Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support.

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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.

Background: Treatment of older patients with myelodysplastic syndrome (MDS) is based on disease biology and performance status. Performance status, however, does not reflect increasing co-morbidities, functional dependence or psychosocial issues in older patients. Patients and Methods: This prospective study evaluated the burden of geriatric related health issues, assessed feasibility of "tailored" Comprehensive Geriatric Assessment (CGA), and compared treatment duration and survival in older patients with MDS and oligoblastic acute myeloid leukemia with and without deficits in CGA domains (n = 98). Results: Although only 27 (28%) patients had an Eastern Cooperative Oncology Group score ≥2, 78% (n = 77) patients had deficits in at least one CGA domain. Deficits were spread across all CGA domains, including dependence for instrumental activity of daily living (iADL; n = 33, 34%). Importantly, patients who were dependent for iADL (3.7 ± 2.6 vs 12.1 ± 7.9; p = .009), had cognitive impairment (3.5 ± 2.1 vs. 10.9 ± 7.9; p = .034) or impaired mobility (3.8 ± 2.5 vs. 13.2 ± 7.6; p = .001) completed significantly less azacitidine cycles as compared to those without these deficits. Cox-proportional regression showed that iADL dependency (hazard ratio 3.37; p = .008) and higher comorbidities (hazard ratio 4.7; p b .001) were associated with poor prognosis independent of disease related factors. Poor survival of iADL dependent patients was seen in both azacitidine (6 vs 19 months; p b .001) and supportive care cohorts (26 vs 48 months; p = .01). Conclusion: CGA detected geriatric related health issues, predicted poor survival and identified patients less likely to continue and benefit from azacitidine. Hence, CGA should be included in the treatment decision algorithm of older patients with MDS.