Hematologic malignancy is the 10^th most common cancer in Hong Kong with more than 1,000 new cases diagnosed each year.¹ While most of the other cancers affect mainly old people, sufferers of hematologic malignancies can be at any age from newborns to the elderly.¹ Although there is a broad range of effective treatments, allogeneic hematopoietic stem-cell transplantation (HSCT) provides the strongest anti-leukemic consolidation effect in patients with acute leukemia and is the only potentially curative procedure for patients with myelodysplastic syndromes and myelofibrosis.^1,2 Owing to the advances in patient and donor selection, stem-cell sources, supportive care, prevention of complications and reduced-toxicity preparative regimens, the indications for HSCT and the pool of eligible patients have expanded significantly.³ Currently, an estimated 55,000-60,000 HSCTs were performed worldwide every year.³

Allogeneic HSCT is a potential chance of cure for selected patients with hematologic malignancies.⁴ However, transplant-associated morbidity and mortality remain substantial and the decision of whom, how and when to transplant is important.⁴ Prognosis for an individual patient after allogeneic HSCT is closely associated with several categories of determinants, including the distinct haemato-oncological entity, genetic risk profile and remission status before HSCT.² Therefore, it is necessary to stratify patients undergoing HSCT by disease risk.⁵

The Disease Risk Index (DRI) was established as a tool to assign patients into four overall survival (OS) risk groups based on disease type and status at the time of transplantation, namely low-risk, intermediate-risk, high-risk, and very-high-risk groups.⁵ This index was developed by using a single-institution patient cohort and has since been successfully applied to other studies.⁵ However, as the index was developed in patients transplanted approximately a decade ago, the DRI does not incorporate prognostic molecular data in acute myeloid leukemia (AML) and is not inclusive of several hematological malignancies.⁶ As the result, a contemporary risk-stratification scheme is needed to overcome these limitations.⁶

A novel disease-risk stratification system (DRSS) was then developed to account for heterogeneous transplantation indications, including acute leukemia, lymphoma, multiple myeloma, and myeloproliferative and myelodysplastic disorders.⁷ Compared to the DRI, the DRSS stratification is finer and provides five risk groups with increasing mortality risk (low-risk, intermediate-1-risk, intermediate-2-risk, high-risk and very-high-risk).⁷

The difference of the DRI and DRSS was demonstrated in a retrospective cohort study that included 55 histology and remission status combinations across hematological malignancies.⁷ A total of 47,265 adult patients who received an allogeneic HSCT between 2012 and 2016 and were reported to the European Society for Blood and Marrow Transplantation registry were included.⁷ The patients were divided into derivation (n=25,534), tuning (n=18,365), and geographical validation (n=3,366) cohorts.⁷ Across all cohorts, 64-65% of patients were categorized as having intermediate-risk disease by the DRI.⁷ In a subanalysis involving the intermediate-risk DRI patients from the tuning and internal geographic validation cohorts (n=14,041), the DRSS then reclassified these patients to low-risk (855; 6%), intermediate-1-risk (7,111; 51%), intermediate-2-risk (5,700; 41%), and high-risk or very-high-risk (375; 3%).⁷ While the DRI projected 2-year overall survival (OS) was 62.1% (95% CI: 61.2–62.9) for these patients, the DRSS reclassified them into finer prognostic groups with OS ranging from 45.7% (95% CI: 37.4–54.0; very-high-risk patients) to 73.1% (95% CI: 70.1–76.2; low-risk patients).⁷

In conclusion, the DRSS is a novel risk stratification tool to facilitate the interpretation and analysis of studies with more inclusive populations by incorporating contemporary disease features related to histology, genetic profile and treatment response.⁷ Providing a finer prediction of survival following allogeneic HSCT than the DRI, the DRSS shall serve as a benchmark prognostic system for future studies.⁷