Non Malignant Late Complications After Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT); Korean Experience

Allo-HSCT is the curative treatment for hematologic fatal diseases, and survival rates have been substantially improved since its introduction. With steadily growing number of long term survivors after transplantation, late physiologic side effects are also increasingly reported in these patients. However, the incidence and the risk factors for post transplant late complications were rarely reported so far.

Medical records of post transplant long term survivors from 3 institutes in Seoul, Korea were retrospectively reviewed. Long term survivors were defined as those who were still alive at least 2 year after allo-HSCT. Data from a total of 634 consecutive patients who received transplantation between July 1988 and Jan 2010 were collected and analyzed.

The median age was 37 (14–70), and there were more male patients (57.6%). Sibling donor was most common (64.5%), and PB rather than BM was frequently used as a source of stem cells (PB=51.5%; BM=48.6%). Majority of patients received transplantation from HLA full-matched donors (90.2%). AML was the most common reason for allo-HSCT (39.9%); SAA (16.9%), ALL (12.6%) and MDS (11.5%) came next. During transplantation, ATG was used in 33.3% of patients, and 10.3% received TBI. RIC transplantation comprised 35.6%. Acute GVHD and chronic GVHD occurred in 26.5% and 57.6% of patients. Among the endocrine dysfunction, hypothyroidism, gonadal failure, and adrenal insufficiency were observed with an incidence of 1.4%, 95.9% and 2.2%. In multivariate analysis, only TBI attained statistical significance for hypothyroidism (HR=7.1) and adrenal insufficiency (HR=9.7). BO/BOS was the most common pulmonary complication (7%) and then the BOOP (2%) and the interstitial pneumonitis (1%). Age≥40, PB source, myeloablative conditioning, no use of ATG and cGHVD (at any organ) were the risk factors for lung complications in univariate analysis; PB source and cGHVD were significant in multivariate analysis (PB, HR=2.3; cGHVD, HR=7.9). Osteoporosis and avascular necrosis (AVN) were observed in 4.1% and 3.9% of patients. Female sex, age≥40, and cGHVD were the significant risk factors for osteoporosis in multivariate analysis with a HR of 9.6, 4.9 and 7.2, respectively. No use of ATG had significance for AVN in univariate analysis but not in multivariate analysis. Among the long term survivors, 6.2% of patients experienced cataract; age≥40, PB source, no use of ATG and cGHVD were significant in univariate analysis, of which, only age≥40 was significant in multivariate analysis (HR=5.5). Nephropathy was observed in 7.4%, and male sex was the risk factor with a HR of 2.3. Cardiovascular diseases involving cardiomyopathy, CHF, arrhythmia and pericarditis were reported from 1.4% of patients, and unrelated donor was the risk factor in multivariate analysis (HR=12.1).

This retrospective data showing the incidence and risk factors for late physiologic side effects could serve as a basis for optimal approach in long term survivors after allogeneic HSCT.

Jang:Alexion Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees.