Effective geriatric management strategies for fatal non-Hodgkin lymphoma: Insights from a case report. / Estrategias geriátricas efectivas para el tratamiento del linfoma no Hodgkin mortal: conclusiones de un estudio de caso.

This case report delves into the intricate medical history of an 85-year-old male who experienced a myriad of health challenges throughout his years. With a medical history full of conditions, such as stroke, sinus bradycardia, chronic obstructive pulmonary disease, severe pulmonary hypertension, and chronic gastritis, the patient´s health profile is further complicated by prostatic hypertrophy, persistent dorsalgia and lumbalgia, the presence of a thyroid nodule, and a recent onset of hypothyroidism. Among the diverse medical conditions of this patient, our narrative is primarily centered on his latest diagnosis: non-Hodgkin´s lymphoma. Non-Hodgkin´s lymphoma is not just a mere addition to his already complex medical history; it is a malignant neoplasm that shapes worldwide patterns of cancer mortality. The first indicators that led to this discovery were the patient´s complaints of persistent pain in the left lateral neck region associated with dysphagia. This was not an isolated symptom; the patient also reported a month-long history of asthenia, myalgias, weakness around the pelvic girdle, fatigue, and hyporexia, depicting a concerning clinical picture. Advanced diagnostic tools, namely ultrasound and computed tomography, shed light on submaxillary and cervical adenopathies. To corroborate such findings and get a definitive diagnosis of malignancy, a fine-needle aspiration was advised. Through this case, we aim not only to describe a clinical scenario but to highlight the challenges involved in the diagnosing and treatment of non-Hodgkin ´s lymphoma, especially in elderly patients. The overlap of multiple comorbidities adds further complexity to the scene, demanding meticulous care and expertise. This report serves as an educational tool for oncology experts, as well as testimony to the complexities of patient care in the oncology diagnostic and treatment setting.

Este reporte de caso se centra en el intricado historial médico de un varon de 85 años que experimenta una miriada de problemas de salud a lo largo de sus años. Con un historial médico lleno de afecciones, como accidente cerebrovascular, bradicardia sinusal, enfermedad pulmonar obstructiva crónica, hipertensión pulmonar grave y gastritis crónica, el perfil de salud del paciente se complica aún más por la presencia de hipertrofia prostática, dorsalgia y lumbalgia persistentes, la presencia de un nódulo tiroideo y el reciente diagnóstico de hipotiroidismo. Entre las diversas afecciones de este paciente, nuestra narración se centra principalmente en su último diagnóstico: linfoma no Hodgkin. El linfoma no hodgkiniano no es un mero añadido a su ya complejo historial médico; es una neoplasia maligna que configura las tendencias de mortalidad por cáncer a nivel mundial. Los primeros indicadores que llevaron a este descubrimiento fueron las quejas del paciente por dolor persistente en la región lateral izquierda del cuello, asociado a disfagia. No se trataba de un síntoma aislado, ya que el paciente también refería desde hacía un mes astenia, mialgias, debilidad alrededor de la cintura pélvica, fatiga e hiporexia, lo que describía un cuadro clínico preocupante. Las herramientas diagnósticas avanzadas, a saber, la ecografía y la tomografía computarizada, arrojaron luz sobre las adenopatías submaxilares y cervicales. revelaron sobre las adenopatías submaxilares y cervicales.

Comparing 2-day vs 3-day flu-CY lymphodepleting regimens for CD19 CAR T-cell therapy in patients with non-hodgkin's lymphoma.

Introduction: Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency. Methods: We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity. Results: From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026). Discussion: As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.

[Research Progress of CAR-T Cell Immunotherapy in B-Cell Non-Hodgkin's Lymphoma--Review].

Chimeric antigen receptor T (CAR-T) cell therapy is a rapidly developing new immunotherapy in recent years. Compared with other therapies, CAR-T has significant advantages for high-risk and relapsed/refractory B cell non-Hodgkin's lymphoma (B-NHL) patients. Currently, a variety of anti-CD19 CAR-T cells have been approved by the FDA for the treatment of B-NHL, such as axicabtagene ciloleucel, tisagenlecucel, lisocababtagene maraleucel and brexucabtagene autoleucel. In addition, many studies are actively exploring and developing different targeted CAR-T cells, which show great potential in B-NHL. This review briefly summarized the latest research progress on the application of CAR-T in common B-NHL.

The Role of [18F]FDG PET/CT in Predicting Toxicity in Patients with NHL Treated with CAR-T: A Systematic Review.

CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin's lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([18F]FDG PET/CT) plays a critical role in tracking treatment response and evaluating the immunotherapy's overall efficacy. The aim of this study is to provide a systematic review of the literature on the studies aiming to assess and predict toxicity by means of [18F]FDG PET/CT in patients with NHL receiving CAR-T-cell therapy. PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were interrogated by two investigators to seek studies involving the use of [18F]FDG PET/CT in patients with lymphoma undergoing CAR-T-cell therapy. The comprehensive computer literature search allowed 11 studies to be included. The risk of bias for the studies included in the systematic review was scored as low by using version 2 of the "Quality Assessment of Diagnostic Accuracy Studies" tool (QUADAS-2). The current literature emphasizes the role of [18F]FDG PET/CT in assessing and predicting toxicity in patients with NHL receiving CAR-T-cell therapy, highlighting the evolving nature of research in CAR-T-cell therapy. Additional studies are warranted to increase the collected evidence in the literature.

Autologous Peripheral Blood Stem Cell Transplantation and Timing of Local Radiation Therapy in Patients With Malignant Lymphoma: Results of the Japanese Radiation Oncology Study Group Questionnaire Survey.

BACKGROUND/AIM: Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. PATIENTS AND METHODS: The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. RESULTS: The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. CONCLUSION: This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

Role of radiation in chimeric antigen receptor T-cell therapy for patients with relapsed/refractory non-Hodgkin lymphoma: Current studies and future prospects.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment approach for patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). However, the long-term prognosis has been discouraging. Moreover, the urgent resolution of two critical issues is necessary: minimize tumor burden before CAR-T infusion and control fatal toxicities post CAR-T therapy. By combining radiotherapy (RT), the safety and efficacy of CAR-T can be improved. RT can serve as bridging therapy, reducing the tumor burden before CAR-T infusion, thus enabling safe and successful CAR-T infusion, and as salvage therapy in cases of CAR-T therapy failure. This review aims to discuss the current evidence supporting the use of RT in CAR-T therapy for patients with R/R NHL. Although most studies have shown a positive role of RT in combined modality treatments for patients undergoing CAR-T therapy, the synergy gained from these remains uncertain. Furthermore, the optimal dose/fraction and radiation response require further investigation.

Safety and Toxicity Profiles of CAR T Cell Therapy in Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The application of CD19-directed chimeric antigen receptor T (CAR T) cell therapy has improved outcomes for thousands of patients with non-Hodgkin B cell lymphoma (NHL). The toxicities associated with various CAR T cell products, however, can be severe and difficult to anticipate. METHODS: In this systematic review and meta-analysis, we set out to determine whether there are measurable differences in common toxicities, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), cytopenias, and infections, between CAR T products that are commercially available for the treatment of NHL. RESULTS: After a stringent study selection process, we used a cohort of 1364 patients enrolled in 15 prospective clinical trials investigating the use of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel). We found that the rates of CRS and ICANS were significantly higher with axi-cel as compared to both liso-cel and tisa-cel. Conversely, we demonstrated that rates of all-grade and severe neutropenia were significantly greater with liso-cel. Febrile neutropenia and all-grade infection rates did not differ significantly between products though rates of severe infection were increased with axi-cel. CONCLUSIONS: Overall, this study serves as the first to delineate toxicity profiles associated with various available CAR T products. By better understanding associated toxicities, it may become possible to tailor therapies towards individual patients and anticipate the development of toxicities at earlier stages.

Impact of patient demographics and neighborhood socioeconomic variables on clinical trial participation patterns for NHL.

ABSTRACT: Prior studies have demonstrated that certain populations including older patients, racial/ethnic minority groups, and women are underrepresented in clinical trials. We performed a retrospective analysis of patients with non-Hodgkin lymphoma (NHL) seen at MD Anderson Cancer Center (MDACC) to investigate the association between trial participation, race/ethnicity, travel distance, and neighborhood socioeconomic status (nSES). Using patient addresses, we ascertained nSES variables on educational attainment, income, poverty, racial composition, and housing at the census tract (CT) level. We also performed geospatial analysis to determine the geographic distribution of clinical trial participants and distance from patient residence to MDACC. We examined 3146 consecutive adult patients with NHL seen between January 2017 and December 2020. The study cohort was predominantly male and non-Hispanic White (NHW). The most common insurance types were private insurance and Medicare; only 1.1% of patients had Medicaid. There was a high overall participation rate of 30.5%, with 20.9% enrolled in therapeutic trials. In univariate analyses, lower participation rates were associated with lower nSES including higher poverty rates and living in crowded households. Racial composition of CT was not associated with differences in trial participation. In multivariable analysis, trial participation varied significantly by histology, and participation declined nonlinearly with age in the overall, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL) models. In the DLBCL subset, Hispanic patients had lower odds of participation than White patients (odds ratio, 0.36; 95% confidence interval, 0.21-0.62; P = .001). In our large academic cohort, race, sex, insurance type, and nSES were not associated with trial participation, whereas age and diagnosis were.

Optimized BEAC conditioning regimen improves clinical outcomes of autologous hematopoietic stem cell transplantation in non-Hodgkin lymphomas.

The conditioning regimen is an important part of autologous hematopoietic stem cell transplantation (ASCT). We explored the efficacy and safety of an optimized BEAC (adjusted-dose, intermediate-dose cytarabine and reduced-dose cyclophosphamide, AD-BEAC) conditioning regimen for non-Hodgkin lymphoma (NHL). A total of 141 NHL patients received AD-BEAC or a standard-dose BEAC (SD-BEAC) conditioning regimen from January 2007 to December 2017, and 104 patients were included in the study after 1:1 propensity matching. The 5-year overall survival (OS) and progression free survival (PFS) rates were significantly higher with AD-BEAC than with SD-BEAC (82.7% vs. 67.3%, P = 0.039; 76.9% vs. 57.7%, P = 0.039). Transplant-related mortality (TRM) was 3.8% in both the AD-BEAC and SD-BEAC groups. The AD-BEAC group had lower incidence of oral ulcers and cardiotoxicity than the SD-BEAC group. An optimized BEAC conditioning regimen is an effective conditioning regimen for ASCT in NHL with acceptable toxicity, that is more effective and safer than a standard BEAC conditioning regimen.

Postinfusion PD-1+ CD8+ CAR T cells identify patients responsive to CD19 CAR T-cell therapy in non-Hodgkin lymphoma.

ABSTRACT: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Robust biomarkers and a complete understanding of CAR T-cell function in the postinfusion phase remain limited. Here, we used a 37-color spectral flow cytometry panel to perform high dimensional single-cell analysis of postinfusion samples in 26 patients treated with CD28 costimulatory domain containing commercial CAR T cells for NHL and focused on computationally gated CD8+ CAR T cells. We found that the presence of postinfusion Programmed cell death protein 1 (PD-1)+ CD8+ CAR T cells at the day 14 time point highly correlated with the ability to achieve complete response (CR) by 6 months. Further analysis identified multiple subtypes of CD8+ PD-1+ CAR T cells, including PD-1+ T cell factor 1 (TCF1)+ stem-like CAR T cells and PD-1+ T-cell immunoglobulin and mucin-domain containing-3 (TIM3)+ effector-like CAR T cells that correlated with improved clinical outcomes such as response and progression-free survival. Additionally, we identified a subset of PD-1+ CD8+ CAR+ T cells with effector-like function that was increased in patients who achieved a CR and was associated with grade 3 or higher immune effector cell-associated neurotoxicity syndrome. Here, we identified robust biomarkers of response to CD28 CAR T cells and highlight the importance of PD-1 positivity in CD8+ CAR T cells after infusion in achieving CR.

Update on FDG-PET in pediatric lymphoma.

Lymphoma represent the third most common malignant disease in childhood and adolescence. They are divided into pediatric Hodgkin lymphoma (P-HL) and pediatric non-Hodgkin lymphoma (P-NHL). In P-HL, excellent cure rates are achieved through combined modality treatment using chemotherapy and radiotherapy. For more than 20 years, FDG-PET has been an integral part of the treatment and guides its intensity through improved staging and precise assessment of chemotherapy response. In P-NHL, good cure rates are achieved with chemotherapy alone. At present FDG-PET plays only a subordinate role in the treatment setting. Its potential to contribute to treatment management is far from being fully utilised. In this article, the current status of FDG-PET in pediatric lymphoma is presented in detail. The core elements are the sections on staging and response assessment. In addition, challenges and pitfalls are discussed and future developments are outlined.

Allogeneic stem cell transplantation and CAR-T in B-cell Non-Hodgkin Lymphoma: a two-center experience and review of the literature.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still a potentially curative option for B-cell Non-Hodgkin Lymphoma (B-NHL) in the modern immunotherapy era. The objective of this study was to analyze long-term outcomes of patients with B-NHL who received allo-HSCT. We analyzed overall survival (OS), progression-free survival (PFS) and graft versus host disease (GVHD) relapse-free survival (GRFS) in 53 patients undergoing allo-HSCT from two institutions. The median follow-up of the study was 72 months (range 29-115 months). The median number of lines of therapy before allo-HSCT was 3 (range 1-6) and twenty-eight patients (53%) had received a previous autologous transplant. The 3-year PFS, OS and GRFS were 55%, 63%, and 55%, respectively. One-year non-relapse mortality was 26%. Karnofsky Performance Scale < 90 was associated with worse OS in multivariable analysis. A non-comparative analysis of a cohort of 44 patients with similar characteristics who received chimeric antigen receptor T-cell therapy was done, showing a 1-year PFS and OS were 60% and 66%, respectively. Our data shows that allo-HSCT is still a useful option for treating selected patients with R/R B-NHL. Our retrospective analysis and review of the literature demonstrate that allo-HSCT can provide durable remissions in a subset of patients with R/R B-NHL.

Anti-CD30 CAR T cells as consolidation after autologous haematopoietic stem-cell transplantation in patients with high-risk CD30+ lymphoma: a phase 1 study.

BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting CD30 are safe and have promising activity when preceded by lymphodepleting chemotherapy. We aimed to determine the safety of anti-CD30 CAR T cells as consolidation after autologous haematopoietic stem-cell transplantation (HSCT) in patients with CD30+ lymphoma at high risk of relapse. METHODS: This phase 1 dose-escalation study was performed at two sites in the USA. Patients aged 3 years and older, with classical Hodgkin lymphoma or non-Hodgkin lymphoma with CD30+ disease documented by immunohistochemistry, and a Karnofsky performance score of more than 60% planned for autologous HSCT were eligible if they were considered high risk for relapse as defined by primary refractory disease or relapse within 12 months of initial therapy or extranodal involvement at the start of pre-transplantation salvage therapy. Patients received a single infusion of CAR T cells (2 × 107 CAR T cells per m2, 1 × 108 CAR T cells per m2, or 2 × 108 CAR T cells per m2) as consolidation after trilineage haematopoietic engraftment (defined as absolute neutrophil count ≥500 cells per µL for 3 days, platelet count ≥25 × 109 platelets per L without transfusion for 5 days, and haemoglobin ≥8 g/dL without transfusion for 5 days) following carmustine, etoposide, cytarabine, and melphalan (BEAM) and HSCT. The primary endpoint was the determination of the maximum tolerated dose, which was based on the rate of dose-limiting toxicity in patients who received CAR T-cell infusion. This study is registered with ClinicalTrials.gov (NCT02663297) and enrolment is complete. FINDINGS: Between June 7, 2016, and Nov 30, 2020, 21 patients were enrolled and 18 patients (11 with Hodgkin lymphoma, six with T-cell lymphoma, one with grey zone lymphoma) were infused with anti-CD30 CAR T cells at a median of 22 days (range 16-44) after autologous HSCT. There were no dose-limiting toxicities observed, so the highest dose tested, 2 × 108 CAR T cells per m2, was determined to be the maximum tolerated dose. One patient had grade 1 cytokine release syndrome. The most common grade 3-4 adverse events were lymphopenia (two [11%] of 18) and leukopenia (two [11%] of 18). There were no treatment-related deaths. Two patients developed secondary malignancies approximately 2 years and 2·5 years following treatment (one stage 4 non-small cell lung cancer and one testicular cancer), but these were judged unrelated to treatment. At a median follow-up of 48·2 months (IQR 27·5-60·7) post-infusion, the median progression-free survival for all treated patients (n=18) was 32·3 months (95% CI 4·6 months to not estimable) and the median progression-free survival for treated patients with Hodgkin lymphoma (n=11) has not been reached. The median overall survival for all treated patients has not been reached. INTERPRETATION: Anti-CD30 CAR T-cell infusion as consolidation after BEAM and autologous HSCT is safe, with low rates of toxicity and encouraging preliminary activity in patients with Hodgkin lymphoma at high risk of relapse, highlighting the need for larger studies to confirm these findings. FUNDING: National Heart Lung and Blood Institute, University Cancer Research Fund at the Lineberger Comprehensive Cancer Center.

Primary vs. pre-emptive anti-seizure medication prophylaxis in anti-CD19 CAR T-cell therapy.

INTRODUCTION: Seizures may occur in up to 30% of non-Hodgkin lymphoma patients who received anti-CD19 CAR T-cell therapy, yet the optimal anti-seizure medication (ASM) prevention strategy has not been thoroughly investigated. METHODS: Consecutive patients affected by refractory non-Hodgkin lymphoma who received anti-CD19 CAR T-cells were included. Patients were selected and assessed using similar internal protocols. ASM was started either as a primary prophylaxis (PP-group) before CAR T-cells infusion or as a pre-emptive therapy (PET-group) only upon the onset of neurotoxicity development. RESULTS: One hundred fifty-six patients were included (PP-group = 88, PET-group = 66). Overall, neurotoxicity and severe neurotoxicity occurred in 45 (29%) and 20 (13%) patients, respectively, equally distributed between the two groups. Five patients experienced epileptic events (PET-group = 3 [4%]; PP-group = 2 [2%]). For all the PET-group patients, seizure/status epilepticus occurred in the absence of overt CAR-T-related neurotoxicity, whereas patients in the PP-group experienced brief seizures only in the context of critical neurotoxicity with progressive severe encephalopathy. ASMs were well-tolerated by all patients, even without titration. No patients developed epilepsy or required long-term ASMs. CONCLUSION: Our data suggest that both primary and pre-emptive anti-seizure prophylaxis are safe and effective in anti-CD19 CAR T-cell recipients. Clinical rationale suggests a possible more favourable profile of primary prophylaxis, yet no definitive conclusion of superiority between the two ASM strategies can be drawn from our study.

Incidence and survival of second primary non-Hodgkin lymphoma: A Surveillance, Epidemiology, and End Results-based cohort study.

BACKGROUND: The aim of this study was to investigate patient survival and factors associated with survival in second primary non-Hodgkin lymphoma (NHL) compared with the first primary NHL. METHODS: The retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Demographic characteristics, histological types, Ann Arbor stage, and treatment information were collected. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with overall survival (OS) and cancer-specific survival (CSS) in the first and second primary NHLs. RESULTS: Of 318,168 cases followed for 5 years, 299,248 patients developed the first primary NHL and 18,920 patients developed the second primary NHL. This study identified a rising incidence of first and second primary NHL from 2000 to 2014. For the second primary NHL, the OS risk was higher when compared to the first primary NHL (HR: 1.13, 95% CI: 1.11 to 1.15, P <0.001). Risk factors that negatively affected OS in the first primary NHL included being male, over 40 years of age, certain marital statuses, specific histological types, and advanced disease stages. In contrast, being of White race and having histological types such as Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and mantle B-cell NHL were associated with better OS outcomes. Treatments like surgery, radiation therapy, and chemotherapy were associated with a lower risk of OS and CSS in the first primary NHL. For the second primary NHL, the detrimental risk factors were similar but also included being over the age of 60. Certain histological types showed a lower OS risk relative to diffuse Large B-cell Lymphoma (DLBCL). While surgery and chemotherapy were beneficial for OS, radiation therapy did not improve survival in second primary NHL cases. Notably, undergoing chemotherapy for the first primary cancer increased the OS risk in the second primary NHL, whereas surgery and radiation seemed to offer a protective effect against OS risk in the second primary NHL (all P <0.05). CONCLUSION: Our findings emphasize the need for tailored strategies in managing the second primary NHL, given the distinct survival patterns and risk factor profiles compared to the first primary NHL. Future research should aim to further elucidate these differences to improve prognosis and treatment approaches for second primary NHL patients.

Management of vaccinations in patients with non-Hodgkin lymphoma.

Vaccinations are fundamental tools in preventing infectious diseases, especially in immunocompromised patients like those affected by non-Hodgkin lymphomas (NHLs). The COVID-19 pandemic made clinicians increasingly aware of the importance of vaccinations in preventing potential life-threatening SARS-CoV-2-related complications in NHL patients. However, several studies have confirmed a significant reduction in vaccine-induced immune responses after anti-CD20 monoclonal antibody treatment, thus underscoring the need for refined immunization strategies in NHL patients. In this review, we summarize the existing data about COVID-19 and other vaccine's efficacy in patients with NHL and propose multidisciplinary team-based recommendations for the management of vaccines in this specific group of patients.

G-CSF + plerixafor versus G-CSF alone mobilized hematopoietic stem cells in patients with multiple myeloma and lymphoma: a systematic review and meta-analysis.

AIM: The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. METHODS: We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). RESULTS: Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80). CONCLUSIONS: This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.

The asymptomatic follicular lymphoma (AFL) trial: single-agent rituximab immunotherapy versus 90Y-ibritumomab tiuxetan radioimmunotherapy (RIT) for patients with new, untreated follicular lymphoma.

Patients with asymptomatic follicular lymphoma (AFL) are candidates for observation or immunotherapy. Given the effectiveness of radiation therapy in FL, another option is 90Yttrium-ibritumomab tiuxetan radioimmunotherapy (RIT). We conducted a trial where untreated AFL patients were randomized to rituximab 375 mg/m2 weekly × 4 or rituximab 250 mg/m2 days 1, 8, and 0.4 mCi/kg (maximum 32 mCi) of RIT day 8. Twenty patients were enrolled before the study was halted due to unavailability of RIT. The ORR for rituximab and RIT were 90% and 80%, respectively; the CR rate at 6 months was 30% and 60%, respectively. After a median follow-up of 67 months, eight patients have progressed-three in the rituximab arm and five in the RIT arm and five have required systemic therapy. All patients remain alive. Both agents are highly active for AFL. The 1-week treatment with RIT and sparing of T-cells make combination therapy with newer agents attractive.