Manual erythroexchange for chronic transfusion therapy in patients with sickle cell syndromes unresponsive to hydroxyurea: A long-term follow-up Between 1981 and 2010, we have treated 40 patients requiring chronic transfu- sion 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 fol- lowed 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 Rh- matched, 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 manifes- tations. None of the seven patients experienced alloimmunization and all but one patient had normal liver iron concentrations [assessed by superconduct- ing quantum interference device, magnetic iron detector, magnetic reso- nance 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 sub- jects 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 fe- mur 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 num- ber 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 alterna- tive to both HU and simple transfusions for preventing complications of SCD and improving patients’ quality of life [1,2]. Our results with MEEX confirm previous findings including that if MEEX is started before significant iron overload occurs, the need for chelation therapy may be obviated [3]. Given the relative simplicity and the lower cost, MEEX should be considered for chronic transfusion therapy in developing countries [4]. ACKNOWLEDGMENTS The authors thank Jane Tricker and Dr. Silvia Caviglia for editorial assis- tance in the preparation of this article. PAOLA CARRARA 1 MANUELA BALOCCO 1 VALERIA PINTO 1 FRANCESCA OLCESE 1 ANNA SOLDA ` 2 PAOLO STRADA 3 GIAN LUCA FORNI 1 1 Ematologia, Centro della Microcitemia e delle Anemie Congenite, E.O. Galliera di Genova, Genoa, Italy; 2 S.C. Servizio Immunoematologia e Trasfusionale, E.O. Galliera di Genova, Genoa, Italy; 3 U.O.C. Centro Trasfusionale, Azienda Ospedaliera Universitaria ‘‘San Martino’’, Genoa, Italy Additional Supporting Information may be found in the online version of this article. Published online 30 September 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/ajh.21895 Conflict of interest: Nothing to report. References 1.Lee MT, Piomelli S, Granger S, et al. Stroke prevention trial in sickle cell ane- mia (STOP): Extended follow-up and final results. Blood 2006;108:847–852. 2.Khalique Z, Pavlu J, Lefroy D, Layton M. Erythrocytapheresis in the prevention of recurrent myocardial infarction in sickle cell disease. Am J Hematol 2010; 85:91. 3.Masera N, Tavecchia L, Pozzi L, et al. Periodic erythroexchange is an effective strategy for high risk paediatric patients with sickle-cell disease. Transfus Apher Sci 2007;37:241–247. 4.Kauf TL, Coates TD, Huazhi L, et al. The cost of health care for children and adults with sickle cell disease. Am J Hematol 2009;84:323–327. Constitutional trisomy 8 mosaicism in a healthy bone marrow donor: Confirmation of first reported donor origin trisomy 8 To the editor: Incidental identification of constitutional chromosomal aberra- tions in bone marrow donors is occasionally documented in the literature. Frey et al. in 2008 [1] published the report of a stem cell recipient who developed trisomy 8 (T8) post transplant and based on the recipient workup suggested a donor origin of T8. Here, we present the donor workup that cor- roborated their suspicion and confirmed, for the first time, donor origin of T8 in the stem cell recipient. We have also discussed the management dilemma such incidental diagnosis presented for the donor and other implications of this diagnosis. The donor, a 29-year-old female, was referred to our institute for evalua- tion of possible constitutional trisomy 8 mosaicism (CT8M) after the recipient (published by Frey et al. [1]) developed T8 with complete engraftment. The donor had normal predonation peripheral blood counts and donated for a same gender, matched unrelated recipient. TABLE I. Estimated Annual Treatment Costs a for Chronic Transfusion Therapy: Comparison of Simple Transfusion Versus Manual, or Automated Erythroexchange STT €/year MEEX €/year AEEX €/year RBC U/year 5976 € (24 U/year) 2988 € (24 U/year) 5976 € (24 U/year) Desferoxamine 2873 € Consumables 66.72 €/year 2500.48 €/year Total cost 8849 € 3054.72 € 8476.48 € Costs quantified according to prices applied by local health authorities and tax free. STT, simple transfusion therapy; MEEX, manual erythroexchange; AEEX, auto- mated erythroexchange. a Costs estimates for a 55-Kg patient based on: STT 5 2: filtered, washed, without buffy coat red blood cell units (250 ml Ht 80%)/ 4 week ? 249/ RBC U € 3 2 5 498 €. Desferoxamine f. 2g ? 11.05 € (40 mg/kg 3 5 days/week 5 11 g/week ? 5 f/ week 3 52 weeks/year). MEEX 5 2: filtered, washed, without buffy coat red blood cell units per procedure (498 €) 3 6 procedures/year. Consumables total 509.12 €/procedure, based on: saline solution 500 ml/proce- dure 5 0.9 €; needle/procedure 5 0.52 €; quadruple transfusion bag 5 6.4 €; sin- gle transfusion bag 5 3.3 €. EEX 5 6 filtered, washed, without buffy coat red blood cell units per procedure ? 249/ RBC U € 3 6 5 1494 €. Consumables total 2119.12 €/procedure, based on: kit for flow cell separator/pro- cedure (625 €) 3 4 procedures/year; calcium gluconate per procedure 5 0.12 €. Correspondence V V C 2010 Wiley-Liss, Inc. American Journal of Hematology 974 http://wileyonlinelibrary.com/cgi-bin/jhome/35105