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SummaryTwenty-five elderly patients with untreated indolent non-Hodgkin lymphoma were treated with oral fludarabine 25 mg/m 2 /d (40 mg total dose) and cyclophosphamide 150 mg/m 2 /d, both for four consecutive days, repeated every 28 d for four cycles. In all, 21 (84%) patients were responsive: 10 patients achieved complete remission while partial response was obtained in 11. During an observation period of 37 months, there was an overall survival rate of 70% and a median event-free survival of 20 months. Haematological and extra-haematological toxicity were mild. This reduceddose Flu-based oral regimen showed good efficacy and was simple to administer on an outpatient basis.

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Between 1981 and 2010, we have treated 40 patients requiring chronic transfusion with periodic manual erythrocyte exchange and autologous plasma rescue (MEEX). Here, we present retrospective, long-term (median 22, range 14-29 years) follow-up data for a subset of seven patients with sickle cell syndromes who did not respond to hydroxyurea (HU). Patient characteristics are listed in Supporting Information, Tables I and II. MEEX was accomplished by using a single venous access and infusing 500 ml of isotonic solution (for adults) and removing 500 ml blood (range 400-600 ml according to the patient's weight and the physician's discretion). The rescue process involves centrifugation of the collected blood product and reinfusion of autologous plasma. This is followed by another 500 ml phlebotomy and the infusion of 2-3 units of packed Rh-matched, leuko-filtered, plasma-depleted red cells, with the aim of lowering HbS levels to around 40%. For pediatric patients, the bleeding volume is smaller (5-10 cc/Kg) and the volumes of infused saline and packed Rhmatched, leuko-filtered, plasma-depleted red cells are equal to the phlebotomy volumes, without plasma rescue.The interval between each MEEX procedure for these seven patients ranged from 45 to 90 days to maintain at all times HbS concentrations below 60-70% and the median number of procedures was 133 (range 85-204). None of the seven patients experienced acute complications of sickle cell disease (SCD), such as acute chest syndrome, splenic sequestration, stroke, bone necrosis, or priapism, or long-term complications such as renal failure, cerebrovascular or retinal damage, or pseudoxanthoma-like manifestations. None of the seven patients experienced alloimmunization and all but one patient had normal liver iron concentrations [assessed by superconducting quantum interference device, magnetic iron detector, magnetic resonance imaging (MRI), or biopsy]. This patient, who started the program at the age of 26 years with iron overload due to previous transfusions, required regular iron chelation therapy. Cardiac function tests indicated that all subjects had a left ventricular ejection fraction of >60% and cardiac T 2 * > 20 mms (measured by MRI). There was no evidence of pulmonary arterial hypertension on echocardiography. During the observation period, five patients required hospitalization (four with acute cholecystitis and one due to venous occlusive crisis). Only one patient requires chronic analgesia (to relieve pain caused by pre-existing femur head necrosis).Automated EEX (AEEX) ensures lower postprocedural HbS levels (30% HbS vs. 40% with our MEEX protocol) because it makes use of two distal ports to increase the volume of red cells removed. However, the larger number of transfused units in AEEX exposes the patient to a higher transfusional risk. In addition, the automated procedure is significantly more expensive than the manual one, as indicated in Table I.Previous studies have indicated that EEX is a safe and efficacious alternative to both HU and simple transf...

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