A scoring system that categorises patients with severe aplastic anaemia (SAA) as either low, medium, or high risk of death after haematopoietic stem cell transplant (HSCT) could be of value in clinical practice.
This was the finding of a retrospective analysis by a team from Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking, China.
SAA represents a rare, life-threatening disease with an estimated prevalence of 1.5–7 cases per million inhabitants per year.1 Immunosuppressive therapy (IST) would normally be started for patients with SAA, especially in cases where there is no matched sibling donor; however, evidence suggests that up to a third of patients do not respond to IST and also that a third relapse after initial therapy. In contrast, haploidentical donor HSCT is a curative treatment approach for those with SAA especially in the absence of a suitable identical donor and in those who are refractory to IST.2
Nevertheless, there are mortality risks associated with HSCT and thus a pre-transplant risk assessment should be undertaken for all patients. Although several risk assessment tools are available, most have been derived from patients with haematological malignancies and none have been validated for patients with SAA. This led the Chinese team to develop a scoring system to enable the prediction of post-transplant mortality incorporating several different factors.3
The team turned to data held in a single centre and included all patients who had been diagnosed with SAA and who had subsequently undergone haplo-HSCT. They defined death without disease progression as ‘treatment-related mortality’ (TRM) and this served as the primary outcome measure. Prior to the transplant, co-morbidities were assessed using the haematopoietic cell transplantation specific co-morbidity index (HCT-CI) and the Eastern Cooperative Oncology group (ECOG) performance status score and for both tools, lower values are associated with a reduced risk. For the purposes of training and validating the predictive model, patients were randomly assigned to either subset, with the training set used to develop the scoring system and the validation cohort to test the model.
The analysis included 432 patients who were divided into training (288) and validation (144) cohorts. The median age of patients in the training cohort was 16 years (57.6% male) and slightly younger (median age 13 years) and median duration of follow-up was 1131 days. In addition, among those in the training cohort, for 42.7% of patients, the time from SAA diagnosis to HSCT was less than 12 months, with a similar proportion (45.1%) in the validation cohort. The two groups were also matched in terms ECOG and HCT-CI scores prior to their transplant.
In the overall population, the probability of TRM after three years was estimated to be 12% and the 3-year overall survival, was estimated to be 87%. In the predictive model, only three variables were found to be independent predictors of TRM; time for diagnosis to HSCT and both ECOG and HCT-CI scores. Combining these three variables, the authors categorised patients as being at a low, intermediate, and high risk of TRM. Using the model, they calculated the hazard ratio for TRM to be 3.43 for intermediate risk patients and 9.57 for those at high risk when using the low-risk group as the reference point.
The authors concluded that the use of these three parameters would be useful in predicting treatment-related mortality for patients with SAA after HSCT.
- Vaht K et al. Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000–2011. Haematologica 2017;102(10):1683–90.
- Xu LP et al. Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant. J Hematol Oncol 2017;10:25.
- Xu LP et al. Development and validation of a mortality predicting scoring system for severe aplastic anaemia patients receiving haploidentical allogeneic transplantation. Br J Haematol 2021: doi: 10.1111/bjh.17916.