54 research outputs found
Therapy-Related Myeloid Neoplasm in Non-Hodgkin Lymphoma Survivors
Relatively little data on secondary cancers is available regarding patients treated for non-Hodgkin lymphoma (NHL), compared with those treated for Hodgkin lymphoma. Evolving treatment regimens have improved survival outcomes for NHL patients. As a result of this improvement, secondary malignancies are becoming an important issue in NHL survivors. This review aims to report data on this topic previously published by our group, adding unpublished results from the Modena Cancer Registry (MCR). We recently performed four studies about secondary neoplasms in NHL survivors: two studies analysing the risk of secondary neoplasms in patients treated for indolent and aggressive NHL; a meta-analysis of 23 studies investigating the risk of secondary malignant neoplasm (SMN) after NHL treatment; and a still-unpublished study evaluating the incidence of therapy-related myeloid neoplasm (t-MN) in patients treated for NHL (from the MCR database). The first two studies analysed 563 patients with indolent NHL and 1280 patients with diffuse large B-cell lymphoma (DLBCL) enrolled in the Gruppo Italiano Studio Linfomi (GISL) trials. Results showed that the cumulative incidence of secondary tumours was 10.5% at 12 years for indolent NHL and 8.2% at 15 years for DLBCL. Results of the meta-analysis indicated that NHL patients experienced a 1.88-fold increased risk for SMN compared with the general population; the standardized incidence risk (SIR) for secondary acute myeloid leukaemia (AML) was 11.07. Based on data from the MCR from 2000 through 2008, we found that the SIR was 1.63 for developing a secondary malignancy after NHL, and 1.99 for developing secondary haematological malignancies. Regarding myelodysplastic syndrome and/or AML incidence, nine NHL patients developed t-MN with a higher risk than expected (SIR 8.8, 95% CI: 4.0â16.6). In conclusion, patients treated for NHL are at increased risk of developing SMN. Regarding t-MN, data from the meta-analysis and the MCR demonstrate an excessive risk of developing AML (SIR 11.07 and 5.7, respectively) compared with solid SMN after treatment for NHL. Thus long-term monitoring should be considered for NHL survivors
Risk of second primary malignancy in breast cancer survivors: A nested population-based case-control study
Purpose: Evolving therapies have improved the prognoses of patients with breast cancer; and currently, the number of long-term survivors is continuously increasing. However, these patients are at increased risk of developing a second cancer. Thus, late side effects are becoming an important issue. In this study, we aimed to investigate whether patient and tumor characteristics, and treatment type correlate with secondary tumor risk. Methods: This case-control study included 305 patients with a diagnosed second malignancy after almost 6 months after the diagnosis of primary breast cancer and 1,525 controls (ratio 1:5 of cases to controls) from a population-based cohort of 6,325 women. The control patients were randomly selected from the cohort and matched to the cases according to age at diagnosis, calendar period of diagnosis, disease stage, and time of follow-up. Results: BRCA1 or BRCA2 mutation, human epidermal growth factor receptor 2 (HER2)+ status, chemotherapy, and radiotherapy were related to increased risk of developing a second cancer, whereas hormonotherapy showed a protective effect. Chemotherapy, radiotherapy, and estrogenic receptor level <10% increased the risk of controlateral breast cancer. HER2+ status increased the risk of digestive system and thyroid tumors, while BRCA1 or BRCA2 mutation increased the risk of cancer in the genital system. Conclusion: Breast cancer survivors are exposed to an excess of risk of developing a second primary cancer. The development of excess of malignancies may be related either to patient and tumor characteristics, such as BRCA1 or BRCA2 mutation and HER2+ status, or to treatments factors
Second malignancies after treatment of diffuse large B-cell non-Hodgkin's lymphoma: a GISL cohort study
BACKGROUND: Improved treatment has increased the life expectancy of patients with non-Hodgkin's lymphoma, but few studies have addressed the issue of second cancer in patients treated for diffuse large B-cell lymphoma. The aims of this study were to determine the incidence and time free of second cancers in this subset of patients. DESIGN AND METHODS: We evaluated a cohort of 1280 patients with diffuse large B-cell lymphoma who were first treated between 1988 and 2003. We utilized the central database of the Gruppo Italiano Studio Linfomi, which includes data on demographics, clinical characteristics, laboratory parameters, treatment and follow-up of all patients with non-Hodgkin's lymphoma enrolled in clinical trials. RESULTS: After a median follow-up of 51 months, 48 patients had developed a second cancer: 13 hematologic malignancies and 35 solid tumors. The overall standardized incidence ratio in our cohort (with a median age of 58 years) matched that of the general Italian population. The incidence ratio of second tumors was age related, and the age groups 20-39 and 40-59 years showed an increased risk. Overall, the cumulative incidence of second cancer was 8.2% at 15 years. A multivariate analysis showed that older age at the time of diagnosis of lymphoma had a negative influence on the time free of second tumors. CONCLUSIONS: In our cohort, only young patients showed an increased incidence ratio of second malignancies, while the incidence ratio in patients aged over 59 years matched the incidence in the Italian general population. Demographics, baseline characteristics, laboratory parameters and treatment modalities did not have any significant impact on the incidence ratio of a second cancer
Absolute monocyte count at diagnosis could improve the prognostic role of early FDG-PET in classical Hodgkin lymphoma patients
Recently published international guidelines suggested that
positron emission tomography (PET)-computed tomography
(CT) could be utilized for response assessment using the
Deauville criteria in ďŹuorodeoxyglucose (FDG)-avid lym-
phomas (Meignan et al, 2012). Interim PET (I-PET) scan-
ning seems highly predictive of treatment failure in Hodgkin
Lymphoma (HL) patients.
We recently showed that the absolute monocyte count
(AMC) has prognostic value in patients with classical HL
(cHL) (Tadmor et al, 2015). Here, we show that the com-
bined use of I-PET and AMC at diagnosis enables a more
accurate projection of patient outcome in cHL.
The present study is an ancillary branch of the analysis
reported by Tadmor et al, (2015). Patients with histopatho-
logical diagnosis of cHL previously enrolled in the Gruppo
Italiano Studio Linfomi trials were eligible if data on all clini-
cal and laboratory features and treatments, reported I-PET
results, treatment response and follow-up were available.
Response was deďŹned according to the revised International
Working Group guidelines (Cheson et al, 1999). An absolute
lymphocyte count <06 9 10
9
/l and AMC > 075 9 10
9
/l
were used as cut-off points. I-PET was performed after 2
cycles of treatment. A positive or negative I-PET was deďŹned
by the local investigatorsâ interpretation of the nuclear physi-
cianâs scan report, which was based on a visual qualitative
assessment.
The principal end-point of the study was the impact of
I-PET and AMC on progression-free survival (PFS); their
impact on overall survival (OS) was the secondary end-point.
Survival functions were estimated using the KaplanâMeier
method. Statistical comparisons between curves were per-
formed with log-rank test, and the effect of the covariate was
reported as hazard ratios (HR), from Cox regression.
All patients had a diagnosis of cHL; 76% of cases had the
nodular sclerosis (NS) subtype. Seventy-six patients (64%)
were treated with classical ABVD (doxorubicin, bleomycin,
vincristine, dacarbazine), and 23 (19%) and 19 (16%) with
the more intensive BEACOPP (bleomycin, etoposide, doxoru-
bicin, cyclophosphamide, vincristine, procarbazine, pred-
nisone) and COPPEBVCAD (cyclophosphamide, lomustine,
vindesine, melphalan, prednisone, epidoxirubicin, vincristine,
procarbazine, vinblastine, bleomycin) regimens (Federico
et al, 2009), respectively. Of the entire cohort, 104 patients
(88%) achieved complete remission. Twenty-six patients had
a positive I-PET (22%) and 28 (24%) had AMC > 075 9
10
9
/l at diagnosis.
The median follow-up of the entire cohort was 88 months
(range 5â142 months). The estimated 5-year OS was 91%
(95% conďŹdence interval [CI]: 84â95%). The 5-year PFS was
80% (95% CI: 71â86%). Patients with positive I-PET showed
a worse PFS compared to patients with negative I-PET (51%
and 88%, respectively; HR 587 [95% CI: 256â135]).
Patients with AMC > 075 9 10
9
/l at diagnosis had a worse
PFS compared to patients with AMC ⤠075 9 10
9
/l (58%
and 87%, respectively; HR 373 [95% CI: 161â864]). Multi-
ple Cox proportional hazards (PH) regression, adjusted for
International Prognostic Score 3â7, conďŹrmed the prognostic
role of I-PET (HR 532 [95% CI: 230â123]; P < 0001) and
AMC >075 9 10
9
/l (HR 319 [95% CI: 132â768];
P = 0010). Figure 1A, B shows the PFS for I-PET and AMC,
and Table I shows the uni- and multivariate Cox PH regres-
sion for PFS. The prognostic role of I-PET and AMC on OS
was also conďŹrmed.
Given the strong predictive value of both I-PET and
AMC, we stratiďŹed patients by positive or negative I-PET
and AMC > 075 9 10
9
/l or â¤075 9 10
9
/l into 3 groups
with different levels of risk. The low risk level (negative I-
PET and AMC ⤠075 9 10
9
/l; n = 73, 62%) had a 5-year
PFS of 90% (95% CI: 80â96%), the intermediate level
(I-PET positive or AMC > 075 9 10
9
/l; n = 36, 51%) had a
5-year PFS of 73% (95% CI: 55â85%), and the high risk level
(I-PET positive and AMC > 075 9 10
9
/l; n = 9, 8%) had a
5-year PFS of 17% (95% CI: 1â49%). The log-rank test
between the intermediate and low levels and between the
high and intermediate levels were signiďŹcant (P = 0 007,
P = 0001, respectively). For OS, the difference between the
intermediate and low risk levels tended to narrow
(P = 0232), while the difference between the high and inter-
mediate levels was signiďŹcantly different (P < 0001). Fig-
ure 1C, D shows the PFS and OS stratiďŹed by risk group.
The test for trend in PFS and OS was signiďŹcant
(P < 0001).
The rationale for using AMC as a prognostic parameter in
cHL is relevant because immunohistochemical and molecular
data, including the gene expression proďŹle, have identiďŹed a
key role for monocytes and macrophages in the biology of
cHL (Steidl et al, 2010; Porrata et al, 2012; Tan et al, 2012;
Koh et al , 2015; Tadmor et al, 2015). It might therefore bepossible that AMC is associated with the number of tumour-
associated macrophages (TAMs) in the microenvironment. If
so, then it could be considered as a biomarker of reactive
cells that is easily detectable in peripheral blood. The FDG-
PET scan is currently considered the most precise staging
method and may also be used to provide an early prediction
of treatment efďŹcacy There is a strong suggestion that reactive cells are respon-
sible for the increased FDG uptake at baseline, as they
account for 99% of Hodgkin tumours (Gallamini, 2010).
Furthermore, early responses to treatment have been sug-
gested to demonstrate the elimination of reactive cells, or at
least the disappearance of their activity, and are indirect
surrogates of tumour chemo-sensitivity (Gallamini &
Kostakoglu, 2012). Thus, the FDG-PET scan could be
considered a biomarker of the extent and activity of the
tumour microenvironment.
However, in clinical practice, patients with negative I-PET
can rapidly progress during induction treatment, while other
patients with positive I-PET may eventually achieve a CR.
Therefore, there is a need to further improve the predictive
power of I-PET. By combining the AMC at diagnosis with
the I-PET results, we showed that it is possible to increase
the discriminatory power of I-PET alone in identifying cHL
patients with poor PFS and OS. We are fully aware that our
study has many weaknesses, such as its retrospective nature,
the small number of patients and the lack of use of the
Deauville criteria. However, our results suggest that it is pos-
sible to further improve the already high predictive power of
PET by combining it with a simple and inexpensive surrogate
biomarker of reactive cells that are easily detectable in
peripheral blood
Secondary malignancies after treatment for indolent non-Hodgkin's lymphoma: a 16-year follow-up study.
Relatively little information is available on the incidence of secondary cancer in non-Hodgkin's lymphoma. The aim of this long-term follow-up study was to determine the incidence, the time free of second tumors, and risk factors for developing secondary cancer in a homogeneous group of patients with non-Hodgkin's lymphoma. DESIGN AND METHODS: We evaluated a total of 563 patients with indolent non-Hodgkin's lymphoma enrolled in Gruppo Italiano Studio Linfomi trials from 1988 to 2003. RESULTS: After a median follow-up of 62 months, 39 patients (6.9%) developed secondary cancer: 12 myelodysplastic syndromes/acute myeloid leukemia, and 27 solid tumors. The overall standardized incidence ratio of secondary malignancy in patients with non-Hodgkin's lymphoma was higher than the risk of malignancy in the general population. The standardized incidence ratio was elevated in male patients and in patients under 65 years old at first treatment. Overall, the cumulative incidence of secondary cancer at 12 years was 10.5%, after correction in a competing-risk model. Univariate and multivariate Cox regression analyses showed that older age at the time of diagnosis, male sex, and fludarabine-containing therapy had significant negative impacts on the time free of second tumors. CONCLUSIONS: We have identified subgroups of non-Hodgkin's lymphoma patients with increased standardized incidence ratios of secondary malignancy and variables that have a negative impact on the time free of second tumors. This information could help physicians to select the most appropriate treatments. Finally, taking into account the possible occurrence of secondary neoplasia, long-term monitoring must be considered
Neutrophil-lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: Results of a large multicenter study involving 990 patients
Several studies have demonstrated the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with solid tumors and non-Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)-cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression-free survival and overall survival compared to those with NLR â¤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression-free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS-cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS-cHL patients
Rituximab in combination with fludarabine and cyclophosphamide in the treatment of patients with recurrent follicular lymphoma
The current study was conducted to asses the safety profile and clinical activity of rituximab in combination with fludarabine and cyclophosphamide in patients with recurrent follicular lymphoma (FL). METHODS: This study was a noncomparative, multicenter, phase II study. Between March 2000 and December 2002, 54 patients with recurrent FL were enrolled in the FC+R trial. Patients received fludarabine at a dose of 25 mg/m(2) and cyclophosphamide at a dose of 300 mg/m(2) daily for 3 consecutive days, every 3 weeks for 4 cycles. Rituximab was administered at a dose of 375 mg/m(2) beginning 2 weeks after the first course of fludarabine and cyclophosphamide and then on Day 1 of each cycle thereafter. The planned treatment duration was 10 weeks. RESULTS: Overall, 92% of patients completed the planned therapy in 10 to 14 weeks and 74% achieved a complete response (CR). Among patients with BCL2-positive bone marrow, 86% obtained a molecular disease remission (MR). The median survival from treatment (SFT), the duration of disease remission (DR), and time to disease progression (TTP) had not been reached after a median follow-up of 45 months. Of the baseline characteristics, >2 previous treatments, BCL2-positive bone marrow, and low Follicular Lymphoma International Prognostic Index (FLIPI) score were found to be associated with better DR and/or TTP. Hematologic toxicity was transient and reversible, with the exception of 3 patients with severe and prolonged neutropenia. Three patients presented with infections, 1 of whom died of bronchopneumonia. CONCLUSIONS: The FC+R scheme, a nonanthracycline-containing regimen lasting up to 10 weeks, was found to be relatively well-tolerated and demonstrated significant antilymphoma activity with excellent clinical CR and molecular response rates
The prognostic role of end of treatment FDG-PET-CT in patients with diffuse large B cell lymphoma can be improved by considering it with absolute monocyte count at diagnosis
AbstractIt is well established that some patients with diffuse large B-cell lymphoma (DLBCL) and the negative end of treatment PET-CT (EOT-PET-CT) will relapse, while a proportion with positive upt..
Age-related differences in the expression of circulating microRNAs: miR-21 as a new circulating marker of inflammaging.
none15noopenF Olivieri; L Spazzafumo; G Santini; R Lazzarini; MC Albertini; MR Rippo; R Galeazzi; AM Abbatecola; F Marcheselli; D Monti; R Ostan; E Cevenini; R Antonicelli; C Franceschi; AD Procopio.F., Olivieri; L., Spazzafumo; G., Santini; R., Lazzarini; Albertini, MARIA CRISTINA; Mr, Rippo; R., Galeazzi; Am, Abbatecola; F., Marcheselli; D., Monti; R., Ostan; E., Cevenini; R., Antonicelli; C., Franceschi; Ad, Procopi
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