FCγRIIIA and FCγRIIA polymorphisms are not associated with response to rituximab and CHOP in patients with diffuse large B-cell lymphomaWe investigated the association of Fcγ γRIIIa and Fcγ γRIIa polymorphisms and response to R-CHOP in 58 patients with diffuse large B-cell lymphoma (DLBCL). Fcγ γRIIIa and Fcγ γRIIa polymorphisms did not influence response, event-free or overall survival. These results suggest that ADCC via Fcγ γRIIIa and Fcγ γRIIa may not be the major mechanism of activity of the R-CHOP combination in DLBCL. Haematologica 2007; 92:998-999 Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm accounting for approximately 30-40% of all non-Hodgkin lymphomas (NHLs). Recently, the combination of rituximab (R) and CHOP (cyclophosphamide, doxorubicin, vincristin, prednisone) led to significant improvement in the outcomes of patients with DLBCL, establishing R-CHOP as the new standard treatment.1,2 The proposed mechanisms of rituximab activity include: antibody dependent cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), direct induction of apoptosis and chemosensitization of tumor cells to the cytotoxic effects of chemotherapy.3,4 The clinical importance of each is still a matter of debate. ADCC is mediated by effector cells that engage the Fc portion of the antibody via receptors for immunoglobulin (FcγRs). Three FcγR classes (FcγRI, II, III) and eight subclasses have been described with significantly different haplotype distribution between various ethnic groups.5 FcγRIIIa receptor is expressed on natural killer (NK) cells, macrophages, while FcγRIIa is expressed on neutrophils and macrophages. Genomic polymorphism of the FcγRIIIa receptor corresponding to phenotypic expression of valine (V) or phenylalanine (F) at position 158 influences the binding of IgG1 to this receptor.6 It has been shown that NK cells with valine homozygous FcγRIIIa receptors (V/V) have a higher affinity to rituximab than those with phenylalanine homozygous receptors (F/F) resulting in more effective ADCC.7 Several studies investigated the influence of FcγRIIIa and FcγRIIa polymorphisms on response to rituximab-containing treatment in different types of lymphoma. In follicular lymphoma (FL), patients with FcγRIIIa 158 V/V phenotype respond better than F carriers to rituximab monotherapy, 8,9 but not to R-CHOP. 10,11FcγRIIIa 158 V/V phenotype is associated with improved response to rituximab monotherapy in Waldenstrom's macroglobulinemia, 12 in contrast to chronic lymphocytic leukemia (CLL).13 A recently published study found that Korean DLBCL patients with FcγRIIIa 158 V/V phenotype respond better to R-CHOP than F carriers, although there were no differences in event-free survival (EFS) and overall survival (OS).14 In one series, patients with FL homozygous for histidine (H) on position 131 of FcγRIIa responded better to rituximab monotherapy than heterozygous patients or patients homozygous for arginine (R).9 Others failed to confirm this association. 8,10,13,14 We examined the cor...

Efforts are underway to translate previous microarray findings to platforms that can be readily used in routine clinical practice with high reproducibility, precise measurements, and minimal loss of information. At the present time, there is no consensus on which biological prognostic markers should be routinely assessed in patients with DLBCL, and practices vary widely among different institutions. With more global approaches, the ability to assess biomarkers in the cellular or tumor context may be possible, resulting in a better understanding of their biological and prognostic significance.

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Lymphopenia is a marker of inferior survival in patients with various malignancies. However, the prognostic significance of lymphopenia in peripheral T‐cell lymphoma (PTCL) is unclear. We analyzed the prognostic significance of lymphopenia in 826 patients with different types of PTCL and natural killer/T‐cell lymphoma (NKTCL) from the International Peripheral T‐cell Lymphoma Project. Lymphopenia was defined as an absolute lymphocyte count of less than 1,000 cells per microliter. The overall frequency of lymphopenia was 35.3%, ranging from 21.1% in ALK+ anaplastic large cell lymphoma (ALCL) to 47.5% in angioimmunoblastic T‐cell lymphoma (AITL). Lymphopenia was independently associated with an inferior overall survival (OS) in patients with the lymphoma type of adult T‐cell leukemia/lymphoma (ATLL), with a 2‐year OS of 15% versus 40% for those without lymphopenia (P < 0.001). Lymphopenia was also an adverse predictor of survival in PTCL, not otherwise specified, but was associated with other unfavorable prognostic factors. A trend toward inferior survival for lymphopenic patients was also observed in AITL, ALK− ALCL and extranasal NKTCL lymphoma, whereas no difference in survival was found in nasal NKTCL, ALK+ ALCL, or enteropathy‐associated T‐cell lymphoma. In this study, lymphopenia was identified as a new adverse prognostic factor in the lymphoma type of ATLL. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.