Brachial Plexopathy Following High-Dose Melphalan and Autologous Peripheral Blood Stem Cell Transplantation

LETTER TO THE EDITOR Brachial plexopathy following high-dose melphalan and autologous peripheral blood stem cell transplantation

Bone Marrow Transplantation (2010) 45, 951–952; Tone and power were normal throughout, lower limb deep doi:10.1038/bmt.2009.243; published online 21 September 2009 tendon reflexes were absent and plantars were downgoing. Magnetic resonance imaging of the whole spine at this point revealed widespread myelomatous involvement of the Neuromuscular pathologies are a recognized complication bony spine but no cord compromise. Thalidomide was of SCT, often occurring as a result of infection or continued with no alteration in dosage. The patient haemorrhage, but also in association with GVHD follow- subsequently underwent a PBSCT with high-dose melpha- ing allogeneic SCT.1 The published literature on post- lan as the conditioning regime. transplant peripheral nervous system pathologies includes Within 14 days of stem-cell infusion the patient devel- descriptions of myasthenia gravis, Guillain-Barre´ oped progressive proximal weakness affecting predomi- syndrome, polymyositis and peripheral neuropathy.2–5 nantly the upper limbs. There was no neck pain or Ocular toxicity, radiculopathy and plexopathy have also involvement of bladder or bowel. Examination revealed rarely been reported. We report three cases of brachial bilateral wrist-drop with grade 3–4 weakness of the small plexopathy occurring after autologous peripheral blood muscles of the hand, elbow flexors and extensors and stem cell transplantation (PBSCT). shoulder abduction. Upper limb reflexes were absent. The neurological findings in the lower limbs were unchanged. Neurophysiological testing revealed profound axonal Case 1 degenerative lesions of upper limb nerves, but not those of the lower limbs, with myopathic concentric needle A 64-year-old man was initially treated with adriamycin, electrode findings in proximal muscles and a mild sural carmustine, CY and melphalan for symptomatic multiple sensory nerve action potential abnormality. An magnetic myeloma. Following a poor response the patient was resonance imaging scan of the whole spine was repeated switched to oral melphalan, which was continued for 6 and again showed no significant neurological abnormal- months. At first progression, 4 years later, chemotherapy ities. Two years post-transplant the patient’s neuropathy was restarted with VCR, CY, doxorubicin and methyl- continues to improve gradually. prednisolone . This was followed by an autologous PBSCT 2 with high-dose melphalan (200 mg/m ) conditioning. Case 3 Fourteen days post-transplant he developed rapidly progressive proximal weakness in both upper limbs. This A 46-year-old man received high-dose melphalan for was associated with pain in both shoulders radiating to treatment of myeloma. Routine blood testing 2 years both hands. Clinical examination revealed bilateral prox- previously resulted in a diagnosis of asymptomatic imal upper limb weakness with wasting and areflexia. The myeloma. Six months later the patient developed persistent remainder of the neurological examination was normal. lower back pain and a skeletal survey revealed lytic lesions Magnetic resonance imaging of the cervical spinal cord in both humeri. Chemotherapy was started with four cycles and brachial plexi was unremarkable but a chest radio- of idarubicin and dexamethasone followed by high-dose graph showed bilateral diaphragmatic paralysis. Nerve melphalan and PBSCT. conduction studies showed bilateral brachial plexus neuro- Two weeks post-transplant the patient developed persis- pathy with predominant involvement of the upper trunks. tent and progressive neuropathic pain in the right hand. The patient is now 9 years post-transplant and there has This rapidly evolved into paraesthesia and muscle wasting been no improvement in the neuropathy. of the right arm. Examination revealed wasting and weakness of the muscles innervated by C5/6, winging of the right scapula, decreased biceps and supinator reflexes Case 2 on the right side and decreased pin prick sensation in the C5 dermatome. A magnetic resonance imaging scan of the A 62-year-old man underwent autologous PBSCT for cervical spine showed no significant abnormalities and treatment of multiple myeloma. At presentation three following a neurological opinion a diagnosis of brachial months previously the patient had received oral CY, plexopathy was made. Neurophysiological studies were not thalidomide and dexamethasone as induction chemother- performed. Over the subsequent 18 months his myeloma apy. After 2 weeks of thalidomide the patient complained remained stable and his neurological function improved but of numbness and paraesthesia in both arms and legs. significant disability persists. Letter to the Editor 952 Brachial plexopathy results in the rapid onset of dull pain Conflict of interest affecting the shoulder girdle accompanied by weakness of the proximal upper limb, as observed in our cases. Sensory The authors declare no conflict of interest. loss is typically less prominent than motor features. Sporadic cases occur in the general population often having a temporal association with infection, vaccination, preg- C Parrish1, A Ming2, R Patmore1, M Shields1 nancy, surgery or drug therapy. and D Allsup1 Neuromuscular pathologies after allogeneic BMT are 1Queens Centre for Oncology and Haematology, Castle Hill well documented and have variously been attributed to Hospital, Cottingham, East Yorkshire, UK and GVHD-induced immune dysregulation, the conditioning 2Department of Neurology, Hull Royal Infirmary, Hull, UK chemotherapy and side-effects of immunosuppression.4–6 E-mail: [email protected] The cases reported here developed brachial plexopathy early after autologous PBSCT with two of the cases having no neurological symptoms before PBSCT. The remaining References case had a pre-existing thalidomide-induced sensory peripheral neuropathy, but developed a second distinct 1 Antonini G, Ceschin V, Morino S, Fiorelli M, Gragnani F, neurological lesion after PBSCT. Neurophysiological test- Mengarelli A et al. Early neurologic complications following ing on this patient revealed a sensory nerve action potential allogeneic bone marrow transplant for leukemia: a prospective that was only mildly reduced. This is in contrast to the study. Neurology 1998; 50: 1441–1445. greater than 50% reduction characteristically seen with 2 Rabinstein AA, Dispenzieri A, Micallef IN, Inwards DJ, thalidomide-related neuropathy, which is typically sensory Litzow MR, Wijdicks EF. Acute neuropathies after peripheral 7,8 blood stem cell and bone marrow transplantation. Muscle rather than motor. Toxicity from induction chemother- Nerve 2003; 28: 733–736. apy seems an unlikely cause for the brachial plexopathies 3 Rodriguez V, Kuehnle I, Heslop HE, Khan S, Krance RA. occurring in these cases as the patients had received three Guillain-Barre´ syndrome after allogeneic hematopoietic different chemotherapy regimens before their PBSCT. All stem cell transplantation. Bone Marrow Transplant 2002; 29: three received high-dose melphalan as the conditioning 515–517. regimen, which is not thought to be associated with 4 Baron F, Sadzot B, Wang F, Beguin Y. Myasthenia gravis neuromuscular toxicity. Paraneoplastic neuropathy also without chronic GVHD after allogeneic bone marrow trans- seems unlikely as the onset followed PBSCT in each case. plantation. Bone Marrow Transplant 1998; 22: 197–200. In previously reported cases (unrelated to PBSCT) 5 Couriel DR, Beguelin GZ, Giralt S, De Lima M, Hosing C, et al. brachial plexus biopsy specimens have revealed inflamma- Kharfan-Dabaja MA Chronic graft-versus-host disease manifesting as polymyositis: an uncommon presentation. Bone tory infiltrates and cultured PBLs have been demonstrated Marrow Transplant 2002; 30: 543–546. to increase their mitogenic activity in response to brachial 6 Openshaw H. Peripheral neuropathy after bone marrow 9,10 plexus nerves. These observations support an autoim- transplantation. Biol Blood Marrow Transplant 1997; 3: mune theory of pathogenesis. There is a delay in immune 202–209. reconstitution following autologous PBSCT and a loss of 7 Mileshkin L, Stark R, Day B, Seymour JF, Zeldis JB, Prince self-tolerance resulting in autoimmune phenomena is HM. Development of neuropathy in patients with myeloma documented in both the allogeneic and autologous treated with thalidomide: patterns of occurrence and the setting.11,12 We suggest that the neuromuscular sequelae role of electrophysiologic monitoring. J Clin Oncol 2006; 24: of PBSCT described here result from an autoimmune 4507–4514. process targeting peripheral nervous system antigens as 8 Plasmati R, Pastorelli F, Cavo M, Petracci E, Zamagni E, Tosi P et al. Neuropathy in multiple myeloma treated opposed to a toxic effect of previously administered drugs. with thalidomide: a prospective study. Neurology 2007; 69: Identification of demyelinating as opposed to axonal 573–581. features on neurophysiological testing would further 9 Sierra A, Prat J, Bas J, Romeu A, Montero J, Matos JA et al. strengthen this hypothesis. This distinction was not possible Blood lymphocytes are sensitized to branchial plexus nerves in in our patients and is likely to prove difficult in patients patients with neuralgic amyotrophy. Acta Neurol Scand 1991; with pre-existing severe axonal neuropathy from neurotoxic 83: 183–186. chemotherapy. 10 Suarez GA, Giannini C, Bosch EP, Barohn RJ, Wodak J, The cases presented here received PBSCT over a 7-year Ebeling P et al. Immune brachial plexus neuropathy: period, with an average of 12.3 patients per year receiving suggestive evidence for an inflammatory-immune pathogenesis. Neurology PBSCT with this conditioning regimen for multiple 1996; 46: 559–561. 11 Porrata LF, Litzow MR, Markovic SN. Immune reconstitu- myeloma in our institution over this period. Brachial tion after autologous hematopoietic stem cell transplantation. plexopathy is therefore an uncommon but potentially Mayo Clin Proc 2001; 76: 407–412. debilitating complication of autologous PBSCT with none 12 Daikeler T, Tyndall A. Autoimmunity following haemato- of our cases experiencing complete resolution of their neuro- poietic stem-cell transplantation. Best Pract Res Clin Haematol logical symptoms after prolonged periods of follow-up. 2007; 20: 349–360.

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