Early Transplantation-Related Mortality within 50 Days after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia and Myelodysplastic Syndrome

Background : Transplantation-related mortality (TRM) is a major obstacle to allogeneic hematopoietic stem cell transplantation (HSCT). Patient age, donor type, disease state, and regimen intensity are known to be associated factors of TRM. Within 50 days after transplantation, there is a high incidence of infection prior to engraftment and a high incidence of organ toxicity associated with the conditioning regimen. Patients without special complications will also be discharged within 50 days of transplantation. However, there is no study of early TRM within 50 days. Based on big data from National Health Insurance Service, we conducted a study to identify the incidence and risk factors associated with early TRM within 50 days in allogeneic HSCT.

Methods : Patients were enrolled from 2003 to 2015 with the diagnostic codes of acute leukemia or myelodysplastic syndrome (MDS) and the infusion codes of allogeneic HSCT in South Korea. Based on the medical charge and drug codes, we compared the clinical characteristics of early TRM and non-TRM group.

Results : The total number of patients was 5,487, the median age was 38 years and the male was 55.2%. Acute myeloid leukemia was 3,490 (63.6%), acute lymphoblastic leukemia was 1,905 (34.7%), and MDS was 92 (1.7%). The 5,268 (96%) patients were received myeloablative conditioning regimen and 219 (4%) patients received reduced intensity of conditioning. The number of transplants increased from 710 in 2003-2006, 1,321 in 2007-2009, 1,590 in 2010-2012, and 1,866 in 2013-2015. The 155 patients (2.8%) died within 50 days. The median age of non-TRM and early TRM group was 38 and 41 years, respectively (p=0.010). The proportion of women was higher in the early TRM group than non-TRM group (54.2% versus 44.6%, p=0.017). There was no difference in early TRM according to year, diagnosis, and regimen intensity. The duration from diagnosis to transplantation was significantly longer in the early TRM group (6.1 versus 5.1 months, p<0.001). The 335 patients (6.1%) had previously received at least one HSCT and early mortality was higher in these patients (9.3%, p<0.001). Also, the interval from the previous transplantation was significantly shorter in early TRM (11.1 versus 15.3 months, p=0.013). Early TRM was higher in patients who received more than 13 platelet transfusions (p=0.033) and 8 more red blood cell transfusions (p=0.003). The 803 patients (14.6%) had iron chelation prior to transplantation and their early TRM rate was as low as 0.2% (p<0.001). There was no increase in TRM in patients with more than 3 underlying diseases. Early TRM rates in peripheral blood, bone marrow, and cord blood HSCT were 3.0%, 1.7%, and 6.0%, respectively (p=0.001), cord blood transplant was significantly higher.

Conclusions : In this study, the incidence of early TRM within 50 days was 2.8%. Early TRM was associated with age, gender, previous transplantation, duration of diagnosis-transplantation, previous transfusion, iron chelation, and stem cell source.