Transfusion Dependency Is Associated With Inferior Survival Even In Very Low and Low Risk IPSS-R Patients
Authors: Hiwase Devendra K. , Kutyna Monika M , Chhetri Rakchha , Howell Stuart , Harrison Peter B , Nath Shriram V , Nath Lakshmi S , Wickham Nicholas , Szabo Ferenc , Hui Chi-Hung , Ross David , Gray James , Melo Junia V , Bardy Peter , To L. Bik 
Published: October 2019

Abstract

Background
The International Prognostic Scoring System (IPSS) is commonly used for predicting the outcome of myelodysplastic syndrome (MDS) patients. Recently, a Revised IPSS (IPSS-R) has been developed to address the limitations of IPSS. IPSS-R identifies five different categories and stratifies patients better than IPSS. Although transfusion dependency is associated with inferior survival outcome, it has not been included in the risk stratification of IPSS-R mainly due to limited availability of transfusion data on patients used for deriving the IPSS-R.

Aim
To evaluate the impact of RBC transfusion on survival outcome in IPSS-R subgroups and assess the validity of IPSS-R in an independent cohort of patients.

Materials and Methods
To match the patient selection criteria used for generating the IPSS-R scoring system, primary MDS patients who were not treated with disease modifying agents or stem cell transplantation were included for this analysis. The impact of RBC transfusion on overall survival (OS) was assessed in IPSS-R subgroups. RBC transfusion dependency was defined as transfusion of at least 1 unit/8 weeks for at least 4 months.

Results
A total of 182 patients were included in this analysis. Their median age was 73 years (21 to 91 years) and 66% patients were male. 106 patients were in the Very Low or Low risk groups (termed ‘lower risk'). The median OS of IPSS-R Very Low, Low, Intermediate, High and Very High risk groups was 87.1, 63.9, 24.5, 17.2 and 7.8 months, respectively (Fig.1. p<0.0001), consistent with previously published results (Greenberg et al, Blood 2012).
Of the 182 patients, 115 (63%) patients were RBC transfusion dependent. RBC transfusion dependency was more frequent in Very High (18/18, 100%), High (25/28, 89%) and Intermediate (21/31, 68%) risk groups as compared to lower risk IPSS-R groups: Low (35/67, 52%) and Very Low (17/39, 43%). The mean pre-transfusion Hb was 79.1 ±12.3 gm/L, and the trigger for transfusion was Hb ≤90, >90 to ≤100 and >100 gm/L in 83%, 11% and 6% of episodes, respectively. In a multivariate analysis, RBC-transfusion dependency (HR 3.18; P<0.0001) was associated with poor survival, independent of the IPSS-R category and age at diagnosis (Table 2). The median OS of transfusion-dependent patients (n=115) was significantly lower (23.8 vs. 117.8 months; p<0.0001) than that of transfusion-independent patients (n=67).
As the majority of IPSS-R higher risk patients were transfusion dependent, we restricted further assessment to IPSS-R lower risk groups. The median OS between Low and Very Low risk group was not significantly different (87.1 vs Low 63.2 months; p=0.1), hence they were grouped together. The median OS of transfusion-dependent lower risk IPSS-R patients (n=52) was significantly shorter than that of transfusion-independent (n=54) patients (52.7 vs 122.5 months; p=0.001).

Conclusions
We have demonstrated that transfusion dependency is associated with inferior survival even in Very Low and Low risk IPSS-R group patients. This warrants further refinement of IPSS-R scoring system specifically for lower risk group patients. IPSS-R scoring system is validated in our independent cohort of patients.

Disclosures:
Hiwase: Novartis Australia: Research Funding; Celgene Australia: Research Funding.