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Predicting Response to SCT in Patients With MDS


A new study has identified key mutations that can direct the conditioning regimen prior to an allogenic hematopoietic stem cell transplant (SCT) in patients with myelodysplastic syndrome (MDS), leading to a better response.

Identifying the presence of key mutations can help direct the conditioning regimen prior to an allogenic hematopoietic stem cell transplant (SCT) in patients with myelodysplastic syndrome (MDS), leading to a better response. These are the findings of a new research study published by scientists at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital.

The researchers performed targeted mutational analysis on 1514 patients with MDS—between 6 months and 70 years old—prior to their transplantation between 2005 and 2014. Donor stem cell transplantation is the only treatment choice in patients who are at a high risk of dying with standard treatments, and complications associated with the transplant itself or disease relapse are usually responsible, according to R. Coleman Lindsley, MD, PhD, lead author on the paper.

“As physicians, one of our major challenges is to be able to predict which patients are most likely to benefit from a transplant,” Lindsley said in a statement. “Improving our ability to identify patients who are most likely to have a relapse or to experience life-threatening complications from a transplant could lead to better pre-transplant therapies and strategies for preventing relapse.”

To pinpoint the specific genes that could influence patient response to SCT, researchers analyzed the patient blood samples and identified TP53 as the single most important gene responsible for determining characteristics of a patient’s MDS, and was present in 19% of patients in this cohort. Mutations in TP53 were a definite indicator of quicker relapse and a shorter survival following transplant (P <.001 for both), irrespective of the prior conditioning regimen that a patient would have received—standard treatment (chemotherapy and/or radiation therapy) or reduced-intensity conditioning (lower doses of chemotherapy and/or radiation therapy).

Among patients (40 years or older) who did not have TP53 mutations, the RAS pathway proteins played an important role in predicting survival posttransplant. Patients who had mutations had a shorter time to relapse than those who did not (P = .004). Similarly, patients with JAK2 mutations had a shorter survival than those without (P = .001), but these patients did not relapse. As opposed to TP53 mutations, the effect of RAS mutations was only evident under the reduced-intensity preconditioning regimen, indicating that these patients could perform better under a high-intensity regimen.

The researchers observed heterozygous mutations in the Shwachman—Diamond syndrome–associated SBDS gene in tandem with TP53 mutations in 4% of young adult patients (18 to 40 years), along with a poor prognosis following transplantation. They also found that mutations in TP53 and in PPM1D were more common among patients who were treatment-naïve.

“In deciding whether a stem cell transplant is appropriate for a patient with MDS, it’s always necessary to balance the potential benefit with the risk of complications,” Lindsley said. “Our findings offer physicians a guide—based on the genetic profile of the disease and certain clinical factors&mdash;to identifying patients for whom a transplant is appropriate, and the intensity of treatment most likely to be effective.”


Lindsley RC, Saber W, Mar BG, et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N Engl J Med. 2017;376(6):536-547. doi: 10.1056/NEJMoa1611604.

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