Skip to main content
Erschienen in: Annals of Hematology 8/2018

22.03.2018 | Original Article

IgG synthesis rate and anti-myelin oligodendrocyte glycoprotein antibody in CSF may be associated with the onset of CNS demyelination after haplo-HSCT

verfasst von: Xiao-hui Zhang, Xin Zhao, Chen-cong Wang, Wei Han, Huan Chen, Yu-hong Chen, Feng-rong Wang, Jing-zhi Wang, Yuan-yuan Zhang, Xiao-dong Mo, Yao Chen, Yu Wang, Hai-xia Fu, Ying-jun Chang, Lan-ping Xu, Kai-yan Liu, Xiao-jun Huang

Erschienen in: Annals of Hematology | Ausgabe 8/2018

Einloggen, um Zugang zu erhalten

Abstract

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) is an upfront and effective therapy for hematology patients, but it usually has many complications, such as neurological complications. As one of the neurological complications following haplo-HSCT, immune-mediated demyelinating diseases of the central nervous system (CNS) seriously affect a patient’s quality of life. However, the incidence, risk factors, and pathogenesis of CNS demyelination are not very well understood. Thirty of the 1526 patients (1.96%) suffered from CNS demyelination. In univariate analysis, we found that blood-brain barrier (BBB) permeability and the CSF IgG synthesis index (IgG-Syn) were related to the occurrence of CNS demyelination (p < 0.05). In a multivariate analysis, the IgG-Syn (OR = 1.017, 95% CI 1.003–1.031, p = 0.019) and CSF anti-myelin oligodendrocyte glycoprotein antibody (MOG.Ab) (OR = 12.059, 95% CI 1.141–127.458, p = 0.038) were independently associated with the onset of CNS demyelination. We also studied the possible pathogenesis of CNS demyelination. Immune reconstitution (the cell proportions of CD19+ B cells, CD3+ T cells, and CD4+ T cells); the counts of leucocytes, lymphocytes, monocytes, and platelets; and the levels of immunoglobulins A, G, and M 30, 60, and 90 days after HSCT showed no significant differences between CNS demyelination and no demyelination (p > 0.05). The probabilities of overall survival showed no significant differences between patients with and without demyelination (p > 0.05). Only four deaths in 30 patients, but bringing projected survival to less than 20%.We imply that IgG-Syn and CSF MOG. Ab may be associated with the onset of CNS demyelination during 2 weeks of neurological symptoms in patients with brain or spinal cord MRI abnormality. Immune reconstitution may not be the pathogenesis of CNS demyelination.
Literatur
1.
Zurück zum Zitat Ende M, Ende FI (2006) Hematopoietic stem-cell transplantation. N Engl J Med 355:1070, 1070–1070, 1071PubMed Ende M, Ende FI (2006) Hematopoietic stem-cell transplantation. N Engl J Med 355:1070, 1070–1070, 1071PubMed
2.
Zurück zum Zitat Wang Y, Liu QF, Xu LP et al (2015) Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 125:3956–3962CrossRefPubMed Wang Y, Liu QF, Xu LP et al (2015) Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 125:3956–3962CrossRefPubMed
3.
Zurück zum Zitat Huang XJ, Zhu HH, Chang YJ et al (2012) The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission. Blood 119:5584–5590CrossRefPubMed Huang XJ, Zhu HH, Chang YJ et al (2012) The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission. Blood 119:5584–5590CrossRefPubMed
4.
Zurück zum Zitat Solaro C, Murialdo A, Giunti D, Mancardi G, Uccelli A (2001) Central and peripheral nervous system complications following allogeneic bone marrow transplantation. Eur J Neurol 8:77–80CrossRefPubMed Solaro C, Murialdo A, Giunti D, Mancardi G, Uccelli A (2001) Central and peripheral nervous system complications following allogeneic bone marrow transplantation. Eur J Neurol 8:77–80CrossRefPubMed
5.
Zurück zum Zitat Iguchi A, Kobayashi R, Yoshida M et al (1999) Neurological complications after stem cell transplantation in childhood. Bone Marrow Transplant 24:647–652CrossRefPubMed Iguchi A, Kobayashi R, Yoshida M et al (1999) Neurological complications after stem cell transplantation in childhood. Bone Marrow Transplant 24:647–652CrossRefPubMed
6.
Zurück zum Zitat Barba P, Piñana JL, Valcárcel D et al (2009) Early and late neurological complications after reduced-intensity conditioning allogeneic stem cell transplantation. Biol Blood Marrow Transplant 15:1439–1446CrossRefPubMed Barba P, Piñana JL, Valcárcel D et al (2009) Early and late neurological complications after reduced-intensity conditioning allogeneic stem cell transplantation. Biol Blood Marrow Transplant 15:1439–1446CrossRefPubMed
7.
Zurück zum Zitat Siegal D, Keller A, Xu W et al (2007) Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance. Biol Blood Marrow Transplant 13:1369–1379CrossRefPubMed Siegal D, Keller A, Xu W et al (2007) Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations, and clinical significance. Biol Blood Marrow Transplant 13:1369–1379CrossRefPubMed
8.
Zurück zum Zitat Uckan D, Cetin M, Yigitkanli I et al (2005) Life-threatening neurological complications after bone marrow transplantation in children. Bone Marrow Transplant 35:71–76CrossRefPubMed Uckan D, Cetin M, Yigitkanli I et al (2005) Life-threatening neurological complications after bone marrow transplantation in children. Bone Marrow Transplant 35:71–76CrossRefPubMed
9.
Zurück zum Zitat Pustavoitau A, Bhardwaj A, Stevens R (2011) Analytic review: neurological complications of transplantation. J Intensive Care Med 26:209–222CrossRefPubMed Pustavoitau A, Bhardwaj A, Stevens R (2011) Analytic review: neurological complications of transplantation. J Intensive Care Med 26:209–222CrossRefPubMed
10.
Zurück zum Zitat 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 110:251–256CrossRef 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 110:251–256CrossRef
11.
Zurück zum Zitat Sakai M, Ohashi K, Ohta K et al (2006) Immune-mediated myelopathy following allogeneic stem cell transplantation. Int J Hematol 84:272–275CrossRefPubMed Sakai M, Ohashi K, Ohta K et al (2006) Immune-mediated myelopathy following allogeneic stem cell transplantation. Int J Hematol 84:272–275CrossRefPubMed
12.
Zurück zum Zitat Karam C, Mauermann ML, Johnston PB, Lahoria R, Engelstad JK, Dyck PJB (2014) Immune-mediated neuropathies following stem cell transplantation. J Neurol Neurosurg Psychiatry 85:638–642CrossRefPubMed Karam C, Mauermann ML, Johnston PB, Lahoria R, Engelstad JK, Dyck PJB (2014) Immune-mediated neuropathies following stem cell transplantation. J Neurol Neurosurg Psychiatry 85:638–642CrossRefPubMed
13.
Zurück zum Zitat Liu D, Huang X, Liu K et al (2008) Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for treatment of hematological malignancies in children. Biol Blood Marrow Transplant 14:469–477CrossRefPubMed Liu D, Huang X, Liu K et al (2008) Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for treatment of hematological malignancies in children. Biol Blood Marrow Transplant 14:469–477CrossRefPubMed
14.
Zurück zum Zitat Lu DP, Dong L, Wu T (2006) Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood 107:3065–3073CrossRefPubMed Lu DP, Dong L, Wu T (2006) Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood 107:3065–3073CrossRefPubMed
15.
Zurück zum Zitat Zhang X, Fu H, Xu L et al (2011) Prolonged thrombocytopenia following allogeneic hematopoietic stem cell transplantation and its association with a reduction in ploidy and an immaturation of megakaryocytes. Biol Blood Marrow Transplant 17:274–280CrossRefPubMed Zhang X, Fu H, Xu L et al (2011) Prolonged thrombocytopenia following allogeneic hematopoietic stem cell transplantation and its association with a reduction in ploidy and an immaturation of megakaryocytes. Biol Blood Marrow Transplant 17:274–280CrossRefPubMed
16.
Zurück zum Zitat Thomas E, Storb R, Clift RA et al (1975) Bone-marrow transplantation (first of two parts). N Engl J Med 292:832–843CrossRefPubMed Thomas E, Storb R, Clift RA et al (1975) Bone-marrow transplantation (first of two parts). N Engl J Med 292:832–843CrossRefPubMed
17.
Zurück zum Zitat Grauer O, Wolff D, Bertz H et al (2010) Neurological manifestations of chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease. Brain 133:2852–2865CrossRefPubMed Grauer O, Wolff D, Bertz H et al (2010) Neurological manifestations of chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease. Brain 133:2852–2865CrossRefPubMed
18.
Zurück zum Zitat Openshaw H, Slatkin NE, Parker PM, Forman SJ (1995) Immune-mediated myelopathy after allogeneic marrow transplantation. Bone Marrow Transplant 15:633–636PubMed Openshaw H, Slatkin NE, Parker PM, Forman SJ (1995) Immune-mediated myelopathy after allogeneic marrow transplantation. Bone Marrow Transplant 15:633–636PubMed
19.
Zurück zum Zitat Matsuo Y, Kamezaki K, Takeishi S et al (2009) Encephalomyelitis mimicking multiple sclerosis associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation. Intern Med 48:1453–1456CrossRefPubMed Matsuo Y, Kamezaki K, Takeishi S et al (2009) Encephalomyelitis mimicking multiple sclerosis associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation. Intern Med 48:1453–1456CrossRefPubMed
20.
Zurück zum Zitat Yamout B, Alroughani R, Al-Jumah M, Khoury S, Abouzeid N (2013) Consensus guidelines for the diagnosis and treatment of multiple sclerosis. Curr Med Res Opin 29(6):611–621CrossRefPubMed Yamout B, Alroughani R, Al-Jumah M, Khoury S, Abouzeid N (2013) Consensus guidelines for the diagnosis and treatment of multiple sclerosis. Curr Med Res Opin 29(6):611–621CrossRefPubMed
21.
Zurück zum Zitat Bluke, Karl G (2016) Thomas hematopoietic cell transplantation. In: Openshaw H (ed) Neurologic Complications of Hematopoietic Cell Transplantation. Wiley, Blackwell, pp 1287–1292 Bluke, Karl G (2016) Thomas hematopoietic cell transplantation. In: Openshaw H (ed) Neurologic Complications of Hematopoietic Cell Transplantation. Wiley, Blackwell, pp 1287–1292
22.
Zurück zum Zitat Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302CrossRefPubMedPubMedCentral Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Lorenzoni PJ, Scola RH, Carsten AL et al (2007) Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report. Arq Neuropsiquiatr 65:700–704CrossRefPubMed Lorenzoni PJ, Scola RH, Carsten AL et al (2007) Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report. Arq Neuropsiquiatr 65:700–704CrossRefPubMed
25.
Zurück zum Zitat Su L, Ji B, Hu R, Lan X, Xia C (2014) Immune-mediated neuromuscular complications after haploidendtical hematopoietic stem cell transplantation. Chin Med J 127:2865–2867PubMed Su L, Ji B, Hu R, Lan X, Xia C (2014) Immune-mediated neuromuscular complications after haploidendtical hematopoietic stem cell transplantation. Chin Med J 127:2865–2867PubMed
26.
Zurück zum Zitat Zhang XH (2013) Idiopathic inflammatory demyelinating diseases of the central nervous system in patients following allogeneic hematopoietic stem cell transplantation: a retrospective analysis of incidence, risk factors and survival. Chin Med J 126:1096–1102PubMed Zhang XH (2013) Idiopathic inflammatory demyelinating diseases of the central nervous system in patients following allogeneic hematopoietic stem cell transplantation: a retrospective analysis of incidence, risk factors and survival. Chin Med J 126:1096–1102PubMed
27.
Zurück zum Zitat Sostak P, Padovan CS, Eigenbrod S et al (2009) Cerebral angiitis in four patients with chronic GVHD. Bone Marrow Transplant 45:1181–1188CrossRefPubMed Sostak P, Padovan CS, Eigenbrod S et al (2009) Cerebral angiitis in four patients with chronic GVHD. Bone Marrow Transplant 45:1181–1188CrossRefPubMed
28.
29.
Zurück zum Zitat Zhang X, Zhang J, Han W et al (2017) Viral encephalitis after haplo-identical hematopoietic stem cell transplantation: causative viral spectrum, characteristics, and risk factors. Eur J Haematol 98:450–458CrossRefPubMed Zhang X, Zhang J, Han W et al (2017) Viral encephalitis after haplo-identical hematopoietic stem cell transplantation: causative viral spectrum, characteristics, and risk factors. Eur J Haematol 98:450–458CrossRefPubMed
30.
Zurück zum Zitat Saito T, Saito O, Kawano T, Tamemoto H, Kusano E (2007) Elevation of serum adiponectin and CD146 levels in diabetic nephropathy. Diabetes Res Clin Pract 78:85–92CrossRefPubMed Saito T, Saito O, Kawano T, Tamemoto H, Kusano E (2007) Elevation of serum adiponectin and CD146 levels in diabetic nephropathy. Diabetes Res Clin Pract 78:85–92CrossRefPubMed
31.
Zurück zum Zitat Duan H, Luo Y, Hao H (2013) Soluble CD146 in cerebrospinal fluid of active multiple sclerosis. Neuroscience 235:16–26CrossRefPubMed Duan H, Luo Y, Hao H (2013) Soluble CD146 in cerebrospinal fluid of active multiple sclerosis. Neuroscience 235:16–26CrossRefPubMed
32.
Zurück zum Zitat Bonnan M (2015) Intrathecal IgG synthesis: a resistant and valuable target for future multiple sclerosis treatments. Mult Scler Int 2015:1–15CrossRef Bonnan M (2015) Intrathecal IgG synthesis: a resistant and valuable target for future multiple sclerosis treatments. Mult Scler Int 2015:1–15CrossRef
33.
Zurück zum Zitat Reindl M, Linington C, Brehm U et al (1999) Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 122(Pt 11):2047–2056CrossRefPubMed Reindl M, Linington C, Brehm U et al (1999) Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 122(Pt 11):2047–2056CrossRefPubMed
34.
Zurück zum Zitat Tanaka M, Tanaka K (2014) Anti-MOG antibodies in adult patients with demyelinating disorders of the central nervous system. J Neuroimmunol 270:98–99CrossRefPubMed Tanaka M, Tanaka K (2014) Anti-MOG antibodies in adult patients with demyelinating disorders of the central nervous system. J Neuroimmunol 270:98–99CrossRefPubMed
35.
Zurück zum Zitat Sellebjerg F, Jensen CV, Christiansen M (2000) Intrathecal IgG synthesis and autoantibody-secreting cells in multiple sclerosis. J Neuroimmunol 108:207–215CrossRefPubMed Sellebjerg F, Jensen CV, Christiansen M (2000) Intrathecal IgG synthesis and autoantibody-secreting cells in multiple sclerosis. J Neuroimmunol 108:207–215CrossRefPubMed
36.
Zurück zum Zitat Wang H, Munger KL, Reindl M et al (2008) Myelin oligodendrocyte glycoprotein antibodies and multiple sclerosis in healthy young adults. Neurology 71:1142–1146CrossRefPubMed Wang H, Munger KL, Reindl M et al (2008) Myelin oligodendrocyte glycoprotein antibodies and multiple sclerosis in healthy young adults. Neurology 71:1142–1146CrossRefPubMed
37.
Zurück zum Zitat Reder AT, Oger JJ (2004) Anti-myelin oligodendrocyte glycoprotein antibodies in multiple sclerosis. Neurology 62:1922–1923CrossRefPubMed Reder AT, Oger JJ (2004) Anti-myelin oligodendrocyte glycoprotein antibodies in multiple sclerosis. Neurology 62:1922–1923CrossRefPubMed
38.
Zurück zum Zitat Elovaara I, Apostolski S, van Doorn P et al (2008) EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol 15:893–908CrossRefPubMed Elovaara I, Apostolski S, van Doorn P et al (2008) EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases. Eur J Neurol 15:893–908CrossRefPubMed
39.
Zurück zum Zitat Waldman AT, Gorman MP, Rensel MR, Austin TE, Hertz DP, Kuntz NL (2011) Management of pediatric central nervous system demyelinating disorders: Consensus of United States Neurologists. J Child Neurol 26:675–682CrossRefPubMedPubMedCentral Waldman AT, Gorman MP, Rensel MR, Austin TE, Hertz DP, Kuntz NL (2011) Management of pediatric central nervous system demyelinating disorders: Consensus of United States Neurologists. J Child Neurol 26:675–682CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Probstel AK, Dornmair K, Bittner R et al (2011) Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 77:580–588CrossRefPubMed Probstel AK, Dornmair K, Bittner R et al (2011) Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 77:580–588CrossRefPubMed
Metadaten
Titel
IgG synthesis rate and anti-myelin oligodendrocyte glycoprotein antibody in CSF may be associated with the onset of CNS demyelination after haplo-HSCT
verfasst von
Xiao-hui Zhang
Xin Zhao
Chen-cong Wang
Wei Han
Huan Chen
Yu-hong Chen
Feng-rong Wang
Jing-zhi Wang
Yuan-yuan Zhang
Xiao-dong Mo
Yao Chen
Yu Wang
Hai-xia Fu
Ying-jun Chang
Lan-ping Xu
Kai-yan Liu
Xiao-jun Huang
Publikationsdatum
22.03.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 8/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3299-4

Weitere Artikel der Ausgabe 8/2018

Annals of Hematology 8/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.