified the progressive increase of BCR/ABL⁺ cases with age, which are potentially manageable by targeted therapies.     

Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma

Purpose: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in patients with advanced low-grade lymphoma.Patients and methods: Twenty-five adults with pretreated advanced-stage low-grade NHL were treated with three-day courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and dexamethasone 20 mg/day, every four weeks for a maximum of six courses.Results: Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR. Seven were failures. The median follow-up was 21 months (5–26). Eight CR patients remain in CR after 5–21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Myelosuppression was the most prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir <500/µl) and thrombocytopenia (platelet count nadir <50,000/µl) occurred in only 10% and 16% of courses, respectively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy because of persistent granulocytopenia and/or thrombocytopenia: three after one course, three after 2–4 courses, and three after five courses. Thirteen infectious episodes in 11 patients complicated 11% of courses. Two of 10 patients monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pre-therapy median value of 425/µl to 141/µl post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild.Conclusions: The combination of fludarabine with cyclophosphamide and dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may broaden the range of therapeutic options in the salvage treatment of these patients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granulocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated.     

Pathogenesis and prevention of central pontine myelinolysis: A case report

Central pontine myelinolysis (CPM) is a demyelinating disease producing serious or even fatal illness. The cause of the disease has been primarily attributed to alcoholism. Recently hyponatremia and its rapid correction have been related to CPM. We describe an alcoholic patient who developed the disease. The case has given us the opportunity of reflecting on CPM pathogenesis and management.

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Sommario La mielinolisi centrale del ponte è una malattia demielinizzante che può anche essere fatale. La sua causa è stata, in principio, riconosciuta nell;alcolismo. Recentemente l’iponatremia e la sua rapida correzione sono state messe in rapporto alle mielinolisi. In questa nota viene descritto un paziente alcolista cronico affetto da una forma lieve di mielinolisi centrale del ponte. L’osservazione di questo caso ha suggerito interessanti considerazioni patogenetiche e terapeutiche più generali.

     

Traumatic aneurysms of the carotid artery. Case report

The Authors report a rare case of traumatic aneurysm of the internal carotid artery observed in a 19-year-old man after a car accident. The aneurysm was recognized by cerebral angiography performed immediately after trauma and clipped to avoid delayed rupture. The literature on traumatic aneurysms is reviewed.     

Evaluation at midterm of the clinico-instrumental efficacy and tolerance of picotamide in patients with obliterative arteriopathy of the lower limbs

After a 4-week wash-out period, picotamide was administered to 25 patients affected by chronic arteriopathy of the lower limbs (scale 2 according to Fontaine) at a dose of 900 mg/die for 90 days, and then at a dose of 600 mg/die for a further 90 days, in order to assess its efficacy according to the following parameters: duration of gait, residual pressure index (RPI) resting the ankles, hematochemicals, electrocardiogram. At the end of the study a statistically significant increase was observed in the duration of gait and RPI at the ankles and, of the hematochemical parameters, in an increase in fibrogenic degradation products. Adverse reactions were only observed in 3 patients and regressed spontaneously. In conclusion, picotamide was found to be efficacious in patients affected by chronic obliterating arteriopathy of the lower limbs with the possibility of reducing the dose after 3 months of therapy.