Chronic Granulomatous Disease with the McLeod Phenotype: a French National Retrospective Case Series.

BACKGROUND: X-linked chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the CYBB gene (located on Xp21.1). Patients with large deletions on chromosome Xp21.1 can present with the McLeod phenotype and also Duchenne muscular dystrophy or retinitis pigmentosa. The objective of the present study was to describe a series of French patients with CGD and the McLeod phenotype. METHODS: We retrospectively collected data from the medical records of 8 patients with CGD and the McLeod phenotype registered at the French National Reference Center for blood types. RESULTS: The median age at diagnosis of CGD was 1.2 years, the median age at diagnosis of the McLeod phenotype was 4.5 years, and the median length of follow-up was 15.2 years. Four patients displayed allo-immunization, with anti-KEL20 and anti-XK1 (formerly known as anti-KL) antibodies. Five of the 6 patients with available blood smears had acanthocytosis. Neuropsychiatric, muscle-related, and ocular manifestations were present in 4, 2, and 1 of the patients, respectively. Three of the 4 patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT) are alive. Overall, 5 patients are alive, and 3 are alive and well. CONCLUSION: This is the largest yet descriptive study of a series of patients with X-linked CGD and the McLeod phenotype. Although this disease combination is rare, the timely, accurate diagnosis of the McLeod phenotype is critical because of the serious post-transfusion complications. However, HSCT can be considered in these patients.

Delayed hemolytic transfusion reaction in children with sickle cell disease.

BACKGROUND: Transfusion is a cornerstone of the management of sickle cell disease but carries a high risk of hemolytic transfusion reaction, probably because of differences in erythrocyte antigens between blood donors of European descent and patients of African descent. Patients may experience hemolytic transfusion reactions that are delayed by from a few days to two weeks and manifest as acute hemolysis (hemoglobinuria, jaundice, and pallor), symptoms suggesting severe vaso-occlusive crisis (pain, fever, and acute chest syndrome), and profound anemia, often with reticulocytopenia. This case-series study aims to describe the main characteristics of this syndrome, to discuss its pathophysiology, and to propose a management strategy. DESIGN AND METHODS: We identified 8 pediatric cases of delayed hemolytic transfusion reactions between 2006 and 2009 in the database of the Necker Hospital, France. All patients had received cross-matched red cell units compatible in the ABO, RH, and KEL systems. We reviewed the medical charts in the computerized blood transfusion databases. All patients were admitted to the intensive care unit. We progressively adopted the following strategy: intravenous immunoglobulins, and darbopoietin alpha when the reticulocyte count was below 150×10(9)/L, without further blood transfusion during the acute episode unless absolutely necessary. RESULTS: The median time between the transfusion and the diagnosis of delayed hemolytic transfusion reaction was six days. All patients had severe bone pain; all but one had a high-grade fever. Five patients had hemoglobin levels less than than 4 g/dL and 3 had reticulocytopenia. In 5 patients, no new antibody was found; one patient had weakly reactive antibodies. Only 2 patients had new allo-antibodies possibly responsible for the delayed hemolytic reaction. CONCLUSIONS: The initial symptoms of delayed hemolytic transfusion reaction were complex and mimicked other complications of sickle cell disease. In most of our cases, no new antibody was identified, which underlines the complexity of the pathophysiology of this syndrome.

Feasibility and efficacy of chronic transfusion for stroke prevention in children with sickle cell disease.

OBJECTIVES: In children with sickle cell disease (SCD), chronic transfusion to maintain haemoglobin S (HbS) below 30% markedly decreases both the risk of a first stroke when transcranial Doppler (TCD) ultrasonography shows abnormal cerebral blood flow velocities and the risk of recurrent stroke. Maintaining HbS below 30% may be difficult, especially in countries where blood donors and recipients belong to different ethnic groups and where the availability of closely matched blood products is limited. We assessed the feasibility and efficacy of chronic transfusion with an HbS target of 30% in children with SCD living in the Paris area. METHODS: We retrospectively studied 29 children aged 6.8 +/- 3.0 yr (3-15 yr) at inclusion who received chronic transfusion either because of abnormal TCD findings (primary prevention group, PPG, n = 17) or because of a previous cerebrovascular event (secondary prevention group, SPG, n = 12 including nine with a history of stroke and three of transient ischaemic attacks). RESULTS: Mean follow-up was 3.5 +/- 3.0 yr (0.5-12 yr). No cases of stroke occurred in the PPG. In the SPG, one patient with a history of stroke and severe cerebrovascular disease had a recurrence after 11 yr of chronic transfusion, when the HbS level was 20%. The stroke recurrence rate (SPG group) was 1.6/100 patient-years. Mean HbS levels before and after transfusion were 30 +/- 10% and 20.6 +/- 7%, respectively. Two patients acquired red-cell alloantibodies. Of the 29 patients, 22 required iron chelation. CONCLUSIONS: Regular transfusion maintaining HbS below 30% is feasible and safe in children with SCD in France and protects from overt stroke.