Histologic transformation in marginal zone lymphomas Conconi, A.; Franceschetti, S.; Aprile von Hohenstaufen, K. ...
Annals of oncology,
November 2015, 2015-Nov, 2015-11-00, 20151101, Letnik:
26, Številka:
11
Journal Article
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Histologic transformation (HT) is a poorly understood event in patients with marginal zone lymphoma (MZL). The aim of this study was to analyze incidence and risk factors for HT in a large series of ...MZL patients.
The studied cohort included 340 MZL patients diagnosed and treated between 1995 and 2012: 157 extranodal MZLs mucosa-associated lymphoid tissue (MALT) lymphoma, 46%, 85 splenic MZLs (SMZLs, 25%) and 37 nodal MZLs (NMZLs, 11%). Sixty-one patients (18%) had bone marrow infiltration at presentation, with or without detectable involvement of peripheral blood, but without other involved sites; they were considered clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ).
With a median follow-up of 4.8 years, the median overall survival and progression-free survival of the whole population were 14.5 and 5 years, respectively. HT was observed in 13 cases 3.8%, 95% confidence interval (95% CI) 2%–6.5%. Elevated lactate dehydrogenase (LDH) at diagnosis was associated with the risk of HT (P = 0.019). HT occurred in 5% of SMZLs, 4% of MALT lymphomas, 3% of NMZLs and 3% of CBL-MZ (P = 0.974). The risk of HT was 5% (95% CI 3–9%) at 5 and 10 years after diagnosis and 10% (95% CI 5%–20%) at 12 years. At the time of HT, most patients had high LDH and B symptoms. At a median follow-up of 12 months after HT, 4 of 13 patients died, all for lymphoma-related causes, with a 2-year post-transformation survival rate of 57% (95% CI 13%–86%).
In this large retrospective series, the risk of HT across all MZL types appeared lower than the one reported for follicular lymphoma.
In this paper, it is shown how to extract a hypothesis with small risk from the ensemble of hypotheses generated by an arbitrary on-line learning algorithm run on an independent and identically ...distributed (i.i.d.) sample of data. Using a simple large deviation argument, we prove tight data-dependent bounds for the risk of this hypothesis in terms of an easily computable statistic M/sub n/ associated with the on-line performance of the ensemble. Via sharp pointwise bounds on M/sub n/, we then obtain risk tail bounds for kernel perceptron algorithms in terms of the spectrum of the empirical kernel matrix. These bounds reveal that the linear hypotheses found via our approach achieve optimal tradeoffs between hinge loss and margin size over the class of all linear functions, an issue that was left open by previous results. A distinctive feature of our approach is that the key tools for our analysis come from the model of prediction of individual sequences; i.e., a model making no probabilistic assumptions on the source generating the data. In fact, these tools turn out to be so powerful that we only need very elementary statistical facts to obtain our final risk bounds.
The clinical activity of rituximab has been evaluated in a phase 2 study in both untreated and relapsed mucosa-associated lymphoid tissue (MALT) lymphomas. Treatment consisted of 4 standard (375 ...mg/m2) weekly doses. Thirty-five patients were enrolled, and 34 completed the treatment program. The primary lymphoma location was stomach in 15 patients, and extragastric in 20. Eleven patients had previously been treated with chemotherapy. At study entry 12 patients had Ann Arbor stage IE, 3 had stage IIE, and 20 had stage IV disease. The overall response rate was 73% (95% confidence interval, 56%-87%), with 15 complete responses and 10 partial responses, and the response rate was significantly higher in the chemotherapy-naive patients, who had an 87% response rate compared with 45% of the previously treated patients (P = .03). The median response duration was 10.5 months. At a median follow-up of 15 months, 9 patients (26%) relapsed. The median time to treatment failure was 14.2 months in the whole series, but it was significantly longer (22 versus 12 months) in the chemotherapynaive patients compared with those who had prior chemotherapy (P = .001). Most adverse events were of mild to moderate severity with no grade 4 toxicity. This study indicates that rituximab is safe with significant activity in MALT lymphomas.
Patients younger than 40 years with a diagnosis of follicular lymphoma have a longer survival than the older ones, whose survival is strongly affected by competing causes of death. Importantly, ...cause-specific survival of patients younger than 40 is similar to that of patients 41-59 years old in agreement with the concept that biological features of the disease do not differ across age groups.
To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL).
A retrospective international survey of 373 patients with primary testicular DLCL.
...Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy.
Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.
This study was aimed at investigating the clinical features and outcomes of follicular lymphoma (FL) patients younger than 40 years, which have not been extensively investigated yet.
One hundred and ...fifty-five patients younger than 40 years were retrospectively studied from a series of 1002FL patients diagnosed in four different European Oncology Centres (Barcelona, Spain; Bellinzona, Switzerland; London, UK; Novara, Italy) from 1985 to 2010.
Patients younger than 40 had a lower incidence of elevated LDH, high beta2-microglobulin, and a high-risk Follicular Lymphoma International Prognostic Index (FLIPI) score, whereas bone marrow involvement and bulky and disseminated lymphadenopathy were more frequent. At a median follow-up of 10 years, younger patients, in comparison with those older than 40, had significantly better overall (OS), cause-specific survival (CSS), and progression-free survival (PFS), with 10-year OS rate of 81% versus 51% (P < 0.0001), 10-year CSS rate of 82% versus 60% (P < 0.0001), and 10-year PFS of 39% versus 24% (P = 0.0098). However, there were no significant CSS and PFS differences in comparison with the patients aged 40–60. In multivariate analysis, having the lymphoma diagnosed in the last two decades and a favourable FLIPI score were associated with a significantly longer PFS and CSS in younger patients, whereas only FLIPI retained statistical significance for OS.
In our series, FL patients younger than 40 have a median OS of 24 years and their outcome seems to be improving over time. However, they still have a significantly shorter life expectancy than that of an age-matched general healthy population.
The nuclear factor-kappa B activation in mucosa-associated lymphoid tissue (MALT) lymphoma pathogenesis provided the rationale for the evaluation of bortezomib in this malignancy.
Thirty-two patients ...with relapsed/refractory MALT lymphoma were enrolled. Thirty-one patients received bortezomib 1.3 mg/m2 i.v., on days 1, 4, 8, and 11, for up to six 21-day cycles.
Median age was 63 years (range, 37–82 years). Median number of prior therapies was 2 (range, 1–4). Nine patients had Ann Arbor stage I, 7 patients had stage II, and 16 patients had stage IV. Primary lymphoma localization was the stomach in 14 patients; multiple extranodal sites were present in 10 patients. Among the 29 patients assessable for response, the overall response rate was 48% 95% confidence interval (CI) 29% to 67%, with 9 complete and 5 partial responses. Nine patients experienced stable disease and six had disease progression during therapy. The most relevant adverse events were fatigue, thrombocytopenia, neutropenia, and peripheral neuropathy. After a median follow-up of 24 months, the median duration of response was not reached yet. Five deaths were reported, in two patients due to disease progression.
Bortezomib is active in relapsed MALT lymphomas. Further investigations to identify optimal bortezomib dose, schedule, and combination regimens are needed since the frequent detection of dose-limiting peripheral neuropathy.
Knowledge on the impact of pharmacogenetics in predicting outcome and toxicity in diffuse large B-cell lymphoma (DLBCL) is scant. We tested 106 consecutive DLBCL treated with R-CHOP21 for 19 single ...nucleotide polymorphisms (SNPs) from 15 genes potentially relevant to rituximab-CHOP (R-CHOP) pharmacogenetics. Associations of SNPs with event-free survival (EFS) and toxicity were controlled for multiple testing. Genotypic variants of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase p22phox (CYBA rs4673) and alpha1 class glutathione S-transferase (GSTA1 rs3957357) were independent predictors of EFS (CYBA rs4673 TT genotype: HR 2.06, P=0.038; GSTA1 rs3957357 CT/TT genotypes: HR 0.38, P=0.003), after adjusting for International Prognostic Index (IPI). CYBA rs4673 and GSTA1 rs3957357 also predicted outcome in DLBCL subgroups by IPI. Impact of SNPs on toxicity was evaluated in 658 R-CHOP21 courses utilizing generalized estimating equations. NCF4 rs1883112 was an independent predictor against hematologic (odds ratios (OR): 0.45; P=0.018), infectious (OR: 0.46; P=0.003) and cardiac toxicity (OR: 0.37; P=0.023). Overall, host SNPs affecting doxorubicin pharmacodynamics (CYBA rs4673) and alkylator detoxification (GSTA1 rs3957357) may predict outcome in R-CHOP21-treated DLBCL. Also, NCF4 rs1883112, a SNP of NAD(P)H oxidase p40phox, may have a function in protecting against hematologic and nonhematologic toxicity. These results highlight the need to improve characterization of the host genetic background for a better prognostication of DLBCL.
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