Objective: To examine the feasibility, safety and efficacy of bone marrow transplantation in high-risk adult patients with chronic granulomatous disease (CGD) using a modified low-toxicity conditioning regimen. Patients and Methods: Three adult patients with chronic granulomatous disease (CGD) (18, 35 and 39 ys; n=2 with gp91-phox and n=1 female with p22-phox deficiency) are decribed. All patients were therapy-refractory to conventional treatment suffering from infectious and inflammatory complications: active colitis (n=1), former brain abscess (n=2), former lung aspergillosis (n=2), active lung aspergillosis (n=1), active liver abscess (n=1), diabetes type 2 with nephropathy (n=1). Bone marrow donors consisted of two matched sibling donors (18 and 40 ys) and one HLA-identical matched unrelated (12/12; 35 ys) donor. The conditioning regimen was a modified SLAVIN-protocol including 180 mg/qm Fludarabine (d -7 to -2), oral Busulfan (8mg/kg; d -3 to -2) and Antithymocyte-Globulin Fresenius (4 x 10 mg/kg; d -4 to -1). Bone marrow was used (2.27 to 3.0 x 106 CD34/kg recipient). For GVHD-prophylaxis, Cyclosporine A (CSA) and Mofetil-Mycophenolate (MMF) was given. MMF (1200 mg/qm) was administered until d +50 (tapering until d +120). Results: The course of BMT was surprisingly uneventful in all three patients. No acute GHVD was encountered. No infectious or inflammatory flare ups were observed. The hematological reconstitution with neutrophil (d +19 to +26) and platelet engraftment (d +21 to +22) was in time. Six, 12 and 23 months after BMT, all three patients are alive and well with full (100%) donor chimerism and stable hematopoiesis. NBT-tests are normalized (95-98%). All active inflammatory and infectious foci are cured. The patient with the longest follow up has signs of chronic oral GVHD responding to topical steroids. Conclusion: This modified low-toxicity regimen including MMF is a promising transplant modality for high-risk adult CGD-patients.
Full conference title:
30th Annual Meeting of the European Group for Blood and Marrow Transplantation
- EBMT 2004