FROM JCO

A new risk-stratification tool goes one better than the standard tools used to predict survival in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome, based on a study published online April 4 in the Journal of Clinical Oncology.

The concordance index for the new risk-stratification tool was modestly better at 0.575, compared with 0.538 for the standard International Prognostic Scoring System (IPSS) and 0.554 for the revised IPSS (IPSS-R), according to Dr. Brian C. Shaffer of Memorial Sloan Kettering Cancer Center, New York, and his colleagues who participate in the Center for International Blood and Marrow Transplant Research (CIBMTR) network.

“The proposed system generally agrees with the IPSS-R in the very high–risk subcategory; however, a significant portion of patients in high- and very high–risk IPSS-R groups were represented in the low- and intermediate-risk proposed scoring subcategories. The 3-year survival in patients classified as high risk with the IPSS-R was 75%; it was 57% in those classified as low or intermediate risk with the proposed system,” the researchers wrote.

Further, the “scoring system uses readily available clinical data and can be calculated quickly, facilitating patient consultation with respect to allo HCT, and may also be used to identify high-risk populations where interventions such as post–allo HCT maintenance therapies may be of benefit,” they wrote (J Clin Oncol. 2016 April 4. doi: 10.1200/JCO.2015.65.0515).

The data were obtained from the CIBMTR, a combined research program of the Medical College of Wisconsin and the National Marrow Donor Program. The CIBMTR comprises a voluntary network of more than 450 transplantation centers worldwide that contribute data on consecutive allo and autologous HCTs to a centralized statistical center.

The researchers applied the prognostic tool to 2,133 patients with MDS undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT. Factors prognostic of mortality were identified in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was then assigned to the validation cohort of 577 remaining patients undergoing HLA-matched allo HCT as well as to patients undergoing HLA-mismatched allo HCT. The training data set was used to develop a prognostic scoring system, and the validation data set was used to assess the prognostic ability of the scoring system, the researchers noted.

In the scoring system, 1 point was assigned for the following factors: Blood blasts greater than 3%, platelet levels of 50 × 109/L or less at transplantation, Karnofsky performance status less than 90%, comprehensive cytogenetic risk score of poor or very poor, and age 30-49 years. Two points were assigned for monosomal karyotype and age 50 years or older.

Based on the scoring system, 3-year overall survival after transplantation was 71% in patients with scores of 1 point, 49% with scores of 2-3, 41% with scores of 4-5, and 25% with scores of 6 or more. Increasing score was predictive of increased relapse and treatment-related mortality in the HLA-matched set and of relapse in the HLA-mismatched cohort.

To develop the scoring system, the researchers used a model that weighed patient age; sex; and Karnofsky performance status; disease stage at transplantation; comprehensive cytogenetic risk status; bone marrow and peripheral blood blast percentages; hemoglobin, neutrophil, and platelet counts at diagnosis and pretransplantation; lactate dehydrogenase at transplantation; pretransplantation therapy (hypomethylating agents, chemotherapy, neither, or both); time from diagnosis to transplantation; year of transplantation; conditioning regimen and regimen intensity (myeloablative v reduced intensity); donor–recipient sex match or mismatch; graft-versus-host disease prophylaxis; graft type (bone marrow vs. peripheral blood); presence of secondary myelodysplastic syndrome; and unrelated donor vs. related donor.

There were no significant differences in overall survival at 1, 3, and 5 years or in the 3-year incidences of relapse and treatment-related mortality in the training subset and the validation cohort.

Data on somatic mutations have become relevant in myelodysplastic syndrome prognostication and were missing from this analysis, the researchers wrote. “The next generation of prognostic tools will need to account for this information.”

Dr. Shaffer had no relevant financial disclosures.

mdales@frontlinemedcom.com

On Twitter @maryjodales

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