Determination of Red Blood Cell Alloimmunization Rates in Transfused Patients with Hematologic and Oncologic Malignancies

Abstract

Introduction: Patients with hematological and oncological malignancies are among the most frequent recipients of chronic red blood cell (RBC) transfusion therapy. One of the risks associated with chronic RBC exposure is the development of blood group antibodies. However, there are few extensive studies of alloimmunization rates associated with hematological or oncological malignancies in adult patients despite the frequency with which they are transfused. As such, the aims of this study were: 1) to determine the alloimmunization rate associated with malignant conditions in general, 2) to establish and compare alloimmunization rates for individuals with different forms of hematological and oncological neoplasia, and 3) to determine if any oncological disorder(s) appeared to predispose individuals to alloimmunization such that antibody mitigation measures could be employed for these diagnoses. Methods: Patients included were those undergoing type and screen testing at the study site (n=18,750 unique, active subjects in our facility's transfusion record database). For each of these subjects, the electronic medical record was retrospectively reviewed to determine if a history of a hematologic or oncologic malignancy was present. Disorders grouped as 'hematologic malignancies' in this study included: acute leukemia (myeloid or lymphoid), mast cell diseases, multiple myeloma, myelodysplastic syndromes, myeloproliferative disorders, and non-Hodgkin lymphoma (T- or B-cell). 'Non-hematologic' cancers in this study were broadly grouped as follows: bladder, colon, head/neck, lung, prostate, skin, soft tissue/sarcoma. If a patient had a history of any of the above neoplastic diseases, further inclusion in the study required: 1) that the patient undergo at least one RBC unit transfusion after their diagnosis was established and 2) that at least one follow-up antibody screen test be performed after their first RBC transfusion post-diagnosis. When these additional inclusion criteria were met, the following data were collected for each subject: malignancy type, race/ethnicity, gender, and the number and specificity of antibodies detected. Ratio data were compared using the chi-square test with Yates' correction for continuity; P values <0.05 were considered significant. Results: A total of 69 patients became alloimmunized after their diagnosis of a malignancy; these patients were overwhelmingly male (66/69; 95.7%) and most identified as white, non-Hispanic (50/69; 72.5%). The alloimmunization rate among patients with any malignancy diagnosis was 1.5% (69/4687), which was significantly lower than the general, historical alloimmunization rate at our facility (443/18750; 2.4%; P=0.0019). Of total transfused patients with a malignancy, most were diagnosed with a non-hematological disorder(4371/4687; 93.3%) and such malignancies were associated with an alloimmunization rate of 1.3% (55/4371) following transfusion. By comparison, the alloimmunization rate for transfused patients with hematological malignancies was 2.8% (14/501), which was significantly higher (P=0.011). When alloantibody development was analyzed on a disorder-by-disorder basis, the five highest alloimmunization rates were seen in: myelodysplastic syndromes (8/71; 11.2%), soft tissue cancers (3/50; 6.0%), acute leukemia (1/34; 2.9%), renal cancer (3/113; 2.7%), and myeloproliferative disorders (2/75; 2.7%). Alloimmunization rates under 2% were observed for all other hematological and non-hematological malignancies encountered in our patient population. Conclusions: RBC alloimmunization rates in transfused patients with malignancy were significantly lower than historical controls, suggesting that the immunosuppressive nature of these disorders and/or their associated therapies may play a role in limiting blood group antibody development. Hematologic disorders were associated with higher alloimmunization rates than non-hematologic malignancies, which may reflect a larger transfusion burden in these illnesses (a factor to be evaluated in future analyses). Overall, only myelodysplastic syndromes and soft tissue malignancies were associated with antibody formation rates substantially higher than historical controls. Therefore, consideration for prophylactic antigen matching to prevent alloimmunization may be warranted for these conditions. Disclosures No relevant conflicts of interest to declare.

Antibody incidence and red blood cell transfusions in patients on daratumumab

“…These incidence findings were not significantly different from those of a hematologic malignancy patient population with the history of transfusion and follow-up (2.8%, p = .49), although there was a difference compared to all transfused patients in the same reference study (1.47%, 1.15%, 186%) (Table 1). 6 In addition, our overall prevalence of patients with antibodies on Dara was 4.51% (11/244), which was not significantly different from that found in transfused patients (Table 1) (2.95%, p = .16). 7 Four Dara patients formed clinically significant alloantibodies following RBC transfusion (Table 2).…”

RBC alloimmunization and daratumumab: Are efforts to eliminate interferences and prevent new antibodies necessary?

“…The incidence of newly identified antibodies in all daratumumab-treated patients (1.64%) was not statistically significantly different from the control population (1.57%), which had unknown transfusion histories. Similarly, no statistically significant differences were noted in the incidence of newly identified antibodies in the daratumumab-treated patients who had been transfused when compared to patients with hematologic malignancies as described by Asare et al 5 These results expand on previous retrospective studies that also suggest low rates of RBC alloimmunization in patients treated with daratumumab. [6][7][8][9][10][11][12][13] However, conclusions from these studies are limited by small sample sizes, relatively short follow-up periods, or the use of extended phenotypically matched RBC units (e.g., extended Rh, K, Fy a /Fy b , Jk a /Jk b , and S/s matching 6 ).…”

“…14 Several issues limit the certainty of these conclusions from this study. The control population was derived from patients from a different time period (September 2007 to April 2012) than the cohort, and there is no discussion about how comparable their cohort is to the two different reference populations from Asare et al and Hoeltge et al 5,15 In addition, the wide confidence interval for the incidence of new alloantibodies in the transfused daratumumab-treated patients suggests a degree of statistical uncertainty. Other considerations not addressed include whether the timing or duration of daratumumab treatment or other demographic features may have any correlation with alloimmunization.…”

Frequency and specificity of erythrocyte alloimmunization in patients at a reference hospital in Alagoas, Brazil

“…An inspiring study determined the rate of erythrocyte alloimmunization in patients with hematological neoplasms and found rates of variable alloimmunization according to the type of pathology (Asare et al, 2016). For the authors, the highest rates were for myelodysplastic syndromes (8/71; 11.2%), acute leukemia (1/34; 2.9%) and myeloproliferative disorders (2/75; 2.7%).…”