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The Clinical Significance of Molecular Response in Indolent
Follicular Lymphomas
Armando López-Guillermo,
Fernando Cabanillas,
Peter McLaughlin,
Terry Smith,
Fredrick Hagemeister,
María A. Rodríguez,
Jorge E. Romaguera,
Anas Younes,
Andreas H. Sarris,
H. Alejandro Preti,
William Pugh, and
Ming-Seng Lee
From the Departments of Lymphoma, Biomathematics, Pathology, and
Laboratory Medicine, University of Texas, M.D. Anderson Cancer Center,
Houston, TX.
Most patients with follicular lymphoma (FL) achieve a
complete response (CR) after treatment, but eventually most of them, particularly those with stage IV, relapse due to minimal residual disease (MRD). The t(14;18) gives rise to a rearrangement of the bcl-2
oncogene that constitutes an excellent target for detection of MRD by
polymerase chain reaction (PCR). One hundred ninety-four previously
untreated patients with indolent FL and detectable bcl-2 rearrangement
were studied. The PCR assay was used to detect bcl-2-rearranged cells
in blood and marrow before and after treatment. Molecular response rate
was 37%, 53%, 56%, and 66% at 3 to 5, 6 to 8, 9 to 14, and 15 to 18 months from the start of therapy, respectively. Although molecular
response was higher among clinical CRs, one third of partial responders
at 3 to 5 months also achieved a molecular response. Patients who
achieved a molecular response during the first year of treatment had a
significantly longer failure-free survival (FFS) than those who did not
(4-year FFS: 76% v 38%, respectively; P < .001).
Similar results were also observed in the subset of patients in
clinical CR 1 year after treatment. By multivariate analysis,
 2-microglobulin (2-M; P < .01), and molecular response
(P < .001) were the most important variables associated with
outcome. When we combined 2-M and molecular response, three
prognostic groups emerged: (1) low 2-M and molecular responders, (2)
low 2-M and nonresponders or high 2-M and responders, and (3)
high 2-M and nonresponders. The 4-year FFS of these 3 groups were
86%, 65%, and 23%, respectively. Finally, patients who achieved
molecular response and sustained it had better FFS than those who
either reverted back to PCR-positive or who never achieved molecular
response. Serial PCR analysis to determine the molecular response in FL
correlates well with outcome especially when combined with pretreatment
2-M.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2955-2960
© 1998 by The American Society of Hematology.
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