Recurrence of Bcl-2/IgH polymerase chain reaction positivity following a prolonged molecular remission can be unrelated to the original follicular lymphoma clone.
OBJECTIVE
The aim of this study was to evaluate whether reappearance of polymerase chain reaction (PCR) positivity for the Bcl-2/IgH translocation following a phase of molecular remission in autografted follicular lymphoma (FL) patients is always associated with reappearance of the original neoplastic clone.


METHODS
The molecular follow-up of 119 autografted Bcl-2/IgH positive patients was evaluated by nested PCR. In case of molecular recurrence, direct sequencing of involved rearrangements has been performed both at diagnosis and at the time of recurrence. The two sequences then were compared in terms of breakpoints, N insertions, and JH usage.


RESULTS
Seventy-five patients achieving molecular remission were identified in our patient sample (63%). Of these patients, eight (10.6%) experienced molecular recurrence. Direct sequencing of the Bcl-2/IgH translocation performed at diagnosis and recurrence showed identical rearrangements in six subjects and unrelated rearrangements in two. As opposed to most true molecular relapses, unrelated rearrangements always occurred several years after transplantation. To date, the two subjects carrying unrelated rearrangements show no signs of active lymphoproliferative disease.


CONCLUSIONS
This report is the first evidence that Bcl-2/IgH rearrangements unrelated to the original tumor clone can lead to false-positive results during the molecular follow-up of autografted FL patients. Based on these results, we recommend confirmation by direct sequencing, at least for patients experiencing molecular relapse 2 or more years after the end of treatment. This will be particularly important for patients enrolled in clinical trials that schedule additional treatment in case of molecular evidence of persistent disease activity.
Ladetto
Marco
M
Divisione di Ematologia Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, A.O. San Giovanni Battista della Citta' di Torino, Torino, Italy. marco.ladetto@unito.it
Mantoan
Barbara
B
Ricca
Irene
I
Astolfi
Monica
M
Drandi
Daniela
D
Compagno
Mara
M
Vallet
Sonia
S
dell'Aquila
Maria
M
Alfarano
Alda
A
Rossatto
Paola
P
Rocci
Alberto
A
Vitolo
Umberto
U
Corradini
Paolo
P
Boccadoro
Mario
M
Tarella
Corrado
C
D014408:Biomarkers, Tumor / Q000235:genetics; D005189:False Positive Reactions; D015972:Gene Expression Regulation, Neoplastic; D005803:Genes, Immunoglobulin; D019254:Genes, bcl-2; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012008:Recurrence; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor