Outcome of Allogeneic Hematopoietic Cell Transplantation (HCT) for Patients with Severe Aplastic Anemia (SAA) above the Age of 40 Years.

Abstract

Allogeneic HCT for SAA is definitive curative therapy for this otherwise fatal hematologic disease. For younger SAA patients, long-term survival of approximately 90% can be expected after HCT from HLA-identical siblings with cyclophosphamide/ antithymocyte globulin (CY/ATG) conditioning and post-grafting methotrexate/cyclosporine (MTX/CSP) immunosuppression. Most transplant center guidelines and many published reports restrict allogeneic HCT to SAA patients under the age of 40 years, due to concern of increased morbidity and mortality from HCT in older patients. We reviewed the clinical records of all 20 patients with a diagnosis of SAA who were treated with HCT from an HLA-identical sibling at the Fred Hutchinson Cancer Research Center from July 1988 to January 2006 and were above the age of 40 years at the time of HCT. The conditioning regimen consisted of CY/ATG for all but 2 patients who did not receive ATG. MTX and CSP were used as post grafting immunosuppression. The median age of the 10 men and 10 women was 47 (40–63) years. The median time from diagnosis to HCT was 2.7 (0.8–48.5) months. Ten patients had previously received immunosuppressive treatment and all 20 patients had received multiple red blood cell and platelet transfusions before HCT. The median follow-up of surviving patients was 86 (range, 17–194) months after HCT. One patient had graft rejection on day 28 and is alive and well following reconditioning and repeat marrow grafting from original donor. The incidence of acute grades II and III graft-versus-host-disease (GVHD) was 41% and 6%, respectively, the incidence of chronic GVHD (cGVHD) was 37% (6 patients). Overall survival was 70% (fig. 1). Three patients died before engraftment: from preexisting disseminated aspergillosis (n=1), congestive heart failure likely related to CY toxicity (n=1) and preexisting disseminated candidiasis (n=1) on days 2, 3 and 6, respectively. Three patients died from infections on days 83, 179 and 223; in the latter 2 cases, the infections were related to cGVHD and its treatment. The median time to discontinuation of immune suppression was 6 (range, 6–46) months (fig. 1). At last follow-up, 2 patients remain on immune suppression for treatment of cGVHD at 24 and 41 months, respectively. Three patients experienced avascular joint necroses 3, 6 and 9 years after HCT; they had cGVHD (n=2) and/or received extensive steroid treatment before HCT (n=2). Two patients developed superficial basal cell carcinoma at 5.5 and 15 years after HCT. Our data suggest that allogeneic HCT from sibling donor can be successfully extended to SAA patients older than 40 years. Although the number of patients are limited, survival after HLA-identical sibling HCT appears superior to published results of immune suppression therapy for patients >40 years of age. Pre-HCT cardiac screening is indicated to minimize the risk of conditioning related toxicity. Improved treatment to effectively treat or prevent cGVHD and associated infections remain important issues. [Display omitted]