Kinetics of plasma-cell chimerism after allogeneic stem cell transplantation by highly sensitive real-time PCR based on sequence polymorphism and its value to quantify minimal residual disease in patients with multiple myeloma.
OBJECTIVE
To investigate lineage-specific chimerism of plasma cells after allogeneic transplantation by real-time PCR based on bi-allelic sequence polymorphism or, in case of female-to-male transplantation, on the detection of the DFFRY gene and to determine its value to quantify minimal residual disease in myeloma patients.


METHODS
Forty-eight samples from bone marrow samples and peripheral blood from 34 nonmyeloma patients were analyzed at different times after transplantation. Sixty-two samples from 22 myeloma patients were analyzed at different times after allogeneic stem cell transplantation, and results were compared with immunofixation and, in some cases, with PCR data using patient-specific primers.


RESULTS
The median chimerism for T cells at day +100 was greater than 99.9% and remained stable on day +180 and 1 year after transplantation. In contrast, the median donor plasma cell chimerism at day +100 was 95.5%, at day +180 98.6%, at day +360 99.8%, and 2 or more years after transplantation greater than 99.9%. Sensitivity of real-time PCR using human short insertion/deletion polymorphisms (SIDP) was 10(-4) and in case of Y-PCR 10(-5). Sequential monitoring of donor plasma cell chimerism showed that increasing and stable chimerism were associated with ongoing remission in 15 out of 16 samples (93%), and decreases in chimerism predicted relapse in 5 out of 6 patients.


CONCLUSIONS
We conclude that plasma cell chimerism after allogeneic stem cell transplantation is delayed in comparison to T-cell chimerism. Sequential quantitative measurement of plasma cells after allogeneic stem cell transplantation with highly sensitive real-time PCR allows monitoring of residual host-tumor cells in patients with multiple myeloma and allows guiding adoptive immunotherapy strategies to enhance remission status and to prevent clinical relapse.
Kröger
Nicolaus
N
Department of Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. nkroeger@uke.uni-hamburg.de
Zagrivnaja
Maria
M
Schwartz
Sabine
S
Badbaran
Anita
A
Zabelina
Tatjana
T
Lioznov
Michael
M
Ayuk
Francis
F
Zander
Axel
A
Fehse
Boris
B
D002678:Chimera; D005819:Genetic Markers; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
D005819:Genetic Markers