Current efforts aimed at validation of the Molecular International Prognostic Scoring System (IPSS-M) in several settings of myelodysplastic neoplasm/syndrome (MDS), including paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA), are key to defining its role in daily clinical practice and allocating patients for clinical trial participation.

Findings from the current cohort study, in which data were obtained from a large multicenter data set, were published in the journal Blood.

In patients with PNH or AA, clonal evolution to MDS or acute myeloid leukemia is the most severe late adverse reaction reported. Most individuals who present with post-PNH/AA MDS exhibit high-risk features with abnormalities in chromosome 7, along with mutations in ASXL1, RUNX1, SETBP1, and RAS genes. In contrast, in those who present with such low-risk cytogenic alterations as del(13q) and del(20q), more favorable outcomes are reported.

Recognizing that the applicability of IPSS-M in individuals with post-PNH/AA MDS remains to be elucidated, the researchers sought to use the tool in this unexplored patient population. Sixty-nine individuals who developed MDS were chosen from a large data set of 1008 patients with PNH/AA. Participants were selected who had data available on complete clinical information and molecular annotations.

Read more about paroxysmal nocturnal hemoglobinuria (PNH)

An MDS diagnosis, which was rendered according to the World Health Organization 2016 criteria, was corroborated with the new attainment of cytogenetic abnormalities or considerable dysplastic changes in previously normal bone marrow findings. The average score on the IPSS-M was used to define risk categories for future outcome analyses.

The definition of overall survival used was “the time from MDS onset to last follow-up or death from any cause.” A 1:1 matched-pair evaluation was used to compare MDS cases associated with PNH or AA and matches from a control cohort of de novo MDS based on gender, age, and type of treatment. Comparisons between the use of IPSS-M and Revised International Prognostic Scoring System (IPSS-R) were performed.

Results of the study revealed that evolution to MDS was reported at a median of 4.9 years (range, 1.9-8.3 years) from initial diagnosis of PNH or AA. Patients’ age at MDS onset was 63 years (range, 34-70 years); a majority of the patients were male.

Read more about PNH guidelines

Although low bone marrow blast percentages were reported (median, 2%; range, 0%-7%), 71% of the participants exhibited high-risk features based on IPSS-R (ie, scores of >3.5), due primarily to enrichment in poor-risk cytogenetics.

The participants were treated with hypomethylating agents (28%), hematopoietic stem cell transplantation (60%), or both (12%). Based on a median follow-up of 55.6 months (95% CI, 42.5-75.8 months), the 60-month overall survival was 44%. Based on IPSS-R, distribution of the study cohort was as follows:

  • Very low: 6%
  • Low: 23%
  • Intermediate: 30%
  • High: 23%
  • Very high: 18%

When the IPSS-M tool was applied, participants were redistributed as follows:

  • Very low: 5%
  • Low: 19%
  • Moderate low: 14%
  • Moderate high: 14%
  • High: 29%
  • Very high: 19%

The researchers concluded, “[T]he specific genomic makeup, the rarity of the disease, and information scarcity make the prognostication of MDS arising from AA and PNH challenging for routine clinical practice.”


Gurnari C, Prata P, Cátto LF, et al. IPSS-M in myelodysplastic neoplasms arising from aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood. Published online April 13, 2023. doi:10.1182/blood.2023020108