To the editor:

Despite the proven curative potential of allogeneic hematopoietic cell transplantation (HCT) for patients with myelodysplastic syndrome, posttransplant relapse is common in patients with high-risk cytogenetics. One strategy to improve post-HCT outcome may be to accurately identify high-risk patients in order to intervene with novel therapies aimed at reducing relapse after transplantation. Many disease factors have been independently associated with increased risk of relapse and mortality after transplant, three of which—marrow myeloblast count, cytogenetics, and peripheral blood cytopenias—are components of the International Prognostic Scoring System (IPSS).1  Although it was developed in the nontransplant setting, the IPSS has been useful for estimating posttransplant prognosis as well.2,3  The recent revision of the IPSS (IPSS-R)4  places greater weight on cytogenetic risk within the prognostic model after incorporating a more refined system of classifying cytogenetic abnormalities.5  In an analysis of more than 1000 patients, we showed that this new cytogenetic classification system enhances prognostic accuracy for transplanted patients over the previous system, primarily by distinguishing between patients with poor and very poor-risk cytogenetics.6  With the subsequent reporting of the IPSS-R, we evaluated the other components of the final IPSS-R model to determine whether those parameters added to the prognostic power of cytogenetics in predicting post-HCT outcome.

We reviewed results in 544 patients with complete IPSS-R data who underwent HCT between 1996 and 2010, all of whom were included in the previous publication.6  As with the initial analysis, increased cytogenetic risk was associated with increased relapse, nonrelapse mortality, and overall mortality after HCT (Table 1). Adjustment for blast count, hemoglobin level, platelet count, and neutrophil count did not qualitatively change the association of cytogenetic risk and outcome. Similarly, lactate dehydrogenase (LDH),4,7  also included in the IPSS-R report, albeit not reflected in the IPSS-R scoring system, did not significantly alter the impact of cytogenetics by themselves.

Table 1

Univariate and multivariable models for posttransplant outcome

Cytogenetic risk5 No. of patientsRelapseOverall mortalityNonrelapse mortalityTreatment failure*
HR95% CIPHR95% CIPHR95% CIPHR95% CIP
Univariate model              
Good 270         
Intermediate 108 0.98 0.62-1.57 .94 1.11 0.82-1.50 .50 1.21 0.83-1.76 .33 1.11 0.83-1.49 .49 
Poor 73 1.54 0.98-2.43 .06 0.98 0.68-1.41 .92 0.75 0.45-1.26 .28 1.09 0.78-1.53 .62 
Very poor 82 5.07 3.40-7.56 <.0001 3.35 2.51-4.46 <.0001 2.95 1.97-4.41 <.0001 3.83 2.89-5.08 <.0001 
Multivariable model adjusting for blast count, hemoglobin, platelet count, neutrophil count, and LDH 
Good 270         
Intermediate 108 0.94 0.58-1.51 .80 1.02 0.75-1.39 .89 1.08 0.74-1.59 .68 1.03 0.77-1.39 .83 
Poor 73 1.59 1.00-2.52 .05 0.95 0.66-1.37 .80 0.70 0.42-1.19 .19 1.07 0.76-1.51 .69 
Very poor 82 5.19 3.42-7.87 <.0001 3.05 2.26-4.11 <.0001 2.54 1.66-3.88 <.0001 3.59 2.67-4.83 <.0001 
Cytogenetic risk5 No. of patientsRelapseOverall mortalityNonrelapse mortalityTreatment failure*
HR95% CIPHR95% CIPHR95% CIPHR95% CIP
Univariate model              
Good 270         
Intermediate 108 0.98 0.62-1.57 .94 1.11 0.82-1.50 .50 1.21 0.83-1.76 .33 1.11 0.83-1.49 .49 
Poor 73 1.54 0.98-2.43 .06 0.98 0.68-1.41 .92 0.75 0.45-1.26 .28 1.09 0.78-1.53 .62 
Very poor 82 5.07 3.40-7.56 <.0001 3.35 2.51-4.46 <.0001 2.95 1.97-4.41 <.0001 3.83 2.89-5.08 <.0001 
Multivariable model adjusting for blast count, hemoglobin, platelet count, neutrophil count, and LDH 
Good 270         
Intermediate 108 0.94 0.58-1.51 .80 1.02 0.75-1.39 .89 1.08 0.74-1.59 .68 1.03 0.77-1.39 .83 
Poor 73 1.59 1.00-2.52 .05 0.95 0.66-1.37 .80 0.70 0.42-1.19 .19 1.07 0.76-1.51 .69 
Very poor 82 5.19 3.42-7.87 <.0001 3.05 2.26-4.11 <.0001 2.54 1.66-3.88 <.0001 3.59 2.67-4.83 <.0001 

HR, hazard ratio.

*

Death or relapse.

Patients with very good cytogenetics are not included due to small numbers (n = 9); 2 patients with unknown cytogenetics.

Thus, our analysis of the impact of the individual components of the IPSS-R and LDH on post-HCT outcome confirms the central role of cytogenetics. The additional risk factors included in the IPSS-R, as well as LDH, did not appear to add significantly to post-HCT prognosis. Those factors appear to play a lesser role in the transplant setting than in nontransplanted patients, presumably because parameters such as anemia, neutropenia, and thrombocytopenia are corrected by HCT and do not necessarily imply that the myelodysplastic syndrome clonal precursors have been eradicated. A criticism of the current IPSS-R cytogenetic classification system is that it does not include recently identified molecular markers such as TP53, ASXL1, and SF3B1,8,9  which do have clear prognostic implications. Because these markers are being incorporated into prognostic models, it is likely that the weight of traditional markers, such as morphologic myeloblast count, cytopenias, and inflammatory markers, will diminish.

Contribution: A.T.G., T.A.G., and H.J.D., designed and carried out the analysis and wrote the manuscript; A.T.G and W.A.W. verified and collated data for analysis; and all the authors have read and provided critique for the manuscript.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Aaron T. Gerds, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109; e-mail: agerds@fhcrc.org.

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