Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T-cell lymphoblastic lymphoma stage III, detected by flow cytometry (FC) and real-time quantitative polymerase chain reaction (RQ-PCR).
BACKGROUND
Despite overlapping features of T-cell lymphoblastic lymphoma (T-LLy) and T-cell acute lymphoblastic leukemia (T-ALL), which respond favorably to T-ALL treatment, clinical and biological differences exist. We retrospectively assessed the prevalence of submicroscopic bone marrow (BM) minimal disseminated disease (MDD) at diagnosis and the early response to treatment (minimal residual disease--MRD) and their prognostic significance in 17 children with stage III T-LLy treated according to Berlin-Frankfurt-Munster (BFM) non-Hodgkin lymphoma protocols.


METHODS
Four-color flow cytometry (FC) was used for lymphoma associated immunophenotype and real-time quantitative polymerase chain reaction (RQ-PCR) for T-cell receptor (TCR beta/delta/gamma) gene rearrangements with at least 0.01% sensitivity.


RESULTS
Two markers per patient were identified in all cases using FC and in 80% using RQ-PCR. BM MDD at diagnosis of >or=0.01% was detected by FC and RQ-PCR in 88% and 80% of patients, respectively, and by at least one of the methods in all patients. A significant correlation was achieved between the methods by Pearson correlation analysis (P = 0.004). MRD levels significantly decreased to very low levels on day 33 in 9 out of 10 patients studied. The only patient that remained positive relapsed.


CONCLUSIONS
MDD was prevalent in stage III T-LLy, for which we could not prove a prognostic significance in the context of ALL-like treatment. This study shows that both FC and RQ-PCR methods are efficient for MDD and MRD analyses in T-LLy.
Stark
Batia
B
Center of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel. bstark@clalit.org.il
Avigad
Smadar
S
Luria
Drorit
D
Manor
Sigal
S
Reshef-Ronen
Tali
T
Avrahami
Gali
G
Yaniv
Isaac
I
D000293:Adolescent; D001855:Bone Marrow Diseases / Q000175:diagnosis* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000473:pathology; D016133:Polymerase Chain Reaction; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies