Abstract
Abstract 2011
Residual disease at the time of allogeneic hematopoietic cell transplant (HCT) has been shown to adversely affect outcomes in patients with acute myelogenous leukemia (AML). Assessment of the impact of MDS disease burden at HCT on post-transplant outcomes is less well defined. While blast percentage is easily quantified on morphology and flow cytometry, the blast percentage captures only a fraction of the true MDS clone. Consequently, improved measures of residual disease in MDS patients are needed to improve post HCT outcome prediction. We hypothesized that a more stringent blast percentage cutoff as well as an assessment of recognizable residual cytogenetic disease burden would better predict outcome post HCT. Disease burden at HCT was characterized as reported in the Revised International Prognostic Scoring System (IPSS-R) (<2%, >2-<5%, 5–10% and >10%) and by assessment of cytogenetic residual disease by calculating the percent of metaphases with ongoing cytogenetic abnormalities immediately prior to transplant (% positive metaphases <25%, 25–50%, and > 50%). Metaphase data was unavailable in n=7. Those patients with normal cytogenetics (n=26) were classified in the <25% category.
One hundred consecutive patients with MDS undergoing allogeneic HCT at the University of Minnesota between 1995 –2011 were studied. Their median age was 52 (18–69). At diagnosis, the majority of patients had either refractory cytopenia of multilineage dysplasia (RCMD) (25%) or refractory anemia with excess blasts (RAEB) 1 or 2 (49%) and were INT-1 (37%) or INT-2/High risk (60%). Donor type was related donor (52%), matched unrelated (13%) and umbilical cord blood (35%). Half received myeloablative conditioning and Karnofsky Performance Status (KPS) > 80 in 95%.
(Table)
Both higher blast percentage at HCT and high percentage of residual cytogenetically positive cells correlated with inferior overall survival as well as more frequent NRM. Relapse incidence was similar in those with blasts up to 10%. Percentage of abnormal metaphases was not predictive of relapse. Conditioning intensity was the only factor that impacted the 2 year relapse rate with decreased relapse seen with myeloablative conditioning.
| % of Patients Per Strata | Strata | 2 year Overall Survival (OS)% (CI 95%) | P value | 2 year Non-Relapse Mortality (NRM) % (CI 95%) | P value | 2 year Relapse % (95% CI) | P value | |
|---|---|---|---|---|---|---|---|---|
| Percentage Blasts at HCT | ||||||||
| 49% | ≤2% | 46% (32–59%) | <0.01 | 33% (20–46%) | 0.02 | 29% (15–42%) | 0.89 | |
| 28% | >2–<5 | 36% (19–53%) | 46% (27–66%) | 21% (6–37%) | ||||
| 16% | 5–10% | 50% (25–71%) | 38% (14–61%) | 25% (11–56%) | ||||
| 7% | >10% | 0% | 86% (55–100%) | NE | ||||
| Percentage Abnormal Metaphases At HCT | ||||||||
| 42% | <25% | 56% (39–70%) | 0.03 | 26% (12–39%) | 0.06 | 31% (16–46%) | 0.33 | |
| 11% | 25–50% | 50% (18–75%) | 40% (11–69%) | 10% (0–27%) | ||||
| 47% | >50% | 28% (16–42%) | 51% (35–67%) | 25% (12–38% | ||||
| Conditioning Intensity | ||||||||
| Myeloablative | 50% | 42% (28–55%) | 0.99 | 48% (33–63%) | 0.33 | 14% (4–24%) | 0.02 | |
| Reduced Intensity | 50% | 39% (26–53%) | 34% (21–48%) | 37% (22–51% |
| % of Patients Per Strata | Strata | 2 year Overall Survival (OS)% (CI 95%) | P value | 2 year Non-Relapse Mortality (NRM) % (CI 95%) | P value | 2 year Relapse % (95% CI) | P value | |
|---|---|---|---|---|---|---|---|---|
| Percentage Blasts at HCT | ||||||||
| 49% | ≤2% | 46% (32–59%) | <0.01 | 33% (20–46%) | 0.02 | 29% (15–42%) | 0.89 | |
| 28% | >2–<5 | 36% (19–53%) | 46% (27–66%) | 21% (6–37%) | ||||
| 16% | 5–10% | 50% (25–71%) | 38% (14–61%) | 25% (11–56%) | ||||
| 7% | >10% | 0% | 86% (55–100%) | NE | ||||
| Percentage Abnormal Metaphases At HCT | ||||||||
| 42% | <25% | 56% (39–70%) | 0.03 | 26% (12–39%) | 0.06 | 31% (16–46%) | 0.33 | |
| 11% | 25–50% | 50% (18–75%) | 40% (11–69%) | 10% (0–27%) | ||||
| 47% | >50% | 28% (16–42%) | 51% (35–67%) | 25% (12–38% | ||||
| Conditioning Intensity | ||||||||
| Myeloablative | 50% | 42% (28–55%) | 0.99 | 48% (33–63%) | 0.33 | 14% (4–24%) | 0.02 | |
| Reduced Intensity | 50% | 39% (26–53%) | 34% (21–48%) | 37% (22–51% |
These data suggest that survival and relapse prediction are not improved by using the more stringent IPSS-R blast cutoff of < 2% versus <5% at HCT. Additionally, our data suggest that use of a disease burden measure as represented by % residual positive metaphases at HCT may serve as another predictor of outcome. Survival and NRM were worse with >10% blasts or > 50% residual positive metaphases. These patients require additional therapy or new strategies to improve post HCT outcomes. A refined measure of disease burden at HCT using both blast count and % residual abnormal metaphases may allow for more comprehensive prediction of post HCT outcomes in MDS.
No relevant conflicts of interest to declare.
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