Novel disease-risk stratification system provides a finer prediction of survival following stem-cell transplantation for patients with hematologic malignancies

09 Apr 2021

Hematologic malignancy is the 10th 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

Get access to our exclusive articles.