Diagnostic evaluation in bone marrow failure disorders: what have we learnt to help inform the transplant decision in 2024 and beyond?
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
30 Jan 2024
30 Jan 2024
Historique:
received:
19
10
2023
accepted:
12
01
2024
revised:
11
01
2024
medline:
31
1
2024
pubmed:
31
1
2024
entrez:
30
1
2024
Statut:
aheadofprint
Résumé
Aplastic anemia (AA) is the prototypical bone marrow failure syndrome. In the current era of readily available 'molecular annotation', application of comprehensive next-generation sequencing panels has generated novel insights into underlying pathogenetic mechanisms, potentially leading to improvements in personalized therapeutic approaches. New evidence has emerged as to the role of somatic loss of HLA class I allele expression in 'immune-mediated' AA, associated molecular aberrations, and risk of clonal evolution. A deeper understanding has emerged regarding the role of 'myeloid' gene mutations in this context, translating patho-mechanistic insights derived from wider clinical and translational research within the myeloid disorder arena. Here, we review contemporary 'tools' which aid in confirmation of a diagnosis of AA, with an additional focus on their potential in guiding therapeutic options. A specific emphasis is placed upon interpretation and integration of this detailed diagnostic information and how this may inform optimal transplantation strategies.
Identifiants
pubmed: 38291125
doi: 10.1038/s41409-024-02213-6
pii: 10.1038/s41409-024-02213-6
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Gurnari C, Pagliuca S, Maciejewski JP. Clonal evolution in aplastic anemia: failed tumor surveillance or maladaptive recovery? Leuk Lymphoma. 2023;64:1389–99.
pubmed: 37356012
doi: 10.1080/10428194.2023.2215614
Li SS, Hsu YT, Chang C, Lee SC, Yen CC, Cheng CN, et al. Incidence and treatment outcome of aplastic anemia in Taiwan-real-world data from single-institute experience and a nationwide population-based database. Ann Hematol. 2019;98:29–39.
pubmed: 30178191
doi: 10.1007/s00277-018-3486-3
Vaht K, Göransson M, Carlson K, Isaksson C, Lenhoff S, Sandstedt A, et al. Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-2011. Haematologica. 2017;102:1683–90.
pubmed: 28751565
pmcid: 5622852
doi: 10.3324/haematol.2017.169862
Gurnari C, Maciejewski JP. Aplastic anemia: Quo vadis? Semin Hematol. 2022;59:54–5.
pubmed: 35491060
doi: 10.1053/j.seminhematol.2021.12.001
Pagliuca S, Gurnari C, Hercus C, Hergalant S, Nadarajah N, Wahida A, et al. Molecular landscape of immune pressure and escape in aplastic anemia. Leukemia. 2023;37:202–11.
pubmed: 36253429
doi: 10.1038/s41375-022-01723-w
Gurnari C, Pagliuca S, Prata PH, Galimard J-E, Catto LFB, Larcher L, et al. Clinical and molecular determinants of clonal evolution in aplastic anemia and paroxysmal nocturnal hemoglobinuria. J Clin Oncol. 2022;41:132–42.
pubmed: 36054881
pmcid: 10476808
doi: 10.1200/JCO.22.00710
Young NS. Aplastic anemia. N Engl J Med. 2018;379:1643–56.
pubmed: 30354958
pmcid: 6467577
doi: 10.1056/NEJMra1413485
Bacigalupo A, Hows J, Gluckman E, Nissen C, Marsh J, Van Lint MT, et al. Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): a report of the EBMT SAA working party. Br J Haematol. 1988;70:177–82.
pubmed: 3056497
doi: 10.1111/j.1365-2141.1988.tb02460.x
Gurnari C, Prata PH, Catto LFB, Durmaz A, Larcher L, Sébert M, et al. IPSS-M in myelodysplastic neoplasms arising from aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood. 2023;141:3122–5.
pubmed: 37053552
Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017;129:1428–36.
pubmed: 28096088
doi: 10.1182/blood-2016-08-693481
DeZern AE, Churpek JE. Approach to the diagnosis of aplastic anemia. Blood Adv. 2021;5:2660–71.
pubmed: 34156438
pmcid: 8270669
doi: 10.1182/bloodadvances.2021004345
Gurnari C, Graham AC, Efanov A, Pagliuca S, Durrani J, Awada H, et al. Frequency and perturbations of various peripheral blood cell populations before and after eculizumab treatment in paroxysmal nocturnal hemoglobinuria. Blood Cells Mol Dis. 2021;87:102528.
pubmed: 33341510
doi: 10.1016/j.bcmd.2020.102528
Durrani J, Maciejewski JP. Idiopathic aplastic anemia vs hypocellular myelodysplastic syndrome. Hematol Am Soc Hematol Educ Program. 2019;2019:97–104.
doi: 10.1182/hematology.2019000019
Bejanyan N, Kim S, Hebert KM, Kekre N, Abdel-Azim H, Ahmed I, et al. Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia. Blood Adv. 2019;3:3123–31.
pubmed: 31648332
pmcid: 6849938
doi: 10.1182/bloodadvances.2019000722
Bacigalupo A, Benintende G. Bone marrow transplantation for acquired aplastic anemia: what’s new. Best Pract Res Clin Haematol. 2021;34:101284.
pubmed: 34404530
doi: 10.1016/j.beha.2021.101284
Sakaguchi H, Yoshida N. Recent advances in hematopoietic cell transplantation for inherited bone marrow failure syndromes. Int J Hematol. 2022;116:16–27.
pubmed: 35633493
doi: 10.1007/s12185-022-03362-4
Ogawa S. Clonal hematopoiesis in acquired aplastic anemia. Blood. 2016;128:337–47.
pubmed: 27121470
pmcid: 5054460
doi: 10.1182/blood-2016-01-636381
Gálvez E, Vallespín E, Arias-Salgado EG, Sánchez-Valdepeñas C, Giménez Y, Navarro S, et al. Next-generation sequencing in bone marrow failure syndromes and isolated cytopenias: experience of the Spanish network on bone marrow failure syndromes. Hemasphere. 2021;5:e539.
pubmed: 33718801
pmcid: 7951136
doi: 10.1097/HS9.0000000000000539
Miyata T, Takeda J, Iida Y, Yamada N, Inoue N, Takahashi M, et al. The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science. 1993;259:1318–20.
pubmed: 7680492
doi: 10.1126/science.7680492
Miyata T, Yamada N, Iida Y, Nishimura J, Takeda J, Kitani T, et al. Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria. N. Engl J Med. 1994;330:249–55.
pubmed: 8272086
doi: 10.1056/NEJM199401273300404
Gurnari C, Pagliuca S, Patel BJ, Awada H, Kongkiatkamon S, Terkawi L, et al. Implication of PIGA genotype on erythrocytes phenotype in Paroxysmal Nocturnal Hemoglobinuria. Leukemia. 2021;35:2431–4.
pubmed: 33483614
pmcid: 8299540
doi: 10.1038/s41375-020-01113-0
Araten DJ, Nafa K, Pakdeesuwan K, Luzzatto L. Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci. 1999;96:5209–14.
pubmed: 10220445
pmcid: 21843
doi: 10.1073/pnas.96.9.5209
Hu R, Mukhina GL, Piantadosi S, Barber JP, Jones RJ, Brodsky RA. PIG-A mutations in normal hematopoiesis. Blood. 2005;105:3848–54.
pubmed: 15687243
pmcid: 1895084
doi: 10.1182/blood-2004-04-1472
Gurnari C, Pagliuca S, Kewan T, Bahaj W, Mori M, Patel BJ, et al. Is nature truly healing itself? spontaneous remissions in paroxysmal nocturnal hemoglobinuria. Blood Cancer J. 2021;11:187.
pubmed: 34839350
pmcid: 8627504
doi: 10.1038/s41408-021-00582-5
Borowitz MJ, Craig FE, Digiuseppe JA, Illingworth AJ, Rosse W, Sutherland DR, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytom B Clin Cytom. 2010;78:211–30.
doi: 10.1002/cyto.b.20525
Hernández-Campo PM, Almeida J, Sánchez ML, Malvezzi M, Orfao A. Normal patterns of expression of glycosylphosphatidylinositol-anchored proteins on different subsets of peripheral blood cells: a frame of reference for the diagnosis of paroxysmal nocturnal hemoglobinuria. Cytom B Clin Cytom. 2006;70:71–81.
doi: 10.1002/cyto.b.20087
Brodsky RA, Mukhina GL, Li S, Nelson KL, Chiurazzi PL, Buckley JT, et al. Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin. Am J Clin Pathol. 2000;114:459–66.
pubmed: 10989647
doi: 10.1093/ajcp/114.3.459
Sutherland DR, Illingworth A, Marinov I, Ortiz F, Andreasen J, Payne D, et al. ICCS/ESCCA consensus guidelines to detect GPI-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and related disorders part 2 - reagent selection and assay optimization for high-sensitivity testing. Cytom B Clin Cytom. 2018;94:23–48.
doi: 10.1002/cyto.b.21610
Maciejewski JP, Rivera C, Kook H, Dunn D, Young NS. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br J Haematol. 2001;115:1015–22.
pubmed: 11843844
doi: 10.1046/j.1365-2141.2001.03191.x
Schubert J, Vogt HG, Zielinska-Skowronek M, Freund M, Kaltwasser JP, Hoelzer D, et al. Development of the glycosylphosphatitylinositol-anchoring defect characteristic for paroxysmal nocturnal hemoglobinuria in patients with aplastic anemia. Blood. 1994;83:2323–8.
pubmed: 8161800
doi: 10.1182/blood.V83.8.2323.2323
Griscelli-Bennaceur A, Gluckman E, Scrobohaci ML, Jonveaux P, Vu T, Bazarbachi A, et al. Aplastic anemia and paroxysmal nocturnal hemoglobinuria: search for a pathogenetic link. Blood. 1995;85:1354–63.
pubmed: 7858265
doi: 10.1182/blood.V85.5.1354.bloodjournal8551354
Wang H, Chuhjo T, Yasue S, Omine M, Nakao S. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome. Blood. 2002;100:3897–902.
pubmed: 12393738
doi: 10.1182/blood-2002-03-0799
Raza A, Ravandi F, Rastogi A, Bubis J, Lim SH, Weitz I, et al. A prospective multicenter study of paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure. Cytom B Clin Cytom. 2014;86:175–82.
doi: 10.1002/cytob.21139
Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:3699–709.
pubmed: 16051736
pmcid: 1895106
doi: 10.1182/blood-2005-04-1717
Fattizzo B, Ireland R, Dunlop A, Yallop D, Kassam S, Large J, et al. Clinical and prognostic significance of small paroxysmal nocturnal hemoglobinuria clones in myelodysplastic syndrome and aplastic anemia. Leukemia. 2021;35:3223–31.
pubmed: 33664463
pmcid: 8550969
doi: 10.1038/s41375-021-01190-9
Sugimori C, Mochizuki K, Qi Z, Sugimori N, Ishiyama K, Kondo Y, et al. Origin and fate of blood cells deficient in glycosylphosphatidylinositol-anchored protein among patients with bone marrow failure. Br J Haematol. 2009;147:102–12.
pubmed: 19656154
doi: 10.1111/j.1365-2141.2009.07822.x
Bat T, Abdelhamid ON, Balasubramanian SK, Mai A, Radivoyevitch T, Clemente M, et al. The evolution of paroxysmal nocturnal haemoglobinuria depends on intensity of immunosuppressive therapy. Br J Haematol. 2018;182:730–3.
pubmed: 28804905
doi: 10.1111/bjh.14862
Fattizzo B, Gurnari C, Cassanello G, Bortolotti M, Awada H, Giammarco S, et al. Deciphering treatment patterns in non-severe/moderate aplastic anemia: an international observational study. Leukemia. 2023;37:2479–85.
pubmed: 37794100
pmcid: 10681892
doi: 10.1038/s41375-023-02047-z
Yoshizato T, Dumitriu B, Hosokawa K, Makishima H, Yoshida K, Townsley D, et al. Somatic mutations and clonal hematopoiesis in aplastic anemia. N Engl J Med. 2015;373:35–47.
pubmed: 26132940
pmcid: 7478337
doi: 10.1056/NEJMoa1414799
Stanley N, Olson TS, Babushok DV. Recent advances in understanding clonal haematopoiesis in aplastic anaemia. Br J Haematol. 2017;177:509–25.
pubmed: 28107566
pmcid: 5435524
doi: 10.1111/bjh.14510
Kulasekararaj AG, Jiang J, Smith AE, Mohamedali AM, Mian S, Gandhi S, et al. Somatic mutations identify a subgroup of aplastic anemia patients who progress to myelodysplastic syndrome. Blood. 2014;124:2698–704.
pubmed: 25139356
pmcid: 4383793
doi: 10.1182/blood-2014-05-574889
Peffault de Latour R, Kulasekararaj A, Iacobelli S, Terwel SR, Cook R, Griffin M, et al. Eltrombopag added to immunosuppression in severe aplastic anemia. N Engl J Med. 2022;386:11–23.
pubmed: 34986284
doi: 10.1056/NEJMoa2109965
Groarke EM, Patel BA, Shalhoub R, Gutierrez-Rodrigues F, Desai P, Leuva H, et al. Predictors of clonal evolution and myeloid neoplasia following immunosuppressive therapy in severe aplastic anemia. Leukemia. 2022;36:2328–37.
pubmed: 35896822
pmcid: 9701554
doi: 10.1038/s41375-022-01636-8
Pagliuca S, Gurnari C, Rubio MT, Visconte V, Lenz TL. Individual HLA heterogeneity and its implications for cellular immune evasion in cancer and beyond. Front Immunol. 2022;13:944872.
pubmed: 36131910
pmcid: 9483928
doi: 10.3389/fimmu.2022.944872
Pagliuca S, Gurnari C, Awada H, Kishtagari A, Kongkiatkamon S, Terkawi L, et al. The similarity of class II HLA genotypes defines patterns of autoreactivity in idiopathic bone marrow failure disorders. Blood. 2021;138:2781–98.
pubmed: 34748628
pmcid: 8718627
doi: 10.1182/blood.2021012900
Olson TS, Frost BF, Duke JL, Dribus M, Xie HM, Prudowsky ZD, et al. Pathogenicity and impact of HLA class I alleles in aplastic anemia patients of different ethnicities. JCI Insight. 2022;7:e163040.
pubmed: 36219480
pmcid: 9746824
doi: 10.1172/jci.insight.163040
Babushok DV, Duke JL, Xie HM, Stanley N, Atienza J, Perdigones N, et al. Somatic HLA mutations expose the role of class I–mediated autoimmunity in aplastic anemia and its clonal complications. Blood Adv. 2017;1:1900–10.
pubmed: 28971166
pmcid: 5621748
doi: 10.1182/bloodadvances.2017010918
Zaimoku Y, Patel BA, Adams SD, Shalhoub R, Groarke EM, Lee AAC, et al. HLA associations, somatic loss of HLA expression, and clinical outcomes in immune aplastic anemia. Blood. 2021;138:2799–809.
pubmed: 34724566
pmcid: 8718630
doi: 10.1182/blood.2021012895
Huuhtanen J, Bhattacharya D, Lönnberg T, Kankainen M, Kerr C, Theodoropoulos J, et al. Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8(+) T-cell large granular lymphocytic leukemia. Nat Commun. 2022;13:1981.
pubmed: 35411050
pmcid: 9001660
doi: 10.1038/s41467-022-29173-z
Shah YB, Priore SF, Li Y, Tang CN, Nicholas P, Kurre P, et al. The predictive value of PNH clones, 6p CN-LOH, and clonal TCR gene rearrangement for aplastic anemia diagnosis. Blood Adv. 2021;5:3216–26.
pubmed: 34427585
pmcid: 8405198
doi: 10.1182/bloodadvances.2021004201
Bacigalupo A, Giammarco S, Sica S. Bone marrow transplantation versus immunosuppressive therapy in patients with acquired severe aplastic anemia. Int J Hematol. 2016;104:168–74.
pubmed: 27278666
doi: 10.1007/s12185-016-2037-8
DeZern AE, Zahurak M, Jones RJ, Brodsky RA. Uniform conditioning regardless of donor in bone marrow transplantation for severe aplastic anemia. Haematologica. 2023.
DeZern AE, Eapen M, Wu J, Talano JA, Solh M, Dávila Saldaña BJ, et al. Haploidentical bone marrow transplantation in patients with relapsed or refractory severe aplastic anaemia in the USA (BMT CTN 1502): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2022;9:e660–e9.
pubmed: 35907408
pmcid: 9444987
doi: 10.1016/S2352-3026(22)00206-X
DeZern AE, Zahurak M, Symons HJ, Cooke KR, Huff CA, Jain T, et al. Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia. Blood 2023;141:3031–8.
pubmed: 37084383
Sugimori C, Chuhjo T, Feng X, Yamazaki H, Takami A, Teramura M, et al. Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood. 2006;107:1308–14.
pubmed: 16179371
doi: 10.1182/blood-2005-06-2485
Kulagin A, Lisukov I, Ivanova M, Golubovskaya I, Kruchkova I, Bondarenko S, et al. Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study. Br J Haematol. 2014;164:546–54.
pubmed: 24261566
doi: 10.1111/bjh.12661
Zhao X, Zhang L, Jing L, Zhou K, Li Y, Peng G, et al. The role of paroxysmal nocturnal hemoglobinuria clones in response to immunosuppressive therapy of patients with severe aplastic anemia. Ann Hematol. 2015;94:1105–10.
pubmed: 25784221
doi: 10.1007/s00277-015-2348-5
Yoshida N, Yagasaki H, Takahashi Y, Yamamoto T, Liang J, Wang Y, et al. Clinical impact of HLA-DR15, a minor population of paroxysmal nocturnal haemoglobinuria-type cells, and an aplastic anaemia-associated autoantibody in children with acquired aplastic anaemia. Br J Haematol. 2008;142:427–35.
pubmed: 18537977
doi: 10.1111/j.1365-2141.2008.07182.x
Scheinberg P, Wu CO, Nunez O, Young NS. Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol. 2009;144:206–16.
pubmed: 19036108
doi: 10.1111/j.1365-2141.2008.07450.x
Dalle JH, Peffault de Latour R. Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. Int J Hematol. 2016;103:373–9.
pubmed: 26872907
doi: 10.1007/s12185-016-1951-0