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First autologous hematopoietic SCT for ankylosing spondylitis: a case report and clues to understanding the therapy

Bone Marrow Transplantation volume 47, pages 1479–1481 (2012)Cite this article

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Autologous hematopoietic SCT (HSCT) in combination with high-dose chemotherapy is one of the effective therapies for treating systemic autoimmune diseases, such as multiple sclerosis, systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, or juvenile arthritis.1, 2 Still, after 15 years of clinical experience, the mechanisms that determine efficiency of HSCT treatment remain unexplained, hampering the rational development and optimization of this therapy. As more data are obtained confirming the efficiency and safety of this therapeutic approach, so too will the list of autoimmune diseases for which HSCT can be used expand.2, 3 One such candidate disease is ankylosing spondylitis (AS), an autoimmune disease characterized by chronic inflammation of the spine and sacroiliac joints. Although manifestations of AS can be quite severe, this disease is usually not life-threatening and HSCT is not used to treat it. One case was reported in which a lymphoma patient with active AS received an autologous HSCT.4 In this case, CR was observed for the entire 20-month follow-up period, demonstrating the potential of HSCT therapy for AS. However, the highly cytotoxic BEAM chemotherapy regimen used for lymphoma patients differs from that of modern HSCT protocols for treating autoimmune diseases, which use much milder immunoablative pre-transplant regimens. Here we report the first case of intentional treatment of AS with HSCT performed after immunoablative chemotherapy. Basing on the fate of T-cell clones tracked by quantitative next-generation sequencing (NGS) for 4 years before and for 2 years after the treatment, we suggest basic mechanisms that lead to the protective reconstitution of the immune system after HSCT.

The patient, HLA-B27-positive man born in 1963, was subjected to the high-dose chemotherapy (200 mg/kg of CY for 4 days) and autologous HSCT (2.4 × 106 kg body weight of CD34+ stem cells, no CD34+-positive selection was performed) with infusion of antithymocyte globulin for in vivo T-cell depletion. The procedure was performed in June 2009, in accordance with the European Group for Bone Marrow Transplantation (EBMT) protocol.1, 2 The patient was examined every 3–6 months after HSCT. The BASDAI, BASFI and BAS-G values decreased significantly and remained stably low for the entire 2-year follow-up period (Supplementary Figure S1 on the BMT website). The treatment resulted in the complete resolution of spine and hip pain symptoms. Since the HSCT, the patient has not taken any NSAIDs, disease-modifying antirheumatic drugs or anti-TNF-alpha therapy. During the follow-up period, there were several episodes of fever followed by aphthous stomatitis on the lips and mouth. These symptoms were efficiently suppressed by prompt oral administration of low-dose (800 mg/day) acyclovir, indicating that resistance to herpes virus infections was depressed after HSCT. Magnetic resonance imaging (MRI) of the spine and hips was performed 1 and 2 years after HSCT, and showed the absence of inflammatory lesions in the spine and only mild inflammation in the left hip (BM edema of the femoral head, Supplementary Figure S2 on the BMT website). However, no baseline MRI was available for comparison. X-ray of cervical and lumbar spine did not reveal bone proliferation. Overall, complete clinical remission was observed for the whole follow-up period, indicating that HSCT can be an effective treatment for AS in those cases where anti-TNF-alpha biologics efficiency is low. Blood count and flow cytometry analysis were performed at several time points during the 2 years of observation after HSCT. The total numbers of T, B and NK cells reached the pre-graft levels at 8 months post HSCT. Kinetics of the repopulation of the CD4 and CD8 T cells differed significantly, and both populations consisted of large percentages of activated effector-memory and effector T cells. Both the naïve T-cell pool and the CD4/CD8T-cell ratio partially recovered, indicating general reconstitution of the immune system to a healthy state (for details, see Supplementary Data S1 and Supplementary Table S1 on the BMT website).

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Acknowledgements

We are grateful to Professor Poddubnyy DA for the valuable suggestions and comments on the manuscript. This work was supported by the Molecular and Cell Biology program RAS, Russian Science Support Foundation, Basic Research for Medicine RAS, Russian Foundation for Basic Research (10-04-01771-à, 11-04-12042-ofi-m) and Russian Federation President Grant for young scientists (MK-575.2011.4).

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  1. O V Britanova, A G Bochkova and D B Staroverov: These authors contributed equally to this work.

Authors and Affiliations

  1. Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia

    O V Britanova, D B Staroverov, D A Bolotin, I Z Mamedov, M A Turchaninova, E V Putintseva, A A Kotlobay, S Lukyanov, Y B Lebedev & D M Chudakov

  2. Research Institute of Rheumatology, RAMS, Moscow, Russia

    A G Bochkova

  3. Department of Haematology and Cellular Therapy, Pirogov National Medical Surgical Center, Moscow, Russia

    D A Fedorenko & A A Novik

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  1. O V Britanova
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Correspondence to D M Chudakov.

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Britanova, O., Bochkova, A., Staroverov, D. et al. First autologous hematopoietic SCT for ankylosing spondylitis: a case report and clues to understanding the therapy. Bone Marrow Transplant 47, 1479–1481 (2012). https://doi.org/10.1038/bmt.2012.44

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