BONE-MARROW TRANSPLANTATION (BMT) IN 14 CHILDREN WITH SEVERE SICKLE-CELL DISEASE (SCD) - THE FRENCH EXPERIENCE

Fourteen S/S children with severe SCD were transplanted with marrow fr om HLA identical siblings. All developed frequent (>4/y) vasoocclusive crises (VOC) and recurrent acute chest syndrome episodes (n:10), oste itis (n:3), osteonscrosis (n:3) , strokes (n:3) or frequent massive de globulisation (n: 2). Two children undergone splenectomy, 2 were chela ted and 2 had erythroid allo-immunization. Ethnic origins were from va rious countries in Africa (n:10) , North-Africa (n:3) or West Indies ( n: 1). At BMT, they were 2y 3m to 14y gm old (mean:8y 7m). Donors were AS (n:11) or AA (n:3). At first, various conditioning regimens were u sed consisting of busulfan (BU) plus Cyclophosphamide (CY) at differen t doses: CY:200 mg/kg (n:12) or 260 mg/kg (n:2); BU:14 mg/kg (n:1), 16 mg/kg (n:9), >16 mg/kg (n:4); 1 patient received also TLI and one oth er antithymoglobulin (ATG) : 20 mg/kg. GVHD prophylaxis was CSA alone (n: 4) or CSA plus short-term MTX (n:10). Median follow-up was 23 mont hs (8 m. to 48 m.). All patients had an engraftment (d13 to d32) with a stable total chimerism in 10/14 patients who are cured. In the 4 oth ers, partial chimerism was observed: one patient had a early and progr essive rejection of his graft but is doing very well (28 m. follow-up) without any manifestation of SCD, with a high stable 22% Hb F level. One patient developed an aplastic anaemia 15 m after BMT: a second BMT was achieved 21 m after the first one with engraftment and total chim erism. Two patients have a relatively stable partial chimerism with st ill undergoing CSA therapy (11 m. and 23 m. follow-up). Five acute (3 grade 1, 2 grade 3) and 3 chronic GVHD were observed. Other complicati ons were 2 hemorrogic cystitis, 1 auto-immunehemolysis, 3 pneumonia,1 fulminant pneumococcal sepsis (17 m. post-BMT) with distal necrosis as sequella and seizures in 3 patients with hypertension while receiving CSA and steroids for GVHD. In conclusion, no case of mortality was ob served and none had SCD manifestations since BMT. But the occurrence o f early rejection (n:1) and partial chimerism (n:3) led us to modify t he conditioning regimen in adjusting BU dose to body area and adding A TG: since 01/92, a national SCD-BMT program is undergoing with BU:500 mg/m2+CY: 200 mg/kg+ATG 20 mg/kg. In our opinion, indications still re main difficult to define now in this disease even if beta and alpha-ge nes studies will be useful to appreciate the morbidity risk. BMT shoul d be considered in very symptomatic children with SCD (frequent VOC, s trokes or cerebral stenosis detected by transcranial doppler or MRI, a cute chest syndromes..) and performed relatively early, before vasculo pathy causes irreversible organ damage. Comparative evaluation of long -term effects of the different SCD therapies. hypertransfusion, hydrox yurea, BMT will have to be achieved by strict follow-up.