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1.
Hematol Oncol ; 38(3): 318-325, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32239673

ABSTRACT

Infections during first-line therapy for DLBCL are often associated with chemotherapy dose reductions and increased mortality. Systemic infections have also been suggested as beneficial promotors of immunological responses. However, whether there is an association between the timing of an infectious episode and outcome during treatment has not yet been clarified. We investigated how the occurrence and timing of infectious episodes during the first line of treatment for "de novo" DLBCL influenced patient outcome. We used data on DLBCL patients from the Danish Lymphoma Registry, the Danish National Patient Registry, and the Danish National Pathology Registry. Infections were categorized according to type (ICD-10) and time of occurrence after treatment start. "Early" infections were defined as occurring between days 7 and 42 and "late" infections between days 100 and 150 from treatment start. Patients experiencing both "early and late" infections were categorized separately. We used multivariable Cox regression and Kaplan-Meier estimates to assess the association between infections and survival adjusting for NCCN-IPI, sex, comorbidity, and rituximab treatment. We identified 3546 patients, median age 65 years (IQR 56,73). Infectious episodes occurred in 1171 (33%) patients, of which 666 had "early," 303 "late," and 202 both "early and late" events. Patients without registered infections had a 5-year overall survival (OS) rates of 74%. Those with "early," "late," or "early+late" had 5-year OS of 65%, 62%, and 53%, respectively. Compared with patients without any registered infections, hazard rate ratios (HR) were 1.24 (95% CI 1.05-1.47), 1.32 (95% CI 1.06-1.63), and 1.59 (95% CI 1.27-2.00), respectively, in the multivariable model. We observed that infectious episodes during first-line treatment for "de novo" DLBCL occurred in 44% of the patients. Irrespective of timing, patients with infectious episodes had an inferior outcome compared to those without. Outcome patterns were similar for patients registered with sepsis.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Infections/mortality , Lymphoma, Large B-Cell, Diffuse/mortality , Adult , Aged , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Infections/chemically induced , Infections/pathology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Prednisone/administration & dosage , Prognosis , Rituximab/administration & dosage , Survival Rate , Vincristine/administration & dosage
2.
Br J Haematol ; 183(5): 717-726, 2018 12.
Article in English | MEDLINE | ID: mdl-30406945

ABSTRACT

Cardiotoxicity is a known risk of anthracycline treatment. However, the relative contribution of anthracyclines to the development of congestive heart failure (CHF), when included in a poly-chemotherapy regimen, is unclear. We examined cardiotoxicity in adult patients with diffuse large B-cell lymphoma and follicular lymphoma undergoing first-line immunochemotherapy from 2000-2012. In total, 2440 patients without previous heart disease were identified from the Danish Lymphoma Registry, of which 1994 (81·7%) were treated with anthracycline-containing chemotherapy [R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CHOEP (R-CHOP + etoposide)] and 446 (18·3%) were treated without anthracyclines (reference group). Compared to the reference group, the adjusted hazard ratio of CHF after 3-5 cycles of R-CHOP/CHOEP was 5·0 [95% confidence interval (CI) 1·4; 18·5], 6 cycles 6·8 (95% CI 2·0; 23·3) and >6 cycles 13·4 (95% CI 4·0; 45·0). The cumulative 5-year risk of CHF with all-cause mortality as competing risk was 4·6% after 3-5 cycles of R-CHOP/CHOEP, 4·5% after 6 and 7·9% after more than 6 cycles. Cumulative 5-year risk for patients treated without anthracyclines was 0·8%. Using anthracyclines in first-line lymphoma treatment increases risk of CHF in patients without previous history of heart disease. In particular, treatment with >6 cycles of R-CHOP/CHOEP is associated with a significant increase in CHF rate.


Subject(s)
Anthracyclines/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Arrhythmias, Cardiac/chemically induced , Heart Failure/chemically induced , Adolescent , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antibodies, Monoclonal, Murine-Derived/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Arrhythmias, Cardiac/mortality , Cardiotoxicity/etiology , Cardiotoxicity/mortality , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Denmark/epidemiology , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Heart Failure/mortality , Humans , Immunotherapy/adverse effects , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/mortality , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Prednisone/administration & dosage , Prednisone/adverse effects , Registries , Retrospective Studies , Risk Factors , Rituximab , Vincristine/administration & dosage , Vincristine/adverse effects , Young Adult
3.
Eur J Cancer ; 75: 195-203, 2017 04.
Article in English | MEDLINE | ID: mdl-28237865

ABSTRACT

PURPOSE: Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. METHODS: We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS. RESULTS: Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2-21.2%) compared with 2.6% (95% CI 1.7-3.5) among those with ≤2 sites (P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. CONCLUSIONS: Patients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/diagnostic imaging , Immunotherapy/methods , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Neoplasm Recurrence, Local/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Central Nervous System Neoplasms/prevention & control , Central Nervous System Neoplasms/secondary , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Humans , Lymphoma, Large B-Cell, Diffuse/prevention & control , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Positron Emission Tomography Computed Tomography , Prednisone/administration & dosage , Retrospective Studies , Risk Factors , Rituximab , Treatment Outcome , Vincristine/administration & dosage , Young Adult
4.
Br J Haematol ; 175(5): 876-883, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27681999

ABSTRACT

Involvement of the internal female reproductive organs by diffuse large B-cell lymphoma (DLBCL) is uncommon, and there are sparse data describing the outcomes of such cases. In total, 678 female patients with DLBCL staged with positron emission tomography/computed tomography and treated with rituximab-containing chemotherapy were identified from databases in Denmark, Great Britain, Australia, and Canada. Overall, 27/678 (4%) had internal reproductive organ involvement: uterus (n = 14), ovaries (n = 10) or both (n = 3). In multivariate analysis, women with uterine DLBCL experienced inferior progression-free survival and overall survival compared to those without reproductive organ involvement, whereas ovarian DLBCL was not predictive of outcome. Secondary central nervous system (CNS) involvement (SCNS) occurred in 7/17 (41%) women with uterine DLBCL (two patients with concomitant ovarian DLBCL) and 0/10 women with ovarian DLBCL without concomitant uterine involvement. In multivariate analysis adjusted for other risk factors for SCNS, uterine involvement by DLBCL remained strongly associated with SCNS (Hazard ratio 14·13, 95% confidence interval 5·09-39·25, P < 0·001). Because involvement of the uterus by DLBCL appears to be associated with a high risk of SCNS, those patients should be considered for CNS staging and prophylaxis. However, more studies are needed to determine whether the increased risk of secondary CNS involvement also applies to women with localized reproductive organ DLBCL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/pathology , Uterine Neoplasms , Adolescent , Adult , Aged , Aged, 80 and over , Central Nervous System Neoplasms/mortality , Central Nervous System Neoplasms/secondary , Databases, Factual , Disease-Free Survival , Female , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Middle Aged , Ovarian Neoplasms/complications , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Prognosis , Retrospective Studies , Rituximab/therapeutic use , Survival Rate , Uterine Neoplasms/complications , Uterine Neoplasms/mortality , Uterine Neoplasms/pathology , Young Adult
5.
Br J Haematol ; 169(3): 435-44, 2015 May.
Article in English | MEDLINE | ID: mdl-25709094

ABSTRACT

Watch and wait (WAW) is a common approach for asymptomatic, advanced stage follicular lymphoma (FL), but single-agent rituximab is an alternative for these patients. In this nationwide study we describe the outcome of patients selected for WAW. A cohort of 286 out of 849 (34%) stage III-IVA FL patients seen between 2000 and 2011, were managed expectantly and included. The 5-year progression-free survival (PFS) was 35% [95% confidence interval (CI) 29-42]. The 10-year overall survival (OS) was 65% (95%CI 54-78), and the cumulative risk of dying from lymphoma within 10 years of diagnosis was 13% (95%CI 7-20). Elevated lactate dehydrogenase and > four nodal regions involved were associated with a higher risk of lymphoma treatment and death from lymphoma. The WAW patients and a matched background population had similar OS during the first 50 months after diagnosis (P = 0·7), but WAW patients had increased risk of death after 50 months (P < 0·001). The estimated loss of residual life after 10 years was 6·8 months. The 10-year cumulative risk of histological transformation was 22% (95%CI 15-29) and the 3-year OS after transformation was 71% (95%CI 58-87%). In conclusion, advanced stage FL managed by WAW had a favourable outcome and abandoning this strategy could lead to overtreatment in some patients.


Subject(s)
Lymphoma, Follicular/epidemiology , Lymphoma, Follicular/pathology , Adult , Aged , Aged, 80 and over , Bone Marrow/pathology , Female , Humans , Lymphoma, Follicular/mortality , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Patient Outcome Assessment , Population Surveillance , Prognosis , Retrospective Studies , Watchful Waiting
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