title: Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients.
abstract: RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R. We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time-dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P < 0.0001) at 6- (18 vs. 64 months), 12- (24 vs. 71 months), and 24-months (40 vs. 87 months). In a Cox proportional regression analysis, RBC-TD was an independent adverse prognostic marker in addition to age, sex, and IPSS-R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox-proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC-TD at any time during the course of MDS is associated with poor OS, independent of IPSS-R. This study demonstrates that dynamic assessment of RBC-TD provides additional prognostic value to IPSS-R and should be included in treatment decision algorithms for MDS patients.
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.|Cancer Centre, Royal Adelaide Hospital, Adelaide, Australia.|School of Medicine, University of Adelaide, Adelaide, Australia.|Cancer Research, Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, Australia.
authors.forename: Devendra K
authors.identifier: http://orcid.org/0000-0002-6666-3056
authors.initials: DK
authors.lastname: Hiwase
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.|Cancer Centre, Royal Adelaide Hospital, Adelaide, Australia.|School of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Deepak
authors.initials: D
authors.lastname: Singhal
authors.affiliation: Department of Hematology, Oncology, and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Strupp
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.
authors.forename: Rakchha
authors.initials: R
authors.lastname: Chhetri
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.
authors.forename: Monika M
authors.initials: MM
authors.lastname: Kutyna
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.
authors.forename: L Amilia
authors.initials: LA
authors.lastname: Wee
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Harrison
authors.affiliation: Adelaide Haematology Centre, Ashford Specialist Centre, Adelaide, Australia.
authors.forename: Shriram V
authors.initials: SV
authors.lastname: Nath
authors.affiliation: Adelaide Cancer Centre, Ashford Specialist Centre, Adelaide, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wickham
authors.affiliation: Adelaide Cancer Centre, Ashford Specialist Centre, Adelaide, Australia.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Hui
authors.affiliation: Department of Haematology/Oncology, The Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: James X
authors.initials: JX
authors.lastname: Gray
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.|Cancer Centre, Royal Adelaide Hospital, Adelaide, Australia.|School of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Bardy
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.|Cancer Centre, Royal Adelaide Hospital, Adelaide, Australia.|School of Medicine, University of Adelaide, Adelaide, Australia.|Department of Haematology, Flinders University and Medical Centre, Adelaide, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Ross
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.|Cancer Centre, Royal Adelaide Hospital, Adelaide, Australia.|School of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Lewis
authors.affiliation: Department of Epidemiology and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Haematology Department, SA Pathology, Adelaide, Australia.|Cancer Centre, Royal Adelaide Hospital, Adelaide, Australia.|School of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: L Bik
authors.initials: LB
authors.lastname: To
authors.affiliation: Department of Hematology, Oncology, and Clinical Immunology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D002423:Cause of Death; D003131:Combined Modality Therapy; D019468:Disease Management; D017707:Erythrocyte Transfusion / Q000379:methods; D005260:Female; D005858:Germany; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D015203:Reproducibility of Results; D016896:Treatment Outcome; D055815:Young Adult