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Scoring system predicts outcomes for patients with MDS undergoing HSCT
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A novel scoring system appeared prognostic of outcome for patients with myelodysplastic syndrome undergoing HLA–matched or –mismatched allogeneic hematopoietic stem cell transplantation, according to the results of a validation study.
“Our research is a nice counterpoint to other prognostic systems for myelodysplastic syndrome [MDS] that do not specifically focus on transplant patients,” Brian C. Shaffer, MD, hematologist at Memorial Sloan Kettering Cancer Center, told HemOnc Today. “This study allowed us to determine the role of certain factors in transplant recipients and to have some insight into what is and is not important for this specific subset of patients.”
Shaffer and colleagues evaluated data from the Center for Blood and Marrow Transplant Research registry to identify disease-, patient- and transplant-specific factors associated with outcomes for patients undergoing HSCT for MDS.
The analysis included data from 2,133 patients undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) HSCT between 2000 and 2012.
Researchers identified factors prognostic of mortality in a training subset (n = 1,151; median age, 56 years; 60% men) from the HLA–matched cohort. They then used these factors to assign a weighted score to the remaining patients in the HLA–matched group as a validation cohort (n = 577), as well as patients undergoing HLA–mismatched HSCT.
The development of a risk-stratification system prognostic of survival after transplantation served as the primary study objective. Researchers also sought to evaluate the scoring system’s prognostic ability to determine DFS, relapse and transplant-related mortality.
Median follow-up for survivors was 52 months (range, 3-169) in the HLA–matched training cohort, 48 months (range, 3-145) in the HLA–matched validation cohort and 46 months (range, 4-145) in the HLA–mismatched cohort.
Factors associated with an increased HR for death among transplanted patients included blood blasts greater than 3% (HR = 1.41; 95% CI, 1.08-1.85), platelet count of 50 x 109 per liter or less at transplantation (HR = 1.37; 95% CI, 1.18-1.61), a Karnofsky performance status less than 90% (HR = 1.25; 95% CI, 1.06-1.28), a comprehensive cytogenetic risk score of poor or very poor (HR = 1.43; 95% CI, 1.14-1.8) and age between 30 years and 49 years (HR = 1.6; 95% CI, 1.09-2.35).
The researchers assigned these factors one point in the scoring system.
Factors assigned two points in the scoring system included monosomal karyotype (HR = 2.01; 95% CI, 1.65-2.45) and being aged 50 years or older (HR = 1.93; 95% CI, 1.36-2.83).
Three-year OS was 71% (95% CI; 58-85) for patients with a low-risk score (0-1 points), 49% (95% CI, 42-56) for patients with an intermediate-risk score (2-3 points), 41% (95% CI, 31-51) for patients with a high-risk score (4-5 points) and 25% (95% CI, 4-46) for patients with very high-risk scores ( 6 points; P < .001).
Increased scores appeared predictive of DFS, increased relapse and treatment-related mortality in HLA–matched patients (P < .001 for all). The score predicted relapse in the HLA–mismatched cohort (P < .001).
The researchers acknowledged study limitations, including the potential for bias in using retrospective registry data and the use of Karnofsky performance status — which is subjective and clinician-determined — as a scoring variable.
“This scoring system can act as a decision-making tool for the clinician and the patient who are thinking about pursuing a bone marrow transplant,” Shaffer said. “It will allow us to standardize outcomes across different clinical studies by examining how patients with different scores were able to do with their transplants. This study will allow us to identify specific populations that may benefit from efforts to reduce transplant toxicity, or from relapse-prevention strategies such as post-transplant maintenance therapy.” – by Cameron Kelsall
For more information:
Brian C. Shaffer, MD, can be reached at shaffeb1@mskcc.org.
Disclosure: Shaffer reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Perspective
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Mikkael Sekeres
The median age at diagnosis for patients with myelodysplastic syndrome (MDS) is approximately 70 years. Without doubt, this is the major obstacle to engaging patients with MDS in the only therapy that has a chance of curing them of this insidious disease: hematopoietic stem cell transplantation. My transplant colleagues will often tell me: “There is no upper age limit for a transplant!” However, in truth, there is — if not to the doctors performing the procedure, then to their patients, judging by the incredulous looks I often get from my MDS septuagenarians when I suggest it.
At least we have some guidance regarding when to make a recommendation for HSCT, in the form of two decision analyses — one in patients undergoing fully myeloablative HSCT and the other in those receiving reduced-intensity conditioning. Both report the same results: In lower-risk MDS — as defined by the International Prognostic Scoring System (IPSS) — avoid HSCT as long as possible. In higher-risk disease, however, follow the recommendations of former Chicago mayor Richard J. Daley (if he were a hematologist), and transplant “early and often.”
Along comes the study by Shaffer and colleagues on behalf of the Center for International Blood and Marrow Transplant Research, in which 1,728 patients with MDS who underwent HSCT were divided into training and validation cohorts to develop a risk-stratification tool prognostic of survival after transplantation. With a median follow-up of survivors of longer than 4 years, the researchers found that patient age (older is worse), performance status (lower is worse), cytogenetics (poor risk or monosomal karyotype is worse), blood blast percentage (higher is worse) and platelet count (lower is worse) were all prognostic of survival. None of these is shocking, and the more of these factors that are present, the worse the outcomes with HSCT.
What stands out is the improved prognostication — compared with the IPSS or its revised version — in prediction of survival, and the upstaging of patients in lower-risk categories.
The questions that remain, however, are whether this new system should replace the IPSS in recommending transplantation — given how robustly the IPSS has performed in two decisions analyses — and whether a physician performing transplant should use this system, after HSCT has been recommended to a patient based on his or her IPSS score, to say, “Sorry, no, your modified score would be too high,” when no alternatives for potential cure exist.
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