scholarly journals Physician Experience and Risk of Rituximab Discontinuation in Older Adults With Non-Hodgkin’s Lymphoma

2019 ◽  
Vol 17 (10) ◽  
pp. 1194-1202
Author(s):  
Scott F. Huntington ◽  
Jessica R. Hoag ◽  
Rong Wang ◽  
Amer M. Zeidan ◽  
Smith Giri ◽  
...  
Keyword(s):  
Older Adults ◽  
Hodgkin’S Lymphoma ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hodgkin's Lymphoma ◽  
Risk Of Death ◽  
Non Hodgkin’S Lymphoma ◽  
Increased Risk ◽  
Non Hodgkin's Lymphoma ◽  
The Impact

Background: Provider experience, or clinical volume, is associated with improved outcomes in many complex healthcare settings. Despite increased complexity of anticancer therapies, studies evaluating physician-level experience and cancer treatment outcomes are lacking. Methods: A population-based study was conducted of older adults (aged ≥66 years) diagnosed with B-cell non-Hodgkin’s lymphoma in 2004 through 2011 using SEER-Medicare data. Analysis focused on outcomes in patients receiving rituximab, the first approved monoclonal anticancer immunotherapy. We hypothesized that lower physician experience using rituximab and managing its infusion-related reactions would be associated with early treatment discontinuation. A 12-month look-back from each initiation of rituximab was used to categorize physician volume (0, 1–2, or ≥3 initiations per year). Modified Poisson regression was used to account for provider-level correlation and estimated relative risk (RR) of early rituximab discontinuation (<3 cycles within 180 days of rituximab initiation). Cox proportional hazards were used to measure the impact of rituximab discontinuation on survival. Results: Among 15,110 patients who initiated rituximab with 2,684 physicians, 7.6% experienced early rituximab discontinuation. Approximately one-fourth of patients (26.1%) initiated rituximab with a physician who had no rituximab initiations during the preceding 12 months. Compared with patients treated by physicians who had ≥3 rituximab initiations in the prior year, those treated by physicians without initiations were 57% more likely to experience early discontinuation (adjusted RR [aRR], 1.57; 95% CI, 1.35–1.82; P<.001 for 0 vs ≥3, and aRR, 1.19; 95% CI, 1.03–1.37; P=.02 for 1–2 vs ≥3). Additionally, rituximab discontinuation was associated with higher risk of death (adjusted hazard ratio, 1.39; 95% CI, 1.28–1.52; P<.001). Conclusions: Lower oncologist experience with rituximab was associated with increased risk of early rituximab discontinuation in Medicare beneficiaries with non-Hodgkin’s lymphoma. Physician-level volume may be an important factor in providing high-quality cancer care in the modern era.

Prospective Study of Survival Outcomes in Non-Hodgkin's Lymphoma Patients With Rheumatoid Arthritis

2006 ◽  
Vol 24 (10) ◽  
pp. 1597-1602 ◽  
Author(s):  
Ted R. Mikuls ◽  
Justin O. Endo ◽  
Susan E. Puumala ◽  
Patricia A. Aoun ◽  
Natalie A. Black ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Prospective Study ◽  
Lower Risk ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Risk Of Death ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact

Purpose Although preliminary studies suggest that non-Hodgkin's lymphoma (NHL) complicating rheumatoid arthritis (RA) may be a clinically distinct entity compared with that occurring in the general population, studies examining the impact of antecedent RA on survival are limited. In this prospective study, we examined the association of RA with survival in patients with NHL. Patients and Methods Using two large lymphoma registries, we identified patients with evidence of RA preceding NHL. Survival in RA patients was compared with that of controls using proportional hazards regression, adjusting for the effects of age, sex, lymphoma diagnosis-to-treatment lag time, calendar year, International Prognostic Index score, and NHL grade. Results The frequency of NHL subtypes was similar in RA patients (n = 65) and controls (n = 1,530). Compared with controls, RA patients with NHL had similar overall survival (hazard ratio [HR] = 0.95; 95% CI, 0.70 to 1.30) but were at lower risk of lymphoma progression or relapse (HR = 0.41; 95% CI, 0.25 to 0.68) or death related to lymphoma or its treatment (HR = 0.60; 95% CI, 0.37 to 0.98), but were more than twice as likely to die from causes unrelated to lymphoma (HR = 2.16; 95% CI, 1.33 to 3.50). Conclusion RA is associated with improved NHL-related outcomes, including a 40% reduced risk of death occurring as a result of lymphoma or its treatment and approximately a 60% lower risk of lymphoma relapse or progression compared with non-RA controls. However, the survival advantage gained in RA from the acquisition of lymphomas with favorable prognoses is negated through an increased mortality from other comorbid conditions.

Prognostic factors for treatment outcome in autotransplantation of intermediate-grade and high-grade non-Hodgkin's lymphoma with cyclophosphamide, carmustine, and etoposide.

1993 ◽  
Vol 11 (6) ◽  
pp. 1085-1091 ◽  
Author(s):  
C Wheeler ◽  
M Strawderman ◽  
L Ayash ◽  
W H Churchill ◽  
B E Bierer ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Hodgkin’S Lymphoma ◽  
Proportional Hazards ◽  
Hodgkin's Lymphoma ◽  
Primary Therapy ◽  
High Grade ◽  
Intermediate Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Time To Treatment Failure

PURPOSE We examined a consecutive series of 78 patients with non-Hodgkin's lymphoma treated on prospective protocols with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) plus autotransplantation to determine prognostic factors for time to treatment failure. PATIENTS AND METHODS Patients with relapsed, refractory, or poor-risk intermediate- and high-grade non-Hodgkin's lymphoma were treated with CBV with autologous marrow or peripheral-blood progenitor cell support. Patient characteristics before transplantation were examined in univariate analyses by the log-rank test and simultaneously in a Cox proportional hazards regression analysis. A best-predictive model was determined from those variables significant (P < .10) in the univariate test. RESULTS In univariate analysis, intermediate-grade and immunoblastic lymphoma, responsiveness to pretransplant salvage chemotherapy, and transplantation after primary therapy (first complete response [CR] or partial response [PR]) were associated with prolonged time to treatment failure. In proportional hazards multiple regression analysis, intermediate-grade and immunoblastic histology, responsive disease, and autotransplantation in first CR or PR were positive prognostic factors, and these characteristics are the basis of the best-predictive model for prolonged time to failure. Actuarial 3-year failure-free survival of patients with stable or responding disease at autotransplant was 54%. CONCLUSION CBV is an effective conditioning regimen in intermediate-grade and immunoblastic non-Hodgkin's lymphoma. Patients with these histologies transplanted while responding to primary therapy, or those with stable disease or disease responding to salvage therapy at the time of autotransplant, are most likely to benefit. Patients with lymphoblastic lymphoma or diffuse undifferentiated lymphoma did poorly with CBV and should be offered alternative therapy.

Methylenetetrahydrofolate Reductase and Methionine Synthase Polymorphism and Risk of Non-Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4691-4691
Author(s):  
Hee Nam ◽  
Yeo-Kyeoung Kim ◽  
Il-Kwon Lee ◽  
Deok-Hwan Yang ◽  
Kyeong-Soo Park ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Methylenetetrahydrofolate Reductase ◽  
Methionine Synthase ◽  
Hodgkin's Lymphoma ◽  
B Cell Lymphomas ◽  
Mthfr Polymorphism ◽  
Non Hodgkin’S Lymphoma ◽  
Increased Risk ◽  
Non Hodgkin's Lymphoma

Abstract Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are key enzymes in folate metabolism, which is essential for DNA methylation and synthesis. It is known that polymorphisms in its genes have been associated with some forms of cancer including lymphoma. Previous studies have shown MTHFR 677TT was associated with decreased risk of non-Hodgkin’s lymphoma(NHL). However, recent two reports have shown MTHFR 677TT was associated with increased risk. To evaluate the association between the MTHFR C677T and MTR A2756G polymorphisms and risk of non-Hodgkin’s lymphoma, large-scale population-based case-control study was conducted in Chonnam University Hwasun Hospital between March 1997 and June 2005. Three hundreds sixty-five patients with histologically comfirmed lymphoma and 1,162 controls were evaluated. Genotyping was done using PCR-RFLP. The cases consisted of 203 diffuse large B-cell lymphomas(DLBCL), 77 T-cell lymphomas, 62 other B-cell lymphomas, and 23 unclassifiable lymphomas. The MTHFR 677CT and 677TT genotypes were inversely associated with NHL and DLBCL, respectively. Using subjects with the MTHFR 677CC as reference group, the odds ratio of MTHFR 677CT and 677TT were (0.70, 95% CI 0.54–0.90) and (0.46, 95% CI 0.32–0.68) for NHL. The association was more evident for DLBCL (OR 0.56, 95% CI 0.40–0.78 for 677CT; OR 0.40, 95% CI 0.24–0.65 for 677TT). Dose-response effect was evident for the MTHFR T-allele (p < 0.01). There was no significant association of MTR A2756G with NHL. These results suggest that the MTHFR polymorphism may play an important role in the pathogenesis of NHL, particularly DLBCL.

Cost-Effectiveness of Primary Prophylaxis with Pegfilgrastim Versus Filgrastim in Non-Hodgkin’s Lymphoma Patients Receiving CHOP-21.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5166-5166 ◽  
Author(s):  
John Kim ◽  
Jennifer L. Malin ◽  
Quan V. Doan ◽  
Zhimei Liu ◽  
Robert W. Dubois ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Incremental Cost ◽  
Hodgkin’S Lymphoma ◽  
Primary Prophylaxis ◽  
Quality Adjusted Life Year ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact ◽  
Quality Adjusted Life

Abstract Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) starting in the first and continuing in subsequent chemotherapy cycles when the risk of febrile neutropenia (FN) is ≥20% is recommended in the 2006 ASCO and EORTC clinical guidelines. Although the daily G-CSF filgrastim (Neupogen®, Amgen Inc.) and the long-acting G-CSF pegfilgrastim (Neulasta®, Amgen Inc.) are both commonly used, in practice filgrastim is often administered for shorter-than-recommended courses, eg, 6 days, which has been shown to be associated with less clinical efficacy. The purpose of this study was to evaluate the cost-effectiveness of primary prophylaxis using pegfilgrastim versus 6-day filgrastim in patients with aggressive non-Hodgkin’s lymphoma (NHL) receiving CHOP-21. Without G-CSF support, CHOP-21 is associated with 17%-50% FN risk. We constructed a decision-analytic model from a payer perspective with a life-time study horizon. Outcomes were measured as incremental cost-effectiveness ratios (ICERs) including cost per FN event avoided, cost per life-year-gained (LYG), or cost per quality-adjusted-life-year (QALY) saved. Model inputs including FN risk, FN case-fatality, relative dose intensity (RDI) of chemotherapy, impact of RDI on survival, and utility scores were obtained from a comprehensive literature review. Drug and drug administration costs were obtained from Center for Medicare and Medicaid Services. Cost for FN-related hospitalizations and subsequent medical costs were obtained from the literature. NHL mortality rates and other-cause mortality were based on data from US Surveillance Epidemiology and End Results and National Vital Statistics Reports. Sensitivity analyses were conducted on key variables. Our model simulated 3 clinical scenarios: Scenario 1 included the impact of prophylaxis with pegfilgrastim or filgrastim on FN risk, Scenario 2 included the impact of a difference in FN risk on FN-related mortality, and Scenario 3 included a differential impact on RDI and long-term survival. Extrapolating from the results of a meta-analysis and observational studies, it was estimated that pegfilgrastim decreased the absolute risk of FN by 12% compared with 6-day filgrastim (13.1% versus 25.1%) for a baseline FN risk of approximately 27.9%. Our results showed that compared with 6-day filgrastim, pegfilgrastim was associated with an ICER of $2,133/FN event avoided in Scenario 1, $4,869/LYG or $5,476/QALY saved in Scenario 2, and $1,805/LYG or $2,029/QALY saved in Scenario 3 (Table 1). Key factors influencing ICER estimates included relative risk of FN, cost of pegfilgrastim and filgrastim, and baseline FN risk. Varying these variables within plausible ranges, the ICERs did not exceed $100,000/QALY saved, a commonly cited threshold for judging cost-effectiveness in oncology. Our study suggested that primary prophylaxis with pegfilgrastim is cost-effective compared with filgrastim used for 6 days in NHL patients receiving CHOP-21. Table 1: Cost-effectiveness of pegfilgrastim versus filgrastim Cost ($) Scenario 1 Scenario 2 (LY) Scenario 2 (QALY) Scenario 3 (LY) Scenario 3 (QALY) ICER, incremental cost-effectiveness ratio; LY, life-year; QALY, quality-adjusted life year; numbers may not match due to rounding errors Pegfilgrastim 15,608 13.1% 9.35 8.13 8.09 7.01 Filgrastim 15,352 25.1% 9.29 8.08 7.95 6.89 ICER --- $2,133 per FN event avoided $4,869/LY $5,476/QALY $1,805/LY $2,029/QALY

Tonsil Lymphoma Presenting As Tonsillitis After Bone Marrow Transplantation

1995 ◽  
Vol 112 (4) ◽  
pp. 544-548 ◽  
Author(s):  
Seth A. Yellin ◽  
Michael H. Weiss ◽  
Dennis H. Kraus ◽  
Esperanza B. Papadopoulos
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Medical Therapy ◽  
Marrow Transplantation ◽  
Hodgkin’S Lymphoma ◽  
Cervical Lymphadenopathy ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Increased Risk ◽  
Non Hodgkin's Lymphoma

Bone marrow transplantation for the treatment of leukemia is increasingly successful in rendering patients disease free. However, it has become evident that the associated severe immunosuppression predisposes this population to an increased risk for other neoplastic disorders. We report on six patients in whom non-Hodgkin's lymphoma of the tonsillar region developed within 5 months after T-cell-depleted bone marrow transplantation for the treatment of leukemia at Memorial Sloan-Kettering Cancer Center from October 1990 to October 1992. These patients initially had what appeared to be infectious exudative pharyngitis/tonsillitis; however, they did not improve with medical therapy. Because of the persistence of pharyngitis/tonsillitis in association with cervical lymphadenopathy and odynophagia, the patients underwent definitive biopsy in the form of tonsillectomy, cervical lymph node biopsy, or both. Histopathologic review revealed non-Hodgkin's lymphoma. An association with Epstein-Barr virus has been noted in five of these patients. This article is aimed at alerting the clinician to consider the diagnosis of lymphoma in a patient with persistent pharyngitis/tonsillitis despite adequate medical therapy after bone marrow transplantation.

Risk of Second Malignancy After Non-Hodgkin's Lymphoma: A British Cohort Study

2006 ◽  
Vol 24 (10) ◽  
pp. 1568-1574 ◽  
Author(s):  
Nadejda Y. Mudie ◽  
Anthony J. Swerdlow ◽  
Craig D. Higgins ◽  
Paul Smith ◽  
Zongkai Qiao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Second Malignancy ◽  
Relative Risks ◽  
Non Hodgkin’S Lymphoma ◽  
Increased Risk ◽  
Non Hodgkin's Lymphoma ◽  
British Cohort Study ◽  
Drug Treatments

Purpose To assess long-term site-specific risks of second malignancy following non-Hodgkin's lymphoma (NHL) in relation to treatment and demographic factors. Patients and Methods A cohort of 2,456 patients with NHL who were first treated from 1973 to 2000 and were younger than 60 years from centers in the British National Lymphoma Investigation were observed, and occurrences of second malignancy was compared with expectations based on general population cancer rates in England and Wales. Results In total, 123 second malignancies occurred. Relative risks (RRs) were significantly elevated for all malignancies combined (RR = 1.3; 95% CI, 1.1 to 1.6) and for leukemia (RR = 8.8; 95% CI, 5.1 to 14.1) and lung cancer (RR = 1.6; 95% CI, 1.1 to 2.3). RRs of malignancy overall diminished significantly with increasing age at first treatment. Leukemia risk was significantly increased after chemotherapy (RR = 10.5; 95% CI, 5.0 to 19.3) and mixed-modality treatment (RR = 13.0; 95% CI, 5.2 to 26.7). Relative risks of lung (RR = 1.9; 95% CI, 1.1 to 3.1) and colorectal (RR = 2.1; 95% CI, 1.1 to 3.6) cancers were significantly raised following chemotherapy. Conclusion NHL patients are at elevated risk of developing second malignancy, particularly leukemia and lung cancer. The relative risk is greater with patients who are younger at first treatment. Chemotherapy predisposes patients toan increased risk of leukemia, and possibly lung and colorectal cancers. The role of specific drug treatments in the etiology of solid cancers after NHL deserves further investigation.

scholarly journals Prognostic Significance of Bcl-2 Protein Expression and Bcl-2 Gene Rearrangement in Diffuse Aggressive Non-Hodgkin's Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 244-251 ◽  
Author(s):  
Randy D. Gascoyne ◽  
Sheryle A. Adomat ◽  
Stanislaw Krajewski ◽  
Maryla Krajewska ◽  
Douglas E. Horsman ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hodgkin’S Lymphoma ◽  
Gene Rearrangement ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact

Abstract The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P &lt; .01), DFS (32% v 66%, P &lt; .001), and RFS (25% v 59%, P &lt; .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P &lt; .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.

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