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Open call for collaborative solutions

Posted By Connections Editor, Wednesday, April 24, 2013
Updated: Wednesday, April 24, 2013

Call for case histories of BMT in patients with coincident schizophrenia
I.E.Sommer and D.W. van Bekkum

Recently, the case for an immune component in the etiology of schizophrenia has re-gained support (1, 2), leading to randomized controlled-trials to explore treatment with immunosuppressants and anti-inflammatory drugs (3). Both post-mortem (4) and in-vivo studies (5,6) provided indications for an increased pro-inflammatory status in the brain of patients with recent onset schizophrenia. A common characteristic of most if not all autoimmune diseases (AD) is their favourable response to immunoablation and rescue with bone marrow transplantation. It was established in radiation chimaeras more than 50 years ago that the immunological and hematological systems have a common stem cell. In the wake of this discovery came a strain of investigations into the role of the bone marrow in auto-immune disorders (AD) demonstrating that both hereditary AD and the susceptibility for induced AD could be transferred by hematopoietic stem cell transplants and that both forms of AD in experimental animals could be cured by an allogeneic BMT from healthy donors (7). Accordingly, the records of long term survivors of an allogeneic bone marrow transplant (BMT) were searched for patients with a coexisting AD at the time of the transplant. Up to 1998 case histories of a total of 22 such patients were retrieved, all of whom except one went into complete remission of their AD (8). These findings did not initiate treatment of AD patients with allogeneic BMT because of the high risks of this procedure. However, after it was demonstrated both in rats with induced systemic arthritis and in rats suffering from experimental allergic encephalomyelitis (model for multiple sclerosis) that autologous bone marrow transplants were potentially equally effective as allogeneic transplants, this modality has been widely explored for treating refractory AD of all sorts (9). The European Group for Blood and Bone Marrow Transplantation (EBMT) estimates that world wide around 3000 AD patients have since been treated with autologous BMT; 1200 cases were entered in their database by June 2011 (10). Overall 5 year survival rate of the first 900 cases analysed was 85% , with 43% progression free survival

At present, around 50,000 hematopoietic stem cell transplants are registered annually. Considering a conservative prevalence estimate for schizophrenia of 8 per 1000, the registries can be expected to contain data on many survivors with coincident schizophrenia at the time of transplantation. Information on the clinical course of schizophrenia after BMT would greatly enhance our understanding on the role of immune processes in schizophrenia. We have therefore addressed EBMT and the Medical College of Wisconsin Clinical Cancer Center (CBMTR) concerning the feasibility of initiating such research. Simultaneously we call upon haematologists and psychiatrists to inform us directly of their relevant case histories.by submitting this appeal to their respective professional journals and websites. We venture that this way of crowd sourcing may not only save time and money, but may also bring to light information that has not been put into the data bases of the BMT registries.

Please send the information about your cases, including identification numbers if registered, to >i.sommer@umcutrecht.nl<

References

1. A.L. Jones et al. Immune dysregulation and self-reactivity in schizophrenia: Do some cases of schizophrenia have an autoimmune basis? Immunology and Cell Biology (2005) 83, 9-17

2. C.A.Goldsmith and DP Rogers. The case for autoimmunity in the etiology of schizophrenia. Pharmacotherapy (2008) 28: 730-41

3. I.E. Sommer et al. Nonsteroidal anti-inflammatory drugs in schizophrenia. J.Clin. Psychiatry (2012) 73: 414-419

4. Bayer TA, Buslei R, Havas L, Falkai P. Evidence for activation of microglia in patients with psychiatric illnesses. Neurosci Lett. 1999 Aug 20;271(2):126-8
5. van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E,Luurtsema G, Windhorst AD, Cahn W, Lammertsma AA, Kahn RS. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry. 2008 Nov 1;64(9):820-2
6. Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC. Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med. 2009; 50(11):1801-7

7. DW van Bekkum. BMT in experimental autoimmune disease Bone Marrow Transplantation (1993) 11: 183-187

8. D W van Bekkum .New opportunities for the treatment of severe autoimmune diseases: bone marrow transplantation. Clinical Immunology and Immunopathology (1998) 89:1-10

9. A Gratwohl and A. Tyndall eds. Stem cell transplantation for autoimmune disorders. Best practice&research. Clinical Hematology 17 nr 2, 2004

10. J.A.Snowden et al. Hematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Bone Marrow Transplantation. Bone Marrow Transplantation (2012)47: 770-790

Submitted to the journals:

Bone Marrow Transplantation, Leukemia , Stem Cells, Blood,

Schizophrenia Research, Schizophrenia Bulletin. ISRN Hematology.

And the websites:

Schizophrenia Forum , International Society for Hematology and Stem Cells, American Society of Hematology, European Hematology Association, Japanese Society of Hematology , Taiwan Society for Bone Marrow and Stem Cell Transplantation.

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