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Changes in the autoantibody pattern during allogeneic stem-cell transplantation for acute myeloid leukemia complicated by systemic lupus erythematosus

Bone Marrow Transplantation volume 51, pages 883–884 (2016)Cite this article

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Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease. To date, allogeneic-hematopoietic stem cell transplantations (allo-HSCT) for autoimmune diseases have been theoretically considered to be promising. However, incomplete ablation of autoreactive lymphocytes by conditioning regimens and graft-versus-autoimmunity effects and secondary emergence of autoreactive lymphocytes, referred to as chronic GvHD (cGvHD), are major obstacles.1, 2 Therefore, allo-HSCT may be limited to only patients with SLE complicated with hematologic malignancies.3 Here we present a case in which a patient successfully underwent allo-HSCT for relapsed AML complicated with SLE, antiphospholipid syndrome (APS) and chronic autoimmune thyroiditis. Monitoring of auto-Abs revealed that the staining pattern of antinuclear antibody (ANA) was altered after allo-HSCT. Furthermore, diminished levels of anti-thyroid peroxidase (TPO) Abs reappeared 2 years after allo-HSCT.

A 40-year-old woman visited our hospital with leukocytopenia and excess blasts in the peripheral blood. Because she was diagnosed with SLE and APS with a high titer of ANA (1:640; homogeneous and speckled patterns) and several auto-Abs at the age of 25 (Table 1), she was maintained on 5 mg of prednisolone (PSL) for a long time. She underwent a bone marrow examination and was diagnosed with AML with cytogenetically normal karyotype and monoallelic CEBPA mutation (WHO, 2008,4 AML with CEBPA mutation; FAB, M2). She achieved the first CR after induction chemotherapy; however, she underwent a relapse during consolidation chemotherapy. We conducted allogeneic peripheral blood HSCT from an HLA-matched, blood type-mismatched, sex-matched sibling donor in non-CR. Cytoreductive chemotherapy was performed ~1 month before allo-HSCT because previous reports have suggested that a low tumor burden is necessary for improving the outcomes of allo-HSCT.5 Her conditioning regimen was as follows: 3 g/m2 of cytarabine coupled with granulocyte colony-stimulating factor every 12 h for 2 days, 60 mg/kg of cyclophosphamide for 2 days and 12 Gy/6 fractions of TBI. Cyclosporine and short-term methotrexate were used for prophylaxis of GvHD. She achieved neutrophil engraftment, complete chimera and a second CR on day 14. She was discharged 55 days after allo-HSCT. Cyclosporine was tapered and stopped at day 254. PSL was also tapered after HSCT; however, adrenocortical insufficiency occurred at 1 mg of PSL (day 51). PSL was reincreased to 5 mg, maintained at the same dosage for ~3 years and stopped 3.4 years after HSCT. Grade 1 acute GvHD (skin, stage 2) was observed. cGvHD was not observed and no systemic treatment was required. Regarding ANA and the auto-Abs shown in Table 1, titers of her auto-Abs showed a tendency to reduce after chemotherapy and allo-HSCT. The staining pattern of ANA changed to a nucleolar pattern 6 months after allo-HSCT and the titer of ANA gradually increased without any evidence of cGvHD. Panels of ANA using the EUROLINE assay (Euroimmun AG, Luebeck, Germany) revealed that the ANAs detected were against the U1 small nuclear ribonucleoprotein (70 kDa; referred to as RNP70 thereafter) and the RNA polymerase III subunit RP155. The anti-TPO Ab that had become undetectable 1 year after allo-HSCT reappeared with an increased titer 2 years after allo-HSCT. She survived without leukemia for >4 years and is currently undergoing treatment with a thyroid hormone preparation owing to subclinical hypothyroidism. Complete donor chimerism, based on amplification of short tandem repeats of peripheral blood and bone marrow, was sustained up to the final follow-up. The donor did not show any obvious signs of autoimmune disease 4 years after PBSC apheresis. Although neither ANA immunofluorescence nor anti-TPO Ab was identified, EUROLINE assay detected ANA against RP155 in the donor serum.

Table 1 Titers of antinuclear antibody and auto-Abs before and after allogeneic-hematopoietic stem cell transplantation
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References

  1. Patriarca F, Skert C, Sperotto A, Zaja F, Falleti E, Mestroni R et al. The development of autoantibodies after allogeneic stem cell transplantation is related with chronic graft-vs-host disease and immune recovery. Exp Hematol 2006; 34: 389–396.

    Article  CAS  Google Scholar 

  2. Daikeler T, Labopin M, Ruggeri A, Crotta A, Abinun M, Hussein AA et al. New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation. Blood 2013; 121: 1059–1064.

    Article  CAS  Google Scholar 

  3. Rosario C, Seguro L, Vasconcelos C, Shoenfeld Y . Is there a cure for systemic lupus erythematosus? Lupus 2013; 22: 417–421.

    Article  CAS  Google Scholar 

  4. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edn. IARC: Lyon, France, 2008.

    Google Scholar 

  5. Arita K, Kondo T, Sugita J, Shigematsu A, Shiratori S, Wakasa K et al. Sequential chemotherapy and myeloablative allogeneic hematopoietic stem cell transplantation for refractory acute lymphoblastic leukemia. Int J Hematol 2011; 94: 291–295.

    Article  CAS  Google Scholar 

  6. Hiepe F, Dorner T, Hauser AE, Hoyer BF, Mei H, Radbruch A . Long-lived autoreactive plasma cells drive persistent autoimmune inflammation. Nat Rev Rheumatol 2011; 7: 170–178.

    Article  CAS  Google Scholar 

  7. Hoyer BF, Moser K, Hauser AE, Peddinghaus A, Voigt C, Eilat D et al. Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. J Exp Med 2004; 199: 1577–1584.

    Article  CAS  Google Scholar 

  8. Slifka MK, Antia R, Whitmire JK, Ahmed R . Humoral immunity due to long-lived plasma cells. Immunity 1998; 8: 363–372.

    Article  CAS  Google Scholar 

  9. Smith-Berdan S, Gille D, Weissman IL, Christensen JL . Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white mice by nonmyeloablative transplantation of purified allogeneic hematopoietic stem cells. Blood 2007; 110: 1370–1378.

    Article  CAS  Google Scholar 

  10. Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S et al. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood 2009; 113: 214–223.

    Article  CAS  Google Scholar 

  11. Taniguchi K, Yoshihara S, Maruya E, Ikegame K, Kaida K, Hayashi K et al. Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors. Bone Marrow Transplant 2012; 47: 1338–1342.

    Article  CAS  Google Scholar 

  12. Kohrt HE, Muller A, Baker J, Goldstein MJ, Newell E, Dutt S et al. Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation. Blood 2011; 118: 5319–5329.

    Article  CAS  Google Scholar 

  13. Low AH, Wong S, Thumboo J, Ng SC, Lim JY, Ng X et al. Evaluation of a new multi-parallel line immunoassay for systemic sclerosis-associated antibodies in an Asian population. Rheumatology (Oxford) 2012; 51: 1465–1470.

    Article  CAS  Google Scholar 

  14. Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 2004; 50: 380–386.

    Article  Google Scholar 

  15. Lu M, Bernatsky S, Ramsey-Goldman R, Petri M, Manzi S, Urowitz MB et al. Non-lymphoma hematological malignancies in systemic lupus erythematosus. Oncology 2013; 85: 235–240.

    Article  CAS  Google Scholar 

  16. Saxena SK, Bin Salih SA, Al-Jizeeri AH, Kheir OA . Acute myeloblastic leukemia in a patient with primary antiphospholipid syndrome. Saudi Med J 2003; 24: 1013–1015.

    PubMed  Google Scholar 

Download references

Acknowledgements

We sincerely thank the hospital staff. We are deeply grateful to Dr Takeshi Kondo (Hokkaido University) for the technical support of mutational analysis.

Author contributions

KA, JM and TM were attending physicians in the hospital; AW and TM planned the outpatient management; TS organized the therapeutic team; KA drafted the paper; and all authors read and agreed with its content.

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  1. Department of Gastroenterology and Hematology, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan

    K Arita, J Murakami, A Wada, T Miyazono & T Sugiyama

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  1. K Arita
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  2. J Murakami
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Correspondence to K Arita.

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Arita, K., Murakami, J., Wada, A. et al. Changes in the autoantibody pattern during allogeneic stem-cell transplantation for acute myeloid leukemia complicated by systemic lupus erythematosus. Bone Marrow Transplant 51, 883–884 (2016). https://doi.org/10.1038/bmt.2016.21

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