Abstract
Purpose
The aim of this study was to analyze the occurrence of neuromuscular symptoms in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) for treatment of malignant hematopoietic disease.
Methods
Among 247 outpatients after allogeneic HSCT, we conducted a prospective non-interventional study between July 2011 and August 2013. During follow-up visits, clinical and electrophysiological findings were correlated to the presence of autoantibodies/alloantibodies and to frequencies of lymphocyte subpopulations in peripheral blood.
Results
Resulting in an incidence of 8.1 %, 20 patients were diagnosed with neuromuscular complications at a median onset of 12 months post-transplant. Five patients (25 %) were identified with polyneuropathy (PNP), ten patients (50 %) with combined PNP and myopathy, four patients (20 %) with myopathy or polymyositis (PM), and one patient (5 %) with myasthenia gravis (MG). Immune-mediated sensorimotor PNP after HSCT is characterized by a predominantly axonal lesion and can be overlapping with neurotoxic side effects. The latency between HSCT and development of PM varied between 60 days and 72 months. In general, PM occurs parallel to graft-versus-host disease (GvHD) after tapering of immunosuppressive medication. Typical clinical features are proximal bilateral limb weakness with muscle atrophy. Autoantibodies (Ab) were detected in 12 patients, myositis-specific Ab only in one patient. In patients with progressive neurological symptoms, a decrease in the CD4/CD8 T cell ratio was observed.
Conclusions
GvHD-related myositis appeared similar to idiopathic myositis regarding clinical and electromyographical findings. As outcome measure, sequential analysis of lymphocyte subpopulations in peripheral blood seems to be more suitable than Ab measurements. Whereas peripheral neuropathies are commonly observed shortly after HSCT, MG is a rare complication in the late post-HSCT phase.
Similar content being viewed by others
Abbreviations
- AChR Ab:
-
Acetylcholine receptor antibody
- AL:
-
Acute leukemia
- ALL:
-
Acute lymphocytic leukemia
- ANA:
-
Antinuclear antibodies
- AML:
-
Acute myeloid leukemia
- Ab:
-
Autoantibodies
- CK-MB:
-
Creatine kinase-MB
- CLL:
-
Chronic lymphocytic leukemia
- CML:
-
Chronic myeloid leukemia
- GvHD:
-
Graft-versus-host disease
- HSCT:
-
Hematopoietic stem cell transplantation
- ND:
-
Not done
- MCL:
-
Mantle cell lymphoma
- MG:
-
Myasthenia gravis
- MM:
-
Multiple myeloma
- MPN:
-
Myeloproliferative neoplasm
- OMF:
-
Osteomyelofibrosis
- PM:
-
Polymyositis
- PNP:
-
Polyneuropathy
References
de Brabander C, Cornelissen J, Smitt PA, Vecht CJ, van den Bent MJ (2000) Increased incidence of neurological complications in patients receiving an allogenic bone marrow transplantation from alternative donors. J Neurol Neurosurg Psychiatry 68(1):36–40, Epub 1999/12/22
Teive HA, Funke V, Bitencourt MA, de Oliveira MM, Bonfim C, Zanis-Neto J et al (2008) Neurological complications of hematopoietic stem cell transplantation (HSCT): a retrospective study in a HSCT center in Brazil. Arquivos de neuro-psiquiatria 66(3B):685–690, Epub 2008/10/25
Uckan D, Cetin M, Yigitkanli I, Tezcan I, Tuncer M, Karasimav D et al (2005) Life-threatening neurological complications after bone marrow transplantation in children. Bone Marrow Transplant 35(1):71–76, Epub 2004/11/09
Kotani A, Ishikawa T, Matsumura Y, Ichinohe T, Ohno H, Hori T et al (2001) Correlation of peripheral blood OX40 + (CD134+) T cells with chronic graft-versus-host disease in patients who underwent allogeneic hematopoietic stem cell transplantation. Blood 98(10):3162–3164, Epub 2001/11/08
Jaglowski SM, Devine SM (2014) Graft-versus-host disease: why have we not made more progress? Curr Opin Hematol 21(2):141–147, Epub 2014/01/29
Delios AM, Rosenblum M, Jakubowski AA, DeAngelis LM (2012) Central and peripheral nervous system immune mediated demyelinating disease after allogeneic hemopoietic stem cell transplantation for hematologic disease. J Neuro-Oncol 110(2):251–256, Epub 2012/08/24
Sostak P, Padovan CS, Yousry TA, Ledderose G, Kolb HJ, Straube A (2003) Prospective evaluation of neurological complications after allogeneic bone marrow transplantation. Neurology 60(5):842–848, Epub 2003/03/12
Ahn JS, Cho SH, Kim YK, Yang DH, Bae WK, Shim HJ et al (2009) Polymyositis and myocarditis after donor lymphocyte infusion. Int J Hematol 90(1):113–116, Epub 2009/05/28
Allen JA, Greenberg SA, Amato AA (2009) Dermatomyositis-like muscle pathology in patients with chronic graft-versus-host disease. Muscle Nerve 40(4):643–647, Epub 2009/08/12
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 11(12):945–956, Epub 2005/12/13
Antonini G, Ceschin V, Morino S, Fiorelli M, Gragnani F, Mengarelli A et al (1998) Early neurologic complications following allogeneic bone marrow transplant for leukemia: a prospective study. Neurology 50(5):1441–1445, Epub 1998/05/22
Couriel DR, Beguelin GZ, Giralt S, De Lima M, Hosing C, Kharfan-Dabaja MA et al (2002) Chronic graft-versus-host disease manifesting as polymyositis: an uncommon presentation. Bone Marrow Transplant 30(8):543–546, Epub 2002/10/16
Dowell JE, Moots PL, Stein RS (1999) Myasthenia gravis after allogeneic bone marrow transplantation for lymphoblastic lymphoma. Bone Marrow Transplant 24(12):1359–1361, Epub 2000/01/11
Openshaw H (1997) Peripheral neuropathy after bone marrow transplantation. Biology of blood and marrow transplantation. J Am Soc Blood Marrow Transplant 3(4):202–209, Epub 1997/11/14
Lin PC, Hsiao LT, Chen PM (2005) Acute polymyositis after donor lymphocyte infusion. Eur J Haematol 74(2):166–168, Epub 2005/01/19
Montoro J, Hernandez-Boluda JC, Arbona C, Solano C (2012) Polymyositis after donor lymphocyte infusion. Int J Hematol 96(3):386–389, Epub 2012/08/21
Liu FC, Chen CH, Chao TY (2007) Polymyositis complicating donor lymphocyte infusion after stem cell transplantation for relapsed chronic myeloid leukemia: report of a case and review of literature. Clin Rheumatol 26(7):1207–1210, Epub 2006/08/29
Wechalekar A, Cranfield T, Sinclair D, Ganzckowski M (2005) Occurrence of autoantibodies in chronic graft vs. host disease after allogeneic stem cell transplantation. Clin Lab Haematol 27(4):247–249, Epub 2005/07/29
Maillard-Lefebvre H, Morell-Dubois S, Lambert M, Charlanne H, Launay D, Hachulla E et al (2010) Graft-versus-host disease-related polymyositis. Clin Rheumatol 29(4):431–433, Epub 2010/01/14
Stevens AM, Sullivan KM, Nelson JL (2003) Polymyositis as a manifestation of chronic graft-versus-host disease. Rheumatology (Oxford) 42(1):34–39, Epub 2003/01/02
Mackey JR, Desai S, Larratt L, Cwik V, Nabholtz JM (1997) Myasthenia gravis in association with allogeneic bone marrow transplantation: clinical observations, therapeutic implications and review of literature. Bone Marrow Transplant 19(9):939–942, Epub 1997/05/01
Tse S, Saunders EF, Silverman E, Vajsar J, Becker L, Meaney B (1999) Myasthenia gravis and polymyositis as manifestations of chronic graft-versus-host-disease. Bone Marrow Transplant 23(4):397–399, Epub 1999/04/01
Kotani A, Takahashi A, Koga H, Morita R, Fukuyama H, Ichinohe T et al (2002) Myasthenia gravis after allogeneic bone marrow transplantation treated with mycophenolate mofetil monitored by peripheral blood OX40+ CD4+ T cells. Eur J Haematol 69(5–6):318–320, Epub 2002/12/04
Nagashima T, Sato F, Chuma T, Mano Y, Sasaki I, Mori M et al (2002) Chronic demyelinating polyneuropathy in graft-versus-host disease following allogeneic bone marrow transplantation. Neuropathol Off J Jpn Soc Neuropathol 22(1):1–8, Epub 2002/05/28
Rabinstein AA, Dispenzieri A, Micallef IN, Inwards DJ, Litzow MR, Wijdicks EF (2003) Acute neuropathies after peripheral blood stem cell and bone marrow transplantation. Muscle Nerve 28(6):733–736, Epub 2003/11/26
Lee HJ, Oran B, Saliba RM, Couriel DM, Shin K, Massey P et al (2006) Steroid myopathy in patients with acute graft-versus-host disease treated with high-dose steroid therapy. Bone Marrow Transplant 38(4):299–303, Epub 2006/07/05
Conflict of interest
The authors declare no conflict of interest. They also state that they have full control of primary data and that they agree to allow the journal to review their data if requested.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Koeppen, S., Thirugnanasambanthan, A. & Koldehoff, M. Neuromuscular complications after hematopoietic stem cell transplantation. Support Care Cancer 22, 2337–2341 (2014). https://doi.org/10.1007/s00520-014-2225-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00520-014-2225-0