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.
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Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and life-threatening delayed drug hypersensitivity reaction characterized by skin eruption, fever and visceral involvement that typically presents in response to certain medications. Most publications focus on the clinical and dermatologic aspects of this syndrome. However, this report will describe clinicopathologic features of DRESS, focusing on the histologic and immunohistochemical findings in the skin, pericardium and cerebral cortex. This is the case of a 30-year-old African American HIV-positive woman, who was evaluated in the emergency department after experiencing chest pain for 1 week and generalized pruritus for 6 weeks. Highly active antiretroviral therapy (HAART) had been discontinued 1 week before presentation due to suspicion of an allergic reaction. After an extensive workup, her chest pain was diagnosed as pericarditis. Subsequently, she rapidly deteriorated, experiencing seizures and requiring intubation. She developed cerebral edema with transtentorial and uncal herniation on the 14th day of admission. Gross autopsy findings included uncal herniation, fibrinous pericarditis, and a diffuse erythematous rash over the dorsum of the hands and bilateral lower extremities. Microscopic findings included organizing fibrinous pericarditis, diffuse epidermal necrosis and mixed inflammatory infiltrate within vessel walls in the dermis. Sections from the cerebral cortex showed scattered areas with lymphocytic perivascular cuffing and invasion into the vessel walls by CD3-positive T lymphocytes (T cells). These T cells showed staining with TIA-1 and granzyme B, features consistent with a cytotoxic T cell infiltrate. The constellation of findings, including history of HAART, peripheral eosinophilia, pericarditis, and vasculitis in the skin and cerebral cortex, are consistent with DRESS. DRESS is an uncommon disorder; better characterization of the pathologic features will lead to better understanding of its pathogenesis, and potentially more targets for treatment.
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