Bone-Marrow and Stem Cell Transplantation

Bone Marrow and Stem Cell Transplantation

Research on bone marrow transplantation in the department of Pathology of the UMC Utrecht is focussed on the analysis of donor and recipient cells in the peripheral blood after bone marrow or stem cell transplantation (BMT or SCT). Initial studies were performed on viral infections after BMT and chimerism analysis after BMT by Variable Number of Tandem Repeats (VNTR). Later VNTR were replaced by short tandem repeats (STR) and our group participated in the European Chimerism Consortium (www.eurochimerism.org).
The aim of this Concerted Action, which included leading laboratories in this field from 10 European countries, was the development of a standardized diagnostic methodology for the detection and monitoring of chimerism (i.e. patient/donor origin of hemopoiesis) in patients undergoing allogeneic stem cell transplantation (SCT). The methodology had to meet stringent quality criteria regarding reproducibility, sensitivity, and ability to quantify patient- and donor derived hematopoietic cells after allogeneic SCT.
Presently, the main involvement of our laboratory in this field of research is, next to the diagnostics, support of clinical research, clinical trials and case reports.


Publications

  1. Verdonck, L.F., G.C. De Gast, A.W. Dekker, R.A. De Weger, H.-J. Schuurman, and M. Rozenberg-Arska,. Treatment of cytomegalovirus pneumonia after bone marrow transplantati¬on with cytomegalovirus immunoglobulin combined with ganciclovir. Bone Marrow Transpl. 4, 187-189, 1989. 
  2. Schuurman, H.-J., M.H.G. Schemmannn, R.A. De Weger, H. Aanstoot, and R. Hene. Epstein-barr virus in the sublabial salivary gland in Sjögren's syndrome. Am. J. Clin. Pathol. 91, 461-463, 1989. 
  3. Rasing, L.A.J., R.A. De Weger, L.F. Verdonck, W. Van Der Bij, Ph.I. Compier-Spies, G.C. De Gast, C.D.H. Van Basten, and H.J. Schuurman. The value of immunohistohistochemistry and in situ hybridization in detec¬ting cytomegalovirus in bone marrow transplant recipients. APMIS 98, 479-488, 1990. 
  4. De Graeff-Meeder, E.R., I. Hiemstra, W. Kuis, W. Vooys, J. Middeldorp, J. Le Poultre, R.C.M. Hennekam, R.A. De Weger, H.-J. Schuurman, G.T. Rijkers, B.A. Van Oost, and B.J.M. Zegers.
    Abnormal course of Epstein Barr virus infection in two siblings of north african origin. In: Progress in Immune Deficiency III, Eds: H.M. Chapel, R.J. Levinsky, and A.D.B. Webster. Royal Soc. Med. Services, London, Int. Congress and Symp. series 173, pp 329-330, 1991.
  5. Boland, G.J., R.A. De Weger, M. G.J. Tilanus, C. Ververs, K. Bos¬boom-Kalsbeek, and G.C. De Gast. Detection of cytomegalovirus (CMV) in granulocytes by polymerase chain reacti¬on compared to CMV immediate early antigen-test. J. Clin Microbi¬ol. 30, 1763-1767, 1992. 
  6. De Gast, G.C., G.J. Boland, A.M. Vlieger, R.A. De Weger, L.F. Verdonck, F.E. Zwaan, and N.M. Jiwa. Abortive human cytomegalovirus infection in patients after allogeneic bone marrow transplantation. Bone Marrow Transpl. 9, 221-225, 1992. 
  7. Vlieger, A.M., G.J. Boland, N.M. Jiwa, R.A. De Weger, R. Willemze, G.C. De Gast, and J.H.F. Falkenburg. Cytomegalovirus antigenemia assay and PCR can be used to monitor bone marrow transplant recipients treated with ganciclovir. Bone marrow Transpl. 9, 247-253, 1992. 
  8. Van Gorp, J., Liu Wei-ping, K. Jacobse, Liu Yong-Huei, Li Feng-Yuan, R.A. De Weger, and Li Gan-di. Epstein Barr virus in nasal T-cell lymphomas (Polymorphic Reticulosis/Midline Malignant Reticulosis) in Western China. Journal of Pathology 173, 81-87, 1994. 
  9. Lokhorst, H.M., T. Lamme, M. De Smet, S. Klein, R.A. De Weger, R. Van Oers, and Andries C. Bloem. Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures. Blood 84, 2269-2277, 1994. 
  10. Van De Kaa, C.A., C.M.R. Weemaes, P. Wesseling, E. Schaafsma, Asgeir Haraldson and R.A. De Weger. Postmortem findings in the Nijmegen breakage syndrome. Pediatric Pathology 14, 787-796, 1994. 
  11. De Gast, G.C., I-A. Haagen, A.A. Van Houten, S.C. Klein, A.J. Duits, R.A. De Weger, Th.M. Vroom, M.R. Clark, J. Phillips, A.J.G. Van Dijk, W.B.M. De Lau, B.J.E.G. Bast. CD8 T-cell activation after intraveneous administration of CD3xCD19 bispecific antibody in patients with non-Hodgkin lymphoma. Cancer Immunology and Immunotherapy 40, 390-396, 1995. 
  12. De Gast, G.C., A.A. Van Houten, I-A. Haagen, S.C. Klein, R.A. De Weger, A.J.G. Van Dijk, J. Phillips, M.R. Clark, and B.J.E.G. Bast. Clinical experience with CD3 X CD19 bispecific antibodies in patients with B-cell malignancies. Journal of Hematotherapy 4, 433-437, 1995. 
  13. Van Prooijen, H.C., M.I. Aarts-Riemens, W.R. Van Oostendorp, R.J. Hené, F.H.J. Gmelig-Meyling and R.A. De Weger. Prevention of donor-specific T-cell unresponsiveness after buffy coat-depleted blood transfusion. British Journal of Heamatology 91, 219-223, 1995. 
  14. Verdonck, L.F., W.T.M. van Blokland, E. C. Bosboom-Kalsbeek, H.G. van Heugten, M.G.J. Tilanus, and R.A. De Weger. Complete donor T cell chimerism is accomplished in patients transplanted with bone marrow grafts containing a fixed low number of T cells. Bone Marrow Transplantation 18, 389-395, 1996. 
  15. Van Blokland, W.T.M., M.G. Ignitiadis, E.C. Bosboom, L.F. Verdonck, D.F. Van Wichen, M.G.J. Tilanus and R.A. De Weger. An optimal microsatellite analysis for donor and recipient cells after bone marrow transplantation. In: Genetic Diversity of HLA Functional and Medical Implication (Ed. D. Charron), EDK Medical and Scientific Publisher, Paris, France. Volume II, 586-588, 1997 
  16. Vooijs, W.C., H,G. Otten, M. Van Vliet, A.J. van Vliet, A.J. Van Dijk, R.A. De Weger, M. De Boer, H. Bohlen, A. Bolognesi, L. Polito and G.C. De Gast. B7-1 (CD80) as target for immunotoxin therapy for Hodgkin’s disease. Br. J. Cancer 76, 1163-1169, 1997. 
  17. Verdonck, L.F., E.J. Petersen, H.M. Lokhorst, H.K. Nieuwenhuis, A.W. Dekker, M.G.J. Tilanus, and R.A. De Weger. Donor leukocyte infusions for recurrent hematologic malignancies after allogeneic bone marrow transplantation: impact of infused and residual donor T cells. Bone Marrow Transplantation 22, 1057-1063, 1998. 
  18. Vyth-Dreese, F.A., H. Boot, T.A.M. Dellemijn, D.M. Majoor, L.C.J.M. Oomen, J.D. Laman, M. Van Meurs, R.A. De Weger, and D. De Jong. Localization in situ of co-stimulatory molecules and cytokines in B-cell non-Hodgkins lymphoma. Immunology 94, 580-586, 1998. 
  19. De Weger, R.A., M.G.J. Tilanus, C.C. Scheidel, J.G. van den Tweel en L.F. Verdonck.
    Monitoring of residual disease and guided donor leucocyte infusion after allogeneic bone marrow transplantation by chimaerism analysis with short tandem repeats. British Journal of Haematology, 110, 647-653, 2000. 
  20. Kolen, S. M. Weijtens, A. Hagenbeek, A. van Spronsen, S. Smulders, R. de Weger, T. de Witte, H. Dolstra, E. van de Wiel- Van Kemenade, and A. Martens. Monitoring of developing graft-versus-host disease mediated by Herpes Simplex virus thymidine kinase gene transduced T-cells. Human Gene Therapy 14, 341-351, 2003. 
  21. Fijnheer, R., C.J. Sanders, M.R. Canninga, R.A. De Weger, and L.F. Verdonck. Complete remission of a radiochemotherapy-resistant cutaneous T-cell lymphoma with allogeneic non-myeloablative stem cell transplantation. Bone Marrow Transplantation 32, 345-347, 2003. 
  22. van Royen-Kerkhof, A., N.M. Wulffraat, S.S.M. Kamphuis, R.A. Brooimans, R.A. de Weger, M.G.J. Tilanus, E.F. van Leeuwen, G.T. Rijkers. Non-Lethal transfusion associated graft versus host disease (GVHD) in a severe combined immunodeficient SCID) Patient. Running title: TA-GVHD in SCID. Bone Marrow transplantation 32, 1027-1030, 2003. 
  23. De Weger, RA and J.G. van den Tweel. The molecular detection of recurrent disease after bone marrow transplantation. In: Update in Pathology (Eds A. Vizjak, D. Ferluga, G. Bussolati) p. 221-222, 2003. 
  24. Weijtens M., A. van Spronsen, A. Hagenbeek, R.A. de Weger, A. Martens. Ganciclovir-mediated elimination of HSV-Tk+ T cells and cure of graft-vs-host disease in an allogeneic bone marrow transplantation model in the rat. Experimental Hematology 32, 962-969, 2004. 
  25. Canninga-van Dijk MC, van Rijn RS, Simonetti ER, et al. Induction of xenogeneic graft-versus-host disease through administration of HuPBMC to immune deficient RAG2(-/-)gamma c(-/-) mice: A model for B cell-involvement in chronic graft-versus-host disease. Blood 106, 866A-867A Part 1, 2005. 
  26. De Weger, R.A., I. Verbrugge, A.H. Bruggink, M.F.M.Van Oosterhout, Y de Souza, D.F. Van Wichen , F. H.J. Gmelig Meyling, N.De Jonge, and L.F. Verdonck. Stem cell derived cardiomyocytes after bone marrow and heart transplantation. Bone Marrow Transplantation 41, 563-569, 2008. 
  27. Huisman C, de Weger RA, de Vries L, et al. Chimerism analysis within 6 months of allogeneic stem cell transplantation predicts relapse in acute myeloid leukemia Bone Marrow transplantation 39, 285-291, 2007.De Weger, R.A., I. Verbrugge, A.H. Bruggink, M.F.M.Van Oosterhout, Y de Souza, D.F. Van Wichen, F. H.J. Gmelig Meyling, N.De Jonge, and L.F. Verdonck. Stem cell derived cardiomyocytes after bone marrow and heart transplantation. Bone Marrow Transplantation 41, 563-569, 2008. 
  28. Lankester, A.C., M.B. Bierings, E.R. Van Wering, A.J. Wijkhuis, R.A. De Weger, J.T. Wijnen, J.M. Vossen, B. Versluys, R.M. Egeler, M.J. van Tol, H. Putter, T. Revesz, J.J. Van Dongen, V.H. Van Der Velden and M.W. Schilham. Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation. Leukemia 24, 1462-1469, 2010. 
  29. Van Royen-Kerkhof, A., V. Walraven, E.A. Sanders, R.A. de Weger, D.F. van Wichen, E. de Koning, T. Thepen, J.G. van de Winkel, and J.H. Leusen. Expression of CD64 (FcγRI) in skin of patients with acute GVHD. Bone Marrow Transplant. In press, 2011
    30. Bloemers, B.L.P., L. Bont, R. de Weger, J.A.M. Borghans, S.A. Otto, K. Tesselaar. Decreased thymic output accounts for decreased naive T-cell numbers in children with Down syndrome. Journal of Immunology 186, 4500-4507, 2011.

On behalf of the European Chimerism Consortium:

  1. Tilanus, M.G.J.; on behalf of Eurochimerism Consortium Short tandem repeat markers in diagnostics: what’s in a repeat. Leukemia 20, 1353-1355, 2006.
  2. Watzinger, F., T. Lion, and C. Steward; on behalf of Eurochimerism Consortium.
    The RSD code: proposal for a nomenclature of allelic configurations in STR-PCR-based chimerism testing after allogeneic stem cell transplantation. Leukemia 20, 1448-1452, 2006


Published abstracts:

  1. van Loon, J.H., L. de Vries, E.H. Rozemuller, R.A. De weger and M.G.J. Tilanus. Identification of the most informative STR markers for monitoring chimerism after stem cell transplantation. Tissue Antigens 67, 453, 2006. 
  2. De Vries, L., J.H. Van Loon, E.H. Rozemuller, R.A. De Weger, M.G.J. Tilanus. A two step approach to monitor patient-donor chimerism after stem cell transplantation. Tissue Antigens 67, 476, 2006. 
  3. Van Loon, J.H., L. De Vries, R.A. De Weger, M.G.J. Tilanus. Short tandem repeat markers in chimerism analysis: What’s in a repeat? Tissue Antigens 67, 482, 2006. 
  4. Van Loon, J.H., L. De Vries, R.A. De Weger, M.G.J. Tilanus. Short tandem repeat markers in chimerism analysis: What’s in a repeat? Human Immunology 67, S138, 2006. 
  5. Van Loon, J.H., L. de Vries, E.H. Rozemuller, R.A. De Weger and M.G.J. Tilanus. Identification of the most informative STR markers for monitoring chimerism after stem cell transplantation. Human Immunology 67, S32, 2006. 
  6. Lion, T, Watzinger, F., Preuner S, Kreyenberg H, Tilanus M, De Weger R , Van Loon J, De Fries L , Cave H, Acquaviva C, Lawler M, Crampe M, Serra A, Saglio B Colnaghi F, Biondi B, Van Dongen J, Van den Burg M, Gonzalez M, Alcoceba M, Barbany G, Hermansson M, Roosnek E, Steward C, Harvey J , Bader P . The eurochimerism concept for a standardized approach to chimerism analysis following allogeneic stem cell transplantation. Haematologica- The haematology journal 92, 132-132, Suppl. 1, 2007. 
  7. Lion, T, Watzinger, F., Preuner S , Kreyenberg H , Tilanus M , De Weger R , Van Loon J , De Fries L, Cave H , Acquaviva C, Lawler M , Crampe M, Serra A , Saglio B Colnaghi F, Biondi B , Van Dongen J, Van den Burg M , Gonzalez M , Alcoceba M , Barbany G , Hermansson M, Roosnek E , Steward C , Harvey J , Frommlet, F., Bader, P. The EuroChimerism concept for a standardized approach to chimerism analysis following allogeneic stem cell transplantation. Bone marrow transplantation 39, S45-S45, Suppl., 2007.

The BMT and SCT Study Group UMC Utrecht

Department of Pathology
dr. Roel De Weger, Immunologist/Molecular Pathologist
drs. Roos Leguit, Pathologist

Patricia Bachmann - Plomp Management Assistant

Technicians:
Joyce van Loon; Chimerism analysis
Marja van Blokland; Chief technician Molecular Pathology
Dick Van Wichen; Immunohistochemistry
All technicians of the Molecular Pathology Lab participate in the diagnostics of chimerism analysis.

Collaboration in the UMC-U
Dr E. Petersen and dr. J. Kuball, Department of Hematology.
Dr. M. Bierings and dr. J.J. Boelens, Department of Hematology, Wilhelmina Children’s Hospital.
Dr. E. Spierings, HLA-Lab, Department of Medical Immunology.

Disclaimer© 2006-2012 UMC Utrecht, Alle rechten voorbehouden