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Analysis of chimaerism in thalassaemic children undergoing stem cell transplantation

We have prospectively assessed the relative contribution of host and donor to haemopoiesis following stem cell transplantation (SCT) in children with β‐thalassaemia major (n = 35), using karyotype analysis or Southern blot/polymerase chain reaction analysis of variable number tandem repeats on genom...

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Published in:British journal of haematology 2001-07, Vol.114 (1), p.219-225
Main Authors: Amrolia, P. J., Vulliamy, T., Vassiliou, G ., Lawson, S., Bryon, J., Kaeda, J., Dokal, I., Johnston, R., Veys, P., Darbyshire, P., Roberts, I. A. G.
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container_title British journal of haematology
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creator Amrolia, P. J.
Vulliamy, T.
Vassiliou, G .
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Bryon, J.
Kaeda, J.
Dokal, I.
Johnston, R.
Veys, P.
Darbyshire, P.
Roberts, I. A. G.
description We have prospectively assessed the relative contribution of host and donor to haemopoiesis following stem cell transplantation (SCT) in children with β‐thalassaemia major (n = 35), using karyotype analysis or Southern blot/polymerase chain reaction analysis of variable number tandem repeats on genomic DNA from peripheral blood. Early haemopoiesis was fully donor in origin in 24 out of 35 cases and remained so throughout the post‐transplant course in all but one patient, who evolved to stable mixed chimaerism. The remaining 11 cases (31%) initially showed mixed chimaerism: four of these rejected, one eventually eradicated host haemopoiesis to become fully donor haemopoietic, and the remaining six had persistent mixed chimaerism, with 5–38% host haemopoiesis. The risk of graft rejection was high when > 15% host haemopoiesis was present at 3 months post transplant: four out of six such patients rejected their grafts; conversely, zero out of 29 patients with
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J. ; Vulliamy, T. ; Vassiliou, G . ; Lawson, S. ; Bryon, J. ; Kaeda, J. ; Dokal, I. ; Johnston, R. ; Veys, P. ; Darbyshire, P. ; Roberts, I. A. G.</creator><creatorcontrib>Amrolia, P. J. ; Vulliamy, T. ; Vassiliou, G . ; Lawson, S. ; Bryon, J. ; Kaeda, J. ; Dokal, I. ; Johnston, R. ; Veys, P. ; Darbyshire, P. ; Roberts, I. A. G.</creatorcontrib><description>We have prospectively assessed the relative contribution of host and donor to haemopoiesis following stem cell transplantation (SCT) in children with β‐thalassaemia major (n = 35), using karyotype analysis or Southern blot/polymerase chain reaction analysis of variable number tandem repeats on genomic DNA from peripheral blood. Early haemopoiesis was fully donor in origin in 24 out of 35 cases and remained so throughout the post‐transplant course in all but one patient, who evolved to stable mixed chimaerism. The remaining 11 cases (31%) initially showed mixed chimaerism: four of these rejected, one eventually eradicated host haemopoiesis to become fully donor haemopoietic, and the remaining six had persistent mixed chimaerism, with 5–38% host haemopoiesis. The risk of graft rejection was high when &gt; 15% host haemopoiesis was present at 3 months post transplant: four out of six such patients rejected their grafts; conversely, zero out of 29 patients with &lt; 15% host haemopoiesis at 3 months rejected (P &lt; 0·0001). There was a higher incidence of significant acute and chronic graft‐versus‐host disease in patients with full donor chimaerism. These studies confirm that the mixed chimaeric state is common following SCT for thalassaemia, often persists (with up to 4 years follow‐up) and is compatible with long‐term cure. Analysis of chimaerism in patients undergoing SCT for β‐thalassaemia enables monitoring of engraftment in the early post‐transplant period, provides insight into the biology of engraftment and may be useful in identifying patients at high risk of rejection.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1046/j.1365-2141.2001.02931.x</identifier><identifier>PMID: 11472371</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>ABO Blood-Group System ; Adolescent ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; beta-Thalassemia - genetics ; beta-Thalassemia - therapy ; Biological and medical sciences ; bone marrow transplantation ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Child ; Child, Preschool ; chimaerism ; Chimera ; Graft Rejection - genetics ; Graft vs Host Disease - genetics ; Hematology ; Hematopoietic Stem Cell Transplantation ; Humans ; Medical sciences ; Minisatellite Repeats ; non‐myeloablative conditioning ; Prospective Studies ; rejection ; thalassaemia ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Transplantation Conditioning</subject><ispartof>British journal of haematology, 2001-07, Vol.114 (1), p.219-225</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. 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J.</creatorcontrib><creatorcontrib>Vulliamy, T.</creatorcontrib><creatorcontrib>Vassiliou, G .</creatorcontrib><creatorcontrib>Lawson, S.</creatorcontrib><creatorcontrib>Bryon, J.</creatorcontrib><creatorcontrib>Kaeda, J.</creatorcontrib><creatorcontrib>Dokal, I.</creatorcontrib><creatorcontrib>Johnston, R.</creatorcontrib><creatorcontrib>Veys, P.</creatorcontrib><creatorcontrib>Darbyshire, P.</creatorcontrib><creatorcontrib>Roberts, I. A. G.</creatorcontrib><title>Analysis of chimaerism in thalassaemic children undergoing stem cell transplantation</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>We have prospectively assessed the relative contribution of host and donor to haemopoiesis following stem cell transplantation (SCT) in children with β‐thalassaemia major (n = 35), using karyotype analysis or Southern blot/polymerase chain reaction analysis of variable number tandem repeats on genomic DNA from peripheral blood. Early haemopoiesis was fully donor in origin in 24 out of 35 cases and remained so throughout the post‐transplant course in all but one patient, who evolved to stable mixed chimaerism. The remaining 11 cases (31%) initially showed mixed chimaerism: four of these rejected, one eventually eradicated host haemopoiesis to become fully donor haemopoietic, and the remaining six had persistent mixed chimaerism, with 5–38% host haemopoiesis. The risk of graft rejection was high when &gt; 15% host haemopoiesis was present at 3 months post transplant: four out of six such patients rejected their grafts; conversely, zero out of 29 patients with &lt; 15% host haemopoiesis at 3 months rejected (P &lt; 0·0001). There was a higher incidence of significant acute and chronic graft‐versus‐host disease in patients with full donor chimaerism. These studies confirm that the mixed chimaeric state is common following SCT for thalassaemia, often persists (with up to 4 years follow‐up) and is compatible with long‐term cure. Analysis of chimaerism in patients undergoing SCT for β‐thalassaemia enables monitoring of engraftment in the early post‐transplant period, provides insight into the biology of engraftment and may be useful in identifying patients at high risk of rejection.</description><subject>ABO Blood-Group System</subject><subject>Adolescent</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>beta-Thalassemia - genetics</subject><subject>beta-Thalassemia - therapy</subject><subject>Biological and medical sciences</subject><subject>bone marrow transplantation</subject><subject>Bone marrow, stem cells transplantation. 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subjects ABO Blood-Group System
Adolescent
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
beta-Thalassemia - genetics
beta-Thalassemia - therapy
Biological and medical sciences
bone marrow transplantation
Bone marrow, stem cells transplantation. Graft versus host reaction
Child
Child, Preschool
chimaerism
Chimera
Graft Rejection - genetics
Graft vs Host Disease - genetics
Hematology
Hematopoietic Stem Cell Transplantation
Humans
Medical sciences
Minisatellite Repeats
non‐myeloablative conditioning
Prospective Studies
rejection
thalassaemia
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Transplantation Conditioning
title Analysis of chimaerism in thalassaemic children undergoing stem cell transplantation
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