15 October 2018

A team of scientists from the USA and Taiwan have unveiled a new genetics-based prognostic tool for myelodysplastic syndrome.

The researchers at the Mayo Clinic, in Rochester, Minnesota, and the National Taiwan University Hospital, Taipei, say the system is simpler than existing techniques and integrates both genetic and clinical information.

Haematologist Dr Ayalew Tefferi, lead author of the study, described the new tool as a “complete makeover” of the recognised ‘International Prognostic Scoring System’.

“In addition to accommodating genetic information, it offers more user-friendly cytogenetic risk stratification, accounts for gender differences in haemoglobin levels and uses a single threshold value for bone marrow blast percentages,” he said.

 “The Mayo Alliance Prognostic System for myelodysplastic syndrome is not an enhancement of the International Prognostic Scoring System tool, it's a complete makeover.”

He said survival rates from the disease have not improved over several decades and that current drug therapy is not curative.

“The only treatment that offers a chance for cure or prolonged survival is allogeneic hematopoietic stem cell transplant,” he said.

“Unfortunately, this procedure is associated with substantial risk of treatment-related death and morbidity, so an accurate and reliable prognostic tool is needed to select suitable patients for transplant."

Dr Tefferi and colleagues examined gene mutations and their effect on survival among 685 patients with myelodysplastic syndrome.

They identified gene mutations which had an influence on overall survival, with mutations in SF3B1 being favourable, and mutations in either ASXL1 or RUNX1 being unfavourable. They used this information alongside several conventional clinical measures to develop the Mayo Alliance Prognostic System for myelodysplastic syndrome.

The findings are published in the current edition of Mayo Clinic Proceedings.

Another paper is due to be published soon in the American Journal of Hematology, in which Dr Tefferi and team demonstrate the impact of gene mutations on treatment response in patients with myelodysplastic syndrome.

They found that ASXL1 and U2AF1 mutations undermine treatment response to hypomethylating agents and the drug lenalidomide, while patients with SF3B1 mutations are more likely to benefit from lenalidomide therapy.

Source: Tefferi, A., Gangat, N., Mudireddy, M., Lasho, T.L., Finke, C., Begna, K.H., Elliott, M.A., Al-Kali, A., Litzow, M.R., Hook, C.C., Wolanskyj, A.P., Hogan, W.J., Patnaik, M.M., Pardanani, A., Zblewski, D.L., He, R., Viswanatha, D., Hanson, C.A., Ketterling, R.P., Tang, J.L., Chou, W.C., Lin, C.C., Tsai, C.H., Tien, H.F., Hou, H.A.. (2018) “Mayo Alliance Prognostic Model for Myelodysplastic Syndromes: Integration of Genetic and Clinical Information”, Mayo Clinic Proceedings, available at doi: 10.1016/j.mayocp.2018.04.013


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