Summary:
We report the incidence, characteristics and outcome of neurological complications occurring following reduced-intensity conditioning (RIC) in 85 patients who received a related/unrelated donor stem cell transplantation following therapy with alemtuzumab, fludarabine and melphalan. Six patients (probability 8.9%) developed severe neurological complications at a median of 151 days (24–334 days). Five of them presented with progressive peripheral sensori-motor radiculo-neuropathy and/or myelitis, preceded by one or more viral reactivation/infection. Despite treatment with immunoglobulins/plasmapheresis/steroids, four died of respiratory failure due to progressive peripheral neurophathy. Viral infection was identified as the only risk factor for the development of neurological complications. Patients who are treated with alemtuzumab-based RIC may have a lower risk of developing regimen-related neurological complications, but are more susceptible to develop peripheral radiculo-neuropathy or myelitis. This phenomenon may be possibly related to viral infection associated with delayed immunological recovery or immunological dysregulation caused by alemtuzumab-induced T-cell depletion.
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References
Gallardo D, Ferra C, Berlanga JJ et al. Neurologic complications after allogeneic bone marrow transplantation. Bone Marrow Transplant 1996; 18: 1135–1139.
Graus F, Saiz A, Sierra J et al. Neurologic complications of autologous allogeneic bone marrow transplantation in patients with leukemia: a comparative study. Neurology 1996; 46: 1004–1009.
Bleggi-Torres LF, de Medeiros BC, Werner B et al. Neuropathological findings after bone marrow transplantation: an autopsy study of 180 cases. Bone Marrow Transplant 2000; 25: 301–307.
Sostak P, Padovan CS, Yousry TA et al. Prospective evaluation of neurological complications after allogeneic bone marrow transplantation. Neurology 2003; 60: 842–848.
Perry A, Mehta J, Iveson T et al. Guillain-Barre syndrome after bone marrow transplantation. Bone Marrow Transplant 1994; 14: 165–167.
Adams C, August CS, Maguire H, Sladky JT . Neuromuscular complications of bone marrow transplantation. Pediatr Neurol 1995; 12: 58–61.
Wen PY, Alyea EP, Simon D et al. Guillain-Barre syndrome following allogeneic bone marrow transplantation. Neurology 1997; 49: 1711–1714.
Seneviratne U . Guillain-Barre syndrome. Postgrad Med J 2000; 76: 774–782.
Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem cell transplantation cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant nonmalignant hematologic diseases. Blood 1998; 91: 756–763.
Kottaridis PD, Milligan DW, Chopra R et al. In vivo ALEMTUZUMAB prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.
Giralt S, Thall PF, Khouri I et al. Melphalan purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001; 97: 631–637.
McSweeney PA, Niederwieser D, Shizuru JA et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.
Chakraverty R, Peggs K, Chopra R et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 2002; 99: 1071–1078.
Chakrabarti S, Mackinnon S, Chopra R et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Alemtuzumab in delaying immune reconstitution. Blood 2002; 99: 4357–4363.
Chakrabarti S, Mautner V, Osman H et al. Adenovirus infections following allogeneic stem cell transplantation: incidence outcome in relation to graft manipulation immunosuppression, immune recovery. Blood 2002; 100: 1619–1627.
Chakrabarti S, Avivi I, Mackinnon S et al. Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Alemtuzumab: high incidence but low mortality. Br J Haematol 2002; 119: 1125–1132.
Myer SE, Williams SF . Guillain-Barre syndrome after autologous bone marrow transplantation for breast cancer: report of two cases. Bone Marrow Transplant 1994; 13: 341–344.
Lind MJ, McWilliam L, Jip J et al. Cyclosporin associated demyelination following allogeneic bone marrow transplantation. Hematol Oncol 1989; 7: 49–52.
Imrie KR, Couture F, Turner CC et al. Peripheral neuropathy following high-dose etoposide autologous bone marrow transplantation. Bone Marrow Transplant 1994; 13: 77–79.
Openshaw H . Peripheral neuropathy after bone marrow transplantation. Biol Blood Marrow Transplant 1997; 3: 202–209.
Eliashiv S, Brenner T, Abramsky O et al. Acute inflammatory demyelinating polyneuropathy following bone marrow transplantation. Bone Marrow Transplant 1991; 8: 315–317.
Solaro C, Murialdo A, Giunti D et al. Central peripheral nervous system complications following allogeneic bone marrow transplantation. Eur J Neurol 2001; 8: 77–80.
Winer J . Guillain-Barre syndrome. Br J Hosp Med 1994; 51: 313.
Hagensee ME, Benyunes M, Miller JA, Spach DH . Campylobacter jejuni bacteremia Guillain-Barre syndrome in a patient with GVHD after allogeneic BMT. Bone Marrow Transplant 1994; 13: 349–351.
Jacobs BC, Rothbarth PH, van der Meche FG et al. The spectrum of antecedent infections in Guillain-Barre syndrome: a case–control study. Neurology 1998; 51: 1110–1115.
Yuki N, Taki T, Inagak F et al. A bacterium lipopolysaccharide that elicits Guillain-Barre syndrome has a GM1 ganglioside-like structure. J Exp Med 1993; 178: 1771–1775.
Yuki N . Infectious origins of, molecular mimicry in Guillain-Barre Fisher syndromes. Lancet Infect Dis 2001; 1: 29–37.
Rees JH, Soudain SE, Gregson NA, Hughes RA . Campylobacter jejuni infection Guillain-Barre syndrome. N Engl J Med 1995; 333: 1374–1379.
Rees JH, Gregson NA, Hughes RA . Anti-ganglioside antibodies in patients with Guillain-Barre syndrome Campylobacter jejuni infection. J Infect Dis 1995; 172: 605–606.
Yuki N, Tagawa Y . Acute cytomegalovirus infection IgM anti-GM2 antibody. J Neurol Sci 1998; 154: 14–17.
Yuki N, Yamamoto T, Hirata K . Correlation between cytomegalovirus infection IgM anti-MAG/SGPG antibody-associated neuropathy. Ann Neurol 1998; 44: 408–410.
Horn B, Viele M, Mentzer W et al. Autoimmune hemolytic anemia in patients with SCID after T cell-depleted BM PBSC transplantation. Bone Marrow Transplant 1999; 24: 1009–1013.
Cwynarski K, Goulding R, Pocock C et al. Immune haemolytic anaemia following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukaemia: association with leukaemic relapse treatment with donor lymphocyte infusions. Bone Marrow Transplant 2001; 28: 581–586.
Haddad N, Katz T, Fineman R et al. Allogeneic BMT for CML using partial T-cell depletion no post-transplant GVHD prophylaxis, an effective regimen with reduced toxicity: 31 patients treated in a single institution. Blood 2003; 102: 2625a.
Coles AJ, Wing M, Smith S et al. Pulsed monoclonal antibody treatment autoimmune thyroid disease in multiple sclerosis. Lancet 1999; 354: 1691–1695.
Abe Y, Choi I, Hara K et al. Hemophagocytic syndrome: a rare complication of allogeneic nonmyeloablative hematopoietic stem cell transplantation. Bone Marrow Transplant 2002; 29: 799–801.
Spriggs DR, Stopa E, Mayer RJ et al. Fludarabine phosphate (NSC 312878) infusions for the treatment of acute leukemia: phase neuropathological study and I. Cancer Res 1986; 46: 5953–5958.
Merkel DE, Griffin NL, Kagan-Hallet K, Von Hoff DD . Central nervous system toxicity with fludarabine. Cancer Treat Rep 1986; 70: 1449–1450.
Kornblau SM, Cortes-Franco J, Estey E . Neurotoxicity associated with fludarabine and cytosine arabinoside chemotherapy for acute leukemia and myelodysplasia. Leukemia 1993; 7: 378–383.
Liedtke W, Quabeck K, Beelen DW et al. Recurrent acute inflammatory demyelinating polyradiculitis after allogeneic bone marrow transplantation. J Neurol Sci 1994; 125: 110–111.
Medina PJ, Sipols JM, George JN . Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol 2001; 8: 286–293.
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Avivi, I., Chakrabarti, S., Kottaridis, P. et al. Neurological complications following alemtuzumab-based reduced-intensity allogeneic transplantation. Bone Marrow Transplant 34, 137–142 (2004). https://doi.org/10.1038/sj.bmt.1704538
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DOI: https://doi.org/10.1038/sj.bmt.1704538
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