Manual Erythro-Exchange (MEEX) to Prevent Complications of Sickle Cell Disease in Patients Unresponsive to Hydroxyurea: A Long-Term Follow-up

Background: Hydroxyurea (HU) therapy reduces considerably mortality and morbility in sickle cell disease (SCD). In about 10–25% of adult patients HU is ineffective therefore other therapeutic options such as chronic red cell transfusions (CRT) or erythroexchange (EEX) are needed. From 1981 to 2007 in our Center 40 patients affected by homozygous sickle cell (S-S) and sickle-β⁰ thalassemia (S/β⁰) with a previous history of major events, pregnancy or prior to surgery were treated with periodic Manual Erithroexchange (MEEX). 1133 MEEX procedures were performed with only one case of immunization in a pregnant woman. Consequentely MEEX resulted to be safe and efficacious in preventing SCD manifestations as well as significantly inexpensive. Even if, since 1995 HU has been accepted as first line therapy, seven out of 40 patients, unresponsive to HU treatment, had been continuing on a program of periodic EEX. On the basis of our own experience, we decided to use manual EEX instead of automatic one. We retrospectively report the data referring to a long-term follow-up (11–26 yrs, medium 16,5 yrs) of these 7 patients.

Methods and Patients: MEEX always started with an infusion of a 500 ml Ringer lactate solution followed by a phlebotomy (400–600 ml depending on weight and HbS level); autologous plasma derived from drawn blood centrifugation was re-infused to the patient. Thereafter a second phlebotomy was performed as previously described. Finally, depending on Hb level, each patient received two or three packed, Rh matched, leuko-filtered and plasma-depleted red cells units. A single peripheral venous access was required. The gap between each MEEX ranged from 45 to 90 days in order to maintain HbS levels below 60%. The seven patients (3 males and 4 females) affected by S/beta° (6 pts) and S-S (1pts), at the beginning of the MEEX program were aged 8 to 26 years (mean 14yrs). They were enrolled because of acute chest syndrome (2 pts) and >3 painful crises/yr (5pts). Patients underwent a median of 109 (61–180) MEEX procedures.

Results: In the seven observed patients no adverse events related to the procedure (i.e. alloimmunization) was reported. During the follow-up neither typical acute complications of SCD, such as acute chest syndrome, splenic sequestration, stroke, bone necrosis, priapism, nor long term complications like renal failure, cerebrovascular or retinic damage, pseudoxanthoma like manifestations were observed. None of the typical iron overload consequences (hypogonadism, growth failure, hypotiroidism and diabetes) were noted. Concerning cardiac function, all subjects showed a left ventricular ejection fraction > 60% with no evidence of pulmonary hypertension, evaluated by echocardiography. LIC, assessed by SQUID or liver biopsy, was normal in all patients except one. This patient developed iron overload, requiring steady iron chelation therapy, due to CRT before entering the MEEX program at the age of 26 yrs. Cardiac T2* measured by MRI resulted >22mms in each patient. During the observation period 5 hospitalizations (4 acute cholecystitis and 1 Venous Occlusive Crisis) occurred. Only one patient needed chronic analgesic therapy to relieve head femur necrosis pain developed before starting periodic MEEXes. According to age all patients attended school or had a regular job.

Discussion: The long-term follow-up revealed the above described procedure to be safe and efficacious in preventing acute and chronic complications of SCD in patients unresponsive to HU therapy, allowing them to have a good quality of life. This approach is less invasive and significantly less expensive than both CTR-chelation and automated EEX. Furthermore since MEEX is feasible and easy to manage it should be considered a treatment option also in developing countries, according to ASH SDC Policy Statements.