Chimaerism analyses and subsequent immunological intervention after stem cell transplantation in patients with juvenile myelomonocytic leukaemia.
Chimaerism analysis was performed by polymerase chain reaction amplification of short-tandem repeat markers in 30 children following haematopoietic stem cell transplantation for juvenile myelomonocytic leukaemia (JMML). Fourteen patients always had complete chimaerism (CC); one of them relapsed after the discontinuation of the study and 13 continued in complete remission (CR). Mixed chimaerism (MC) was noted in 16 patients. Of those 12 patients demonstrated increasing MC (i-MC); 10 relapsed and two achieved CC following discontinuation of immunosuppressive therapy (IST). Four other patients demonstrating only transient MC are alive in CR. MC with up to 20% of autologous cells could be successfully eradicated without induction of severe graft-versus-host disease when IST was reduced or discontinued directly after the first demonstration of MC. At the same time, MC with up to 10% of autologous cells could disappear without intervention. The interval between MC and relapse ranged from 0-320 d (median 38 d). Donor leucocyte infusion was given to six patients with i-MC, but only one patient responded. Peripheral blood seems as valuable as bone marrow for chimaerism studies. In conclusion, serial quantitative chimaerism studies can identify patients with i-MC who are at high risk for relapse of JMML. Immediate withdrawal of IST is advised in these patients.
Yoshimi
Ayami
A
Department of Paediatrics and Adolescent Medicine, University of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany. yoshimi@kikli.ukl.uni-freiburg.de
Niemeyer
Charlotte M
CM
Bohmer
Viktoria
V
Duffner
Ulrich
U
Strahm
Brigitte
B
Kreyenberg
Hermann
H
Dilloo
Dagmar
D
Zintl
Felix
F
Claviez
Alexander
A
Wössmann
Willi
W
Kremens
Bernhard
B
Holter
Wolfgang
W
Niethammer
Dietrich
D
Beck
James F
JF
Kontny
Udo
U
Nöllke
Peter
P
Klingebiel
Thomas
T
Bader
Peter
P
D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D020544:Graft vs Leukemia Effect; D006801:Humans; D007223:Infant; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000276:immunology / Q000601:surgery*; D017708:Leukocyte Transfusion; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D012074:Remission Induction; D033581:Stem Cell Transplantation; D015996:Survival Rate; D020080:Tandem Repeat Sequences; D018183:Transplantation Chimera / Q000235:genetics*
D005819:Genetic Markers