title: Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization.
abstract: Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19-0.68) and 0.30 (range 0.12-0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09-0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16-0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization.
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands.|Department of Immuno-hematology and Blood Transfusion, Leiden University Medical Center, the Netherlands.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Evers
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands.|Department of Immuno-hematology and Blood Transfusion, Leiden University Medical Center, the Netherlands.
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Zwaginga
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands.|Department of Immuno-hematology and Blood Transfusion, Leiden University Medical Center, the Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Tijmensen
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands.|Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands.
authors.forename: Rutger A
authors.initials: RA
authors.lastname: Middelburg
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands.|Department of Immuno-hematology and Blood Transfusion, Leiden University Medical Center, the Netherlands.|Department of Immunohematology Diagnostics, Sanquin, Amsterdam, the Netherlands.
authors.forename: Masja
authors.initials: M
authors.lastname: de Haas
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center, Utrecht, the Netherlands.
authors.forename: Karen M K
authors.initials: KM
authors.lastname: de Vooght
authors.affiliation: Department of Clinical Chemistry and Hematology, Catharina Hospital, Eindhoven, the Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: van de Kerkhof
authors.affiliation: Department of Hematology, VU Medical Center, Amsterdam, the Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Visser
authors.affiliation: Department of Clinical Chemistry and Hematology, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands.
authors.forename: Nathalie C V
authors.initials: NC
authors.lastname: Péquériaux
authors.affiliation: LabWest, Haga Teaching Hospital, The Hague, the Netherlands.
authors.forename: Francisca
authors.initials: F
authors.lastname: Hudig
authors.affiliation: Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands j.g.vanderbom@lumc.nl.|Department of Clinical Epidemiology, Leiden University Medical Center, the Netherlands.
authors.forename: Johanna G
authors.initials: JG
authors.lastname: van der Bom
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D019337:Hematologic Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007114:Immunization; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy*; D009426:Netherlands / Q000453:epidemiology; D011159:Population Surveillance; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007518:Isoantibodies