Validation and cost-effectiveness of an in-house dithiothreitol (DTT) treatment protocol for daratumumab patients in a large tertiary care hospital provides gateway for implementation in smaller community hospitals

Youssef, Mariam; Arnesen, Christine; Arledge, Cindy; Langley, Connie; Sylvester, D.G.H.; Sikora, James; Marques, Marisa B.; Zheng, X. Long; Williams, Lance A.

doi:10.1016/j.transci.2018.12.019

Cited by 6 publications

(7 citation statements)

References 23 publications

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“…5,10 Altogether, transfusion services for patients receiving daratumumab require increased labor and costs, estimated to be in the hundreds of dollars per patient per year, and determining both cost/time-effective and clinically appropriate transfusion practices is beneficial. 11,12 The best transfusion practices for these patients have not been identified, and management varies by institution. 13 In our hospital transfusion service, we request an extended RBC phenotype (or genotype) prior to daratumumab initiation in order to provide RBCs that are phenotypically matched for the D, C, c, E, e, and K antigens.…”

Section: Introductionmentioning

confidence: 99%

“…Safe patient management requires transfusing patients on daratumumab with K‐negative RBCs unless they have been shown to be K‐positive 5,10 . Altogether, transfusion services for patients receiving daratumumab require increased labor and costs, estimated to be in the hundreds of dollars per patient per year, and determining both cost/time‐effective and clinically appropriate transfusion practices is beneficial 11,12 …”

Section: Introductionmentioning

confidence: 99%

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Optimizing transfusion management of multiple myeloma patients receiving daratumumab‐based regimens

et al. 2021

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Background: Daratumumab, a human anti-CD38 monoclonal antibody used to treat multiple myeloma, interferes with pretransfusion testing and can mask alloantibodies. Incidence of alloimmunization in patients on daratumumab has not been well characterized, and optimal transfusion guidelines regarding prophylactic antigen matching, accounting for both patient safety and efficiency, have not been well established for these patients.Methods: Records of patients who received daratumumab between January 1, 2014 and July 2, 2019 were reviewed. Daratumumab interference with pretransfusion testing was managed by testing with reagent red blood cells (RBCs) treated with 0.2 M dithiothreitol. When daratumumab was present during antibody testing, patients were transfused with RBC units prophylactically matched for D, C, c, E, e, and K antigens per hospital policy.Results: Out of 90 patients identified, 52 received a total of 638 RBC transfusions (average of 12.3 units per patient, SD 17.2, range 1-105, median 5 among those transfused). Alloantibodies existing before daratumumab initiation were identified in seven patients. No new alloantibodies were detected in any patients after starting daratumumab treatment. Conclusions:The incidence of alloimmunization in patients receiving daratumumab is low. Whether this is due to the effect of daratumumab, underlying pathophysiology, or other factors, is unknown. Because these patients require a large number of RBC transfusions overall and have little observed alloimmunization, phenotype matching (beyond RhD) may be unnecessary.Since the use of dithiothreitol cannot rule out the presence of anti-K, we recommend transfusion of ABO-compatible units, prophylactically matched for the D and K antigens only.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimizing transfusion management of multiple myeloma patients receiving daratumumab‐based regimens

et al. 2021

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“…Safety Data Sheets generally recommend a local (fume hood) or general exhaust/ventilation system to avoid respiratory irritation during its preparation. While such facilities are likely available in larger institutions, blood bank laboratories in smaller community hospitals may find it impractical to carry out these recommendations, leading to outsourcing of testing that introduces significant costs and delays as described elsewhere 27 . By contrast, the preparation of trypsin stock solutions involves relatively minimal hazard, as the pH titration steps with NaOH utilized a dilute 0.1‐molar solution in our case.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, the preparation of trypsin stock solutions involves relatively minimal hazard, as the pH titration steps with NaOH utilized a dilute 0.1‐molar solution in our case. Therefore, our simple in‐house technique can facilitate safe blood transfusion for DARA‐treated patients while mitigating the delays and expenses of unnecessary testing and outsourcing 27 …”

Section: Discussionmentioning

confidence: 99%

Use of an in‐house trypsin‐based method to resolve the interference of daratumumab

et al. 2021

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Background Daratumumab (DARA) is a monoclonal antibody for treatment of plasma cell myeloma targeting CD38, a surface molecule expressed on plasma cells and red blood cells (RBCs). This complicates blood bank testing, requiring dithiothreitol (DTT) to remove DARA interference. A simple in‐house method of removing DARA interference without use of DTT, a potentially hazardous chemical, is desirable. We demonstrate a trypsin‐based method to remove interference in antibody testing at a medical center (MC), with parallel testing at an immunohematology reference laboratory (IRL). Study design and methods Pre‐DARA type and screen (T&S) samples were obtained from 61 patients for antibody testing and RBC phenotyping using untreated reagent RBCs. Subsequent post‐DARA T&S testing was performed with untreated reagent RBCs to demonstrate interference and repeated after trypsin treatment. Positive trypsin‐treated antibody screens were reflexed to antibody identification using trypsin‐treated panel cells. Parallel testing was performed on the same post‐DARA samples at IRL. Results DARA interference was detected in 61/61 (100%) samples by MC and IRL. After trypsin treatment, DARA interference was eliminated in 60/61 (98.4%) antibody screens by both institutions with an overall percent agreement of 96.7% (95% confidence interval [CI] 88.7%–99.6%). Identification of known alloantibodies was confirmed in 3/3 patients with 100% concordant results between MC and IRL. There were no false‐negative results demonstrated by IRL's functionally CD38‐negative controls. Conclusion Our in‐house trypsin‐based method enables pretransfusion testing of patients receiving DARA in an accurate and cost‐effective manner without missing clinically significant alloantibodies. This presents an additional testing option where DTT use is undesirable.

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“…Several antigens, such as Fy a , Fy b and M, are more susceptible to undergoing antigenic variation [34]. Previous reports suggest that if marked haemolysis occurs after 0·2 mol/l DTT treatment, the procedure should be repeated with fresher reagent RBCs and a smaller volume of DTT [39]. However, these reports did not give details of variations in DTT treatment.…”

Section: Discussionmentioning

confidence: 99%

A newly devised flow cytometric antibody binding assay helps evaluation of dithiothreitol treatment for the inactivation of CD38 on red blood cells

et al. 2020

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Background and objectives Anti-CD38 monoclonal antibodies, including daratumumab and isatuximab, often interfere with pretransfusion testing. Dithiothreitol (DTT) treatment of red blood cells (RBCs) negates this interference. However, the optimum DTT concentration and treatment time have not been well defined. Here, we quantified CD38 on RBCs before and after DTT treatment using a flow cytometric antibody binding assay (FABA) to specify the optimum conditions for CD38 inactivation.Materials and methods For FABA, untreated or DTT-treated RBCs were incubated with fluorescein isothiocyanate-labelled anti-CD38 antibody, in the presence or absence of 100-fold or more excess of unlabelled anti-CD38 antibody, and then analysed by flow cytometry (FCM). Dissociation of CD38-positive and control histograms was determined from the D-value using the Kolmogorov-Smirnov test. The results from FABA were compared with those from conventional FCM, indirect antiglobulin test (IAT) and Western blotting. ResultsThe results from FABA were more consistent than those from conventional FCM. The D-value was found to be reliable in the analysis of difference between CD38 before and after DTT treatment. Our data showed that 0Á0075 mol/ l DTT for 30 min is sufficient to inactivate CD38 on RBCs. These results were stable and consistent with the findings from IAT.Conclusion Flow cytometric antibody binding assay is an objective way of evaluating the efficacy of DTT treatment for CD38 on RBCs. This approach allows the detection of a small number of cell surface antigens and will be useful for assessing the various chemical treatments to denature RBC antigens.

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Validation and cost-effectiveness of an in-house dithiothreitol (DTT) treatment protocol for daratumumab patients in a large tertiary care hospital provides gateway for implementation in smaller community hospitals

Cited by 6 publications

References 23 publications

Optimizing transfusion management of multiple myeloma patients receiving daratumumab‐based regimens

Optimizing transfusion management of multiple myeloma patients receiving daratumumab‐based regimens

Use of an in‐house trypsin‐based method to resolve the interference of daratumumab

A newly devised flow cytometric antibody binding assay helps evaluation of dithiothreitol treatment for the inactivation of CD38 on red blood cells

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