Survival In Hodgkin Lymphoma Research Articles

Is Diagnostic Season Associated with Hodgkin Lymphoma Survival?

Is Diagnostic Season Associated with Hodgkin Lymphoma Survival?

P041: Low percentage of T lymphocytes in Hodgkin’s Lymphoma lymph nodes, measured by flow cytometry, is associated with inferior progression free survival regardless of negative interim pet scan status

Figure 1: Kaplan-Meier estimates of progression free survival stratified according to T-lymphocyte percentage in lymph node biopsies in Hodgkin lymphoma Background: Tumor microenvironment (TME) can influence antitumor immunity and survival in Hodgkin lymphoma (HL) as previously published. However, most of this data has sparse clinical applicability. Flow cytometry (FC) has limited utility in HL diagnosis but its potential to assess TME has not been fully explored yet. Aims: To determine the prognostic impact on survival of the percentage (%) of tumor infiltrating lymphocytes (TIL) and CD4/CD8 ratio in lymph nodes (LN) measured by FC. Methods: We selected patients (pts) with HL, available LN FC data at diagnosis and i-PET scan, treated at our center from 2012–2020. FC was performed with 8-color panels according to Euroflow protocols. TIL % and CD4/CD8 ratio in LN by FC were compared to normal values reported (Battaglia, Immunology 2003) and stratified as low, normal and high. Response was assessed per Lugano recommendations. Progression free survival (PFS) was estimated with Kaplan-Meier, multivariate analysis with Cox regression, and variables were compared with log-rank test. Results: 46 pts were included. Median age: 34 years. 24/27 with early stage had unfavorable risk and 11/19 with advanced disease had IPS≥3. 95% received ABVD. Complete response rate was 91.3%. 2 pts died. Median PFS: not reached (NR), 75th percentile 43 months (m), and median follow up: 49 m. i-PET negative (neg) pts had significantly better PFS (median NR vs 13.7 m in i-PET positive subgroup, p:0.014). Low LN TIL % was associated with inferior PFS (median 24.4 m vs. NR in pts with normal or high TIL, p:0.024). Regarding CD4/CD8 ratio, PFS rates were 100%, 75% and 60% in normal, low and high subgroups respectively, p:0.041. Both low TIL and positive i-PET remained independent predictors of survival on multivariate analysis with HR of 11.8 (CI 95% 1.9–72.7, p:0.021), and 7.7 (CI 95% 1.6–36.4, p:0.01) respectively. LN TIL % could further stratify outcomes in pts with neg i-PET scans. In this subset, pts with low TIL had a median PFS of 24.4 m and PFS rates of 33.3% vs. median NR in normal and high subgroups and PFS rates of 88.9 and 87.5% respectively, p:0.006. Conclusions: LN TIL % measured by FC showed prognostic impact in our cohort of HL pts. Pts with low TIL had inferior PFS, even in those with optimal interim response where the median was only 2 years. This finding denotes the critical role of T cells to achieve cure. Checkpoint blockade might constitute an appealing approach in these pts to restore effective antitumor immunity.

HIV and Hodgkin Lymphoma Survival: A Prospective Study in Botswana.

PURPOSEPeople living with HIV (PLWH) experience increased risk of Hodgkin lymphoma (HL) despite effective initiation of antiretroviral therapy (ART). In high-income countries, outcomes following HIV HL have been reported to be non-differential, or inferior for PLWH. We sought to assess the effect of HIV on HL survival in Botswana, an African country with a generalized HIV epidemic and high ART coverage, to describe a context more reflective of global HIV populations.PATIENTS AND METHODSIn the Thabatse Cancer Cohort, consenting participants initiating treatment for HL at one of four cancer centers in Botswana were enrolled from 2010 to 2020. Patients were followed quarterly for up to 5 years. The impact of HIV on survival following treatment initiation was assessed using an inverse probability–weighted Cox marginal structural model adjusted for age, performance status, and disease stage.RESULTSSeventy-eight new HL cases were enrolled, 47 (60%) were PLWH and 31 (40%) were HIV-uninfected. Baseline characteristics were similar between groups. The majority (61%) of patients presented with regional disease (stage I or II) with no statistically significant difference by HIV status (P = .38). Nearly all (87%) PLWH participants were on ART before their HL diagnosis (median ART duration 42 months), and median CD4 count was 413 cells/μL (interquartile range 253-691). Survival, in unadjusted analyses, was lower among patients without HIV compared with PLWH (log rank P = .021). In adjusted analysis, HIV infection was not significantly associated with survival in inverse probability–weighted Cox model (hazard ratio 0.43; 95% CI, 0.16 to 1.16; P = .094).CONCLUSIONIn this cohort of patients treated for HL in Botswana, survival in PLWH (87% on long-standing ART) was at least as good as in individuals without HIV.

Survival By Race/Ethnicity in Children and Adolescents with Hodgkin Lymphoma Treated on Cooperative Group Trials in the U.S. and Canada: A Pooled Analysis of Children's Oncology Group Trials

Introduction:While survival in Hodgkin Lymphoma (HL) is excellent, disparities by race/ethnicity have been described. Population-based and single center studies of children and adolescents with HL suggest that those who are black or Hispanic (vs. non-Hispanic white) have worse outcomes (Grubb Pediatr Blood Cancer 2016; Metzger JCO 2008). Whether race/ethnicity is predictive of survival in children and adolescents with HL after adjusting for clinical features and treatment-related variables is unknown. Our objective was to examine whether race/ethnicity was predictive of event-free survival (EFS), relapse, and overall survival (OS) in patients enrolled on contemporary Children's Oncology Group (COG) trials with response-based therapy for treatment of newly diagnosed HL.Methods:We conducted a pooled analysis of individual level data in children and adolescents enrolled on 3 consecutive Phase III clinical trials for treatment of intermediate, low and high-risk HL (AHOD0031, AHOD0431, AHOD0831). Five-year EFS and OS were compared across racial/ethnic groups and were estimated using the Kaplan-Meier method. Cumulative incidence of relapse was similarly constructed with K-sample tests. Cox regression models were constructed to examine the influence of race/ethnicity on EFS and OS, and were adjusted for age, sex, insurance status, histology, Ann Arbor stage, B symptoms, bulk disease, COG study, and radiation therapy (RT).Results:Between 2002 and 2012, 2155 patients 1-21 years of age enrolled on 3 COG trials, 2071 (96%) of whom were included in this analysis. Patients treated outside the US and Canada (n=84) were excluded. The distribution of race/ethnicity as reported to COG by treating institutions was: 64% non-Hispanic white (N=1334), 11% non-Hispanic black (N=236), 16% Hispanic (N=329), 3% Asian/Pacific Islander (N=66), and 5% other (N=106). Compared to other groups, more non-Hispanic white patients had private (vs. government) insurance (p<0.0001). The cohort was 53% male (N=1090) and a mean of 14.6 (±3.5) years at enrollment, with 46% (N=950) <15 years of age. Whilestage III/IV disease was more prevalent in black and Hispanic patients (p=0.0002), there was no difference in B-symptoms (p=0.19) or bulk (p=0.88) by race/ethnicity. Nodular sclerosing histology was more prevalent among non-Hispanic whites (p<0.0001). There was no difference in receipt of RT by race/ethnicity (p=0.53).Survival: In pooled analysis, with a median follow-up of 6.9 years, 5-year EFS was 83%, OS was 97%, and neither outcome differed by race/ethnicity (EFS: p=0.98; OS: p=0.29). Cumulative incidence of relapse was 16.8% and did not differ by race/ethnicity (p=0.93). In the multivariable model for EFS, there was no significant effect of race/ethnicity (p=0.95). Similarly, race/ethnicity was not significant in the multivariable model for OS (p=0.14). Finally, race/ethnicity was not significantly associated with EFS or OS in multivariable models by individual study, accounting for risk group.Conclusion:We observed no difference in survival by race/ethnicity among children and adolescents treated for HL with contemporary, risk adapted response-based therapy on COG Phase III trials. This suggests that the survival gap observed in population-based studies is largely reduced by access to clinical trials and by receipt of comparable therapy between cohorts. In light of this, it can be hypothesized that inequities in access to high-quality care, rather than differences in individual disease biology may underlie racial disparities observed in the community oncology setting. To examine whether response-based paradigms mitigated biologic differences between groups, further analyses will explore early response to treatment by race/ethnicity. Further analyses will also examine treatment-related toxicities and second malignant neoplasms by race/ethnicity, as well as the independent contribution of socioeconomic status to outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The impact of autoimmune cytopenias on the clinical course and survival of Hodgkin lymphoma.

The characteristics of autoimmune cytopenias (AICP) associated with Hodgkin lymphoma (HL) are not thoroughly defined. We retrospectively assessed the clinical features of HL-associated AICPs in 563 HL patients diagnosed over a period of 28years. We identified 8 cases of autoimmune hemolytic anemia (AIHA) and 8 cases of autoimmune thrombocytopenia among 14 patients altogether. Four (26%) AICPs were present at lymphoma diagnosis, while 11 (74%) cytopenias occurred during follow-up after first-line therapy. The overall incidence of HL-associated AICPs was 2.8%. Nine (75%) cytopenias responded to intravenous steroids. Seven (46%) AICPs led to the diagnosis of HL, indicated a relapse, or revealed secondary malignancies. AIHAs and AICPs altogether were more likely to develop in patients with advanced-stage HL (p = 0.010 and p < 0.004, respectively). HL patients experiencing AICPs had an increased short-term (1-year) mortality compared to the general HL population (p < 0.022). The 5-year OS of HL patients with concurrent AICPs at diagnosis was inferior compared to HL patients developing AICPs during follow-up (p = 0.005), and to HL patients without AICPs (p < 0.001). Patients with HL-associated AICPs appear to have a particular disease-related profile. The association of HL and AICPs may increase short-term mortality, while patients with concurrent AICPs at HL diagnosis have a dismal prognosis.

Abstract IA37: Survival by race and ethnicity in pediatric and adolescent patients with Hodgkin lymphoma: A report from the Children’s Oncology Group

Abstract IA37: Survival by race and ethnicity in pediatric and adolescent patients with Hodgkin lymphoma: A report from the Children’s Oncology Group

The Incidence of Venous Thromboembolism and Impact on Survival in Hodgkin Lymphoma

BackgroundThrombosis increase the acute and long-term morbidity and mortality in malignancy patients. We analyzed venous thromboembolism (VTE) in patients with Hodgkin lymphoma, the impact of VTE on survival, predisposing factors for VTE, and predicting value of Khorana and ThroLy score models. Patients and MethodsWe included 150 adult patients with Hodgkin lymphoma between January 2010 and 2018 at our university hospital. ResultsVTE was observed in 31 patients (20.7%). The types of VTE were 18 upper and 3 lower extremity deep vein thrombosis and 10 pulmonary embolism (1 with lower extremity deep vein thrombosis). Twenty-nine patients developed VTE during the treatment with a median time of episode as 5 months. In logistic regression analysis, a body mass index of >32 kg/m2, high fibrinogen levels, initial thrombocytosis and leukocytosis, splenic and extranodal involvement, presence of a central venous line, advanced stage, line of treatment status of thromboprophylaxis, VTE timing, and better Eastern Cooperative Oncology Group performance scores were observed to be related with VTE. Kaplan Meier survival analysis showed a negative impact of VTE on survival. Khorana and ThroLy risk assessment models were found predictive for VTE (P = .000 and P = .003, respectively), although only ThroLy score was associated with the survival. ConclusionThromboprophylaxis and precautions for VTE in patients with Hodgkin lymphoma according to validated risk assessment models can improve prognosis and quality of life owing to the impact of VTE on survival in the study.

EFFECTIVENESS OF PET/CT IN EVALUATION OF THE LYMPHOMA

Aims: Prognosis and survival of Hodgkin lymphoma have been improved dramatically by the development of treatments as well as the sensitivity of evaluation tools. In this case report, we aimed to emphasize the importance of positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography in the initial staging of Hodgkin’s lymp - homa, evaluating the response to treatment, and to demonstrate residual tissue or recurrence. Case Report: A 25-year-old male patient presented to Trakya University Hospital with swelling in the right groin and was diagnosed with Hodgkin’s lymphoma. Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography scan was used for initial staging and assessment of response to treatment. Conclusion: Positron emission tomography is a feasible imaging modality for the evaluation of lymphomas. It is sensitive to detect minimal recurrence as well as alterations of lesions’ metabolic activity. Keywords: Positron emission tomography, lymphoma, hodgkin disease

Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma.

Vitamin D deficiency is described as a modifiable risk factor for the incidence of and mortality in many common cancers; however, data in Hodgkin lymphoma (HL) are lacking. We thus performed a study measuring pretreatment vitamin D levels in prospectively treated patients with HL and correlated this with clinical outcomes. A total of 351 patients from the German Hodgkin Study Group clinical trials (HD7, HD8, and HD9) were included. Fifty percent of patients were vitamin D deficient (< 30 nmol/L) before planned chemotherapy. Pretreatment vitamin D deficiency was more common in relapsed/refractory patients than matched relapse-free controls (median baseline vitamin D, 21.4 nmol/L v 35.5 nmol/L; proportion with vitamin D deficiency, 68% v 41%; P < .001). Vitamin D-deficient patients had impaired progression-free survival (10-year difference, 17.6%; 95% CI, 6.9% to 28.4%; hazard ratio, 2.13; 95% CI, 1.84 to 2.48; P < .001) and overall survival (10-year difference, 11.1%; 95% CI, 2.1% to 20.2%; hazard ratio, 1.82; 95% CI, 1.53 to 2.15; P < .001), consistent across trials and treatment groups. We demonstrated that vitamin D status is an independent predictor of outcome and hypothesized that vitamin D status might be important for the chemosensitivity of HL. We subsequently performed experiments supplementing physiologic doses of vitamin D (calcitriol) to cultured HL cell lines and demonstrated increased antiproliferative effects in combination with chemotherapy. In an HL-xenograft animal model, we showed that supplemental vitamin D (dietary supplement, cholecalciferol) improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone. On the basis of our clinical and preclinical findings, we encourage that vitamin D screening and replacement be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement therapy in HL.

Long-term time trends in incidence, survival and mortality of Hodgkin lymphoma in the United States: A surveillance, epidemiology, and end results (SEER) database study 1975-2015.

e19014 Background: We examined epidemiological trends and patient characteristics such as age, gender, race, incidence and survival in Hodgkin Lymphoma (HL) using the updated largest population-based cancer registry in the US. Methods: Patients diagnosed with HL between 1975-2015 were identified in SEER registries. We incorporated SEER 9 registries to calculate incidence, race, disease characteristics and relative survival. Age-standard incidence rates (AI) were calculated using SEER 18 data and overall survival (OS) trends compared among different groups. Results: Rates for HL cases have been falling on average 1.8% per year and mortality rates (MR) have been falling on average 2.8% per year from 2006-2015. Males had higher incidence rates than females (3/100000 vs.2.3/100000). Bimodal distribution with prominent peaks at ages 20-24 and 75-79 years were noted among all groups except black (B) men. AI for women are higher at age of 20-24 years, but for men, higher at the later peak of 75-79 years. The AI for B men was highest at 50-54 years. The 10-year OS is 83.1% (Cl 82.3-83.9) in women with no significant difference between B, non-Hispanic white (NHW) or Asian Pacific Islander (API). In men, 10-year OS was 79.3% (Cl 78.4-80.1); lowest for B compared to NHW and API (72.6% vs. 80.0% vs.78.6). B patients had higher proportion of cases diagnosed with stage III/IV HL than NHW and API (48%. vs.40.6% and 39.9%, p &lt; 0.001). Males and patients &gt; 50 years were more frequently diagnosed with stage III/IV HL. The 10-year OS was only 40.8% for patients &gt; 65 years (CI 38.2-43.5) in contrast to 86.8% for patients &lt; 65 year (CI 86.3-87.4, p &lt; 0.001). Interestingly, first year MR was 33.1% (CI 34.7-31.7) for patients &gt; 65 years compared to 4.1% (CI 3.9-4.3) to those &lt; 65 year. Conclusions: Epidemiological trends show improved OS in HL among all groups. B men, patients with advanced age and stage III/IV have poor outcomes. First year MR are exceptionally high in patients &gt; 65years among all groups. Since B men have poor survival than B women, we postulate underlying disease biology may be a potential factor for worse outcome in this group.

Prognostic factors and outcome of ABVD chemotherapy in childhood Hodgkin lymphoma: a single center experience

Aim: The aim was to analyze the outcome of pediatric Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy + adjuvant radiotherapy according to the risk groups and determine the adverse prognostic factors affecting survival in Hodgkin lymphoma. Material and methods: A retrospective study was performed on 52 pediatric patients with Hodgkin lymphoma who were treated with ABVD between 1997 and 2018. Patients with early-stage favorable disease received 4 cycles of ABVD + radiotherapy. Early-stage unfavorable and advanced-stage patients received 6 cycles of ABVD + radiotherapy. Results: Thirty (57.7%) boys and 22 (42.3%) girls were included in the study. The median age of the patients was 9 years and 3 months (1 year and 10 month – 17 years and 7 months). Overall survival rate was 94.2% and the mean survival time was 19.5 ± 0.70 (95% CI, 18.1 - 20.9) years. The mean event-free survival time was 9.5 ± 6.5 years. Overall survival rate was 90%, and the mean event-free survival time was 8.2 ± 6.1 years in early-stage favorable disease. Overall survival rate was 100%, and the mean event-free survival time was 1.9 ± 7.0 years in early-stage unfavorable disease. Overall survival rate was 94.1 %, and the mean event-free survival time was 8.9 ± 6.3 years in advanced-stage disease. Presence of bulky disease, nodular sclerosing histologic subtype and leukocytosis had a negative prognostic effect on relapse and bulky disease had adverse effect on overall survival (p

Expression of PIM kinases in Reed-Sternberg cells fosters immune privilege and tumor cell survival in Hodgkin lymphoma

AbstractReed-Sternberg (RS) cells of classical Hodgkin lymphoma (cHL) express multiple immunoregulatory proteins that shape the cHL microenvironment and allow tumor cells to evade immune surveillance. Expression of certain immunoregulatory proteins is modulated by prosurvival transcription factors, such as NFκB and STATs. Because these factors also induce expression of the oncogenic PIM1/2/3 serine/threonine kinases, and as PIMs modulate transcriptional activity of NFκB and STATs, we hypothesized that these kinases support RS cell survival and foster their immune privilege. Here, we investigated PIM1/2/3 expression in cHL and assessed their role in developing RS cell immune privilege and survival. PIM1/2/3 were ubiquitously expressed in primary and cultured RS cells, and their expression was driven by JAK-STAT and NFκB activity. Genetic or chemical PIM inhibition with a newly developed pan-PIM inhibitor, SEL24-B489, induced RS cell apoptosis. PIM inhibition decreased cap-dependent protein translation, blocked JAK-STAT signaling, and markedly attenuated NFκB-dependent gene expression. In a cHL xenograft model, SEL24-B489 delayed tumor growth by 95.8% (P = .0002). Furthermore, SEL24-B489 decreased the expression of multiple molecules engaged in developing the immunosuppressive microenvironment, including galectin-1 and PD-L1/2. In coculture experiments, T cells incubated with SEL24-B489-treated RS cells exhibited higher expression of activation markers than T cells coincubated with control RS cells. Taken together, our data indicate that PIM kinases in cHL exhibit pleiotropic effects, orchestrating tumor immune escape and supporting RS cell survival. Inhibition of PIM kinases decreases RS cell viability and disrupts signaling circuits that link these cells with their niches. Thus, PIM kinases are promising therapeutic targets in cHL.

Childhood Hodgkin International Prognostic Score (CHIPS) Predicts event-free survival in Hodgkin Lymphoma: A Report from the Children's Oncology Group.

Early response to initial chemotherapy in Hodgkin lymphoma (HL) measured by computed tomography (CT) and/or positron emission tomography (PET) after two to three cycles of chemotherapy may inform therapeutic decisions. Risk stratification at diagnosis could, however, allow earlier and potentially more efficacious treatment modifications. We developed a predictive model for event-free survival (EFS) in pediatric/adolescent HL using clinical data known at diagnosis from 1103 intermediate-risk HL patients treated on Children's Oncology Group protocol AHOD0031 with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and radiation. Independent predictors of EFS were identified and used to develop and validate a prognostic score (Childhood Hodgkin International Prognostic Score [CHIPS]). A training cohort was randomly selected to include approximately half of the overall cohort, with the remainder forming the validation cohort. Stage 4 disease, large mediastinal mass, albumin (<3.5), and fever were independent predictors of EFS that were each assigned one point in the CHIPS. Four-year EFS was 93.1% for patients with CHIPS = 0, 88.5% for patients with CHIPS = 1, 77.6% for patients with CHIPS = 2, and 69.2% for patients with CHIPS = 3. CHIPS was highly predictive of EFS, identifying a subset (with CHIPS 2 or 3) that comprises 27% of intermediate-risk patients who have a 4-year EFS of <80% and who may benefit from early therapeutic augmentation. Furthermore, CHIPS identified higher risk patients who were not identified by early PET or CT response. CHIPS is a robust and inexpensive approach to predicting risk in patients with intermediate-risk HL that may improve ability to tailor therapy to risk factors known at diagnosis.

Prognostic Value of Interim and End of Treatment FDG-PET/CT Scan Results in Adult Patients with Burkitt Lymphoma - a Retrospective Analysis of a Single Center Cohort

Introduction: End of treatment FDG-PET/CT activity is a powerful predictor of survival outcome in patients with Hodgkin, Diffuse large B cell and Follicular lymphomas. The predictive value of interim PET/CT scan on survival in Hodgkin lymphoma is also well established. To date, there are limited data regarding the prognostic significance of interim and end of treatment FDG-PET/scan results in adult patients with Burkitt lymphoma (BL), mainly due to the rarity of this entity. In this single-center retrospective study we analyzed the survival outcomes of patients with BL according to the findings on interim and end of treatment FDG-PET/CT scans using the Deauville criteria.Methods: We thoroughly reviewed the clinical records of all BL patients who were treated in our medical center between 2005-2014. Thirty three patients and 104 scans were included in our final analysis. Interim PET/CT scan was performed before starting the 3rd cycle of the therapy. PET/CT scans were scored as positive or negative based on the five-point scale: scores 1-3 represented complete metabolic response (CMR) and scores 4-5 defined persistent or progressive disease. Response and survival outcomes were defined according to the Lugano Classification. Survival was calculated with the Kaplan-Meier method and survival comparison was analyzed with the Log-Rank test.Results: Twenty four (73 %) were males and median age was 48 years (22-78). Two patients were HIV positive. Twenty four patients (73%) had stage 3 or 4 disease and 25 patients (76%) had high-intermediate or high risk disease according to the International Prognostic Index. All patients received intensive regimens, and the majority of them (78%) were treated according to the GMALL-B-ALL/NHL2002 protocol. Rituximab was part of treatment in 28 (85%) patients. After a median follow-up of 1.92 years (yrs) (0.08-9.58), 7 patients (21%) have died: six due to advanced BL and one from treatment related toxicity. The overall (OS) and progression-free survival (PFS) at 3-yrs for all patients were 76% and 70%, respectively. Importantly, OS was predicted by the results of end of treatment PET/CT scans: patients in CMR (n=21) had OS of 90% while those with positive PET/CT (n=5) had OS of 30% at 3 years (Figure 1, p=0.001). Early-interim PET/CT results did not predict either PFS or OS at 3 years (OS - 85% for patients in CMR and 60% for patients with positive PET, p=0.27).Conclusions: The current retrospective study indicates that adult patients with BL, who receive rituximab-based intensive regimens, such as the GMALL-B-ALL/NHL2002 protocol, have a favorable outcome. End of treatment PET activity strongly predicted survival outcomes while interim PET result did not correlate with prognosis. Based on our data, it appears that changing treatment in adult patients with BL only on the basis of interim PET/CT results is not advised, unless there is clear evidence of progression.*Authors EP, MK & TD equally contributed to this study. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Interim Absolute Lymphocyte Count (ALC) As a Predictor of Survival in Hodgkin Lymphoma

▪Introduction: Patients with Hodgkin lymphoma (HL) have excellent response to current chemotherapy, however, up to 20% may have relapsed/refractory disease. Lymphocytopenia at diagnosis has been found to be predictive of survival in patients with advanced stage HL. An ALC of <600/μlat diagnosis as part of the Hasenclever predictive score is associated with a poorer prognosis. Furthermore, lymphocyte count at the time of apheresis and at day 15 after autologous SCT has been found to be predictive of survival in patients of HL. ALC is considered a surrogate indicator for the tumor microenvironment as well as immune recovery post treatment. There are no large studies evaluating the clinical significance of ALC recovery in patients with HL during initial chemotherapy treatment. In this study, we evaluated the role of lymphocyte recovery during and after standard chemotherapy in patients with HL.Patients and Methods: We analyzed 183 patients with Classical Hodgkin lymphoma treated at our institution between 1996 and 2014 following IRB approval. Complete data was available for 115 patients. We evaluated the absolute lymphocyte count at diagnosis, interim staging (after 2 cycles, Òinterim ALCÓ), at time of completion of chemotherapy and at 6 weeks and 3 months post completion of chemotherapy. Patients were categorized into two groups based on ALC where lymphocytopenia was defined as an ALC of <1x103/µl for adults based on standard criteria. Differences between the two groups were analyzed using Chi- square and t -Student tests. Statistical significance was set at P <0.05. Kaplan Meier method was used to calculate the Progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. Statistical analysis was performed using SPSS.22 software.Results: The median age of patients was 31 years (yrs.) (range: 17-76 yrs.) and 53% of patients were male. 100% patients had an ECOG status of 0-1. 48% patients presented with B symptoms, 42% had advanced stage disease (Stage III and IV) and 22% had bulky disease (defined as a mass > 10 cm or mediastinal mass >1/3 of diameter of thorax at T5-T6). In terms of histology, 68% patients had classical nodular sclerosis HL, 19% syncytial variant of nodular sclerosis HL, 8% mixed cellularity HL and 5% Classical HL (NOS). 90% patients received ABVD as their initial chemotherapy, 2% received Stanford V and 1% received MOPP. The remaining patients were treated on a clinical trial. In the analysis of the 115 patients for whom the lymphocyte data was available, at a median follow up of 40 months, 57% in the ALC <1x103/µl group versus 66% in the ALC >1x103/µlgroup had not progressed. The median overall survival was not reached in the two groups. In the multivariate analysis, for PFS, interim ALC predicted survival independent of the interim staging response. The ALC at the time of interim staging scan (interim ALC) was associated with a significantly superior PFS in the group with ALC>1x103/µl(HR=4.16, 95% CI 2.37 to 7.28, P=0.024). There was no difference in overall survival between the groups (Fig. 1&2,P=0.28). For ALC at other time points, no statistically significant differences in PFS or OS were found in the two groups based on ALC at diagnosis, completion of therapy, six weeks and three months post therapy.Discussion: In summary, our results suggest that for patients across all stages and histopathologic subtypes of classical HL receiving first line chemotherapy, interim ALC >1x103/µl (after 2 cycles) is associated with a superior PFS as compared with ALC <1 x103/µl and this is independent of the interim staging response. This did not translate into a difference in OS. Further studies are underway to determine the role of immune effector cells in the context of newer therapeutic agents. [Display omitted] [Display omitted] DisclosuresReddy:Gilead: Other: Speaker; Seattle Genetics: Consultancy; ImmunoGen: Consultancy; PCYC: Consultancy; Celgene: Consultancy, Research Funding.

Epigenetic regulation of microRNA expression in Hodgkin lymphoma

Epigenetic mechanisms are crucial for the inactivation of key genes related to the survival of Hodgkin lymphoma (HL) cells, and methylation is a frequent epigenetic mechanism of microRNA silencing. We have examined the methylation-induced silencing of tumor suppressor microRNAs in HL cell lines and confirmed our results in patient lymph nodes. In addition, we evaluated the in vitro effectiveness of 5-aza-2-deoxycytidine (5-Aza-dC) in HL cell lines. Ten microRNAs containing CpG islands in their promoter region were re-expressed in both the L-428 and L-1236 cell lines. Interestingly, miR-34a and miR-203, both known tumor suppressor microRNAs, were found to be methylated in cell lines and in patient samples. 5-Aza-dC treatment resulted in a dose-dependent antiproliferative effect at 72 h in all the HL cell lines. In summary, 5-Aza-dC treatment of HL cell lines inhibits proliferation at high doses and produces re-expression of the tumor suppressor microRNAs at low-intermediate doses.

Late pulmonary complications of treating Hodgkin lymphoma: bleomycin-induced toxicity

Introduction: Survival of Hodgkin lymphoma (HL) patients has significantly improved in recent decades. The current first-line therapy is doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) ± irradiation and may cause pulmonary toxicity. Strategies to reduce late toxicity as well as increase survival rate are of interest.Patients and methods: Pulmonary function of previously treated HL patients was collected over a 12-month period using St. George Respiratory Questionnaire (SGRQ), chest X-ray, dynamic inhalation lung scintigraphy and spirometry.Results: A total of 137 patients’ data were reviewed. Median time elapsed since diagnosis was 11 years (range was 2 – 30 years). Chest irradiation did not significantly worsen pulmonary function. Number of ABVD cycles with consequential bleomycin dose showed significant correlation with SGRQ total score in patients receiving ABVD plus chest irradiation (p = 0.01). Scintigraphy results correlated with bleomycin dose in patients receiving ABVD without chest irradiation (right side: p = 0.099, left side: p = 0.051).Discussion: An additive negative effect of chest irradiation was not confirmed as reflected in the literature; however, increasing cumulative bleomycin dose worsened pulmonary function.

Prognostic impact of monocyte count at presentation in mantle cell lymphoma

An increased number of circulating monocytes at presentation has recently been associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). AMC at diagnosis was available in 97 MCL cases recorded in the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy). With a median follow up of 7years, the 5-year overall survival was 29% for patients with AMC >0·50×10(9) /l and 62% for patients with AMC ≤0·50×10(9) /l (P=0·008). Elevated AMC and beta-2 microglobulin at diagnosis remained independent outcome predictors at multivariate analysis, controlling for the MCL International Prognostic Index (MIPI), and have been used to build a simple prognostic scoring system. In this relatively small and heterogeneous series an increased AMC identified poor-risk patients. Our results suggest that AMC together with the beta-2 microglobulin level might provide an inexpensive way to stratify MCL patient risk as a complement to the MIPI, which was confirmed to be a very powerful prognostic tool.

Elevated serum free light chains are associated with inferior event free and overall survival in Hodgkin lymphoma

The serum free light chain (FLC) assay quantitates free immunoglobulin kappa and lambda light chains, which has prognostic value in plasma cell dyscrasias. However, there is limited data on serum FLC in lymphoid malignancies. We analyzed the association of pretreatment FLC with event-free survival (EFS) and overall survival (OS) in 100 patients with Hodgkin lymphoma (HL). Elevated polyclonal FLC were present in 30% of patients; these patients had an inferior EFS (HR = 4.84; 95% CI: 1.84-12.7) and OS (HR = 8.87; 95% CI: 2.35-33.52) compared to patients with normal FLC. Further studies of FLC in HL are warranted.

Predictors of early response and event-free survival in Hodgkin lymphoma (HL): PET versus CT imaging.

8006 Background: Early PET imaging has emerged as a predictor of EFS in HL, but comparisons of early response assessment by PET vs. CT are limited. Children’s Oncology Group (COG) study AHOD0031 wa...