Haematopoietic stem cell transplantation for severe sickle cell disease in childhood: a single centre experience of 50 patients.

Despite improvements in medical management, sickle cell disease (SCD) remains associated with severe morbidity and decreased survival. Allogeneic haematopoietic stem cell transplantation (HSCT) remains the only curative approach. We report the outcome of 50 consecutive children with severe SCD that received HSCT in our unit between November 1988 and April 2013. The stem cell source was bone marrow (n = 39), cord blood (n = 3), bone marrow and cord blood (n = 7) and peripheral blood stem cells (n = 1). All patients had ≥1 severe manifestation: 37 presented with recurrent vaso-occlusive crises/acute chest syndrome, 27 cerebral vasculopathy and 1 nephropathy. The conditioning regimen consisted of busulfan + cyclophosphamide (BuCy) before November 1991 and BuCy + rabbit antithymocyte globulin after that date. Since 1995, all patients have been treated with hydroxycarbamide (HC) prior to transplantation for a median duration of 2·7 years. Median age at transplantation and median follow-up was 8·3 and 7·7 years, respectively. Acute graft-versus-host disease (GVHD) and chronic GVHD were observed in 11 and 10 patients, respectively. An excellent outcome was achieved, with 8-year overall survival and event-free survival (EFS) rates of 94·1% and 85·6%, respectively. Since HC introduction, no graft failure occurred and EFS reached 97·4%. Prior treatment with HC may have contributed to successful engraftment.

Thrombin generation in children with sickle cell disease: relationship with age, hemolysis, transcranial Doppler velocity, and hydroxyurea treatment.

INTRODUCTION: Increased thrombin generation (TG) was described in sickle cell disease (SCD) children. The aim of this study was to characterize TG at the individual level and assess its relationship with age, hemolysis, transcranial Doppler velocity (TCD), and hydroxyurea treatment. PATIENTS AND METHODS: TG was triggered in the platelet-poor plasma using tissue factor and phospholipids with addition of thrombomodulin in 97 SCD at steady state and 80 control children. Patients and controls were aged from 2 to 20 years, and they were distributed in four categories of age: [2-5], [6-10], [11-15], and [16-20] years. For each subject, ratio of endogenous thrombin potential (rETP) and peak height (rPeak) was calculated as subject's value divided by the mean value of controls of the same age range. rETP and rPeak of patients were considered abnormal when > mean + 2SD of controls. LDH, total hemoglobin, and reticulocyte count were measured as markers of hemolysis. Data on hydroxyurea treatment and TCD were collected from medical records. RESULTS: Overall, 38.1% and 44.3% of patients showed elevated rETP and rPeak, respectively. rETP and rPeak decreased significantly with increasing age. In homozygous (SS) patients, TCD velocities and all markers of hemolysis correlated significantly with both rETp and rPeak. Negative correlations were observed between these ratios and the duration of hydroxyurea treatment. CONCLUSION: Elevated TG in SCD children is mainly related to younger age and to the intensity of hemolysis. There probably a link between TG and cerebral vasculopathy in these patients. Hydroxyurea may have a beneficial effect, which could be related to the duration of treatment.