Lack of treatment response and age were risk factors for the development of a secondary myeloid neoplasm (sMN) among patients with severe aplastic anemia, according to a retrospective cohort study published in the Journal of Clinical Oncology.

“Over the course of 10 years from diagnosis, one fifth of patients with aplastic anemia treated with immunosuppressive therapy will experience late clonal complications,” the authors wrote in their report.

Because aplastic anemia is rare, prospective studies to assess risk factors for clonal evolution are difficult to conduct to identify risk factors, surveillance measures, or early interventions. The aim of this study was to characterize clinical and molecular factors associated with clonal evolution in aplastic anemia and paroxysmal nocturnal hemoglobinuria (PNH).

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The multicenter, retrospective cohort study evaluated data from 999 patients with aplastic anemia and PNH who were consecutively diagnosed between 1972 and 2020. The median age of the cohort was 34 and 50.3% were female. There were 48% of patients who had a PNH clone at diagnosis and median PNH clone was 11%. The karyotype was normal at diagnosis among 93% of patients. There were 78.5% and 36% of patients with aplastic anemia or PNH, respectively, with severe disease.

Clonal evolution was not observed among patients who underwent early hematopoietic stem cell transplant (HSCT) during a median follow-up of 8.2 years. These patients had a 10-year overall survival (OS) of 86.7%.

The 10-year cumulative incidence of sMN was 11.6% among patients who did not undergo HSCT, with a 10-year OS was 76.4%. Survival was longer among patients with classic PNH with a 10-year rate of 95.2% compared with 72.1% among patients with aplastic anemia or 88.8% among patients with aplastic anemia/PNH (global P <.001).

The greatest independent risk factor for developing sMN among patients with severe aplastic anemia was lack of response to immunosuppressive therapy (hazard ratio [HR], 2.60; 95% CI, 1.39-4.84; P =.003). Partial or no response to immunosuppressive therapy was associated with higher rates of sMN at 15.7% compared with 8.5% among patients who achieved complete response (P =.02).

Age older than 35 was also associated with higher rates of sMN at 20% compared with 6.6% of younger patients (P <.001). Older age at presentation was an independent risk factor for the development of sMN and survival (HR, 1.37; 95% CI, 1.20-1.56; P <.001).

Patients with nonsevere aplastic anemia who did not receive treatment demonstrated the greatest risk of developing sMN, with a 10-year rate of 21.9% compared with 8.9% and 8.3% among patients who had a poor or good response, respectively, to immunosuppressive therapy (P =.04).

Patients with PNH hemolytic clones of nonsevere (13.6%) and severe (12.4%) demonstrated similar rates of progression to sMN (P =.86). However, patients with nonsevere PNH demonstrated longer OS at 81.3% compared with patients with 71.0% with severe disease (P <.001).

There were 9.4% of patients in the entire cohort who progressed to sMN during a median follow-up of 4.5 years. The most common sMN was myelodysplastic syndrome (MDS), followed by acute myeloid leukemia and MDS/myeloproliferative neoplasm.

At 5 years, the overall survival of patients with sMN was 40%. Shorter survival was significantly associated with 5% or more of bone marrow blasts at the onset of sMN (HR, 3.64; 95% CI, 1.82-7.30; P <.001). Patients diagnosed with MDS demonstrated higher Revised International Prognostic Scoring System scores due to the frequency of poor cytogenetic risk.

The authors concluded that “our results call for a close monitoring of patients with aplastic anemia with classical bone marrow smear examination and cytogenetics.”

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Gurnari C, Pagliuca S, Prata PH, et al. Clinical and molecular determinants of clonal evolution in aplastic anemia and paroxysmal nocturnal hemoglobinuria. J Clin Oncol. Published online July 18, 2022. doi: 10.1200/JCO.22.00710