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1267 Higher Rate of Red Blood Cell (RBC) Alloimmunization in RBC-Transfused Myelodysplastic Syndrome Compared to Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 401. Blood Transfusion: Poster I
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, MDS, Clinical Practice (Health Services and Quality), Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Thomas Wiseman1,2*, Michaela Spooner, BSc(LabMed)1*, Shreyas Khanna1,2*, Kevin Hung, MBBS, FRACP, FRCPA1, Carla Toop, PhD1*, Deepak Singhal, MBBS, MD, FRACP, FRCPA1*, David T Yeung, MBBS, PhD, BSc, FRACP, FRCPA1,2,3, Hamish S Scott, PhD4,5, Christopher N. Hahn, PhD4*, Daniel Thomas, MBBS, PhD3,4,6*, Chung How Kok, BSc, PhD4,5* and Devendra Hiwase, MD, MBBS, PhD, FRACP, FRCPA1,2,3,4

1Royal Adelaide Hospital, Adelaide, SA, Australia
2University of Adelaide, Adelaide, SA, Australia
3South Australian Health and Medical Research Institute, Adelaide, SA, Australia
4University of South Australia, Adelaide, SA, Australia
5SA Pathology, Adelaide, SA, Australia
6Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia

Background: Up to 90% of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia require red blood cell (RBC) transfusions and 11–14% of RBC-transfused MDS patients develop RBC alloantibodies (Singhal et al., Haematologica 2017; Chhetri et al., Haematologica 2019), most commonly against Rhesus (Rh) and Kell (K).

Method: Myeloid neoplasm (MN; n=1961) patients enrolled in the South Australian Myeloid Neoplasm registry with complete data to a censor date of January 1, 2023, were included for further analysis. We first characterized the RBC transfusion burden and alloimmunization rate in RBC-transfused patients. Then, we assessed the risk factors associated with RBC alloimmunization and its impact on transfusion requirements.

Results: Our study of 1961 MN patients included MDS (n=1077, 54.9%), AML (n=644; 32.8%), MDS and myeloproliferative neoplasm (MPN) overlap syndrome (n=222, 11.3%) and related MN/bone marrow failure syndrome (n=18; 0.9%). Although the majority of MN patients (n=1660, 84.7%) were de novo, 15.3% (n=301) had therapy-related MN (t-MN) following prior exposure to cytotoxic therapies for independent primary cancers. The median age at MN diagnosis was 69.2 years (interquartile range 58.6, 78.4) and 63.2% (n=1240) of patients were male.

The majority of patients (n=1452, 74.0%) had died by the censor date. The overall survival (OS) of AML was significantly shorter than MDS and MDS-MPN overlap cases (10.8 vs. 36.3 vs. 30.9 months; P <0.0001). The median OS of t-MDS (14.2 vs. 42.0; P < 0.0001) and t-AML (6.9 vs. 11.7 months; P <0.0001) was significantly worse than their de novo counterparts.

After MN diagnosis, 1732 (88.3%) patients received at least one RBC unit and 11% (n=191) of these patients developed 264 alloantibodies. The most common alloantibodies were E (n=69, 45.1%), K (n=37, 24.2%), C (n=25, 16.3%), D (n=23, 15.0%), and Jka (n=22, 14.4%). The rate of alloimmunization was significantly higher in RBC-transfused MDS than AML (12.3% vs. 3.6%; P < 0.001), despite similar rates of antibody screens between the two groups (42.9% vs. 46.2%; P = 0.062), which could explain the higher RBC transfusion requirement in MDS compared to AML patients (40.75 vs. 30.40 units; P < 0.001). Higher alloimmunization in MDS compared to AML is probably related to the highly myelosuppressive treatment used in AML. Furthermore, the RBC alloimmunization rate was significantly higher in t-MN compared to de novo (12.5% vs. 8.1%; P =0.023), despite receiving a comparable number of RBCs (37.0 vs. 35.8 units; P = 0.7). Although the RBC alloimmunization rate was higher in females compared to males, it was not statistically significant (10.5% vs. 7.8%; P =0.06).

Next, we assessed the clinical consequences of RBC alloimmunization. RBC autoantibodies were detected in 16 MN patients and alloimmunized patients were significantly more likely to develop autoantibodies (7.2% vs. 0.3%; P < 0.001). The RBC transfusion burden in alloimmunized patients was significantly higher compared to non-alloimmunized patients (72.1±77.2 vs. 32.9±50.0 units; P<0.001). In RBC-alloimmunized patients, the RBC transfusion burden significantly increased after alloantibody formation compared to before the alloimmunization (22.5±42.0 vs. 50.1±57.2 units; P <0.0001).

Conclusion: To our knowledge, this is the largest cohort characterizing RBC alloimmunization in MN (n~2000). The key findings of the study include the high burden of RBC alloimmunization in RBC-transfused MDS compared to AML. Antibodies against Rh and Kell were most prevalent and RBC-alloimmunization is associated with increased autoantibody formation. Importantly, RBC alloimmunization is associated with increased transfusion burden. This study provides compelling evidence of extended phenotyping to provide Rh and Kell phenotype-matched RBC transfusions to MDS patients.

Disclosures: Yeung: Novartis: Honoraria, Research Funding; BMS: Research Funding; Ascentage: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Hiwase: Astella Pharma: Honoraria; Otsuka: Honoraria; Abbvie: Honoraria.

*signifies non-member of ASH