No abstract

Summary 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.

The aim of this study is to describe the growth, pubertal development, and gonadal function of a cohort of 30 sickle cell disease children who underwent bone marrow transplantation. They all received the standard pretransplant conditioning regimen of busulfan (14 or 16 mg/kg) and cyclophosphamide (200 mg/kg). Growth was normal both before and after transplant. Seven out of 10 girls had severe ovarian failure and requirement for estrogen replacement. Three out of 10 girls recovered some ovarian function posttransplant, with spontaneous pubertal development, menses, and 1 successful normal pregnancy. Follicle-stimulating hormone (FSH) serum levels were very high during spontaneous puberty and slowly normalized thereafter in these 3 patients. The 3 girls with ovarian function recovery differed from the 7 others by the lower busulphan dose of the conditioning regimen they received (14 rather than 16 mg/kg). All boys showed spontaneous pubertal development. However, most of them had small testis and elevated serum FSH levels, reflecting germinal epithelium damage. Testosterone level was low normal and luteinizing hormone elevated, reflecting Leydig cell insufficiency. In conclusion, 7/10 girls had complete gonadal failure and most of the boys had spontaneous puberty but germinal epithelial failure. Serum FSH levels showed important variations over time in the same patient.

In addition to mostly asymptomatic classical MTX neurotoxicity, MTX may induce severe but reversible unusual leukoencephalopathy. It is important to recognize this clinicoradiological presentation in the differential diagnosis of acute neurological deterioration in children treated with MTX.