BACKGROUND: Neurotoxicity is one of the dangerous complications of chimeric antigen receptor (CAR) T-cell therapy, while its pathophysiology remains to be fully understood. Motor weakness not associated with central nervous system (CNS) toxicity has rarely been reported after CAR T-cell therapy. CASE REPORT: A 42-year-old female with a refractory diffuse large B-cell lymphoma received tisagenlecleucel (tisa-cel) and developed cytokine release syndrome (CRS) on day 3. She was treated with tocilizumab and methylprednisolone, which resolved CRS promptly. On day 7, motor weakness in lower extremities appeared, and she gradually became unable to walk without showing any other symptoms attributed to CNS disturbances. Whereas dexamethasone and tocilizumab were ineffective, neuropathy improved after high dose chemotherapy followed by autologous stem cell transplantation. Nerve conduction study (NCS) in lower extremities showed a decline in compound muscle action potential amplitude along with worsening of motor weakness, which was restored after improvement of symptoms. Based on symptoms and NCS, her motor weakness was thought to be due to disturbance in peripheral nerves. CONCLUSION: This study reports a patient who developed severe motor weakness due to disturbance in peripheral nerves after tisa-cel therapy. Neurotoxicity of non-CNS origin should also be noted in CAR T-cell therapy.
BACKGROUND: Neurotoxicity is one of the dangerous complications of chimeric antigen receptor (CAR) T-cell therapy, while its pathophysiology remains to be fully understood. Motor weakness not associated with central nervous system (CNS) toxicity has rarely been reported after CAR T-cell therapy. CASE REPORT: A 42-year-old female with a refractory diffuse large B-cell lymphoma received tisagenlecleucel (tisa-cel) and developed cytokine release syndrome (CRS) on day 3. She was treated with tocilizumab and methylprednisolone, which resolved CRS promptly. On day 7, motor weakness in lower extremities appeared, and she gradually became unable to walk without showing any other symptoms attributed to CNS disturbances. Whereas dexamethasone and tocilizumab were ineffective, neuropathy improved after high dose chemotherapy followed by autologous stem cell transplantation. Nerve conduction study (NCS) in lower extremities showed a decline in compound muscle action potential amplitude along with worsening of motor weakness, which was restored after improvement of symptoms. Based on symptoms and NCS, her motor weakness was thought to be due to disturbance in peripheral nerves. CONCLUSION: This study reports a patient who developed severe motor weakness due to disturbance in peripheral nerves after tisa-cel therapy. Neurotoxicity of non-CNS origin should also be noted in CAR T-cell therapy.
Authors: Stephen J Schuster; Michael R Bishop; Constantine S Tam; Edmund K Waller; Peter Borchmann; Joseph P McGuirk; Ulrich Jäger; Samantha Jaglowski; Charalambos Andreadis; Jason R Westin; Isabelle Fleury; Veronika Bachanova; S Ronan Foley; P Joy Ho; Stephan Mielke; John M Magenau; Harald Holte; Serafino Pantano; Lida B Pacaud; Rakesh Awasthi; Jufen Chu; Özlem Anak; Gilles Salles; Richard T Maziarz Journal: N Engl J Med Date: 2018-12-01 Impact factor: 91.245
Authors: Daniel B Rubin; Husain H Danish; Ali Basil Ali; Karen Li; Sarah LaRose; Andrew D Monk; David J Cote; Lauren Spendley; Angela H Kim; Matthew S Robertson; Matthew Torre; Timothy R Smith; Saef Izzy; Caron A Jacobson; Jong Woo Lee; Henrikas Vaitkevicius Journal: Brain Date: 2019-05-01 Impact factor: 13.501
Authors: Jeremy S Abramson; M Lia Palomba; Leo I Gordon; Matthew A Lunning; Michael Wang; Jon Arnason; Amitkumar Mehta; Enkhtsetseg Purev; David G Maloney; Charalambos Andreadis; Alison Sehgal; Scott R Solomon; Nilanjan Ghosh; Tina M Albertson; Jacob Garcia; Ana Kostic; Mary Mallaney; Ken Ogasawara; Kathryn Newhall; Yeonhee Kim; Daniel Li; Tanya Siddiqi Journal: Lancet Date: 2020-09-01 Impact factor: 79.321
Authors: Shannon L Maude; Theodore W Laetsch; Jochen Buechner; Susana Rives; Michael Boyer; Henrique Bittencourt; Peter Bader; Michael R Verneris; Heather E Stefanski; Gary D Myers; Muna Qayed; Barbara De Moerloose; Hidefumi Hiramatsu; Krysta Schlis; Kara L Davis; Paul L Martin; Eneida R Nemecek; Gregory A Yanik; Christina Peters; Andre Baruchel; Nicolas Boissel; Francoise Mechinaud; Adriana Balduzzi; Joerg Krueger; Carl H June; Bruce L Levine; Patricia Wood; Tetiana Taran; Mimi Leung; Karen T Mueller; Yiyun Zhang; Kapildeb Sen; David Lebwohl; Michael A Pulsipher; Stephan A Grupp Journal: N Engl J Med Date: 2018-02-01 Impact factor: 91.245