CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia.

Identification of prognosticators for Binet A chronic lymphocytic leukemia is important for selecting patients with dismal prognosis. We analyzed CD49d expression in 140 consecutive Binet A chronic lymphocytic leukemia. At diagnosis, CD49d >or=30% (54/140, 38.6%) associated with proliferation markers, namely CD38 >or=30% (p=3.9 x 10(-6)), LDH (p=0.007) and beta2-microglobulin (p=0.020). Univariate log-rank analysis identified CD49d >or=30% as a risk factor of treatment free survival (p=8.3 x 10(-5)), time to progression to a more advanced stage (p=4.7 x 10(-4)), and time to lymphocyte doubling (p=0.009). Multivariate analysis selected CD49d >or=30% as an independent treatment free survival predictor after adjustment for biological (HR 2.28; 95% CI 1.71-4.45, p=0.015) and both biological and clinical variables analyzed together (HR 3.33, 95% CI 1.61-6.90, p=0.001). Within Binet A subgroups harboring favorable biological variables (IGHV homology <98%, favorable karyotype, CD38 <30%, ZAP70 <20%) or clinical variables, CD49d >or=30% consistently identified a subset of patients with short treatment free survival. Our observations indicate CD49d >or=30% as a new marker for the initial prognostic assessment of Binet A chronic lymphocytic leukemia.

Cells carrying nonlymphoma-associated bcl-2/IgH rearrangements (NLABR) are phenotypically related to follicular lymphoma and can establish as long-term persisting clonal populations.

OBJECTIVE: Nonlymphoma-associated bcl-2/IgH rearrangements (NLABRs) are frequently amplified by PCR in blood of lymphoma-free subjects (LFS), but the temporal kinetics and phenotypic nature of NLABR-positive cells are unknown. To address these issues we prospectively monitored a panel of NLABR-positive LFS. METHODS: LFS have been studied by nested PCR, real-time PCR, and DNA sequencing. Cell selection studies were also performed to define the nature of NLABR-bearing clones. RESULTS: Of 125 donors, 16 (12.8%) were found to be bcl-2/IgH positive and were monitored at least every 6 months for a median time of 22 months (range 6-50). In half of the subjects the same NLABR detected initially was again reamplified at follow-up thrice or more. In 5, the same NLABR was constantly amplified in every follow-up sample. With a median follow-up of 22 months (range 9-50), no stable disappearance of a recurrent clone has been so far recorded. Real-time PCR indicated that persistent NLABR-positive clones are stable over time in the same subject. Cell separation studies indicate that NLABRs belong to CD19+, CD5-, CD23-, CD10+/- cells. CONCLUSIONS: Our results indicate that NLABR-positive clones are persistent populations phenotypically related to follicular lymphoma (FL). This suggests the existence of a FL-related clonal expansion of undetermined significance, which might be either a premalignant or a nonmalignant counterpart of FL.

Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma.

Molecular remission (MR) is associated with improved outcome in mantle cell lymphoma (MCL). If MR is not achieved, patients are at high risk of relapse. We retrospectively describe the molecular and clinical follow-ups of 4 patients with molecular relapses (M-rels) who were treated with rituximab. The 4 patients received rituximab-supplemented, high-dose sequential chemotherapy and autologous stem cell transplantation as induction treatment and achieved clinical remission and MR. M-rel was defined as polymerase chain reaction (PCR) positivity in 2 consecutive samples in the absence of clinical relapse. M-rels occurred at 3, 6, 39, and 52 months and were always confirmed by direct sequencing of the clonal rearrangement. Minimal residual disease was monitored by qualitative and real-time quantitative PCR. All patients received 4 courses of rituximab, with 2 additional infusions if PCR positivity remained. After 4-6 courses of rituximab, all patients re-entered MR. No clinical relapses were recorded at 3, 6, 18, and 62 months from treatment, although 1 patient had a second M-rel that was sensitive to rituximab. Our results indicate that rituximab is active against residual MCL cells and suggest that molecularly tailored maintenance therapy needs to be investigated in clinical trials.