Favorable Results After GCSF-Primed Allogeneic BMT for Children with Severe Aplastic Anemia Using Busulfan, Cyclophosphamide and ATG as Conditioning Regimen and Cyclosporine-A and Micofenolate Mofetil as Graft-Versus-Host-Disease Prophylaxys: Rapid Engraftment, Low Incidence of Chronic Gvhd and Reduced Graft Rejection Rates.

Abstract 3489

Patients with SAA in Brazil, in general, receive multiple transfusions and prolonged immunosuppresion with steroids and/ or cyclosporine (CSA) prior to undergoing allo-SCT. Therefore the rate of early and late graft rejection and infectious complications are high.

GCSF-primed allo-BMT has shown to accelerate neutrophil recovery after allo-BMT from HLA-matched related donor (Ostronoff M. et al. Biol Blood Marrow Transplant 2006; 12:729-33). Conditioning regimen using busulfan (Bu) and cyclophosphamide (Cy) for SAA has been shown to decrease graft rejection after allo-BMT in patients who received multiple transfusions. To faster the neutrophil recovery and reduce the incidence of graft rejection, we used GCSF-primed allo-BMT from matched related donor to treat 22 polytransfused patients with SAA after conditioning with Bu and Cy. In addition, we incorporate ATG to our conditioning regimen to reduce both GVHD and graft rejection.

From May 2005, 22 patients with SAA, median age 14 years (range 3–21) mail all heavily transfused (<20 episod) RBC our platelets, underwent GCSF-primed BMT from HLA identical matched siblings. The protocol was approved by our institutional review board and informed consent was obtained from each patient and donor and their parents. Conditioning regimen consisted of Bu (4mg/kg/day on day -6) and Cy (50mg/kg/day, day -5 to day -2) and ATG (3.75mg/kg/day, day -3 to day -1). GVHD prophylaxis consisted of CSA and MMF. The donors received G-CSF 5mg/kg/d SQ for five days before bone marrow harvest (day -4 to day 0).

Median neutrophil and platelet engraftment occurred respectively on day +10 (range 8 to 13 days) and day +22 (range 14–34 days).

There were 3 episodes of serum sickness, manifested by fever, arthralgia, GI symptoms, rash and thrombocytopenia. They all responded to steroids. One patient developed pulmonary tuberculosis; wich was successfully treated with anti-mycobacterium. Three patients (14%) developed BK-virus associated hemorrhagic cystitis. They all improved with hyperhydration and Leflunomide. In one severe case, cidofovir was used. Positive antigenemia (>=2 cells) occurred in 9 patients (40%) and one patient developed CT scan findings suggestive of CMV pneumonia. All patients were successfully treated with gancyclovir.

Grade II-IV acute GVHD extensiv chronic occurred in 6 patients (27%) and grade III-IV occurred in 2 patients (9%). Extensive GVHD occurred in 1 patient (5%). Two patients died: 1 due to complications of acute GVHD and one from aspergillosis which was probably acquired prior to allo-BMT as the patient was leucopenic under immunosuppression with steroids for 4 years prior to transplant. The overall survival was 91%, with median follow up of 36 months (range 6 to 60 months).

The neutrophil engraftment was fast, the incidence of chronic GVHD and graft reject was low. The immunosuppression was significant, requiring constant surveillance for infectious process and treatment with antivirals. The overall survival and quality of life in this patient population was notable.