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The CD45RA and CD45RO isoforms of the leukocyte common antigen identify functionally distinct CD4+ T cell subsets: CD4+/CD45RA+ cells which represent a more 'naive' stage of T cell compartment and CD4+/CD45RO+ 'memory' cells. Phenotypic and functional abnormalities in T cell compartment have been frequently reported in patients with hairy cell leukemia (HCL) and, in more recent studies, a significant reduction in the absolute number of CD4+ lymphocytes bearing the CD45RO antigen has also been recorded. In our study we evaluated the CD45RA and CD45RO expression on CD4+ T cells by three-color staining in flow cytometry in 38 HCL patients, 19 untreated and 19 previously treated with 2-chlorodeoxyadenosine (2-CdA), administered at a daily dose of 0.1 mg/kg c.i. for 7 days. In HCL untreated patients, the proportion and the absolute number of CD4+/CD45RA+ and of CD4+/CD45RO+ T cell subsets were similar to normal controls. In contrast, HCL patients at 3-5 years by the end of treatment with 2-CdA, together with a reduction in the absolute number of CD4+ T cells, showed a persistent and significant decrease in the proportion and absolute number of CD4+/CD45RA+ cells as compared with both untreated HCL patients and normal controls (41 +/- 16% vs 57 +/- 14% and vs 65 +/- 7%) (P = 0.01 and 0.0001) and (0.201 +/- 0.137 x 10(9)/l vs 0.549 +/- 0.238 x 10(9)/l and vs 0.696 +/- 0.078 x 10(9)/l) (P = 0.00009 and P = 0.00001). In addition, together with the reduction of CD4+/CD45RA+ cells, we recorded a concomitant increase in the proportion of the CD4+/CD45RO+ cells as compared to untreated HCL patients and normal controls (62 +/- 16% vs 47 +/- 15% and vs 42 +/- 12%) (P = 0.08 and 0.02). These findings may suggest that CD4+/CD45RA+ cells are more sensitive than CD4+/CD45RO+ to the toxic effect of 2-CdA. [ABSTRACT FROM AUTHOR]

R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 216 any-stage chemonaïve DLBCL patients candidate to R-CHOP were enrolled. The median age of the 185 eligible patients was 59.2 years, 49.7% were women and 45.4% were stage I-II patients. According to the Revised International Prognostic Index (R-IPI), 14.1%, 56.8% and 29.2% were in the very good, good and poor prognosis groups, respectively. Of the patients, 85.9% produced a complete response. Highly significant associations (i.e., p < 5 × 10 -8 ) were found between progression-free survival (PFS) and six SNPs (i.e., rs116665727, rs1607795, rs75614943, rs77241831, rs117500207, rs78466241). Additionally, five SNPs (i.e., rs74832512, rs117500207, rs35789195, rs11721010, rs12356569) were highly associated with overall survival (OS). Wild-type patients showed a prolonged PFS or OS compared with patients carrying deleterious alleles ( p < 0.001). No association with the adequate significant threshold was observed between SNPs and the objective response or toxicity. In the future, these SNPs, alone or in combination, after a proper validation in an independent cohort, could contribute to improving the prediction of R-CHOP response.

Ibrutinib represents the first approved treatment for patients with Waldenström macroglobulinemia (WM). There are very few published experiences outside of a clinical trial. In this study, we investigated treatment response, survival, and safety in a real life setting. We retrospectively analyzed 49 consecutive R/R WM patients, managed in 8 Tuscan onco-hematological centers, that received ibrutinib after its approval, at a maximum dose of 420 mg once per day, until disease progression or unacceptable toxicity. Median age was 65 years (range 32-86), and the median number of previous regimens was 2 (range 1-5). Overall and major response rate were 91.8% and 87.7%, respectively. At best response, median IgM level declined from 3,094 to 831 mg/dl, and Hb level increased from 10.4 to 12.7 g/dl. In an intention-to-treat analysis, 36/49 patients (73.5%) were still receiving treatment, while 13/49 (26.5%) had discontinued therapy. Six out of 49 cases (12.2%) relapsed after an initial response, and 13/49 (26.5%) had a dose reduction. Estimated 2-year PFS, DOR, and OS were 76.7%, 88.7%, and 84.1%, respectively. After a median follow-up of 18.3 months, 43/49 patients (87.8%) were alive. The most frequent AE included atrial fibrillation or flutter (6/49 cases, 12.2%), bleeding (6/49 cases, 12.2%), arthralgia/myalgia (5/49 cases, 10.2%). Ibrutinib is a suitable treatment option for R/R WM patients and also suggested by ESMO, NCCN, and other societies. PFS and OS were durable, and DOR was sustained for responsive patients. Treatment toxicity is not negligible, but manageable in most cases without treatment discontinuation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Relapsed or refractory (R/R) mantle-cell lymphoma (MCL) patients have a poor prognosis and their management is challenging, in absence of a golden standard as salvage treatment. Bruton's tyrosine kinase inhibitor ibrutinib represents an effective treatment for R/R MCL patients. We investigated ibrutinib efficacy and safety in daily clinical practice, together with factors that could predict disease outcome., Patients and Methods: We retrospectively analyzed 69 consecutive R/R MCL patients managed in 10 Tuscan onco-hematological centers. The treatment regimen consisted of oral, continuous, single-agent ibrutinib, maximum dosage of 560 mg once per day, until disease progression., Results: Overall response rate was 62.3%, with a CR rate of 39.1%. After a median follow-up of 15.6 months, 40/69 patients (58%) were alive, the main cause of death was progressive disease (PD, 22/69 cases, 31.9%). Median progression-free survival (PFS) and overall survival (OS) were 17 and 34.8 months. Inferior PFS was associated with >1 prior line of therapy and B symptoms. Ibrutinib refractoriness was associated with inferior OS, median OS after ibrutinib failure was only 5 months., Discussion and Conclusion: In this real-life setting ibrutinib treatment prolonged survival in R/R MCL patients, without unexpected adverse events. Patients receiving ibrutinib as 2 nd line regimen had the most favorable outcome., Competing Interests: None., (AJBR Copyright © 2021.)