Outcome Of Lymphoma Patients Research Articles

Predictive value of prognostic nutritional index as prognostic biomarkers in patients with lymphoma: a systematic review and meta-analysis.

Several research have indicated the significant potential of the Prognostic Nutritional Index (PNI) as a prognostic biomarker in lymphoma patients. However, there is some inconsistency in the findings of a few studies. Hence, to offer a thorough evaluation of the predictive significance of PNI in lymphoma patients, we performed a meta-analysis to examine the prognostic value of PNI for survival outcomes in lymphoma patients. We conducted a comprehensive search for pertinent works published up until December 2023 in databases such as PubMed, EMBASE, Cochrane Library, and Web of Science. We obtained hazard ratio (HR) data related to survival outcomes and computed aggregated HRs with their corresponding 95% confidence intervals (CIs) to evaluate the correlation between PNI and both overall survival (OS) and progression-free survival (PFS) in lymphoma patients. By analyzing data from 1260 patients in 28 studies, we found that PNI levels were associated with prognosis in lymphoma patients. High PNI levels predicted that patients had longer OS (HR: 0.46, 95% CI 0.37-0.58, P < 0.05) and better PFS (HR: 0.56, 95% CI 0.45-0.70, P < 0.05). Subgroup analyses showed that the predictive ability of PNI for patient prognosis may differ depending on the type of lymphoma. In addition, we found that the critical PNI value had greater predictive potential at 40-45 and above 45. Our study suggests a strong association between PNI and prognostic outcomes in lymphoma patients, indicating that PNI holds substantial prognostic value in this population.

Day 100 Recovery of Absolute Number of Inhibitory KIR2DL2 and Activating NKp30 Natural Killer Cells Predicts Survival Post-Autologous Stem Cell Transplantation in Lymphomas.

The infusion autograft absolute number of inhibitory killer immunoglobulin-like receptor (KIR) 2DL2 and activating natural killer (NK)p30 cells are predictors of clinical outcomes in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). To assess if the long-term recovery of these NK cell subsets still holds clinical relevance, we set up to investigate their prognostic ability at day 100 post-APBHSCT. This was a retrospective single-institution study including 107 patients from our prior phase III trial who had a clinical assessment at day 100 post-APBHSCT. The median follow-up from day 100 was 168.19 months (interquartile range: 156.85-181.28 months). Patients with day 100 inhibitory KIR2DL2 < 0.08 cells/µL and activating NKp30 ≥ 0.19 cells/µL experienced superior overall survival (OS) and progression-free survival (PFS). A multivariate analysis revealed both the day 100 inhibitory KIR2DL2 [OS: HR = 1.449, 95%CI, 1.231-1.895, p < 0.013; and PFS: HR = 2.069, 95%CI, 1.134-3.775, p < 0.021] and activating NKp30 [OS: HR = 4.985, 95%CI, 2.614-9.506, p < 0.0001; and PFS: HR = 4.661, 95%CI, 2.598-8.393, p < 0.0001] were independent predictors for OS and PFS. Inhibitory KIR2DL2 and activating NKp30 NK cells at day 100 are prognostic immune biomarkers in lymphoma patients treated with APBHSCT.

Prospective study on the impact of BEAM versus FEAM conditioning on occurrence of neutropenic enterocolitis and on transplant outcome in lymphoma patients.

Carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) are a widely used high-dose chemotherapy regimen for autologous stem cell transplantation transplant (ASCT) in lymphoid malignancies. During BCNU shortages, some centers switched to fotemustine-substituted BEAM (FEAM). Neutropenic enterocolitis (NEC) is a life-threatening complication occurring after intestinal mucosa damage related to intensive chemotherapy. NEC mortality may be up to 30%-50%. In our study, we compared NEC incidence, symptoms, mortality, and transplant outcome in terms of overall survival (OS) and progression-free survival (PFS) in the BEAM vs. FEAM groups. Furthermore, we compared the cost of hospitalization of patients who did vs. patients who did not experience a NEC episode (NECe). A total of 191 patients were enrolled in this study (N = 129 and N = 62 were conditioned with BEAM and FEAM, respectively). All patients received bed-side high-resolution ultrasound (US) for NEC diagnosis. NEC incidence and NEC-related mortality were similar in the BEAM and FEAM groups (31% and 40.3%, p = 0.653, and 5% and 8%, p = 0.627, respectively). At a median follow-up of 116 months, no difference was noted between BEAM vs. FEAM groups in terms of OS and PFS (p = 0.181 and p = 0.978, respectively). BEAM appeared equivalent to FEAM in terms of NEC incidence and efficacy. The high incidence of NEC and the low mortality is related to a timely US diagnosis and prompt treatment. US knowledge in NEC diagnosis allows to have comparable days of hospitalization of patients NECpos vs. patients NECneg. The cost analysis of NECpos vs. NECneg has been also performed.

Role of interim positron emission tomography/computed tomography in assessment of lymphoma treatment response

BackgroundLymphoma is the most common primary hematological malignancy. FDG PET/CT has recently become the standard imaging modality for clinical management owing to its ability to provide precise, non-invasive anatomical and functional data. The purpose of this study was to highlight the role of 18F FDG-PET/CT in the management of lymphoma by monitoring treatment response, providing a guide for response-adapted therapy, and predicting the final therapeutic outcome.MethodsThis was a prospective monocentric cohort observational study in which thirty-three patients with histopathologically proved lymphoma of different types performed FDG-PET/CT scanning several times throughout the 24-month duration of the study. Early-stage interim SUVmax of the most active lesion (both nodal and/or extra-nodal) was measured and statistically analyzed together with data of the international prognostic index parameters and score.ResultsAmong the included 33 patients of lymphoma, international prognostic index parameters and score together with the early-stage interim SUVmax of the predominant nodal and extra-nodal sites showed statistical significance in predicting the initial as well as the final treatment response after 24 months. Using ROC analysis, we could obtain cutoff values of SUVmax of the predominant nodal lesion of 2.75 (AUC 72%, 95% CI 0.42–1.0) and SUVmax of the predominant extra-nodal lesion of 3 (AUC 70.8% and 95% CI 0.23–1.0); therefore, SUVmax of higher than these values was related to stable or progressive disease, and lower levels than these values were related to complete or partial metabolic response based on Deauville 5-point scale and Lugano response criteria.ConclusionsEarly-stage interim PET-CT SUVmax of the predominant nodal and extra-nodal lesion could be a reliable parameter in predicting initial and final therapeutic outcome in lymphoma patients.

Day 100 Inhibitory KIR2DL2 and Activating NKp30 Natural Killer Cell Receptors Predicts Survival Post-Autologous Stem Cell Transplantation in Lymphomas

Introduction: Our group previously published that the infusion autograft inhibitor KIR2DL2 (CD158b+CD337-) and activating NKp30 (CD158b- CD337+) Natural killer (NK) cells receptors were predictors of clinical outcomes in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) (Porrata et al. Leukemia Research 2019; 81: 1-9). To assess if these subsets of NK cells still hold clinical relevance, we set up to investigate their prognostic ability to predict clinical outcomes at Day 100 post-APBHSCT. Methods: 107 lymphoma patients who participated in our double-blind phase III trail (Porrata et al, Biology of Blood and Marrow Transplantation 2016; 22(6); 1017-1023) and had clinical assessment at Day 100 post-APBHSCT were included in this study. Nkp30 and KIR2DL2 at Day 100 were assessed by flow cytometry analysis. Results: With a median follow-up for the entire cohort from Day 100 was 94.7 months (range: 4.83-158.1 months). Figure 1 shows the overall survival (OS) and progression-free survival (PFS) based on the absolute numbers of KIR2DL2 and Nkp30 NK cells. At Day 100, patients with a KIR2DL2 &amp;lt; 0.08 and Nkp30 ≥0.19 experienced superior OS and PFS compared with patients with a Day 100 KIR2DLD2 ≥0.08 and NKp30 &amp;lt; 0.19. In the multivariate analysis both the KIR2DL2 [OS: HR = 1.767, 95%CI, 1.302-30.31, p &amp;lt; 0.04; and PFS: HR = 2.663, 95%CI, 1.108-6.403, p &amp;lt; 0.03] and Nkp30 [OS: HR = 2.594, 95% CI, 1.239-5.432, p &amp;lt; 0.01; and PFS: HR = 3.676, 95% CI, 1.875-7.206, p &amp;lt; 0.01] were independent predictors for OS and PFS. Conclusion: Day 100 inhibitory KIR2DL2 and activating NKp30 NK cells are prognostic immune-biomarkers in lymphoma patients undergoing APBHSCT.

Lower Body Mass Index and Prognostic Nutritional Index Are Associated with Poor Posttransplant Outcomes in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation

Introduction: Pretransplant inflammatory and nutritional status has not been widely explored in terms of its impact on autologous hematopoietic stem cell transplantation (auto-HSCT) outcomes in lymphoma patients. We aimed to evaluate the impact of body mass index (BMI), prognostic nutritional index (PNI), and C-reactive protein to albumin ratio (CAR) on auto-HSCT outcomes. Methods: We retrospectively analyzed 87 consecutive lymphoma patients who underwent their first auto-HSCT at the Adult Hematopoietic Stem Cell Transplantation Unit at Akdeniz University Hospital. Results: The CAR had no impact on posttransplant outcomes. PNI ≤50 was an independent prognostic factor for both shorter progression-free survival (PFS) (hazard ratio [HR] = 2.43, p = 0.025) and worse overall survival (OS) (HR = 2.93, p = 0.021), respectively. The 5-year PFS rate was significantly lower in patients with PNI ≤50 than in patients with PNI >50 (37.3% vs. 59.9%, p = 0.003). The 5-year OS rate in patients with PNI ≤50 was significantly low when compared with patients who had PNI >50 as well (45.5% vs. 67.2%, p = 0.011). Patients with BMI <25 had higher 100-day transplant-related mortality compared with patients with BMI ≥25 (14.7% vs. 1.9%, p = 0.020). BMI <25 was an independent prognostic factor associated with shorter PFS and OS (HR = 2.98 [p = 0.003], HR = 5.06 [p < 0.001], respectively). The 5-year PFS rate was significantly lower in patients with BMI <25 than patients with BMI ≥25 (40.2% vs. 53.7%, p = 0.037). Similarly, the 5-year OS rate in patients with BMI <25 was significantly inferior compared to patients with BMI ≥25 (42.7% vs. 64.7%, p = 0.002). Conclusion: Our study confirms that lower BMI and CAR have negative impacts on auto-HSCT outcomes in lymphoma patients. Furthermore, higher BMI should not be considered an obstacle for lymphoma patients who need auto-HSCT; conversely, it could be an advantage for posttransplant outcomes.

Day 100 Peripheral Blood Natural Killer Cell/CD14+HLA-DR- Ratio Predicts Clinical Outcomes in Lymphoma Patients Treated with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

Day 100 Peripheral Blood Natural Killer Cell/CD14+HLA-DR- Ratio Predicts Clinical Outcomes in Lymphoma Patients Treated with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

Biological Differences between Axi-Cel and Tisa-Cel Products and Impacts on Outcomes in Lymphoma Patients

Purpose Axicabtagene ciloleucel (axi-cel, Yescarta® (Axi)) and tisagenlecleucel (tisa-cel, Kymriah® (Tisa)) have been approved and commercialized in Europe for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) after 2 or more previous lines of therapy. A recent Lysa Study from a matched analysis of the Descar-T registry has reported that Axi may yield a higher disease control rate compared to Tisa but at the expense of a higher toxicity[Bachy et al. EHA 2022]. Biological reports have shed light on the importance of both expansion and persistence of CAR T-cells to enhance disease control. In addition, in a mouse model, viability levels of CAR T cells both immediately after thawing and after 1 day of in-vitro culture were reported to be important indicator of the CAR-T cells antitumor activity [Zah E et al. Can Im Res. 2016]. In this single-center prospective study, we analyzed biological characteristics of both Axi and Tisa anti-CD19 CAR T-cells infused in 48 patients and looked at their correlation with outcomes. Experimental design From March 2019 to June 2022, residual cells were obtained after washing 48 infusion product bags, 27 Axi and 21 Tisa products. Cells' viability was analyzed immediately, and percentage of CAR positive T-cells was determined by flow cytometry with CD19 CAR detection reagent (Miltenyi Biotec). Cells were put in complete medium (RPMI, glutamax, 8% of human serum and 300 UI of IL-2/ml) at 37°C, viability was analyzed after 1 days of in-vitro culture and doubling population number was followed for 1 to 4 weeks. Results Among the 48 patients (median age: 62 yo, range: 37-78), 56% had a DLBCL, and 29% had a transformed Follicular Lymphoma. Median number of previous lines was 3 (range, 2-10), which included an ASCT in 37.5% of patients. No differences in terms of characteristics were observed between Tisa and Axi cases. Tisa displayed a lesser cell viability (median 57%, range: 28-78) as compared to Axi (81%; range 62-94, p<0.001, (Figure 1). After 24H, the median percentage (%) of live cell recovery were similar (Tisa 89%, vs Axi 84%; p=0.23). However, 43% of Tisa and 20 % of Axi preparations displayed a viable cell yield ≤ 50% the day after thawing. The recommended doses of viable CAR+ T cells to be injected in patients is 0.6 to 6.0 x 108 cells for Tisa and 2 × 106/kg, with a maximum of 2 × 108 cells, for Axi. All patients received the recommended dose even if Tisa products were characterized by a significantly lower fraction of CD3+ CAR+ T-cells as compared to Axi (median 27% , range: 14-53 vs. 70%; range 37-88 P<0.001) (Figure 1). Median CD4/CD8 ratii among CAR+ T cells were similar between both products (Tisa: 3.5 vs Axi 2.3, p=0.35). In vitro and in the absence of antigen stimulation, total T-cells were able to proliferate, Tisa product had a higher amplification capacity (median nbr of division = 8.8 vs 3.1, p=. 6e-6). Finally, the proportion of CAR negative T cells (mostly activated T-cells) injected was highly variable between patients and ranged from 1.3.108 to 61.4.108 for Tisa while it was only from 0.2.108 to 3.4.108 for Axi. All but one patient infused with Axi presented with cytokine release syndrome (CRS) compared to 62% of patients infused with Tisa (p=0.006); the same significant difference was observed for immune effector cell-associated neurotoxicity syndrome (ICANs) (67% vs 14%, p<0.001). Conversely, survivals were comparable in this small cohort. Only the percentage of CD3+ CAR+ T-cells had a clinical impact. Indeed, a significant higher median % of these cells was found in patients developing all grade CRS (58% [range, 24-88%] vs 25% [range, 14-73%], p=0.014). (Figure 2) This was also true when considering only patients receiving Tisa (CRS+ 36.5 % [range, 24-88%] vs CRS- 24% [range, 14-73%], p=0.02. No biological association with ICANs nor hematological toxicity could be reliably reported in this cohort. Discussion In this study, four major biological differences were observed between Tisa and Axi products: the cell viability, the proliferative activity in vitro, the % of CAR positive T-cells and the total amount of CAR negative T-cells injected into the patient. However, impact on outcomes was modest as only CRS were found to be correlated to the percentage of CD3+ CAR+ T-cells injected, of note Axi-cell which was reported to be associated with a better disease control rate developed more CRS in our cohort, which is line with a high and consistent percentage of CD3+ CAR+ T-cells. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Timing of Radiation Therapy and Clinical Outcomes in Lymphoma Patients

<h3>Purpose/Objective(s)</h3> The impact of radiation therapy (RT) timing as part of multimodality therapy in Hodgkin (HL) and non-Hodgkin lymphoma (NHL) requires investigation. In largely refractory/recurrent, heterogeneous lymphoma patients, we hypothesize that earlier implementation of RT will be associated with improved quality of life (QOL), such as pain, and survival outcomes. <h3>Materials/Methods</h3> From 2009-2019, patients with HL or NHL were treated with RT as part of palliation (36.5%) or definitive therapy (63%) at a single institution. On an IRB approved database review, we determined baseline patient and treatment characteristics via univariate analysis reported as median [interquartile range]. Correlations between these characteristics were performed using Spearman correlations. Multivariable analysis (MVA) with cox regression was conducted to determine survival outcomes, controlling for lymphoma subtype, stage, ECOG performance status, number of chemotherapy (chemo) lines, and pain scores self-reported on a scale of 1 to 10. <h3>Results</h3> Of 189 patients, 64% had NHL; 42% were stage IV and 65% had relapsed/refractory disease (Table 1). At diagnosis, 75% of patients received chemo with a median of 2 lines [1-5]. RT was delivered at a median of 10 months [5-21] post-chemo. The median interval from diagnosis to RT was 11 months [4-38] and from diagnosis to chemo was 19 days [7-91]. Median overall survival (OS) was 28 months [14-49] from time of diagnosis. On MVA, average baseline (pre-RT) non-zero pain scores were significantly higher in patients who received RT >12 months versus ≤ 12 months (R²=0.31, F=5.46 p = 0.032) from diagnosis. Interval to RT was also associated with worse OS such that the longer the interval from diagnosis to RT (HR 0.952, p<0.0001) or from chemo to RT (HR 0.954, p<0.0001), the lower the likelihood of OS. On MVA of sub-cohorts, these findings remain significant within the relapse/refractory cohort (HR=0.953, p<0.0001 for diagnosis to RT; HR=0.953, p<0.0001 for chemo to RT) and in patients with bulky disease (HR=0.778, p=0.0002 for diagnosis to RT; HR=0.962, p=0.022 for chemo to RT). <h3>Conclusion</h3> In our single-center experience, receipt of RT > 12 months from diagnosis in lymphoma patients was associated with a decrease in functional and survival outcomes. Further analyses regarding QOL measures and cancer specific outcomes will shed additional light regarding RT timing, for definitive or palliative intent, which may better address pain, refractory disease, and may improve survival.

Improved Survival of Lymphoma Patients with COVID-19 in the Modern Treatment and Vaccination Era.

Simple SummaryPatients with lymphoma are at greater risk of complications from COVID-19 infection. However, limited data exists on COVID-19-related outcomes in lymphoma patients since the use of COVID-19 vaccines and treatments began. Our study reports the real-world outcomes of 68 lymphoma or CLL patients who developed COVID-19 infection during the omicron surge in the US. We found that 34% of patients were hospitalized due to COVID-19 infection. The COVID-19-associated death rate was 9% (6/68) in all patients and 26% (6/23) in hospitalized patients, which was much lower compared to rates earlier in the pandemic prior to the introduction of COVID-19 vaccines and treatments. In 30 patients with data available, 60% did not make antibodies after COVID-19 vaccination. Most patients (74%, 17/23) who were hospitalized did not receive COVID-19 monoclonal antibody treatment. Our results pointed to important differences and the need for a new approach to treating cancer patients with COVID-19 infection.Lymphoma patients are at greater risk of severe consequences from COVID-19 infection, yet most reports of COVID-19-associated outcomes were published before the advent of COVID-19 vaccinations and monoclonal antibodies (mAbs). In this retrospective study, we report the real-world outcomes of 68 lymphoma or CLL patients who developed COVID-19 infection during the omicron surge in the US. We found that 34% of patients were hospitalized as a result of COVID-19 infection. The death rate due to COVID-19 was 9% (6/68) in the overall population and 26% (6/23) in hospitalized patients. During the preintervention COVID-19 era, the mortality rate reported in cancer patients was 34%, which increased to 60.2% in hospitalized patients. Thus, the death rates in our study were much lower when compared to those in cancer patients earlier in the pandemic, and may be attributed to modern interventions. In our study, 60% (18/30) of patients with serology data available did not develop anti-COVID-19 spike protein antibodies following vaccination. Most patients (74%, 17/23) who were hospitalized due to COVID-19 infection did not receive COVID-19 mAb treatment. Our results pointed to the importance of humoral immunity and the protective effect of COVID-19 mAbs in improving outcomes in lymphoma patients.

Use of circulating tumor DNA in newly diagnosed DLBCL patients.

e19552 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. With upfront treatment, 40% of patients relapse. Currently, treatment response and surveillance are monitored using positron emission tomography/computerized tomography (PET/CT). However, no study to date has shown significant improvement in outcomes in lymphoma patients using standard radiographic and clinical surveillance. Most often, relapses likely occur from minimal residual disease (MRD) below the detection of imaging. Thus, a subclinical biomarker to better monitor treatment response and surveillance is needed. Circulating tumor DNA (ctDNA) has emerged as a sensitive biomarker for detecting MRD. Here, we aimed to evaluate the utility of ctDNA as a biomarker for monitoring treatment response and surveillance in patients with lymphoma. Methods: ctDNA analysis using a personalized, tumor-informed assay (Signatera bespoke mPCR NGS assay) was performed on blood samples collected from 15 patients with newly diagnosed DLBCL who presented to Harbor-UCLA Medical Center in 2021. Blood samples were collected at diagnosis, prior to each cycle of therapy, and every 3 months thereafter for surveillance. The primary endpoint was the rate of ctDNA clearance during treatment and its correlation with radiological imaging. Secondary endpoints included ctDNA positivity rate during surveillance and its correlation with radiological imaging. Additional data collected included patient demographics, lymphoma characteristics, and treatment regimen. Results: Of the 15 patients included in this cohort, the median age was 54 years and the percentage of patients with stage 1, 2, 3, and 4 disease was 7%, 20%, 7% and 67%, respectively. A total of 7% had high risk IPI scores. Within this cohort, 80% received RCHOP and 20% received daREPOCH. ctDNA was detected in 93.3% (14/15) of patients at diagnosis, with levels ranging from 2-3,607 mean tumor molecules (MTM)/mL of plasm. Of the ctDNA+ patients, 6 (40%) patients had a complete response to initial therapy as assessed by post-treatment imaging. Longitudinal assessment of ctDNA after each cycle of therapy revealed concordance with radiological findings, where 2/6 cleared ctDNA after cycle 1, 4/6 cleared ctDNA after cycle 2, 5/6 cleared ctDNA after cycle 3, and 6/6 cleared ctDNA after cycle 4 of treatment. One patient had undetectable ctDNA after cycle 4, but had a Deauville score of 4 on post-treatment PET/CT and was referred to radiation. Of the 3 patients who remained ctDNA positive on longitudinal testing, all were confirmed to have primary refractory disease by imaging. Of the remaining patients, 1 patient died after daREPOCH cycle 1 and 3 patients are undergoing initial therapy. Conclusions: ctDNA may serve as an important biomarker to assess response to treatment and for surveillance in DLBCL patients. Further studies evaluating ctDNA use in the clinical setting are needed before its application in routine practice.

Outcome of CBV (Carmustine, Cyclophosphamide, Etoposide) Conditioning Regimen for Autologous Stem Cell Transplant in Lymphoma: A Retrospective Study from a Tertiary Cancer Center in South India

Abstract Background In autologous stem cell transplant (ASCT) for lymphomas, no standard conditioning regimen has been defined so far. Thus, the choice is guided by the center's familiarity and experience with a particular regimen. Objective To determine the response, toxicity, and survival outcomes in lymphoma patients who underwent ASCT with CBV (cyclophosphamide, carmustine, and etoposide) conditioning regimen. Materials and Methods Between January 2013 and May 2019, 45 consecutive lymphoma patients who had ASCT with CBV conditioning regimen were included in this retrospective study. CBV consisted of cyclophosphamide (1.5 g/m2/day × 4 days), carmustine (300 mg/m2 × 1 day), and etoposide (125 mg/m2 twice daily × 3 days). Baseline characteristics, pre transplant response, apheresis, post-transplant toxicities, post-transplant response, and survival outcomes were collected. Endpoints were toxicity, response, event-free survival (EFS), and overall survival (OS). Results The median age was 30 (range: 6–64) years. Diagnosis was Hodgkin lymphoma (HL) in 26 (58%) and non-Hodgkin lymphoma (NHL) in 19 (42%). Forty-three patients (95%) had chemosensitive disease; 22(49%) in CR, and 21 (46%) in PR. The median CD34 was 2.95 × 106/kg (range: 0.9–9.56). The median time to neutrophil engraftment was 11 days (9–23) and 13 (8–36) days for platelets. All patients had febrile neutropenia, clinically and/or microbiologically documented infection was seen in 75% of patients. The most common grade 3/4 toxicities were mucositis (n = 4, 9%), diarrhea (n = 4, 9%), and nausea/vomiting (n = 2, 4%). The average days of hospitalization was 18 (range: 10–37). Day 100 mortality was 6.6% (n = 3). The median follow-up was 44.8 months. The median EFS for the entire cohort was 23.8 months; for HL, the median EFS was not reached, and for NHL, it was 7.97 months (95% confidence interval [CI]: 1.57–14.37). The median OS for the entire cohort and for HL was not reached; for NHL, it was 24.3 months (95% CI: 0.56–48.11). Conclusion CBV conditioning regimen was well tolerated with low grade 3/4 toxicities and efficacy comparable to literature data.

Patient profiles and outcomes of lymphoma patients who underwent autologous stem cell transplant in National Kidney and Transplant Institute: a single-center analysis

Patient profiles and outcomes of lymphoma patients who underwent autologous stem cell transplant in National Kidney and Transplant Institute: a single-center analysis

OUTCOMES OF PATIENTS WITH LYMPHOMA AND COVID‐19: AN OBSERVATIONAL COHORT STUDY FROM GELTAMO SPANISH GROUP

Introduction: COVID-19 is thought to be more frequent and severe in patients with cancer. Lymphoma patients may be especially vulnerable, due to the immunodeficiency and immune dysregulation caused by the lymphoma itself and the antitumor treatments. This study describes the characteristics and outcomes of lymphoma patients after developing COVID-19. Methods: This is a retrospective multicentre study carried out in the hospitals of the GELTAMO group, which included patients with a histological diagnosis of lymphoma and confirmed SARS-COV-2 infection before June 30th, 2020. The primary outcome was overall survival (OS) 60 days after a COVID-19 diagnosis. Results: A total of 218 patients (median sage 69.5 [21-94] years, 54% male) were included;100 patients had an indolent B-cell non-Hodgkin's lymphoma (NHL), 67 aggressive B-cell NHL, 19 mantlecell lymphoma, 15 peripheral T-cell lymphoma, and 17 Hodgkin's lymphoma. Patients had received a median of 1 line (0-7) of therapy, and 44.9% were on active treatment at the time of COVID-19 diagnosis. Only 6.4%, 1.8% and 0.9% of patients had received previously autologous stem-cell transplantation, allogeneic SCT and CAR-T cell therapy, respectively. 89% of patients were hospitalized, 71% required oxygen, and 15% mechanical ventilation. With a median follow-up of 91.5 days (13-203), 65 patients have died (60 from COVID-19, 4 from lymphoma, 1 due to other causes), with an estimated 60-day OS of 68.6% (95% CI 62.1-75.1) (figure 1A). In univariate analysis, baseline characteristics associated with decreased OS were age ≥70 years, hypertension, diabetes, other cancer, active disease and hypogammaglobulinemia, but only age ≥70 years maintained independent influence in the multivariate analysis (HR 3.29, 95% CI 1.86-5.83, p < 0.001). Active treatment did not significantly impact OS (figure 1B). Univariate analysis revealed different prognostic factors, apart from age, for patients with DLBCL (N = 60) and FL (N = 69). While the presence of active disease had a prognostic impact on DLBCL (60-day OS 56% vs 79%, p = 0.038) but not on FL (60-day OS 65% vs 78%, p = 0.181) patients, the opposite occurred in the case of active treatment, which seemed to have a negative influence only in patients with FL, as shown in figures 1C and 1D. Conclusions: Our results confirm a high mortality in patients with lymphoma and COVID-19, especially in those ≥70 years old. In patients with DLBCL, disease control seems essential to reduce the risk of mortality in the event of contracting the infection. By contrast, in patients with FL, delaying the start of treatment until it is not strictly necessary should be considered, and these patients should be prioritized to be vaccinated before starting antitumor treatment. This study provides initial data to develop recommendations for the management of lymphoma patients during the COVID-19 pandemic.

Cachexia is an independent factor for negative clinical and functional outcomes in lymphoma patients receiving CART therapy.

e19504 Background: Cachexia is a known independent factor for negative outcomes in several cancer populations at early and late stages, but has not been in investigated in cancer patients receiving Chimeric Antigen Receptor T-cell therapy (CART). Our objective was to evaluate the relationship between cachexia and clinical and functional outcomes in patients with lymphoma receiving CART. Methods: Design: Retrospective cohort study including 70 adult patients with aggressive B-cell lymphomas (Diffuse Large B-cell or Mantle Cell Lymphoma) who received CART. Cachexia markers: body weight loss (BWL), BMI, albumin, creatinine, and neutrophil-to-lymphocyte ratio (NLR) – each captured at diagnosis, pre-collection, CART initiation, and through day 360 post-CART. Outcome measures: Primary outcomes: Disease relapse after CART and 90-day mortality. Secondary outcome: Need for rehabilitation services post-acute care (inpatient rehabilitation or home physical therapy). Statistical analyses: Linear regression modeling, area under the curve analysis, and multivariate modeling (any univariates with p &lt; 0.25). Co-variates: age, ECOG PS, IPI, cell of origin, MYC status, number of prior cancer therapies, time from diagnosis to CART, and need for bridging / steroid pre-CART. Results: In longitudinal modeling from diagnosis to day 360, CART patients who relapsed had linear associations over time with BWL since diagnosis (p &lt; 0.01), NLR (p &lt; 0.0001), creatinine (p = 0.045), and albumin (p &lt; 0.001). In univariate analyses (see table): at pre-collection, high NLR and BWL increased odds of relapse; at treatment, high NLR and CRP increased odds of mortality; and at D30, and BWL and high NLR increased odds of relapse and mortality, respectively. In multivariate analyses (see table, # = independent association), BWL and high NLR independently associated with relapse and mortality, respectively. Significant covariates included need for bridging (p = 0.02), steroid therapy pre-CART (p &lt; 0.01), and time from diagnosis to CART (p = 0.02). Secondarily, BWL and low albumin pre-CART increased odds of needing rehabilitation services, with BWL independently associating in multivariate models (OR = infinity, p &lt; 0.001). Conclusions: Cachexia markers, such as BWL from diagnosis and NLR, are candidate predictors of relapse and mortality after CART. Specific markers could also assign patients to neo/adjuvant rehabilitative and medical therapies targeted towards cachexia. Overall, this study suggests that cachexia may alter the clinical and functional trajectory of lymphoma patients receiving CART.[Table: see text]

Autologous hematopoietic stem cell transplantation with inadequate stem cell dose in patients with non-Hodgkin lymphoma

Little is known regarding the outcome of lymphoma patients undergoing autologous hematopoietic stem cell transplantation (AHSCT) using inadequate hematopoietic stem cell (HSC) doses. Fifty-six patients were enrolled in the study, and the cohort was subdivided into two groups according to the infusion dose: < 1 × 106/kg (poor HSC group) and 1–2 × 106/kg (unfavorable HSC group). Compared with the unfavorable group, the poor HSC group had a longer median time to neutrophil (13 vs. 11 days, p = .007) and platelet engraftment (17 vs. 13 days, p = .024). CD34+ cell infusion dose of < 1 × 106/kg was the only risk factor for neutrophil and platelet engraftment. The expected 3-year progression-free survival and overall survival rates for the whole cohort were 53% and 66%, and no statistical difference was observed between two groups. In conclusion, inadequate HSC infusion dose did not negatively impact AHSCT patient survival but significantly prolonged the time to hematopoietic engraftment.

Allogeneic stem cell transplantation in elderly lymphoma patients: Single-center experience.

e19519 Background: Autologous stem cell transplantation is used as consolidation therapy in relapsed lymphoma patients. However, outcome of lymphoma patients relapsing after autologous stem cell transplantation is poor and allogeneic stem cell transplantation which can be curative is used in the transplant eligible patients in this setting. Besides, allogeneic stem cell transplantation can be an option before autologous stem cell transplantation in some high risk patients. In this study, we aimed to analyze the results of lymphoma patients older than 60 years of age who had undergone allogeneic transplantation in our center. Methods: We collected the data of lymphoma patients older than 60 years of age who had undergone allogeneic transplantation in our center and analyzed the results. Results: There were 20 patients over the age of 60 who had undergone allogeneic stem cell trasplantation with the diagnosis of lmphoma between 2011 and 2019. 18 patients had Non-Hodgkin lymphoma and 2 patients had Hodgkin lymphoma. 12 patients (60%) had been transplanted from HLA-matched sibling, while 6 patients (30%) had been transplanted from unrelted donors and 2 patients (10%) had been transplanted from haploidentical donors. The median age of the patients was 62 (61-66) and 30% of the patients were female. During the follow-up time only 1 patient had relapsed. The 2 year progression free survival (PFS) rate was 32% and the 2 year overall survival (OS) rate was 32%. The OS curve is shown in Figure 1. 100 day mortality was 30% and 1 year non-relapse mortalty (NRM) was 50%. The characteristics and results of the patients are summarized in Table 1. Conclusions: In the present study, although the number of patients is low, we showed that lymphoma patients over 60 years of age have a 2 year overall survival rate of 32% and a relapse rate of 5% suggesting that allogeneic stem cell transplantation which has a curative potential may be employed in transplant eligible elderly lymphoma patients.

Aberrant peripheral blood CD4+ CD25+ FOXP3+ regulatory T cells/T helper-17 number is associated with the outcome of patients with lymphoma.

Little is known about the clinical significance of the peripheral blood CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) and T helper-17 (Th17) cells in lymphoma patients. In this study, the prognostic and clinical significance of peripheral blood Tregs and Th17 cells were evaluated in lymphoma patients during different phases. The frequency of Tregs and Th17 lymphocytes was measured by flow cytometry method in 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma (DLBCL) patients. Our results showed that the frequency of Tregs and absolute Treg count was significantly reduced in relapsed patients compared to patients at the remission phase, as well as with newly diagnosed untreated patients in both groups. Patients who reached complete remission had elevated frequency of CD4+ FOXP3+ lymphocytes, Tregs, absolute Treg count, Treg/CD4 and Treg/Th17 ratio in the cHL group and CD4+ CD25+ cells in DLBCL group. The frequency of Tregs, absolute Treg count and Treg/Th17 ratio in cHL patients and CD4+ FOXP3+ and CD4+ CD25+ cells in DLBCL patients positively associated with survival rate. Moreover, the percentage of Tregs and absolute Treg count positively correlated with white blood cell, platelet count and ESR level in cHL patients and with white blood cell count in DLBCL patients. The initial number of Tregs/Th17 cells and also the Treg/Th17 ratio was not associated with changes in disease-free survival (DFS) in both groups. Therefore, higher frequency of peripheral blood Tregs and Treg/Th17 ratio might be associated with a favorable outcome in lymphoma patients, better response to chemotherapy and lower rate of relapse.

Impact of Co-Morbidities on Outcome in a Predominantly Hispanic Population of Hodgkin and Non-Hodgkin Lymphoma Patients

BACKGROUND Evidence suggests that co-morbidities at diagnosis can influence treatment decisions and outcomes in lymphoma patients. Considering the bimodal presentation of Hodgkin Lymphoma (HL) and that the majority of Non-Hodgkin lymphoma (NHL) patients are over 65 years of age, it can be especially challenging to manage them as older patients have a higher number of co-morbidities. Studies have shown that comorbidity is associated with an inferior outcome and a lower likelihood of receiving treatment with curative intent. It must also be noted that older adults with significant co-morbidities are often excluded from clinical trials due to co-morbidities and that Hispanics (HI) have been historically underrepresented. There is a need to take a closer look at this precise patient population. The main objective of our study was to determine the common co-morbidities and their impact on outcome in a prevalently Hispanic population with both HL and NHL at the only NCI designated Cancer Center of South Texas. To our knowledge this is the largest cohort of HL patients from a single academic institution that serves primarily Hispanics. METHODS We located and retrospectively analyzed a total of 616 patients with diagnosis of Lymphoma (HL and NHL) by International Classification of Diseases (ICD) codes and identified 477 patients who met criteria for inclusion; the patients all received care at UT Health San Antonio, between 2008-2018. Key variables for each patient included age, gender, race/ ethnicity, comorbidities, and vitality status in 2018. Continuously distributed outcomes were summarized with the mean and standard deviation and categorical outcomes were summarized with frequencies and percentages. The significance of variation in the mean with disease category was assessed with one way ANOVA and the significance of associations between categorical outcomes was assessed with Pearson's Chi Square or Fisher's Exact test as appropriate. Multivariate logistic regression was used to model binary outcomes in terms of covariates and indicators of disease. All statistical testing was two-sided with a significance level of 5%. R1 was used throughout. The study was approved by the local Institutional Review Board. The findings will be available to patients, funders and medical community through traditional publishing and social media. RESULTS We identified 477 patients with HL and NHL, 262 were Hispanic (HI) [55%], 205 non-Hispanic (NH) [43%], 10 not specified [2%]; there were 232 females (49%) and 245 males (51%). Co-morbidities that were identified and analyzed were: Diabetes Mellitus (DM), Hypertension (HTN), Chronic Kidney Disease (CKD), Coronary Artery Disease (CAD) and Congestive Heart Failure (CHF). The most common co-morbidity across all lymphoma subtypes was HTN. More than or equal to 50% of patients with Burkitt's, CTCL, Hodgkin's, Plasmablastic lymphoma, T cell lymphoma had no co-morbidities. In order to determine outcome, we took into consideration vitality status at the end of 2018. When comparing HI vs NH and adjusting for individual co-morbidities (HTN, DM, CAD, CHF, CKD) there is a trend towards a higher risk of poor outcome in NH patients when compared to HI (OR 1.17, CI 0.51-2.69, p-value= 0.7176). When we looked at patients who had both CAD and CHF and adjusted for other co-morbidities the trend remained with a higher risk for poor outcome in NH (OR 1.29, CI 0.57-2.91, p-value=0.53456). Looking at patients with a combination of CAD, CHF, CKD and DM (adjusting for other individual co-morbidities) there was also a trend towards poor outcome in NH (OR 1.26, CI 0.57-2.78, p-value= 0.569316). Overall, patients with CKD had an increased risk of poor outcome (OR 15.13, CI 1.5-153.13, p-value=0.0214) as well as patients with four co-morbidities including CAD, CHF, CKD and DM2 (OR 4.89, CI 1.68-14.23, p-value=0.003597). The absence of co-morbidities shows a trend towards a better outcome (OR 0.77, CI 0.19-3.17, p-value=0.721). CONCLUSION Within the limitations of sample size, our study demonstrates that in the prevalently Hispanic population of our institution, the presence of both CKD on its own as well as CKD with multiple co-morbidities (CKD, CAD, CHF, DM2) increases the risk of poor outcome. There is a trend towards a higher risk of poor outcome in the NH population with co-morbidities when compared to HI but further studies are needed. Disclosures No relevant conflicts of interest to declare.

A French Multicentric Prospective Cohort of 6000 Patients with Integrative Epidemiological, Clinical, Biological and Treatment Data to Improve Knowledge on Outcome of Lymphoma Patients: Pilot Phase Results of the Real World Data in Lymphoma and Survival in Adults (REALYSA) Study

Introduction: Lymphoma incidence continues to rise in France since early 80', although differently among subtypes. Recent improvements in patient survival in major lymphoma subtypes at populational level raise new questions about patient outcome (in specific subgroups) and survivorship (i.e. quality of life, long term sequelae). Numerous epidemiological studies have investigated factors related to lymphoma risk, but far fewer have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour achieved from clinical trials data is partly biased because of patient selection. Study Design and Methods: The REALYSA ("REal world dAta in LYmphoma and Survival in Adults") study is a real-life multicentric cohort set in France areas mostly covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow up. ClinicalTrials.gov identifier is NCT03869619. We aim to include 6000 patients over 4 years. Adult patients without lymphoma history and newly diagnosed of one of the following 7 lymphoma subtypes (diffuse large B cell (DLBCL), follicular (FL), marginal zone (MZL), mantle cell (MCL), Burkitt, Hodgkin (HL), T-cell (T-NHL)) are offered to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. After having given signed informed consent, participants fill in three auto-questionnaires regarding lifelong history of residences and occupations, quality of life (QoL / QLQ-C30 questionnaire) and social support (SS / SSQ6 questionnaire). Patients are then interviewed to collect their sociodemographic characteristics, medical and familial history, professional and domestic exposures to major chemicals and pesticides, lifestyle and women health. Clinical data are obtained using patients medical records, including care pathway, medical history, concomitant treatments, initial diagnosis characteristics, nodal/extra-nodal involvement, exams performed, staging, laboratory data, serologic tests, geriatric screening (G8 questionnaire), treatments received (including pre-phase, detailed treatment phases and molecules, reasons for treatment discontinuation), progressions, and treatment response evaluation. Biological samples at baseline and during treatment are collected including plasma and peripheral mononuclear cells. Additionally, a virtual tumor biobank is constituted for baseline tumor samples. The diagnosis will be ensured thanks to the review of French Lymphopath network. Follow-up, including clinical outcomes, new morbidities, lifestyle, professional situation, QoL, SS, fertility, health behavior, are collected every 6 months in the first 3 years and every year thereafter. Results: A pilot phase was implemented between November 2018 and June 2019 in 7 French hospitals/clinics. By June 30, 328 patients were recruited. Biological samples at baseline were obtained for 81% of included patients (n=265). 52% were male and 48% were female. The median age was 62 years (range: 18-95). The histological subtypes were the following (n=308 patients with complete data): 132 DLBCL (42.8%); 59 FL (19.5%); 52 HL (16.9%); 29 MCL (9.4%); 22 MZL (7.1%); 13 T-NHL (4.2%); 1 other (0.3%). We observed a good adherence to clinical research process despite the complexity of data collection. An extension phase with 10 additional centres will be launched during the last 2019 trimester. Discussion: The pilot phase of REALYSA study showed a good compliance to study guidelines and a good quality of data collected at baseline. Consequently, the study design is prospectively feasible in real-life setting. This cohort will constitute an innovative platform for clinical, biological, epidemiological and socio-economical research projects. Disclosures Oberic: Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees. Salles:Amgen: Honoraria, Other: Educational events; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; BMS: Honoraria; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Honoraria.