Survival Varies By Age and Histology in Classical Hodgkin Lymphoma: A Report from the Children's Oncology Group

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
Justine M. Kahn ◽  
Kara M. Kelly ◽  
Qinglin Pei ◽  
Yue Wu ◽  
Debra L. Friedman ◽  
...  

Introduction While 5-year event-free (EFS) and overall survival (OS) in Hodgkin lymphoma (HL) generally exceed 85% and 95%, respectively, outcomes may not be as favorable in adolescents and young adults (15 - 39 years [y]) compared to children. Small clinical trials have reported better outcomes for pediatric but not adult patients with mixed cellularity (MC) vs. nodular sclerosing (NS) histology, suggesting the possibility of biologic differences across the age-spectrum in HL. We examined survival by age and histology in patients receiving risk-based, response-adapted therapy for de novo HL on contemporary Children's Oncology Group (COG) trials. Methods This was a pooled analysis of individual-level data from 1,907 patients enrolled on three Phase 3 COG clinical trials for treatment of low-risk (AHOD0431), intermediate risk (AHOD0031) and high-risk (AHOD0831) HL between 2002 and 2012. Histologic subgroups included MC, NS and classical HL, not-otherwise-specified (cHL, NOS). Five-year cumulative incidence of relapse, EFS and OS were compared by age group (<15 y vs. ≥15 y) in the pooled cohort, and in histologic subgroups (MC and non-MC) using the Kaplan-Meier method. Effect modification was confirmed between age and histology. Cox proportional hazards regression models were used to examine the influence of age on EFS and OS, adjusted for race/ethnicity, Ann Arbor stage, B symptoms, bulky disease, receipt of radiation therapy (RT), and the interaction between age and histology; COG study was also included in the model, given that the criteria for response adaptation differed across the trials. Results Between 2002 and 2012, N= 2155 patients 1 - 21 y enrolled on three COG trials, 1,907 (88%) of whom were included in this analysis. Mean age of the cohort was 14.6 y (± 3.5) with N= 871 (46%) <15 y and N= 1,036 (54%) ≥15 y. In total, N= 1,547 patients (81%) had NS histology, N= 108 (6%) had cHL, NOS, and N= 196 (10%) had MC histology; by age, MC histology was present in N= 66 patients (7%) ≥15 y and N= 130 patients (15%) <15 y (p< 0.01). A significantly higher proportion of those ≥15 y vs. younger had B-symptoms at diagnosis (29% vs. 21%, p< 0.01), however the presence of bulky disease did not differ by age. Finally, patients ≥15 y (vs. <15 y) were significantly more likely to receive RT as part of their treatment (72% vs. 63%, p<0.01). Survival: Median follow up was 6.9 years. In unadjusted analyses, 5-year EFS and OS were 83% and 97%, respectively. The 5-year EFS was lower for patients ≥15 y vs. <15 y (85% vs 89%, p<0.01), as was the 5-year OS (96% vs. 99%, p< 0.01). In multivariable models, age ≥15 y (vs. younger) was associated with a 1.4-fold increased risk of EFS (HR: 1.4, 95% CI: 1.1, 1.8, p< 0.01), and more than a 3-fold increased risk of death (OS: HR: 3.1, 95% CI: 1.5, 6.4, p< 0.01). The effect of age on EFS varied by histologic subgroup. Among those with non-MC histology, cumulative incidence of relapse did not significantly differ by age in unadjusted models (Figure A), however 5-year EFS was significantly worse in the older group (Figure B). In multivariable analyses, age ≥15 y (vs. younger) was associated with a 1.3-fold increased risk of EFS (HR: 1.3; 1.03 - 1.7, p= 0.03) (Table). Among patients with MC histology, age ≥15 y (vs. younger) was associated with significantly higher relapse rate (22% vs. 5%, p< 0.01) (Figure C) and significantly worse 5-year EFS (75% vs. 94%, p< 0.01) (Figure D). This remained significant in multivariable models: patients with MC histology who were ≥15 y (vs. younger) had a 3.7-fold increased risk of EFS (HR: 3.7, 95% CI: 1.6, 8.9, p< 0.01) (Table). Conclusion In patients receiving response-adapted therapy for de novo HL on contemporary COG trials, adolescents ≥15 y had worse EFS and OS compared to younger groups. The magnitude of the effect of age was higher in patients with MC disease. Although recent pediatric trials in HL have indicated better survival for some children with MC histology, alternative approaches or novel therapies should be considered for older adolescents with MC disease, whose outcomes appear more like adults. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2020 ◽  
Author(s):  
Lisa Giulino-Roth ◽  
Qinglin Pei ◽  
Allen Buxton ◽  
Rizvan Bush ◽  
Yue Wu ◽  
...  

Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs). Response-adapted treatment may decrease this risk by reducing exposure to therapy associated with SMN risk. The Children's Oncology Group Study AHOD0031 evaluated response-adapted therapy for children and adolescents with intermediate-risk HL. We report the SMNs among 1,711 patients enrolled on AHOD0031. Patients were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without involved field radiation therapy (RT). Patients with a slow early response to initial chemotherapy were randomized to two additional cycles of dexamethasone, etoposide, cisplatin and cytarabine or no additional chemotherapy, and all received RT. At a median follow up of 7.3 years, an analysis of SMNs was performed. The 10-year cumulative incidence of SMN was 1.3% (95% CI: 0.6%-2.0%). SMNs included 3 patients with AML, 11 with solid tumors, and 3 with non-Hodgkin lymphoma. Sixteen of 17 patients with an SMN had received combined modality therapy. The standardized incidence ratio for SMN was 9.5 (95% CI 4.5-15.2) with an excess absolute risk of 1.2 per 1,000 person-years. The cumulative incidence of SMNs was higher among patients who received RT (p=0.037). In multivariate analysis, RT, B-symptoms, and race were associated with SMN risk. Given the latency from exposure, we have likely captured all cases of secondary leukemia. Longer follow-up is needed to determine the risk of solid tumors. Avoidance of RT without sacrificing disease control should remain a goal for future therapeutic approaches. ClinicalTrials.gov Identifier: NCT00025259.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 866-866 ◽  
Author(s):  
Alberto Bosi ◽  
Jeffrey Szer ◽  
Jeannine Kassis ◽  
Jorge Sierra ◽  
Claire Desborough ◽  
...  

Abstract BACKGROUND: Heil et al (Blood ‘97) demonstrated that the duration of neutropenia and its clinical consequences following induction chemotherapy for AML were significantly reduced by the addition of filgrastim, with no increased risk of death, second malignancy or relapse (ASH ‘99). A single injection of pegfilgrastim has been shown to be comparable to daily injections of filgrastim in the management of chemotherapy-induced neutropenia. The primary aim of this trial was to estimate the difference in time to recovery from severe neutropenia (SN, ANC < 0.5 x109/L) in the first induction chemotherapy cycle (Induction 1) in AML subjects treated with pegfilgrastim or filgrastim. METHODS: Subjects with de novo AML received 1 or 2 courses of induction chemotherapy (idarubicin 12mg/m2 IV days 1–3, cytarabine 100mg/m2 IV 12 hourly days 1–7 [IA 3+7]) then, if in remission, consolidation chemotherapy (cytarabine 2 [subjects < 55 years] or 3g/m2 [subjects ≥ 55 years] IV 12 hourly days 1, 3, 5). Subjects received either single administration 6μg pegfilgrastim or daily 5μg/kg filgrastim starting 24 hours after completion of chemotherapy until neutrophil recovery. Time to recovery from SN was defined as the number of days from the first day of chemotherapy until the first of two ANC consecutive values after the nadir that were ≥ 0.5 x 109/L whereas duration of SN was defined as the total number of days during the cycle with an ANC < 0.5 x 109/L. RESULTS: Of 84 subjects randomised into the study, 83 received study drug (42 pegfilgrastim, 41 filgrastim). The treatment groups were generally well balanced for demographics and baseline characteristics. The median time to recovery from SN (ANC < 0.5 x109/L) in Induction 1 was 22 days in both treatment groups (95% CI for treatment difference: −1.9, 1.9). There was also no statistically significant difference in the median duration of SN between the 2 groups (21 days pegfilgrastim, 20 days filgrastim). Subjects in the filgrastim group required a median of 16 daily injections compared to a single administration of pegfilgrastim in the second group. Median serum concentration of pegfilgrastim in Induction 1 remained above clinically relevant concentrations until 21 days after the start of chemotherapy, results that are consistent with the neutrophil-mediated clearance of pegfilgrastim. The incidence of serious adverse events was comparable between the 2 groups except for infectious complications, which were higher in the filgrastim group (5 subjects [12%] pegfilgrastim versus 9 subjects [22%] filgrastim). CONCLUSION: In the setting of the first cycle of IA 3+7 induction chemotherapy in AML patients, once per cycle administration of 6 mg pegfilgrastim or daily administration of 5mg/kg filgrastim result in similar median time to recovery to ANC ≥ 0.5 x109/L. Pegfilgrastim is safe and well tolerated in this subject population.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2656-2656
Author(s):  
Carrie A. Thompson ◽  
Hongxiu Luo ◽  
Matthew J Maurer ◽  
Cristine Allmer ◽  
Thomas M. Habermann ◽  
...  

Abstract Abstract 2656 Background Treatment of non-Hodgkin lymphoma (NHL) can lead to development of cardiovascular disease (CVD). We sought to describe the cumulative incidence of CVD in adult NHL survivors diagnosed in the recent treatment era (since 2002) and identify clinical and treatment predictors for its development. Methods All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). The MER offers enrollment to all consecutive patients with newly diagnosed NHL who are US residents and age >18 years. Clinical data from the time of diagnosis and treatment data are abstracted from medical records using a standard protocol. Patients are prospectively contacted via telephone or in person per protocol every 6 months for the first 3 years from diagnosis and yearly afterwards to assess disease status and development of comorbid conditions. CVD events, including heart failure (HF), myocardial infarction (MI), arrhythmia, pericarditis, and valvular heart disease, occurring after diagnosis were identified during follow-up and validated against medical records. HF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. MI was validated using case definition standards of coronary heart disease, while arrhythmia, pericarditis, and valvular heart disease were validated using clinical definitions. The prevalence of CVD and associations between CVD and clinical characteristics (sex, age) and treatment (radiation, anthracyclines) were performed using Cox models with a competing risk approach. Results 1164 patients with NHL were enrolled into the MER at Mayo Clinic between 9/1/2002–2/28/2008. 646 were male (56%) and median age at diagnosis was 62 years (range 20–93). Median follow-up of all cases was 59 months (range 1–105). 131 patients reported CVD prior to the diagnosis of NHL and were excluded from analyses. An additional 76 patients did not have follow-up and were excluded. Of the 957 remaining patients, 75 (7.8%) self-reported a new diagnosis of CVD. Of these, 71 cases had available medical records. 57 of the 71 reviewed cases (80%) were validated (18 HF, 9 MI, 21 arrhythmia, 2 pericarditis, and 10 valvular heart disease). Cumulative incidence of CVD at 1, 3, 5, and 7 years was 1.3%, 3.7%, 5.2%, and 7.4%, respectively. Median time from NHL diagnosis to CVD was 26.5 months (range 1–84). Older age was associated with increased risk of overall CVD (p-value<0.001). Gender (p=0.59), radiation therapy (p=0.61), and anthracycline treatment (p=0.25) were not associated with the incidence of overall CVD. Among types of CVD, anthracycline use was associated with development of HF (HR=5.30; p-value=0.008) and arrhythmia (HR=2.68; p-value=0.04). Radiation was associated with development of arrhythmia (HR=2.73; p-value=0.03), while older age was associated with development of HF (HR=1.36 per 5 year increment; p-value=0.003) and arrhythmia (HR=1.25 per 5 year increment; p-value=0.02). Conclusions The risk of CVD in patients with NHL is approximately 1% per year after the initial diagnosis of lymphoma. The most commonly occurring CVDs in this cohort of NHL survivors were arrhythmia and HF. Treatment with anthracyclines and radiation are associated with increased risk of developing some types of CVD. 80% of self-reported CVD events in NHL survivors were validated using epidemiologic criteria. Future studies will include building models incorporating comorbid health conditions and lifestyle factors to determine risk of CVD as well as the impact of CVD on quality of life. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2609-2609
Author(s):  
Aaron Rosenberg ◽  
Ann Brunson ◽  
Joseph Tuscano ◽  
Richard H. White ◽  
Ted Wun

Abstract Background: Patients (pts) with non-Hodgkins lymphoma (NHL) are at increased risk of venous thromboembolism (VTE). We and others have demonstrated increased risk of death among NHL pts with incident VTE; however, these studies were largely conducted in the pre-rituximab era. We therefore analyzed a large cohort of NHL pts in the California Cancer Registry (CCR), determined the incidence of VTE, and evaluated its effect on survival in the rituximab era. Methods: Using the CCR linked with hospital discharge and emergency department records, we identified adult NHL pts diagnosed in 2005 – 2010, excluding cases ascertained via autopsy or death certificate, and those diagnosed with acute VTE in the 2 months preceding NHL diagnosis. VTE was defined by specific ICD-9-CM codes, and Elixhauser comorbidity score, excluding lymphoma, was calculated. Cumulative incidence was calculated using the Kaplan-Meier (KM) method. Adjusted hazard ratios (aHR) of VTE and death were estimated using Cox proportional hazard models, stratified by indolent vs aggressive NHL subtype, adjusting for age, race, stage, treatment, comorbidity and prior VTE. Analyses of VTE incidence treated death as a competing risk. Cox models for death incorporated VTE as a time-dependent covariate to account for immortal time bias. Results: NHL was identified in 18,424 pts. Most (n=12,963) had aggressive NHL (1,017 mantle cell, 11,246 diffuse large B-cell or follicular grade 3, 170 lymphoblastic, 530 Burkitt), while 5,461 had indolent NHL (2,809 follicular grade 1/2, 2,652 marginal zone). Median age was 64 years (yrs) and was similar in aggressive and indolent cohorts. Men accounted for 54% (n=9926) of cases, and were more common in aggressive compared to indolent NHL (7,317 (56%) vs 2,609 (48%) respectively). Most cases (62% n=11,451) were non-Hispanic White, 4% (n=795) were African American, 21% (n=3866) Hispanic, 11% Asian (n=2013) and 1.6% unknown (n=299). The ethnic distribution was similar in aggressive and indolent NHL. Median number of reported comorbid conditions was 2. Chemotherapy was initiated in 76% (n=9791) of aggressive NHL pts and 41% (n=2250) of indolent pts. The KM cumulative incidence of first time, acute VTE in NHL pts was 4.7% (95% CI 4.4 – 5.0) and 5.3% (95% CI 4.9- 5.6) at 1 and 2 years respectively. The incidence of VTE was higher in patients with aggressive versus indolent NHL (6.5% (95% CI 6.1 - 6.9) vs 2.3% (95% CI 2.0 - 2.8) at 2 yrs respectively P<0.001), and was highest during the first 6 months after dx (Figure). In multivariable analysis of aggressive lymphoma pts, the risk of VTE was higher among pts receiving chemotherapy (Ctx) [aHR 2.3, 95% CI (1.9 – 3.0)], lower in pts with stage II NHL [aHR 0.8, 95% CI (0.6 – 1.0)] while histological subtype of aggressive NHL was not a predictor. For indolent NHL, the risk of developing acute VTE was increased among cases that received Ctx [aHR 2.3, 95% CI (1.6 – 3.4)], and cases with follicular grade 1/2 [aHR 1.6, 95% CI (1.1 – 2.3)] whereas stage was not a significant risk factor. Five year overall survival for aggressive NHL was 55% (95% CI 46 – 56) and 80% (95% CI 69 – 82) for indolent NHL. In multivariable analysis risk of incident VTE after diagnosis of NHL dx was associated with an increased risk of death (Table). Interestingly, this effect was present for only the first 2 years after dx of aggressive NHL, while the effect persisted throughout follow-up for indolent NHL. Conclusions: This large, population based study, which captured essentially all patients diagnosed with NHL in California between 2005-2010, confirms prior reports of VTE incidence in NHL patients. Pts are at highest risk early in their course, and pts undergoing chemotherapy were at increased risk. Moreover, VTE subsequent to NHL diagnosis independently increases the risk of death adjusting for other important covariates. Whereas chemoimmunotherapy has negated the effect of some previous negative prognostic factors, the adverse effect of incident VTE persists in this recent cohort. Table:Association of VTE and Death* Aggressive NHL Indolent NHLTime from NHL dx to VTEaHR95% CIaHR95% CI0 – 6 months1.411.3 – 1.62.071.4 – 3.06 – 12 months1.401.1 – 1.82.591.4 – 4.712 – 24 months1.631.3 – 2.13.201.9 – 5.4>24 months0.940.7 – 1.22.371.6 – 3.6 *Cox models adjusted for Age, Sex, Race, Stage, Treatment, Prior VTE and Comorbidity Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Ilja Kalashnikov ◽  
Tomas Tanskanen ◽  
Janne Pitkäniemi ◽  
Nea Malila ◽  
Sirkku Jyrkkiö ◽  
...  

AbstractNodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49−16.3). Ten-year relative survival was 94% (95% CI, 89%‒100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15‒0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5864
Author(s):  
Chih-Chin Kao ◽  
Jia-Sin Liu ◽  
Yu-Kang Chang ◽  
Ming-Huang Lin ◽  
Yen-Chung Lin ◽  
...  

Background Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60–1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82–1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. Discussion We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9021-9021 ◽  
Author(s):  
I. D. Schnadig ◽  
E. K. Fromme ◽  
C. L. Loprinzi ◽  
J. A. Sloan ◽  
M. Mori ◽  
...  

9021 Background: Physician-reported performance status (PS) is an important prognostic factor in advanced malignancies and is a commonly used stratification variable in cancer clinical trials. However, the extent, predictors, and prognostic importance of disagreement in PS assessment between physicians and patients have not been examined. Methods: Using NCCTG clinical trials from 1987–1990 (J Clin Oncol 19(15):3539–3546, 2001), we analyzed the difference and agreement of PS (ECOG and Karnofsky [KPS]) and nutritional status assessments reported by physicians and patients individually. The degree of disagreement was analyzed using paired t-test. Overall mortality was estimated by Kaplan-Meier method. The effect of disagreement on overall survival was analyzed by Cox regression. Independent predictors of disagreement were identified by logistic regression. Results: 1,636 patients with advanced lung and colorectal cancer had a median survival of 9.8 months (95% CI, 9.4 to 10.4). Percent agreement between patients and physicians about KPS, ECOG PS, and appetite/nutritional status was 32.9%, 43.4% and 42.0% respectively. Physicians were more likely to rate patients better than individual patients were to rate themselves: ECOG (Mean 0.91 vs 1.30, p<.0001), KPS (Mean 83.3 vs. 81.7, p<0.0001), appetite/nutritional status (Mean 1.6 vs. 2.1, p<0.0001). Inability to work, depression and less than a high school education were independently associated with disagreement. An increased risk of death was observed for patient and physician disagreement on KPS (HR=1.15, 95% CI, 1.03 to 1.27 p=0.01) and appetite/nutritional status (HR=1.39, 95% CI, 1.26 to 1.54 p<0.0001). Conclusions: Patients and physicians frequently disagree about patient PS, with physicians tending to rate patients higher than patients do themselves. Baseline patient demographic factors that independently predict disagreement have been identified. Disagreement confers an increased risk of death in the setting of advanced malignancies. These findings illustrate limitations of physician-only assessed PS. No significant financial relationships to disclose.


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