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FLOW CYTOMETRIC RESPONSE MONITORING IN MDS WITH DEL(5Q) USING A SIMPLE 5-PARAMETER-SCORE – A TWO-CENTER-EXPERIANCE
Author(s): ,
Uta Oelschlaegel
Affiliations:
Medical Clinic and Policlinic I, MK1-L06,UNIVERSITY HOSPITAL of TU DRESDEN,Dresden,Germany
,
Theresia M Westers
Affiliations:
VU University Medical Center Amsterdam,Amsterdam,Netherlands
,
Brigitte Mohr
Affiliations:
Medical Clinic and Policlinic I, MK1-L06,UNIVERSITY HOSPITAL of TU DRESDEN,Dresden,Germany
,
Christian Thiede
Affiliations:
Medical Clinic and Policlinic I, MK1-L06,UNIVERSITY HOSPITAL of TU DRESDEN,Dresden,Germany
,
Gerhard Ehninger
Affiliations:
Medical Clinic and Policlinic I, MK1-L06,UNIVERSITY HOSPITAL of TU DRESDEN,Dresden,Germany
,
Martin Bornhäuser
Affiliations:
Medical Clinic and Policlinic I, MK1-L06,UNIVERSITY HOSPITAL of TU DRESDEN,Dresden,Germany
,
Arjan A van de Loosdrecht
Affiliations:
VU University Medical Center Amsterdam,Amsterdam,Netherlands
Uwe Platzbecker
Affiliations:
Medical Clinic and Policlinic I, MK1-L06,UNIVERSITY HOSPITAL of TU DRESDEN,Dresden,Germany
(Abstract release date: 05/19/16) EHA Library. OELSCHLAEGEL U. 06/09/16; 132741; E1192
Dr. Uta OELSCHLAEGEL
Dr. Uta OELSCHLAEGEL
Contributions
Abstract
Abstract: E1192

Type: Eposter Presentation

Background
Recently, we have established a 5-parameter flow cytometry (FCM)-based score allowing for a precise prediction a deletion (5q) in therapy naïve MDS patients (pts.).

Aims
The aim of this prospective study was to test, whether this FCM-based profiling is at least equal to the cytogenetics/FISH-based del(5q) detection for monitoring response to treatment.

Methods
Overall, 164 FCM investigations were performed in 39 pts. with MDS and del(5q) (IPSS-R very low/low: n=17, int: n=9, high/very high n=13) including 27 pts. with isolated del(5q) or one additional cytogenetic abnormality. The majority of analyses were performed in pts. receiving lenalidomide or azacitidine (n=17 and n=15 pts.), or in pts. receiving chemotherapy and/or allogeneic transplantation (n=3), or growth factors (n=4). The del(5q)-FCM-score includes the following 5 parameters: myeloid progenitors (myPC > 2%) = 3 points, CD45 MFI ratio (lymphocytes: myPC ≤ 7.0) = 10, SSC ratio (granulocytes : lymphocytes < 6.0) = 2, CD71 (≤ 20%) on granulocytes = 1.5, and female gender = 1.5; a score ≥ 15.0 indicates the presence of del(5q). A standardized FCM (lyse-stain-wash) and cytogenetics/FISH were performed according to ELN guidelines at the TU of Dresden and VUMC of Amsterdam.

Results
Before therapy, in 56 cytogenetic/FISH analyses in 39 MDS pts. a del(5q) was detectable. In 48/56 (86%) FCM measurements, performed in parallel, a del(5q) could be predicted using the del(5q)-FCM-score. A complete cytogenetic response (CCR) was detectable in 17 pts. (41 different evaluations). Remarkably, all determined del(5q)-FCM-scores matched the above mentioned CCR (sensitivity=100%). Otherwise, in 32 pts. (69 different evaluations) del(5q) was still detectable by cytogenetics/FISH, which was accompanied by a matching del(5q)-FCM-score in 58 measurements (specificity=84%). Next, we focused on those pts. who presented with a typical del(5q)-FCM-score before therapy (32 pts.; 49 measurements; median score=16.5). Again, all 31 cytogenetic evaluations, resulting in a CCR, showed a matching del(5q)-FCM-score (sensitivity=100%; median score=13.0). On the other side, 52 of the 54 analyses (96%) without CCR showed a properly high del(5q)-FCM-score (median score=16.5). Furthermore, we compared cytogenetics/FISH and del(5q)-FCM-score with additional methods for response monitoring as cytomorphology, two well established diagnostic FCM scores: FCSS (flow cytometry scoring system; Wells et al. Blood 2003) and the diagnostic score (Ogata et al. Haematologica 2012), as well as the assessment of hematological improvement (HI). Thus, cytomorphology and FCSS, analyzing dyspoiesis of multiple cell lineages, showed a CR or disappearance of a MDS typical FCSS in only around half of all investigations being in cytogenetic CR (sensitivity: 48% and 58%), but those two methods revealed a high specificity (100% and 96%). On the other side, the analysis of HI was highly sensitive (90%) but not specific (56%). Finally, the use of the 4-parameter Ogata score ended up with a nearly as high sensitivity (90%) and specificity (87%) as cytogenetics/FISH and the del(5q)-FCM-score.

Conclusion
Flow cytometry-based detection of a del(5q)-specific immunophenotype is feasible and can serve as a rapid tool for response monitoring during treatment with disease-modifying drugs. At the moment, we validate the FCM-scores in a larger multicentric study within the iMDS-Flow working group of the ELNet evaluating if response prediction by FCM might result in a better separation of the patients’ survival.

Session topic: E-poster

Keyword(s): Flow cytometry, MDS
Abstract: E1192

Type: Eposter Presentation

Background
Recently, we have established a 5-parameter flow cytometry (FCM)-based score allowing for a precise prediction a deletion (5q) in therapy naïve MDS patients (pts.).

Aims
The aim of this prospective study was to test, whether this FCM-based profiling is at least equal to the cytogenetics/FISH-based del(5q) detection for monitoring response to treatment.

Methods
Overall, 164 FCM investigations were performed in 39 pts. with MDS and del(5q) (IPSS-R very low/low: n=17, int: n=9, high/very high n=13) including 27 pts. with isolated del(5q) or one additional cytogenetic abnormality. The majority of analyses were performed in pts. receiving lenalidomide or azacitidine (n=17 and n=15 pts.), or in pts. receiving chemotherapy and/or allogeneic transplantation (n=3), or growth factors (n=4). The del(5q)-FCM-score includes the following 5 parameters: myeloid progenitors (myPC > 2%) = 3 points, CD45 MFI ratio (lymphocytes: myPC ≤ 7.0) = 10, SSC ratio (granulocytes : lymphocytes < 6.0) = 2, CD71 (≤ 20%) on granulocytes = 1.5, and female gender = 1.5; a score ≥ 15.0 indicates the presence of del(5q). A standardized FCM (lyse-stain-wash) and cytogenetics/FISH were performed according to ELN guidelines at the TU of Dresden and VUMC of Amsterdam.

Results
Before therapy, in 56 cytogenetic/FISH analyses in 39 MDS pts. a del(5q) was detectable. In 48/56 (86%) FCM measurements, performed in parallel, a del(5q) could be predicted using the del(5q)-FCM-score. A complete cytogenetic response (CCR) was detectable in 17 pts. (41 different evaluations). Remarkably, all determined del(5q)-FCM-scores matched the above mentioned CCR (sensitivity=100%). Otherwise, in 32 pts. (69 different evaluations) del(5q) was still detectable by cytogenetics/FISH, which was accompanied by a matching del(5q)-FCM-score in 58 measurements (specificity=84%). Next, we focused on those pts. who presented with a typical del(5q)-FCM-score before therapy (32 pts.; 49 measurements; median score=16.5). Again, all 31 cytogenetic evaluations, resulting in a CCR, showed a matching del(5q)-FCM-score (sensitivity=100%; median score=13.0). On the other side, 52 of the 54 analyses (96%) without CCR showed a properly high del(5q)-FCM-score (median score=16.5). Furthermore, we compared cytogenetics/FISH and del(5q)-FCM-score with additional methods for response monitoring as cytomorphology, two well established diagnostic FCM scores: FCSS (flow cytometry scoring system; Wells et al. Blood 2003) and the diagnostic score (Ogata et al. Haematologica 2012), as well as the assessment of hematological improvement (HI). Thus, cytomorphology and FCSS, analyzing dyspoiesis of multiple cell lineages, showed a CR or disappearance of a MDS typical FCSS in only around half of all investigations being in cytogenetic CR (sensitivity: 48% and 58%), but those two methods revealed a high specificity (100% and 96%). On the other side, the analysis of HI was highly sensitive (90%) but not specific (56%). Finally, the use of the 4-parameter Ogata score ended up with a nearly as high sensitivity (90%) and specificity (87%) as cytogenetics/FISH and the del(5q)-FCM-score.

Conclusion
Flow cytometry-based detection of a del(5q)-specific immunophenotype is feasible and can serve as a rapid tool for response monitoring during treatment with disease-modifying drugs. At the moment, we validate the FCM-scores in a larger multicentric study within the iMDS-Flow working group of the ELNet evaluating if response prediction by FCM might result in a better separation of the patients’ survival.

Session topic: E-poster

Keyword(s): Flow cytometry, MDS

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