Eric Sariban

Bone marrow transplantation for severe sickle cell anaemia

Summary. Five children with sickle cell anaemia underwent bone marrow tranplantation (BMT) for severe clinical disease. The conditioning regimen for BMT was in busulfan plus cyclophosphamide. The allograft contained more than 5.108 nucleated cells per kg recipient. Prophylaxis of GVHD consisted of methotrexate and cyclosporin A. Therapy was well tolerated. Duration of neutropenia (<0.5 × 109/1) was short (14–25 d). Platelet recovery (>50 × 109/1) occurred between day 12 and 45. The patients have been folowed up for 8–28 months. No major infections occurred and long‐term BMT‐related toxicity was limited to mild, chronic GVHD in one patient. Mean haemoglobin levels remained above 10 g/dl. Haemoglobin electrophoresis showed AS patterns in all grafted patients—all marrow donors having sickle cell trait. From our preliminary data, we conclude that BMT or sickle cell anaemia is curative, well tolerated and should be proposed for suitable patients.

Use of recombinant human granulocyte colony stimulating factor in reticular dysgenesis

was negative. Renal and hepatic function tests were within normal limits. No source of infection could be demonstrated on chest X-ray, and blood and urine cultures were negative. She was treated with transfusions of packed red cells and platelet concentrates, and broad-spectrum antibiotics. TWO days after admission, she had massive gastrointestinal haemorrhage as a result of which the haemoglobin decreased to 4 g/dl. Due to lack of availability of a histocompatible sibling for BMT, it was decided to try immunosuppression with total lymphoid irradiation (TLI) and intravenous methylprednisolone. The patient was given 800 cGy TLI in four fractions of 200 cGy each over 2 d followed by intravenous methylprednisolone at the following doses: 30 mg/kg/d x 3 d, 20 mg/kg/ d x 4 d, 10 mg/kg/d x 4 d, and 5 mg/kg/d x 4 d. On the fourth day of therapy the investigations showed: haemoglobin 7.3 g/dl. leucocytes 1.5 x 10y/l (50% granulocytes), platelets 90 x 10y/l, and reticulocytes 0.5%. At the end of 15 d of intravenous steroid administration the counts were: haemoglobin 8 g/dl. leucocytes 2 . 7 x 10y/l (granulocytes 70%), platelets 180 x 10y/l, and reticulocytes 1%. The patient received 4 weeks of oral prednisolone 1 mg/kg after cessation of the intravenous methylprednisolone. At the end of all therapy the counts were: haemoglobin 11.5 g/dl, leucocytes 4.5 x 10y/l (granulocytes 71%). platelets 2 3 0 x 109/1, and reticulocytes 1 * 5%. The patient is asymptomatic and haematologically normal 6 months after therapy. Long-term follow-up of patients of aplastic anaemia who achieved complete haematologic remission with immunosuppression has shown late development of myelodysplasia and acute myeloid leukaemia (De Planque et al. 1988). Because aplastic anaemia is a stem cell disorder, the basic anomaly can be rectified only with BMT. However, BMT is not a suitable option in a number of patients due to lack of availability of suitable donors. While the duration of the follow-up is still short, the preliminary result in this patient seems to be highly encouraging. We did not encounter any serious adverse reaction to the irradiation and the high-dose methylprednisolone. In our opinion, TLI and methylprednisolone should be considered a therapeutic option in patients with SAA who are not candidates for BMT or antithymocyte globulin, or those who have failed one course of therapy with antithymocyte globulin.