Clinical evaluation of busulfan, cladribine and alemtuzumab as reduced intensity conditioning for stem cell transplantation.

BACKGROUND: Reduced intensity conditioning before allogeneic stem cell transplantation is an option for patients not eligible for myeloablative standard procedure. In recent years alemtuzumab, an anti CD52 antibody has gained much interest in this setting for its particular immunosuppresive properties.
MATERIAL/METHODS: We evaluated clinical results of allogeneic stem cell transplantation in nine patients (2 females and 7 males, median age 51, range 26-65) after reduced intensity conditioning consisting of busulfan, cladribine and alemtuzumab. The donors were HLA identical siblings (7) or unrelated (2). Peripheral blood stem cells mobilized with G-CSF were used. Cyclosporine alone was used for GvHD prevention after transplantation. RESULTS: 4 patients (44%) are alive at 24-42 months after transplantation and 3 patients (33%) remain in complete remission at 26-42 months, including one after donor lymphocyte infusion for decreasing hematopoietic chimerism. No acute graft versus host disease was observed and only 3 patients (33%) developed chronic graft versus host disease. High rate (56%) of CMV reactivation and 2 cases of tuberculosis were noted. All deceased patents died due to disease relapse and progression.
CONCLUSIONS: Reduced intensity conditioning with alemtuzumab and allogeneic stem cell transplantation offers potential cure to patients not eligible for conventional procedure. Better methodology of chimerism evaluation is mandatory to improve results of transplantations by implementation donor lymphocyte infusions.

Prevalence of the intron 22 inversion of the factor VIII gene and inhibitor development in Polish patients with severe hemophilia A.

INTRODUCTION: Patients with severe hemophilia A often develop inhibitors (antibodies) against transfused factor VIII. MATERIAL/METHODS: One hundred thirteen Polish patients with severe hemophilia A, who had been treated on demand with cryoprecipitate until 1992 and exclusively with factor VIII concentrates after 1995, were examined for intron 22 inversion by Southern blotting and the presence and magnitude of inhibitor activity in blood as determined by the Bethesda assay. The patients' ages ranged 4--67 years (mean: 33.7+/-12.4 years, median: 32 years). RESULTS: The number of patients with the inversion amounted to 57, while in 56 patients the mutation types were unknown; 47 patients had a distal and 10 patients a proximal type of inversion. Thirteen patients with inversions (22.8%) were found to have inhibitor in their blood. Most patients (14 out of 15) who developed inhibitors in the course of cryoprecipitate therapy were high responders. Conversely, 4 of 5 patients treated between 1992 and 1995 with both cryoprecipitate and intermediate-purity factor VIII concentrates were low responders. One multitransfused patient who had remained inhibitor-free on cryoprecipitate therapy developed inhibitor after receiving a large dose of factor VIII concentrate during surgery. None of these 5 patients developed inhibitors during their 12--40 years of treatment with cryoprecipitate, suggesting that it was less immunogenic than factor VIII concentrates. CONCLUSIONS: The prevalence of the intron 22 inversion mutation of the factor VIII gene in Polish hemophiliacs is similar to that in other European countries. Treatment regimens with either cryoprecipitate or virus-inactivated plasma-derived factor VIII concentrates may affect inhibitor formation in hemophilia A patients.