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Annals of Hematology
Published in: Annals of Hematology 11/2018

01-11-2018 | Review Article

Autoimmune manifestations associated with myelodysplastic syndromes

Authors: Eric Grignano, Vincent Jachiet, Pierre Fenaux, Lionel Ades, Olivier Fain, Arsène Mekinian

Published in: Annals of Hematology | Issue 11/2018

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Abstract

Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with myelodysplastic syndromes (MDS). Available data suggest that ADs concern more often younger patients with higher risk IPSS. MDS subtypes associated with ADs are mainly MDS with single lineage dysplasia (MDS-SLD) and MDS with excess blasts (MDS-EB). Various types of ADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities as vasculitis, connective tissue diseases, inflammatory arthritis, and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can be seen. In general, ADs do not seem to confer worse survival, although certain ADs may be associated with adverse outcomes (i.e., vasculitis) or progression of MDS (Sweet syndrome). While steroids and immunosuppressive treatment (IST) remain the backbone of first-line treatment, increasing evidence suggests that MDS-specific therapy as hypomethylating agents, based on their immunomodulatory effect, may be effective in treating these complications and for sparing steroids.
Literature
1.
Adès L, Itzykson R, Fenaux P (2014) Myelodysplastic syndromes. Lancet
2.
Saif MW, Hopkins JL, Gore SD (2002) Autoimmune phenomena in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Lymphoma 43(11):2083–2092CrossRef
3.
Enright H, Miller W (1997) Autoimmune phenomena in patients with myelodysplastic syndromes. Leuk Lymphoma 24(5–6):483–489CrossRef
4.
Mekinian A et al (2015) Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study. Rheumatology (Oxford)
5.
Castro M, Conn DL, Su WP, Garton JP (1991) Rheumatic manifestations in myelodysplastic syndromes. J Rheumatol 18(5):721–727PubMed
6.
Giannouli S, Voulgarelis M, Zintzaras E, Tzioufas AG, Moutsopoulos HM (2004) Autoimmune phenomena in myelodysplastic syndromes: a 4-yr prospective study. Rheumatology (Oxford, England) 43(5):626–632CrossRef
7.
de Hollanda A, Beucher A, Henrion D, Ghali A, Lavigne C, Lévesque H, Hamidou M, Subra JF, Ifrah N, Belizna C (2011) Systemic and immune manifestations in myelodysplasia: a multicenter retrospective study. Arthritis Care Res 63(8):1188–1194CrossRef
8.
Okamoto T et al (1997) Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients. Int J Hematol 66(3):345–351CrossRef
9.
Billstrom R, Johansson H, Johansson B, Mitelman F (1995) Immune-mediated complications in patients with myelodysplastic syndromes--clinical and cytogenetic features. Eur J Haematol 55(1):42–48CrossRef
10.
Berthier S, Magy N, Gil H, Becker Schneider M, Vuitton DA, Dupond JL (2001) Myélodysplasies et maladies systémiques. Une association non fortuite. Rev Méd Interne 22(5):428–432CrossRef
11.
Hamidou MA, Derenne S, Audrain MA, Berthelot JM, Boumalassa A, Grolleau JY (2000) Prevalence of rheumatic manifestations and antineutrophil cytoplasmic antibodies in haematological malignancies. A prospective study. Rheumatology (Oxford) 39(4):417–420CrossRef
12.
Bouali F et al (2005) Immunological abnormalities in myelodysplastic syndromes. Prospective study (series of 40 patients). Rev Med Interne 26(10):777–783CrossRef
13.
Marisavljević D, Kraguljac N, Rolović Z (2006) Immunologic abnormalities in myelodysplastic syndromes: clinical features and characteristics of the lymphoid population. Med Oncol 23(3):385–391CrossRef
14.
Dalamaga M, Karmaniolas K, Matekovits A, Migdalis I, Papadavid E (2008) Cutaneous manifestations in relation to immunologic parameters in a cohort of primary myelodysplastic syndrome patients. J Eur Acad Dermatol Venereol 22(5):543–548CrossRef
15.
Al Ustwani O, Francis J, Wallace PK, Ambrus J Jr, Wetzler M (2011) Treating myelodysplastic syndrome improves an accompanying autoimmune disease along with a reduction in regulatory T-cells. Leuk Res 35(5):e35–e36CrossRef
16.
Grignano E, Mekinian A, Jachiet V, Coppo P, Fain O (2017) Autoimmune and inflammatory disorders associated with lymphoid hematological malignancies. Rev Med Interne 38(6):374–382CrossRef
17.
Anderson LA, Pfeiffer RM, Landgren O, Gadalla S, Berndt SI, Engels EA (2009) Risks of myeloid malignancies in patients with autoimmune conditions. Br J Cancer 100(5):822–828CrossRef
18.
Kordasti SY, Ingram W, Hayden J, Darling D, Barber L, Afzali B, Lombardi G, Wlodarski MW, Maciejewski JP, Farzaneh F, Mufti GJ (2007) CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Blood 110(3):847–850CrossRef
19.
Mailloux AW, Sugimori C, Komrokji RS, Yang L, Maciejewski JP, Sekeres MA, Paquette R, Loughran TP, List AF, Epling-Burnette PK (2012) Expansion of effector memory regulatory T cells represents a novel prognostic factor in lower risk myelodysplastic syndrome. J Immunol 189(6):3198–3208CrossRef
20.
Costantini B, Kordasti SY, Kulasekararaj AG, Jiang J, Seidl T, Abellan PP, Mohamedali A, Thomas NSB, Farzaneh F, Mufti GJ (2013) The effects of 5-azacytidine on the function and number of regulatory T cells and T-effectors in myelodysplastic syndrome. Haematologica 98(8):1196–1205CrossRef
21.
Hejazi M, Manser AR, Frobel J, Kundgen A, Zhao X, Schonberg K, Germing U, Haas R, Gattermann N, Uhrberg M (2015) Impaired cytotoxicity associated with defective natural killer cell differentiation in myelodysplastic syndromes. Haematologica 100(5):643–652CrossRef
22.
Sohlberg E, Pfefferle A, Andersson S, Baumann BC, Hellström-Lindberg E, Malmberg K-J (2015) Imprint of 5-azacytidine on the natural killer cell repertoire during systemic treatment for high-risk myelodysplastic syndrome. Oncotarget 6(33):34178–34190CrossRef
23.
Sternberg A, Killick S, Littlewood T, Hatton C, Peniket A, Seidl T, Soneji S, Leach J, Bowen D, Chapman C, Standen G, Massey E, Robinson L, Vadher B, Kaczmarski R, Janmohammed R, Clipsham K, Carr A, Vyas P (2005) Evidence for reduced B-cell progenitors in early (low-risk) myelodysplastic syndrome. Blood 106(9):2982–2991CrossRef
24.
Barcellini W, Zaninoni A, Imperiali FG, Boschetti C, Colombi M, Iurlo A, Zanella A (2007) Anti-erythroblast autoimmunity in early myelodysplastic syndromes. Haematologica 92(1):19–26CrossRef
25.
Mekinian A, Dervin G, Lapidus N, Kahn JE, Terriou L, Liozon E, Grignano E, Piette JC, Rauzy OB, Grobost V, Godmer P, Gillard J, Rossignol J, Launay D, Aouba A, Cardon T, Bouillet L, Broner J, Vinit J, Ades L, Carrat F, Salvado C, Toussirot E, Versini M, Costedoat-Chalumeau N, Fraison JB, Guilpain P, Fenaux P, Fain O, GFM, SNFMI, CRI and MINHEMON (2017) Biologics in myelodysplastic syndrome-related systemic inflammatory and autoimmune diseases: French multicenter retrospective study of 29 patients. Autoimmun Rev 16(9):903–910CrossRef
26.
Stifter G, Heiss S, Gastl G, Tzankov A, Stauder R (2005) Over-expression of tumor necrosis factor-alpha in bone marrow biopsies from patients with myelodysplastic syndromes: relationship to anemia and prognosis. Eur J Haematol 75(6):485–491CrossRef
27.
Ustwani OA et al (2013) Myelodysplastic syndromes and autoimmune diseases-case series and review of literature. Leuk Res
28.
Ahn JK, Cha HS, Koh EM, Kim SH, Kim YG, Lee CK, Yoo B (2008) Behcet’s disease associated with bone marrow failure in Korean patients: clinical characteristics and the association of intestinal ulceration and trisomy 8. Rheumatology (Oxford) 47(8):1228–1230CrossRef
29.
Fain O, Braun T, Stirnemann J, Fenaux P (2011) Systemic and autoimmune manifestations in myelodysplastic syndromes. Rev Med Interne 32(9):552–559CrossRef
30.
Toyonaga T, Nakase H, Matsuura M, Minami N, Yamada S, Honzawa Y, Hukata N, Yoshino T, Chiba T, Okazaki K (2013) Refractoriness of intestinal Behçet’s disease with myelodysplastic syndrome involving trisomy 8 to medical therapies - our case experience and review of the literature. Digestion 88(4):217–221CrossRef
31.
Fain O, Hamidou M, Cacoub P, Godeau B, Wechsler B, ParIès J, Stirnemann J, Morin AS, Gatfosse M, Hanslik T, Belmatoug N, Blétry O, Cevallos R, Delevaux I, Fisher E, Hayem G, Kaplan G, le hello C, Mouthon L, Larroche C, Lemaire V, Piette AM, Piette JC, Ponge T, Puechal X, Rossert J, Sarrot-Reynauld F, Sicard D, Ziza JM, Kahn MF, Guillevin L (2007) Vasculitides associated with malignancies: analysis of sixty patients. Arthritis Rheum 57(8):1473–1480CrossRef
32.
Dion J, Costedoat-Chalumeau N, Sène D, Cohen-Bittan J, Leroux G, Dion C, Francès C, Piette JC (2016) Relapsing polychondritis can be characterized by three different clinical phenotypes: analysis of a recent series of 142 patients. Arthritis Rheum (Hoboken, NJ) 68(12):2992–3001CrossRef
33.
Myers B, Gould J, Dolan G (2000) Relapsing polychondritis and myelodysplasia: a report of two cases and review of the current literature. Clin Lab Haematol 22(1):45–48CrossRef
34.
Piette JC, Papo T, Chavanon P, Huong DL, Frances C, Godeau P (1995) Myelodysplasia and relapsing polychondritis. J Rheumatol 22(6):1208–1209PubMed
35.
Espinosa G, Font J, Muñoz-Rodríguez FJ, Cervera R, Ingelmo M (2002) Myelodysplastic and myeloproliferative syndromes associated with giant cell arteritis and polymyalgia rheumatica: a coincidental coexistence or a causal relationship? Clin Rheumatol 21(4):309–313CrossRef
36.
Mekinian A, Braun T, Decaux O, Falgarone G, Toussirot E, Raffray L, Omouri M, Gombert B, de Wazieres B, Buchdaul AL, Ziza JM, Launay D, Denis G, Madaule S, Rose C, Grignano E, Fenaux P, Fain O, Club Rhumatismes et Inflammation (CRI), Groupe Francophone des Myélodysplasies (GFM), Société Nationale Française de Médecine Interne (SNFMI) (2014) Inflammatory arthritis in patients with myelodysplastic syndromes: a multicenter retrospective study and literature review of 68 cases. Medicine (Baltimore) 93(1):1–10CrossRef
37.
Bellan M, Boggio E, Sola D, Gibbin A, Gualerzi A, Favretto S, Guaschino G, Bonometti R, Pedrazzoli R, Pirisi M, Sainaghi PP (2017) Association between rheumatic diseases and cancer: results from a clinical practice cohort study. Intern Emerg Med 12(5):621–627CrossRef
38.
Paira S, Graf C, Roverano S, Rossini J (2002) Remitting seronegative symmetrical synovitis with pitting oedema: a study of 12 cases. Clin Rheumatol 21(2):146–149CrossRef
39.
Lee SJ et al (2016) Certain autoimmune manifestations are associated with distinctive karyotypes and outcomes in patients with myelodysplastic syndrome: a retrospective cohort study. Medicine (Baltimore) 95(13):e3091CrossRef
40.
Kulasekararaj AG, Kordasti S, Basu T, Salisbury JR, Mufti GJ, du Vivier AWP (2015) Chronic relapsing remitting Sweet syndrome--a harbinger of myelodysplastic syndrome. Br J Haematol 170(5):649–656CrossRef
41.
Van Rhee F, Abela M (1991) Coombs negative haemolytic anaemia responding to intravenous immunoglobulins in a patient with myelodysplastic syndrome. Clin Lab Haematol 13(1):99–101CrossRef
42.
Novaretti MC, Sopelete CR, Velloso ER, Rosa MF, Dorlhiac-Llacer PE, Chamone DA (2001) Immunohematological findings in myelodysplastic syndrome. Acta Haematol 105(1):1–6CrossRef
43.
Park S-J, Han CW, Lee JH, Eom HS, Lee SH, Jeong DC, Lim JH (2003) Cyclosporine A in the treatment of a patient with immune thrombocytopenia accompanied by myelodysplastic syndrome and nephrotic syndrome. Acta Haematol 110(1):36–40CrossRef
44.
Xue Y, Han Y, Li T, Chen S, Zhang J, Pan J, Wu Y, Wang Y, Shen J (2010) Pulmonary alveolar proteinosis as a terminal complication in a case of myelodysplastic syndrome with idic(20q-). Acta Haematol 123(1):55–58CrossRef
45.
Wang Z, Zhou Y, Liu Y (2008) Concurrent inflammatory bowel disease and myelodysplastic syndrome: report of nine new cases and a review of the literature. Dig Dis Sci 53(7):1929–1932CrossRef
46.
Fraison JB, Mekinian A, Braun T, Grignano E, Adès L, Brechignac S, Gardin C, Bourgarit-Durand A, Chollet-Martin S, Nicaise-Roland P, Fenaux P, Fain O (2015) 279 frequency of autoantibodies (AAB) in MDS with and without clinical autoimmune disorders (AID). Leuk Res 39:S139–S140CrossRef
47.
Grignano E, Mekinian A, Braun T, Liozon E, Hamidou M, Decaux O, Puéchal X, Kahn JE, Schoindre Y, Rossignol J, Lortholary O, Lioger B, Hermine O, Park S, Ades L, Montestruc F, Ricard L, Gardin C, Fenaux P, Fain O, GFM, SNFMI and CRI (2016) Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: a series of 26 cases and literature review. Leuk Res 47:136–141CrossRef
48.
Hamidou MA, Boumalassa A, Larroche C, Kouri DE, Blétry O, Grolleau J-Y (2001) Systemic medium-sized vessel vasculitis associated with chronic myelomonocytic leukemia. Semin Arthritis Rheum 31(2):119–126CrossRef
49.
Ertz-Archambault N, Kosiorek H, Taylor GE, Kelemen K, Dueck A, Castro J, Marino R, Gauthier S, Finn L, Sproat LZ, Palmer J, Mesa RA, al-Kali A, Foran J, Tibes R (2017) Association of therapy for autoimmune disease with myelodysplastic syndromes and acute myeloid leukemia. JAMA Oncol 3(7):936–943CrossRef
50.
Devauchelle-Pensec V, Berthelot JM, Cornec D, Renaudineau Y, Marhadour T, Jousse-Joulin S, Querellou S, Garrigues F, de Bandt M, Gouillou M, Saraux A (2016) Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study. Ann Rheum Dis 75(8):1506–1510CrossRef
51.
Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, le Toumelin P, French Vasculitis Study Group (FVSG) (2011) The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore) 90(1):19–27CrossRef
52.
Régent A et al (2016) Tocilizumab in giant cell arteritis: a multicenter retrospective study of 34 patients. J Rheumatol 43(8):1547–1552CrossRef
53.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR, International Vidaza High-Risk MDS Survival Study Group (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10(3):223–232CrossRef
54.
Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Bernal del Castillo T, al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Dohner H (2015) International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 126(3):291–299CrossRef
55.
Frietsch JJ, Dornaus S, Neumann T, Scholl S, Schmidt V, Kunert C, Sayer HG, Hochhaus A, la Rosée P (2014) Paraneoplastic inflammation in myelodysplastic syndrome or bone marrow failure: case series with focus on 5-azacytidine and literature review. Eur J Haematol 93(3):247–259CrossRef
56.
Pilorge S, Doleris LM, Dreyfus F, Park S (2011) The autoimmune manifestations associated with myelodysplastic syndrome respond to 5-azacytidine: a report on three cases. Br J Haematol 153(5):664–665CrossRef
57.
Raj K, Ho A, Creamer JD, du Vivier AWP, Salisbury JR, Mufti GJ (2007) Complete response of deep neutrophilic dermatosis associated with myelodysplastic syndrome to 5-azacytidine. Br J Dermatol 156(5):1039–1041CrossRef
58.
Fraison J-B, Mekinian A, Grignano E, Kahn JE, Arlet JB, Decaux O, Denis G, Buchdahl AL, Omouri M, Maigne G, Aouba A, Leon N, Berthier S, Liozon E, Park S, Gardin C, Lortholary O, Rossignol J, Fenaux P, Fain O, Braun T (2016) Efficacy of azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Res 43:13–17CrossRef
59.
Goodyear OC, Dennis M, Jilani NY, Loke J, Siddique S, Ryan G, Nunnick J, Khanum R, Raghavan M, Cook M, Snowden JA, Griffiths M, Russell N, Yin J, Crawley C, Cook G, Vyas P, Moss P, Malladi R, Craddock CF (2012) Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood 119(14):3361–3369CrossRef
60.
Poplutz MK, Wessels I, Rink L, Uciechowski P (2014) Regulation of the Interleukin-6 gene expression during monocytic differentiation of HL-60 cells by chromatin remodeling and methylation. Immunobiology 219(8):619–626CrossRef
61.
Soysal T, Saliho lu A, Esato lu SN, Gulturk E, E kazan AE, Hatemi G, Hatemi I, Ongoren Ayd n, Erzin YZ, Ba lar Z, Tuzuner N, Ferhano lu B, Celik AF (2014) Bone marrow transplantation for Behçet’s disease: a case report and systematic review of the literature. Rheumatology (Oxford) 53(6):1136–1141CrossRef
62.
Daikeler T et al (2009) Allogeneic hematopoietic SCT for patients with autoimmune diseases. Bone Marrow Transplant 44(1):27–33CrossRef
Metadata
Title
Autoimmune manifestations associated with myelodysplastic syndromes
Authors
Eric Grignano
Vincent Jachiet
Pierre Fenaux
Lionel Ades
Olivier Fain
Arsène Mekinian
Publication date
01-11-2018
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 11/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3472-9

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