Lack of clinical utility of minimal residual disease detection in allogeneic stem cell recipients with childhood acute lymphoblastic leukemia: multi-institutional collaborative study in Japan.
The clinical utility of minimal residual disease (MRD) measurements following allogeneic stem cell transplantation (SCT) in childhood ALL is controversial. We therefore performed a multi-institutional study of MRD in bone marrow samples taken before SCT and at 1, 3, 6 and 12 months after SCT. Case-specific clonal rearrangements of IgH and TCR genes and expression levels of Wilms' tumor 1 (WT1) mRNA were determined by PCR or RT-PCR methods. In total, 95 cases met all criteria for analysis of informative IgH/TCR markers and quantitative WT1 mRNA expression levels. During the 2-year (median 414 days) study period, 20 patients relapsed. Although the proportion of patients with a positive IgH/TCR result before SCT was significantly reduced at 1 month after treatment (P<0.001), attesting the efficacy of SCT, serial measurements of IgH/TCR rearrangements did not correlate with leukemic relapse. Clonal switch was demonstrated in 11 of the 14 patients with bone marrow relapse, indicating that the poor predictive power of the MRD assay most likely reflected the loss of PCR targets. WT1 expression was not related to either MRD detection by IgH/TCR assays or to clinical leukemic relapse. The clinical value of serial MRD monitoring would be limited in ALL patients undergoing SCT.
Imashuku
S
S
Kyoto City Institute of Health and Environmental Sciences, Kyoto, Japan.
Terui
K
K
Matsuyama
T
T
Asami
K
K
Tsuchiya
S
S
Ishii
E
E
Kawa
K
K
Kosaka
Y
Y
Eguchi
H
H
Tsuchida
M
M
Ikuta
K
K
Kato
S
S
Koizumi
S
S
Okamura
J
J
Morimoto
A
A
Hibi
S
S
Hamaoka
K
K
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001856:Bone Marrow Examination; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015329:Gene Rearrangement, T-Lymphocyte; D016162:Genes, Wilms Tumor; D016313:Genes, abl; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012008:Recurrence; D014184:Transplantation, Homologous
D012333:RNA, Messenger; D012334:RNA, Neoplasm