FDG–PET in the assessment of patients with follicular lymphoma treated by ibritumomab tiuxetan Y 90: multicentric study

Purpose The randomized First-Line Indolent Trial (FIT) was conducted in patients with advanced follicular lymphoma (FL), to evaluate the safety and efficacy of yttrium-90 (90Y) ibritumomab tiuxetan given as consolidation of complete or partial remission. This study of minimal residual disease was undertaken in parallel, to determine the rate of conversion from bcl-2 polymerase chain reaction (PCR) –detectable to –undetectable status and the corresponding effect on progression-free survival (PFS). Patients and Methods Blood samples from 414 patients (90Y-ibritumomab, n = 208; control, n = 206) were evaluated using real-time quantitative polymerase chain reaction (RQ-PCR); 186 were found to have the bcl-2 rearrangement and were thus eligible for inclusion in the RQ-PCR analysis. Results Overall, 90% of treated patients converted from bcl-2 PCR–detectable to –undetectable disease status, compared with 36% in the control group. Treatment significantly prolonged median PFS in patients converting to bcl-2 PCR-undetectable status (40.8 v 24.0 months in the control group; P < .01, hazard ratio [HR], 0.399). In patients who had bcl-2 PCR-detectable disease at random assignment, treatment significantly prolonged median PFS (38.4 v 8.2 months in the control group; P < .01, HR, 0.293). Conclusion Eradication of PCR-detectable disease occurred more frequently after treatment with 90Y-ibritumomab tiuxetan and was associated with prolongation of PFS.

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Expert-independent classification of mature B-cell neoplasms using standardized flow cytometry: a multicentric study

Blood Advances ◽

10.1182/bloodadvances.2021005725 ◽

2021 ◽

Author(s):

Sebastian Böttcher ◽

Robby Engelmann ◽

Georgiana Grigore ◽

Paula Carolina Fernandez ◽

Joana Caetano ◽

...

Keyword(s):

Flow Cytometry ◽

Differential Diagnosis ◽

Follicular Lymphoma ◽

B Cell ◽

Diagnostic Algorithm ◽

Lymphocytic Leukemia ◽

B Cell Lymphomas ◽

Multicentric Study ◽

Predictive Values ◽

Large B Cell

Reproducible expert-independent flow-cytometric criteria for the differential diagnoses between mature B-cell neoplasms are lacking. We developed an algorithm-driven classification for these lymphomas by flow cytometry and compared it to the WHO gold standard diagnosis. Overall, 662 samples from 662 patients representing nine disease categories were analyzed at 9 laboratories using the previously published EuroFlow 5-tube-8-color B-cell chronic lymphoproliferative disease antibody panel. Expression levels of all 26 markers from the panel were plotted by B-cell entity to construct a univariate, fully standardized diagnostic reference library. For multivariate data analysis we subsequently utilized Canonical Correlation Analysis of 176 training cases to project the multi-dimensional space of all 26 immunophenotypic parameters into 36 two-dimensional plots for each possible pair-wise differential diagnosis. Diagnostic boundaries were fitted according to the distribution of the immunophenotypes of a given differential diagnosis. A diagnostic algorithm based on these projections was developed and subsequently validated using 486 independent cases. Negative predictive values exceeding 92.1% were observed for all disease categories except for follicular lymphoma. Particularly high positive predictive values were returned in chronic lymphocytic leukemia (99.1%), hairy cell leukemia (97.2%), follicular lymphoma (97.2%) and mantle cell lymphoma (95.4%). Burkitt and CD10+ diffuse large B-cell lymphomas were difficult to distinguish by the algorithm. A similar ambiguity was observed between marginal zone, lymphoplasmacytic, and CD10- diffuse large B-cell lymphomas. The specificity of the approach exceeded 98% for all entities. The univariate immunophenotypic library and the multivariate expert-independent diagnostic algorithm might contribute to increased reproducibility of future diagnostics in mature B-cell neoplasms.

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