Are IPSS-R and IPSS Cytogenetic Risk Stratification Informative At the Time of Allogeneic Hematopoietic Cell Transplantation?
Authors: Sachs Zohar , Dollan Michelle , De For Todd E , Shune Leyla , Cooley Sarah , Weisdorf Daniel J. , Warlick Erica D. , Ustun Celalettin 
Published: October 2019

Abstract 1400

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders. Cytogenetic aberrations are one of the main elements of risk stratification among published scoring systems including the International Prognostic Scoring System (IPSS) or its recent revision (R-IPSS). R-IPSS cytogenetic risk stratification has 5 cytogenetic subgroups rather than 3 in the IPSS. We hypothesized that R-IPSS and/or IPSS cytogenetic risk stratification at the time of allogeneic hematopoietic cell transplantation (alloHCT) can better predict outcome afterwards. In patients who had cytogenetic results at both diagnosis and alloHCT, we evaluated the cytogenetic changes over time and compared how well the two cytogenetic risk stratification systems predicted outcome.

One hundred consecutive patients with MDS undergoing an alloHCT (52% related donor, 13% unrelated donor, and 35% umbilical cord blood) at the University of Minnesota between 1995 and 2011 were evaluated. Their median age was 52 years (range, 18–69 years). Seventy-eight percent of the patients had ≥90% Karnofsky performance score, and 60% had INT-2 or a high IPSS score. Half received reduced-intensity conditioning (RIC).

Patients with IPSS good-risk cytogenetics at diagnosis had a significantly better OS (62% at 5-year) compared to patients with intermediate or poor-risk cytogenetics. However, IPSS cytogenetic stratification at the time of transplantation predicted neither overall survival (OS) nor relapse (Table). Patients with IPSS-R very poor risk cytogenetics at either diagnosis or alloHCT had a dismal outcome; no patients in this category at alloHCT survived 5 years, and their relapse rate was also significantly higher (41%) compared to other cytogenetic risk subgroups (Table). In multivariate analysis, the only factor predicting relapse was the intensity of the conditioning regimen: those patients receiving RIC had a higher risk of relapse (HR, 2.5, 95% CI 1.1–5.4, p=0.03) than those who received myeloablative conditioning regimens.

This data indicate that IPSS (at diagnosis) and IPSS-R (at both diagnosis and alloHCT) cytogenetic classifications provide important prognostic information in the best and worst subgroups, respectively, but are not as helpful for patients in the intermediate subgroups.

Table. OS and Relapse by IPSS and R-PSS cytogenetic stratifications at time points of diagnosis and alloHCT Factor Strata N OS @ 5 year CI 95% P-value Relapse @ 5-year CI 95% P-value IPSS Cytogenetics At alloHCT Good 30 48% 28-65% 0.16 29% 11-47% 0.82 Intermediate 21 19% 6-38% 29% 9-48% Poor 41 23% 11-38% 30% 15-45% IPSS-R Cytogenetics   At alloHCT Very good/Good 32 51% 31-67% <0.01 30% 13-48% 0.05 Intermediate 21 17% 5-36% 29% 9-48% Poor 41 41% 22-60% 17% 2-31% Very Poor 18 0% 41% 18-63% IPSS Cytogenetics   At Diagnosis Good 25 62% 39-78% <0.01 22% 5-39% 0.16 Intermediate 24 13% 3-29% 29% 10-48% Poor 47 24% 12-38% 30% 16-44% IPSS-R Cytogenetics   At Diagnosis Very good/Good 28 54% 33-71% <0.01 27% 9-44% 0.21 Intermediate 20 15% 4-33% 25% 6-44% Poor 29 33% 17-51% 21% 6-35% Very Poor 19 7% 0-28% 45% 22-68%

Disclosures:

No relevant conflicts of interest to declare.