In this study we assessed the prognostic significance of absolute monocyte count and selected the best cut-off value at diagnosis in a large cohort of patients with diffuse large B-cell lymphoma. ...Data were retrieved for therapy-naïve patients with diffuse large B-cell lymphoma followed in Israel and Italy during 1993-2010. A final cohort of 1017 patients was analyzed with a median follow up of 48 months and a 5-year overall survival rate of 68%. The best absolute monocyte count cut-off level was 630/mm(3) and the 5-year overall survival for patients with counts below this cut-off was 71%, whereas it was 59% for those with a count >630 mm(3) (P=0.0002). Of the 1017 patients, 521 (51%) were treated with chemo-immunotherapy, and in this cohort, using multivariate analysis, elevated monocyte count retained a negative prognostic value even when adjusted for International Prognostic Index (HR1.54, P=0.009). This large study shows that a simple parameter such as absolute monocyte count (>630/mm(3)) can easily be used routinely in the evaluation of newly diagnosed diffuse large B-cell lymphoma to identify high-risk patients with a worse survival in the rituximab era.
To compare doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) versus bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) versus ...cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxirubicin, vincristine, procarbazine, vinblastine, and bleomycin (COPPEBVCAD; CEC) for advanced Hodgkin's lymphoma (HL).
Three hundred seven patients with advanced HL (stage IIB, III, and IV) were randomly assigned to receive six courses of ABVD, four escalated plus two standard courses of BEACOPP, or six courses of CEC, plus a limited radiation therapy program.
After a median follow-up of 41 months, BEACOPP resulted in a superior progression-free survival (PFS), with a significant reduction in risk of progression (hazard ratio HR = 0.50) compared with ABVD. No differences between BEACOPP and CEC, or CEC and ABVD were observed. The 5-year PFS was 68% (95% CI, 56% to 78%), 81% (95% CI, 70% to 89%), and 78% (95% CI, 68% to 86%), for ABVD, BEACOPP, and CEC, respectively (BEACOPP v ABVD, P = .038; CEC v ABVD and BEACOPP v CEC, P = not significant NS). The 5-year overall survival was 84% (95% CI, 69% to 92%), 92% (95% CI, 84% to 96%), and 91% (95% CI, 81% to 96%) for ABVD, BEACOPP, and CEC, respectively (P = NS). BEACOPP and CEC resulted in higher rates of grade 3-4 neutropenia than ABVD (P = .016); BEACOPP was associated with higher rates of severe infections than ABVD and CEC (P = .003).
As adopted in this study BEACOPP is associated with a significantly improved PFS compared with ABVD, with a predictable higher acute toxicity.
Optimal lymphocyte parameters and thresholds for the diagnosis of chronic lymphocytic leukemia have been proposed by The National Cancer Institute sponsored Working Group and recently updated by the ...International Workshop on chronic lymphocytic leukemia. However, it is not clear how these criteria apply to patient management in daily clinical practice and whether the lymphocyte thresholds recommended truly predict clinical outcome in early chronic lymphocytic leukemia.
For the purpose of this study, an observational database of the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) which included 1,158 patients with newly diagnosed Binet stage A chronic lymphocytic leukemia who were observed at different primary hematology centers during the period 1991-2000, was used.
Among 818 consecutive chronic lymphocytic leukemia patients with Rai stage 0 (i.e. no palpable lymphadenopathy or hepatosplenomegaly) who had flow cytometry evaluations at the time of diagnosis and were included in a GIMEMA database, both absolute lymphocyte count and B-cell count were of a similar value in predicting time to first treatment as continuous variables (P<0.0001). Receiver operating characteristic analysis identified an absolute lymphocyte count of 11.5×10(9)/L and an absolute B-cell count of 10.0×10(9)/L as the best thresholds capable of identifying patients who will require treatment from those with stable disease. However, in a Cox's multivariate analysis only the B-cell count retained its discriminating power (P<0.0001) and the estimated rate of progression to chronic lymphocytic leukemia requiring treatment among subjects with a B-cell count less than 10.0×10(9)/L was approximately 2.3% per year (95% CI 2.1-2.5%) while it was 2-fold higher for patients with a B-cell count of 10.0×10(9)/L or over (i.e. 5.2% per year; 95% CI 4.9-5.5%). Finally, in this community-based patient cohort, the B-cell threshold defined by investigators at the Mayo Clinic (i.e. 11.0×10(9)/L) allowed patients to be divided into two subsets with a higher and lower likelihood of treatment (P<0.0001).
Our results, based on a retrospective patients' cohort, provide a clear justification to retain the B-cell count as the reference gold standard of chronic lymphocytic leukemia diagnosis and imply that a count of 10×10(9)/L B cells is the best lymphocyte threshold to predict time to first treatment. The use of clinical outcome to distinguish chronic lymphocytic leukemia from other premalignant conditions, such as monoclonal B-cell lymphocytosis, is a pragmatic approach meeting the patients' need to minimize the psychological discomfort of receiving a diagnosis of leukemia when the risk of adverse clinical consequences is low.
1 Dipartimento di Oncologia ed Ematologia Università di Modena Centro Oncologico Modenese, Policlinico Modena
2 Dipartimento di Oncologia, Ospedale Santo Spirito, Pescara
3 Dipartimento di Oncologia, ...Sezione Ematologia, Ospedale Santa Chiara, Pisa
4 Medicina Oncologica ed Ematologica, Ospedale Civile, Piacenza
5 Clinica Medica, IRCCS Policlinico San Matteo, Università di Pavia, Pavia
6 Divisione di Ematologia, Presidio Ospedali Riuniti Bianchi, Melacrino, Morelli, Reggio Calabria
7 Unità Operativa di Ematologia, Azienda Ospedaliera dellAnnunziata, Cosenza
8 Divisione di Ematologia, Presidio Ospedaliero A. Perrino, Brindisi
9 Divisione di Ematologia, Azienda Ospedaliera Papardo, Messina, Italy
Correspondence: Stefano Sacchi, MD Dipartimento di Oncologia ed Ematologia, Università di Modena Centro Oncologico Modenese Policlinico, 41100 Modena, Italy. E-mail: ssacchi{at}unimo.it
Background: Relatively little information is available on the incidence of secondary cancer in non-Hodgkins 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-Hodgkins lymphoma.
Design and Methods: We evaluated a total of 563 patients with indolent non-Hodgkins 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-Hodgkins 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-Hodgkins 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.
Key words: second cancer, non-Hodgkin lymphoma, follicular lymphoma, small lymphocytic lymphoma, treatment.
Related Articles
Comment to: Secondary malignancies after treatment for indolent non-Hodgkins lymphoma: a 16-year follow-up study. Haematologica 2008; 93:398-403
Ellen van der Spek, René van der Griend
Haematologica 2008 93: e57.
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Reply to: Comment to: Secondary malignancies after treatment for indolent non-Hodgkins lymphoma: a 16-year follow-up study. Haematologica 2008; 93:398-403
S. Sacchi
Haematologica 2008 93: e58.
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Secondary malignancies after therapy of indolent non-Hodgkins lymphoma
Jonathan W. Friedberg
Haematologica 2008 93: 336-338.
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To determine whether high-dose therapy (HDT) with autologous stem-cell transplantation (ASCT) should be included in the initial consolidative treatment of patients with advanced, unfavorable ...Hodgkin's lymphoma (HL).
One hundred sixty-three patients achieving complete remission (CR) or partial remission (PR) with four initial courses of doxorubicin, bleomycin, vinblastine, and dacarbazine, or other doxorubicin-containing regimens, were randomly assigned to receive HDT plus ASCT (83 patients) versus four courses of conventional chemotherapy (80 patients). Unfavorable HL was defined as the presence of at least two of the following poor prognostic factors: high lactate dehydrogenase level, large mediastinal mass (greater than at least 33% of the thoracic diameter), more than one extranodal site, low hematocrit level, and inguinal involvement.
At the end of the treatment program, 92% of patients in arm A and 89% in arm B achieved a CR (P =.6). After a median follow-up of 48 months, the 5-year failure-free survival rates were 75% (95% confidence interval CI, 65 to 85) in arm A and 82% (95% CI, 73 to 90) in arm B (P =.4). The 5-year overall survival rates were 88% (95% CI, 80 to 96) in arm A and 88% (95% CI, 79 to 96) in arm B (P =.99). The 5-year relapse-free survival rates were 88% in arm A (95% CI, 80 to 96) and 94% in arm B (95% CI, 88 to 100), and the difference was not significant (P =.3).
Patients with advanced unfavorable HL achieving CR or PR after four courses of doxorubicin-containing regimens have a favorable outcome with conventional chemotherapy. No benefit from an early intensification with HDT and ASCT was shown.
1 Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Modena
2 Medicina Interna, Oncologia e Gastroenterologia, Università di Pavia, Pavia
3 Dipartimento di Ematologia, ...Ospedale Spirito Santo, Pescara
4 Divisione di Ematologia, Azienda Ospedaliera Papardo, Messina
5 Ematologia e Trapianto Cellule Staminali, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (PZ), Italy
Correspondence: Stefano Sacchi, Centro Oncologico Modenese, Policlinico, Largo del Pozzo 71, 4100 Modena Italy. E-mail: ssacchi{at}unimo.it
Background: Improved treatment has increased the life expectancy of patients with non-Hodgkins 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-Hodgkins 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.
Key words: second malignancies, non-Hodgkins lymphoma, diffuse large B-cell lymphoma, DLBCL, risk factors, treatment.
Background and Objectives Although serum β2 microglobulin (β2 M) is an easy parameter to measure, and over-expressed in a large number of lymphoproliferative diseases, its prognostic value has been ...largely underestimated. The present study examined the influence of β2M levels on overall survival (OS) of patients with follicular lymphoma (FL).Design and Methods The prognostic role of β2M was evaluated in 236 patients with FL identified from the databases of the Gruppo Italiano per lo Studio dei Linfomi (GISL) and treated with anthracycline-based regimens from 1993 to 2003.Results Elevated serum β2M levels were found in 82 patients (35%). According to multivariate logistic regression analysis, elevated β2M levels were associated with elevated lactate dehydrogenase (LDH) (p=0.021), age (p=0.029), and number of involved nodal areas (p
Although rituximab (R) is commonly used for patients with advanced follicular lymphoma (FL) requiring treatment, the optimal associated chemotherapy regimen has yet to be clarified.
We conducted an ...open-label, multicenter, randomized trial among adult patients with previously untreated stages II to IV FL to compare efficacy of eight doses of R associated with eight cycles of cyclophosphamide, vincristine, and prednisone (CVP) or six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or six cycles of fludarabine and mitoxantrone (FM). The principal end point of the study was time to treatment failure (TTF).
There were 534 patients enrolled onto the study. Overall response rates were 88%, 93%, and 91% for R-CVP, R-CHOP, and R-FM, respectively (P=.247). After a median follow-up of 34 months, 3-year TTFs were 46%, 62%, and 59% for the respective treatment groups (R-CHOP v R-CVP, P=.003; R-FM v R-CVP, P=.006; R-FM v R-CHOP, P=.763). Three-year progression-free survival (PFS) rates were 52%, 68%, and 63% (overall P=.011), respectively, and 3-year overall survival was 95% for the whole series. R-FM resulted in higher rates of grade 3 to 4 neutropenia (64%) compared with R-CVP (28%) and R-CHOP (50%; P< .001). Overall, 23 second malignancies were registered during follow-up: four in R-CVP, five in R-CHOP, and 14 in R-FM.
In this study, R-CHOP and R-FM were superior to R-CVP in terms of 3-year TTF and PFS. In addition, R-CHOP had a better risk-benefit ratio compared with R-FM.
Abstract
We performed a multicenter study to validate the concept that a simple comprehensive geriatric assessment (CGA) can identify elderly, non-fit patients with diffuse large B-cell lymphoma ...(DLBCL) in whom curative treatment is not better then palliation, and to analyze potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria. One hundred and seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgement only were grouped according to CGA into fit (46%), unfit (16%) and frail (38%) categories. Two-year overall survival (OS) was significantly better in fit than in non-fit patients (84% vs. 47%; p < 0.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-year OS in unfit (75% vs. 45%) but not in frail patients (44% vs. 39%). CGA was confirmed as very efficient in identifying elderly patients with DLBCL who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients.
To assess the prognosis of peripheral T-cell lymphoma unspecified, we retrospectively analyzed 385 cases fulfilling the criteria defined by the World Health Organization classification. Factors ...associated with a worse overall survival (OS) in a univariate analysis were age older than 60 years (P= .0002), equal to or more than 2 extranodal sites (P= .0002), lactic dehydrogenase (LDH) value at normal levels or above (P< .0001), performance status (PS) equal to or more than 2 (P≤ .0001), stage III or higher (P= .0001), and bone marrow involvement (P= .0001). Multivariate analysis showed that age (relative risk, 1.732; 95% CI, 1.300-2.309;P< .0001), PS (relative risk, 1.719; 95% CI, 1.269-2.327,P< .0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564;P< .0001), and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023;P= .026) were factors independently predictive for survival. Using these 4 variables we constructed a new prognostic model that singled out 4 groups at different risk: group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%, respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and 38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and 18.0%, respectively; group 4, 3 or 4 factors, with a 5-year and 10-year OS of 18.3 and 12.6%, respectively (P≤ .0001; log-rank, 66.79).
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