Determining hemodilution in diagnostic bone marrow aspirated samples in plasma cell disorders by next-generation flow cytometry: Proposal for a bone marrow quality index

• Main Authors: Óskarsson, Jón Þórir, Rögnvaldsson, Sæmundur, Thorsteinsdottir, Sigrun, Aspelund, Thor, Gunnarsson, Steinar Bragi, Hákonardóttir, Guðlaug Katrín, Sigurðardóttir, Guðrún Ásta, Þórðardóttir, Ásdís Rósa, Gíslason, Gauti Kjartan, Ólafsson, Andri, Sigurðsson, Jón Kristinn, Eyþórsson, Elías, Jónsson, Ásbjörn, Viðarsson, Brynjar, Önundarson, Páll Torfi, Agnarsson, Bjarni A, Pálmason, Róbert, Sigurðardóttir, Margrét, Þorsteinsdóttir, Ingunn, Ólafsson, Ísleifur, Harding, Stephen, Flores-Montero, Juan, Orfao, Alberto, Durie, Brian G. M., Love, Thorvardur Jon, Kristinsson, Sigurdur Yngvi
• Other Authors: International Myeloma Foundation, Icelandic Centre for Research, European Research Council, European Commission, Leukemia & Lymphoma Society (US), University of Iceland, Icelandic Cancer Society
• Format: Article in Journal/Newspaper
• Language: English
• Published: Springer Nature 2023
• Subjects: Cancer microenvironment; Myeloma; Iceland
• Online Access: http://hdl.handle.net/10261/347175; https://doi.org/10.1038/s41408-023-00951-2; https://doi.org/10.13039/100005189; https://doi.org/10.13039/501100000781; https://doi.org/10.13039/501100001840; https://doi.org/10.13039/100003887; https://doi.org/10.13039/501100000780; https://api.elsevier.com/content/abstract/scopus_id/85178181238

Hemodilution of bone marrow (BM) aspirates is a limitation of multiparameter flow cytometry (MFC) in plasma cell disorders. There is a need for a validated approach for assessing sample quality and the distribution of non-plasma cell BM populations by MFC could provide a solution. We evaluated BM-associated cell populations, assessed by next-generation flow cytometry (NGF) and white blood cell (WBC) count in 351 BM aspirated samples from 219 participants with plasma cell disorders in the Iceland Screens, Treats, or Prevents MM study (iStopMM), as markers of hemodilution by their discriminatory ability between first and (generally more hemodiluted) second pull BM aspirated samples. The most discriminating markers were used to derive a novel BM quality index (BMQI). Nucleated red blood cells and myeloid precursors provided the greatest discriminatory ability between first vs second pull samples (area under the curve (AUC): 0.87 and 0.85, respectively), significantly better than B cell precursors (AUC = 0.64; p < 0.001), mast cells (AUC = 0.65; p < 0.001), and the BM WBC count (AUC = 0.77; p < 0.05). We generated a novel BMQI that is intrinsic to current NGF protocols, for evaluating quality of diagnostic BM samples and suggest the use of a BMQI scoring system for interpreting results and guiding appropriate actions. The iStopMM study is funded by the Black Swan Research Initiative by the International Myeloma Foundation and the Icelandic Centre for Research (grant agreement numbers 173857, 217897-051, and 228521-051). Furthermore, this project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement numbers 716677 and 101045549). The project has also received funding from The Leukemia & Lymphoma Society (grant number 2340-23) and the International Myeloma Society. Screening tests are performed by The Binding Site Ltd., Birmingham, UK. Additional funding is provided by the University of Iceland, ...