Title: State of Chimerism as a Promising Tool for Follow up of Hematopoietic Stem Cell Transplantation in Egyptian Patients

Authors: Hala A Talkhan* and Doaa M Abdelaziz

 DOI:  http://dx.doi.org/10.18535/jmscr/v4i7.36

Abstract

Follow up of patients after HSCT by chimerism detection can detect the outcome either engraftment, relapse or rejection. Many variables affect the result of chimerism either increasing or decreasing chimerism. Lineage specific chimerism is specific and sensitive than chimerism detection by whole blood. Here in this study the importance of these variables on the outcome of chimerism detection is studied.

Subject and method: This study was conducted at Ain Shams University Hospital during the period between January 2011and January 2015. 46 patients were included (16 child and 30 adult). They were transplanted for malignant and non malignant hematological diseases from totally matched siblings. The median duration of follow-up was one year.  Chimerism status was detected for all patients by polymerase chain reaction based on amplification of variable number tandem repeat (VNTR) markers. Six VNTR loci were detected in every subject pre-transplant in order to detect an informative locus to be used in follow up post-transplant. Also lineage specific chimerism and dilution experiment were conducted on some patients.

Results: One patient showed no informative locus pre-transplantation, 37 patients showed complete donor chimersm, two patients retained recipient pattern post-transplantation and six patients showed MC. Lineage cell specific chimerism and dilution experiment were conducted for patients who showed failure or mixed chimerism.

Conclusion: Chimerism detection by VNTR is dependable method to follow up patients after BMT however, some cases need some modifications as repeated analysis, short duration, lineage specific in comparison to whole blood analysis, dilution experiments in order to predict the outcome.

Keywords: Chimerism, Hematopoietic stem cells, Hematological diseases, Immunodeficiency.

References

 

  1. Park M, Koh K , Seo J , and Im H. Clinical implications of chimerism after allogeneic hematopoietic stem cell transplantation in children with non-malignant diseases, Korean Journal of Hematology. 4:64; 258–264, 2011.
  2. Svenberg A, Mattsson J,  Ringden O, and Uzunel M. Allogeneic hematopoietic SCT in patients with non-malignant diseases, and importance of chimerism . Bone Marrow Transplantation, vol. 44, no. 11, pp. 757–763, 2009.
  3. Levrat E, Roosnek E, Masouridi S, Mohty B, Ansari M, Villard J, Jakob R. Passweg, and Chalandon Y . Very Long Term Stability of Mixed Chimerism after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Hematolo-gic Malignancies. Bone Marrow Research Volume 2015, Article ID 176526, 6 pages.
  4. Van Besien K,  Dew A ,  Lin S et al., “Patterns and kinetics of T-cell chimerism after allo transplant with alemtuzumab-based conditioning: mixed chimerism protects fromGVHD, but does not portend disease recurrence,” Leukemia and Lymp-homa, vol 50, no 11, pp. 1809–1817, 2009.
  5. Stikvoort A , Gertow J ,  Sundin M , Remberger M, Mattsson J, and  Uhlin M, “Chimerism patterns of long-term stable mixed chimeras posthematopoietic stem cell transplantation in patients with nonmalignant diseases: follow-up of long-term stable mixed chimerism patients,” Biology of Blood and Marrow .Transplan-tation, vol. 19, no. 5, pp. 838–844, 2013.
  6. Frugnoli I, Cappelli B, Chiesa R et al., “Escalating doses of donor lymphocytes for incipient graft rejection following SCT for thalassemia,” Bone Marrow Transpla-ntation, vol 45, no 6, pp 1047–1051, 2010.
  7. Budowle B, Chakraborty R, Giusti A, Eisenberg A and Allen R .Analysis of the VNTR locus D1S80 by PCR followed by high resolution PAGE .American Journal of Human Genetics, 48: 137-144,1991.
  8. Ugozzoli L, Yam P, Petz L   , Ferrara G  , ChamplinR  , Forman S  , Koyal D and Wallace R  : Amplification by the polymerase chain reaction of the human genome for evaluation of chimerism after bone marrow transplantation. Blood, 77: 1607-1615, 1991.
  9. McCann S & Lawler M .Mixed chimerism: detection and significance following BMT. Bone Marrow Transplantation, 11, 91± 94,1993.
  10. Petit T, Raynal B, Socie , Landman-Parker J, Bourhis J, Gluckman E, Pico J & Brison O .Highly sensitive polymerase chain reaction methods show the frequent survival of residual recipient multipotent progenitors after non-T-celldepleted bone marrow transplantation. Blood, 84, 3575±3583, 1994.
  11. Roux, E, Helg C, Chapius B, Jeannet M & Roosnek E .Mixed chimerism after bone marrow transplantation and the risk of relapse [Letter]. Blood, 84, 4385±4386 ,1994.
  12. Socie G, Lawler M, Gluckman E, McCann S & Brison O. Studies on hemopoietic chimerism following allogeneic bone marrow transplantation in the molecular biology era. Leukemia Research, 19, 497±504, 1995.
  13. van Leeuwen J, van Tol M, Joosten A ,Wijnen J ,Verweij P, Khan P & Vossen J  .Persistence of host-type hematopoiesis after allogeneic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but it is not associated with an increased risk of relapse. Blood, 83, 3059±3067, 1994.
  14. RamõÁrez M, DõÁaz M, GarcõÂa-SaÂnchez F, Velasco M, Casado F, Villa M, Vicario J & Madero L .Chimerism after allogeneic hematopoietic cell transplantation in childhood acute lymphoblastic leukemia. Bone Marrow Transplantation, 18, 1161± 1165, 1996.
  15. Bader P, Beck J, Frey A, Schlegel P, Hebarth H, Handgretinger R, Einsele H, Niemeyer C, Benda N, Faul C, Kanz  L , Niethammer D & Klingebiel T.Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT. Bone Marrow Transplantation, 21, 487±495, 1998.
  16. Andreani MTesti M and  Lucarelli G . Mixed chimerism in haemoglobinopathies: from risk of graft rejection to immune tolerance. Tissue Antigens.  83(3):137-46 , 2014.
  17. Burroughs L and Woolfrey A . Hematopoietic  cell  transplantation for treatment of primary immune deficiencies. Cell Ther Transplant.  31;2(8) , 2010.
  18. Bader P,Stoll k  ,  Huber S,  Geiselhart A,  Handgretinger T,  NIEMEYER S, Einsele H ,3 Schlegel P ,  Niethammer D,  Beckand J   ,Klinebiel T.   Character-ization of lineage-specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse. British Journal of Haematology, 108, 761±768, 2000.
  19. Roux, E., Abdi, K., Speiser, D., Helg, C., Chapuis, B., Jeannet, M. & Roosnek, E. Characterisation ofmixed chimerismin patients with chronic myeloid leukemia transplanted with T-cell-depleted bone marrow: involvement of different hematologic lineagesbefore and after relapse. Blood, 81, 243±248, 1993.
  20. Preuner SPeters CPötschger UDaxberger H, Preuner SPeters CPötschger UDaxberger HFritsch GGeyeregger RSchrauder Avon Stackelberg ASchrappe MBader PEbell WEckert CLang PSykora KWSchrum JKremens BEhlert K Albert MH, Meisel RLawitschka AMann GPanzer-Grümayer RGüngör T,Holter WStrahm BGruhn BSchulz AWoessmann WLion T. Risk assessment of relapse by lineage-specific monitoring of chimerismin children undergoingallogeneic  stem  cell  transplantation for acute lymphoblastic leukemia. Haematologica.  2(3):11,2016

Corresponding Author

Dr Hala Talkhan

Adress: 3 Obour Buildings, Salah Salem St. Cairo, Egypt

Telephone: +201001427024