John Koreth , MBBS , DPhil

Bart Scott , MD

Disclaimer : Positions were assigned to the participants and do not necessarily reflect ASH ’ s opinion , the participants ’ opinions , or what they do in daily practice .

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For patients with myelodysplastic syndromes ( MDS ), hematopoietic cell transplantation ( HCT ) is the only potentially curative option , but the rates of transplantrelated morbidity and mortality preclude some patients from receiving this intervention . In this edition of Drawing First Blood , ASH Clinical News invited John Koreth , MBBS , DPhil , and Bart Scott , MD , to debate the question “ Should patients with MDS receive HCT ?” Dr . Koreth , of the Dana-Farber Cancer Institute and Harvard Medical School , will argue on the “ pro ” side , and Dr . Scott , of the Fred Hutchinson Cancer Research Center and the University of Washington , will argue on the “ con ” side .

John Koreth , MBBS , DPhil : Standard therapies for patients with MDS include hypomethylating agents ( HMAs ) and a variety of novel agents outside of allogeneic HCT ( alloHCT ). Although we have seen a substantial survival benefit for patients with higher-risk MDS with non-transplant treatments , in the long term , this disease is fatal . In fact , the survival rates for patients with high-risk MDS and patients with acute myeloid leukemia are not that different . In this setting , the potential benefit of alloHCT should not be taken lightly . Not every patient either qualifies for transplant or should be transplanted , but all patients should be evaluated for transplant .

Bart Scott , MD : Despite the fact that it is the only curative option , I am wary of saying that all patients should be considered for transplant because mortality after allo- HCT is high due to relapsed disease and transplant-related complications . So , clearly , transplant doesn ’ t cure every patient , and some patients die from this intervention . For patients with , for example , many comorbidities , the risk-benefit ratio of transplant is too great to consider it as a viable option : Their survival would likely be relatively short , and likely too short to risk the adverse events associated with transplant .

Dr . Koreth : In the past 15 years , though , the field of transplantation has advanced and transplant-related mortality has declined . Unfortunately , we have not been as effective in addressing relapse , but post-transplant outcomes have improved . This has happened for a few reasons : We have gotten better at matching donors and recipients , treating complications , and overcoming some of the barriers to patients receiving alloHCT .

The issues of patient selection and comorbidity are important , but I also want to emphasize that the barriers to receiving alloHCT should not become barriers to a transplant consultation as early as possible . An early referral does not mean that the transplant itself happens early , simply that the patient is educated about the prospects of transplantation . Our goal is to avoid long gaps between diagnosis and transplant for patients who could be candidates for the procedure .

That determination needs to happen in a transplant center with a transplant

specialist . Researchers from Memorial Sloan Kettering Cancer Center ( MSKCC ) demonstrated the importance of referrals in an analysis presented at the 2016 ASH Annual Meeting . 1 They looked at the frequency of alloHCT in patients with MDS who were seen by leukemia physicians at MSKCC and were potentially eligible for transplant , then at the factors associated with transplant referral and barriers to transplant . Of the 362 patients included in the study , 294 were considered potentially eligible for transplant and 244 ( 67 %) were indicated for transplant . Of those patients , 165 were referred to the transplant team . Of that group , only 120 – essentially onethird of the initial , highly selective patient population – underwent alloHCT .

Notably , the patients in that study did not reflect the average U . S . patient with MDS – they had higher incomes and education levels , were mostly white , and were evaluated at a premier transplant and oncology center . Yet , there was still a substantial drop-off .

The major barrier to transplant was death prior to the actual transplant referral . So , even though patients ’ MDS did not progress to leukemia , their risk of MDSrelated death remained high .

Another factor that precluded referral was the presence of ≥3 comorbidities . Interestingly , the reasons that people did not proceed to transplant were independent of other known risk factors , such as older age and variables included in the International Prognostic Scoring System ( IPSS ) and Revised IPSS ( IPSS-R ). So , I would say that comorbidities can exist , but there is a difference between general comorbidities and comorbidities that are barriers to transplantation . What we think of as barriers may not actually be barriers .

Dr . Scott : But I would like to raise an additional point : There are patients who should not be referred for transplant . Age alone is not a barrier to transplant , though there has to be a point at which transplant loses its clinical utility . Do we want to see a 90-year-old patient with MDS being considered for transplant ? I suspect the answer would be no .

Dr . Koreth : That ’ s a great point , and I agree that age is something we can ’ t ignore . At our institution , our cutoff for transplant