Flow cytometry (FCM) has recently been recognized as an important supplementary tool in the diagnostic work-up of patients with MDS. Within the international MDS-flow working group of the ELN, different and also novel Flow scores have been evaluated and tested in rather small patients series.
Currently available FCM scores have been prospectively compared concerning their potential diagnostic and prognostic impact in patients with proven or suspected MDS.
Patients and Methods:
Bone marrow (BM) samples from 616 patients (951 measurements) with proven or suspected MDS, 42 MPN patients, 30/18 MDS patients in cytomorphologic/cytogenetic CR, 22 patients with inappropriate BM aspirations as well as 48 age matched controls have been analyzed by FCM. For measurement and analysis a FACS-CantoII cytometer including FACS-DiVa software was used, performing an 8-color panel and measuring 200,000 events per sample. The following FCM scores were compared: FCSS (granulopoiesis / monopoiesis), Ogata-score (blasts), ELN-red score and Mathis score (both erythropoiesis), and the new iFScore (granulo-, mono-, erythropoiesis, and blasts). Overall survival (OS) was estimated with a median follow up of 21 month (range: 3.4-77 month) applying the Log-Rank-Test within SPSS software.
The new iFScore, evaluating granulo-, mono-, erythropoiesis and blasts, turned out to be the most comprehensive score with the best balance between sensitivity and specificity (81%; 78%). FCSS indeed showed a comparably high sensitivity (82%) but has a clearly lower specificity (60%). The Ogata-score and the red-scores showed a lower sensitivity (60%, 31%, 40%) but were very specific (92%, 97%, 89%). Interestingly, despite inappropriate bone marrow aspirations (w/o crumbs) in 22 patients the new iFScore accounted for a "MDS conformable" result in 72% of these cases.
Next, the prognostic impact of the different FCM scores was evaluated. Of note, patients with MDS conformable FCM-scores showed a significantly shorter OS compared to patients with scores being not MDS conformable, new iFS, Ogata- and Mathis-score: p = 0.001 (ELN-red: p = 0.003; FCSS: p = 0.005). This also held true evaluating only untreated patients, with Ogata-score exhibiting the highest significance (p < 0.001). Remarkably, even when analyzing the subgroup of MDS-SLD/MLD with normal karyotype and without ringsideroblasts plus non-clonal cytopenias only, a high Ogata score predicted for a significantly lower OS (p = 0.035; median OS = 40 month vs. not reached). Thus, the group of patients with MDS conformable FCM showed significantly higher IPSS-R (p = 0.023) and more mutations (p = 0.0357).
When evaluating MDS patients in cytomorphologic or even cytogenetic CR, 23% (17%) showed a MDS conformable iFS with significantly shorter OS (p = 0.025; p = 0.026).
Finally, 49% or 35% of patients with MPN showed MDS conformable iFS or Ogata scores, respectively. This translated in a shorter OS in those patients (p = 0.048; p = 0.018).
Currently available FCM scores have different sensitivity and specificity in diagnosing MDS, with the novel and comprehensive iFScore, capturing granulo-, mono-, erythropoiesis and blasts together, being superior to other FCM-scores.
Additionally, iFS and Ogata score comprise significant prognostic information, even in lower risk MDS. Remarkably, FCM might be a tool to refine response evaluation in MDS and reveal significant dyspoietic features in a subset of MPN patients.
Platzbecker:Celgene: Research Funding.
Asterisk with author names denotes non-ASH members.