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.

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.

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.

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.

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.

Ofatumumab as part of reduced intensity conditioning in high risk B-cell lymphoma patients: final long-term analysis from a prospective multicenter Phase-II Trial.

Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.

The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma.

Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty-five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3-year duration of response was 56%. The 3-year progression-free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression-free survival. The 3-year incidence of B-cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var-cel was manageable, while B-cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583.

Comparison of diffusion-weighted MRI and [18F]FDG PET/MRI for treatment monitoring in pediatric Hodgkin and non-Hodgkin lymphoma.

OBJECTIVE: To compare tumor therapy response assessments with whole-body diffusion-weighted imaging (WB-DWI) and 18F-fluorodeoxyglucose ([18F]FDG) PET/MRI in pediatric patients with Hodgkin lymphoma and non-Hodgkin lymphoma. MATERIALS AND METHODS: In a retrospective, non-randomized single-center study, we reviewed serial simultaneous WB-DWI and [18F]FDG PET/MRI scans of 45 children and young adults (27 males; mean age, 13 years ± 5 [standard deviation]; age range, 1-21 years) with Hodgkin lymphoma (n = 20) and non-Hodgkin lymphoma (n = 25) between February 2018 and October 2022. We measured minimum tumor apparent diffusion coefficient (ADCmin) and maximum standardized uptake value (SUVmax) of up to six target lesions and assessed therapy response according to Lugano criteria and modified criteria for WB-DWI. We evaluated the agreement between WB-DWI- and [18F]FDG PET/MRI-based response classifications with Gwet's agreement coefficient (AC). RESULTS: After induction chemotherapy, 95% (19 of 20) of patients with Hodgkin lymphoma and 72% (18 of 25) of patients with non-Hodgkin lymphoma showed concordant response in tumor metabolism and proton diffusion. We found a high agreement between treatment response assessments on WB-DWI and [18F]FDG PET/MRI (Gwet's AC = 0.94; 95% confidence interval [CI]: 0.82, 1.00) in patients with Hodgkin lymphoma, and a lower agreement for patients with non-Hodgkin lymphoma (Gwet's AC = 0.66; 95% CI: 0.43, 0.90). After completion of therapy, there was an excellent agreement between WB-DWI and [18F]FDG PET/MRI response assessments (Gwet's AC = 0.97; 95% CI: 0.91, 1). CONCLUSION: Therapy response of Hodgkin lymphoma can be evaluated with either [18F]FDG PET or WB-DWI, whereas patients with non-Hodgkin lymphoma may benefit from a combined approach. CLINICAL RELEVANCE STATEMENT: Hodgkin lymphoma and non-Hodgkin lymphoma exhibit different patterns of tumor response to induction chemotherapy on diffusion-weighted MRI and PET/MRI. KEY POINTS: • Diffusion-weighted imaging has been proposed as an alternative imaging to assess tumor response without ionizing radiation. • After induction therapy, whole-body diffusion-weighted imaging and PET/MRI revealed a higher agreement in patients with Hodgkin lymphoma than in those with non-Hodgkin lymphoma. • At the end of therapy, whole-body diffusion-weighted imaging and PET/MRI revealed an excellent agreement for overall tumor therapy responses for all lymphoma types.

Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study.

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.

Survival of patients living with HIV and cancer in Cali, Colombia.

Background: People living with HIV have an increased risk of cancer compared to the general population. However, with the increase in life expectancy and advances in antiretroviral therapy, the survival of patients with cancer and HIV has changed. Objective: To determine the survival of patients living with HIV and cancer in Cali, Colombia. Methods: A retrospective cohort study was conducted at the Fundación Valle del Lili, Cali, Colombia. Data from the HIV database was crossed with data from the hospital and population-based cancer registries between 2011-2019. Patients <18 years, limited available clinical information on the diagnosis and treatment of HIV and cancer, and non-oncological tumor diagnosis were excluded. Results: A total of 173 patients were included. The frequencies of AIDS-defining neoplasms were: Non-Hodgkin lymphoma (42.8%), Kaposi sarcoma (27.8%), and cervical cancer (4.6%). Overall survival was 76.4% (95% CI 68.9-82.3) at five years. Poorer survival was found in patients with AIDS-defining infections (56.9% vs. 77.8%, p=0.027) and non-AIDS-defining infections (57.8% vs. 84.2%, p=0.013), while there was better survival in patients who received antiretroviral therapy (65.9% vs. 17.9%, p=0.021) and oncological treatment (66.7% vs. 35.4%, p<0.001). The presence of non-AIDS-defining infections increases the risk of dying (HR = 2.39, 95% CI 1.05-5.46, p=0.038), while oncological treatment decreases it (HR = 0.33, 95% CI 0.14-0.80, p=0.014). Conclusions: In people living with HIV, Non-Hodgkin lymphoma and Kaposi sarcoma are the most common neoplasms. Factors such as AIDS-associated and non-AIDS-associated infections have been identified as determinants of survival. Cancer treatment seems to improve survival.

Antecedentes: Las personas que viven con VIH tienen un riesgo mayor de cáncer en comparación con la población general. Sin embargo, con el aumento de la esperanza de vida y los avances en la terapia antirretroviral, la supervivencia de los pacientes con cáncer y VIH ha cambiado. Objetivo: Determinar la supervivencia de los pacientes que viven con VIH y cáncer en Cali, Colombia. Métodos: Se realizó un estudio de cohorte retrospectivo en la Fundación Valle del Lili, Cali, Colombia. Los datos de la base de datos de VIH se cruzaron con los datos de los registros de cáncer de base hospitalaria y poblacional entre 2011-2019. Se excluyeron los pacientes <18 años, con información clínica limitada disponible sobre el diagnóstico y tratamiento del VIH y el cáncer y los casos con diagnóstico de tumor no oncológico. Resultados: Se incluyeron un total de 173 pacientes. Las frecuencias de neoplasias definitorias de SIDA fueron: linfoma no Hodgkin (42.8%), sarcoma de Kaposi (27.8%) y cáncer cervical (4.6%). La supervivencia global fue del 76.4% (IC 95% 68.9-82.3) a los cinco años. Se encontró una peor supervivencia en pacientes con infecciones definitorias de SIDA (56.9% vs. 77.8%, p=0.027) e infecciones no definitorias de SIDA (57.8% vs. 84.2%, p=0.013), mientras que hubo una mejor supervivencia en pacientes que recibieron terapia antirretroviral (65.9% vs. 17.9%, p=0.021) y tratamiento oncológico (66.7% vs. 35.4%, p<0.001). La presencia de infecciones no definitorias de SIDA aumentó el riesgo de morir (HR = 2.39, IC 95% 1.05-5.46, p=0.038), mientras que el tratamiento oncológico lo disminuyó (HR = 0.33, IC 95% 0.14-0.80, p=0.014). Conclusiones: En las personas que viven con VIH, el linfoma no Hodgkin y el sarcoma de Kaposi son las neoplasias más comunes. Se han identificado factores como las infecciones asociadas al SIDA y las infecciones no asociadas al SIDA como determinantes de la supervivencia. El tratamiento del cáncer parece mejorar la supervivencia.

Autologous Stem Cell Transplant in Hodgkin's and Non-Hodgkin's Lymphoma, Multiple Myeloma, and AL Amyloidosis.

Human body cells are stem cell (SC) derivatives originating from bone marrow. Their special characteristics include their capacity to support the formation and self-repair of the cells. Cancer cells multiply uncontrollably and invade healthy tissues, making stem cell transplants a viable option for cancer patients undergoing high-dose chemotherapy (HDC). When chemotherapy is used at very high doses to eradicate all cancer cells from aggressive tumors, blood-forming cells and leukocytes are either completely or partially destroyed. Autologous stem cell transplantation (ASCT) is necessary for patients in those circumstances. The patients who undergo autologous transplants receive their own stem cells (SCs). The transplanted stem cells first come into contact with the bone marrow and then undergo engraftment, before differentiating into blood cells. ASCT is one of the most significant and innovative strategies for treating diseases. Here we focus on the treatment of Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, and AL amyloidosis, using ASCT. This review provides a comprehensive picture of the effectiveness and the safety of ASCT as a therapeutic approach for these diseases, based on the currently available evidence.

Characteristics and outcomes of children, adolescents and young adults with relapsed/refractory non-hodgkin lymphoma undergoing autologous stem cell transplant.

BACKGROUND: There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). METHODS: Patients aged 0-39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed. RESULTS: Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6-39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03). Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0-196.6) months after ASCT, and SPM was the cause of death in five (50%) of them. CONCLUSIONS: CAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS.

Clinical characteristics and prognostic factors for primary pediatric and adolescent Non-Hodgkin Lymphomas of the gastrointestinal tract: a population-based study.

PURPOSE: To investigate the clinical features and survival outcomes of primary gastrointestinal non-Hodgkin lymphomas (PGINHL) in pediatric and adolescent population, we conducted a population-based cohort study. METHODS: All pediatric and adolescent patients with PGINHL diagnosed between 2000 and 2019 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplane-Meier estimations were used to generate survival curves based on various criteria. To compare survival curves, the log-rank test was applied. A multivariate Cox proportional hazards model was developed to investigate the effect of each component on overall survival. RESULTS: A total of 334 pediatric and adolescent with PGINHL patients were identified. The median age at diagnosis was 12 years (range 1.0-19 years). Tumors were most commonly found in the small bowel (47.3%), followed by the large bowel (42.8%) and the stomach (9.9%). Overall, the most common histological subtype was Burkitt lymphoma (56.9%), followed by diffuse large B-cell lymphoma (DLBCL) (27.8%). Overall survival rates for all patients were 92.2% at 5- year and 91.6% at 10- year, respectively. The Cox proportional hazard regression revealed that only chemotherapy was an important independent predictor in this model. Patients with chemotherapy have a higher survival rate than those without. CONCLUSIONS: Our study revealed that only chemotherapy was found to be the most important predictor of the OS in pediatric and adolescent PGINHL, providing critical information for therapeutic care.

Impact of Sarcopenia on Outcome of Exercise Therapy in Older Non-Hodgkin Lymphoma Patients.

PURPOSE: The aim of this study was to investigate the effects of exercise therapy on physical function and quality of life (QOL) in older patients with non-Hodgkin lymphoma undergoing inpatient chemotherapy, including differences between patients with and without sarcopenia. METHODS: Thirty-one inpatients aged 70 years or older participated in this study. Grip and knee extensor strength, 6-minute walking test, body composition, nutritional status, fatigue and health-related QOL at admission and discharge were compared. In addition, the patients were classified into sarcopenic and non-sarcopenic groups, and a comparison between admission and discharge and 2-way ANOVA were performed. RESULTS: Overall, grip strength and skeletal muscle mass were significantly lower at discharge than at admission (P < .05); however, QOL significantly improved (P < .05). In the non-sarcopenia group, grip strength, right knee extension muscle strength, and skeletal muscle mass were all significantly lower at discharge than at admission (P < .05); however, this was not the case in the sarcopenia group. In terms of QOL, improvements were observed in different items in the non-sarcopenia and sarcopenia groups. There was a significant interaction between admission to discharge time period and sarcopenia regarding left grip strength, right knee extensor strength, and QOL. CONCLUSION: Exercise therapy is effective in improving QOL in older non-Hodgkin lymphoma patients undergoing inpatient chemotherapy. However, the effect of exercise therapy and optimal exercise load may differ between non-sarcopenia and sarcopenia patients. Therefore, it is necessary to consider exercise therapy in the future, taking into account the presence or absence of sarcopenia.

Central Nervous System Lymphoma.

Central nervous system lymphoma (CNSL) is a rare and aggressive malignancy that primarily affects the brain, spinal cord, and meninges. This article provides a comprehensive overview of the current understanding of CNSL encompassing its epidemiology, pathophysiology, clinical presentation, diagnosis, treatment modalities, and prognosis. Although the main focus is on primary CNS lymphoma (PCNSL), ocular lymphoma, primary leptomeningeal lymphoma, and secondary CNS lymphoma are also discussed. The pathobiology of CNSL involves the infiltration of malignant lymphocytes within the CNS parenchyma or leptomeninges. Various risk factors and immunological mechanisms contribute to its development, including immunodeficiency states, chronic inflammation, and genomic alterations. Accurate diagnosis is crucial for appropriate management, given the heterogeneous clinical presentation. The neuroimaging, systemic imaging, and other modalities for diagnosis and evaluation for extent of disease involvement will be discussed. Additionally, the importance of histopathological examination, cerebrospinal fluid (CSF) analysis, and molecular testing in confirming the diagnosis and guiding treatment decisions are highlighted. The treatment landscape for CNSL has evolved significantly. Therapeutic approaches encompass a multimodal strategy combining high-dose methotrexate-based chemotherapy, consolidation with whole-brain radiation therapy, and high-dose chemotherapy with stem cell rescue. Recent advancements in targeted therapies and immunomodulatory agents offer promising avenues for future treatment options. We review the clinical outcomes and prognostic factors influencing the survival of CNSL patients, including age, performance status, disease stage, and genetic abnormalities.

Clinical Characteristics And Treatment Outcome Of Paediatric Non-Hodgkin's Lymphoma At A Tertiary Care Hospital In Pakistan.

Objectives: To highlight the clinical characteristics of paediatric patients presenting with non-Hodgkin's lymphoma, treatment toxicities, and outcome. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of all paediatric patients aged 0-18 years diagnosed with non-Hodgkin's lymphoma from 2010 to 2020. Demographic characteristics, presentation, treatment provided, complications, if any, and treatment outcome were recorded. Data was analysed using SPSS 21. RESULTS: Of the 92 patients, 69(75.0%) were males. The overall mean age was 14.35±5.80 years. The most common presenting complaint was pyrexia 42(45.7%), the most common diagnosis was Burkitt lymphoma 40(43.5%), the most common complication related to gastrointestinal issues 8(15.7%), and most toxicities were reported with the use of FAB-LMB96 (French American-British Mature B-Cell Lymphoma 96) for B-cell non-Hodgkin's lymphoma 23 (45.1%). Mortality was the outcome in 17(18.5%) cases, while 19(20.7%) patients were lost to follow-up. PFS and OS was 60.4%, and OS 81.3% respectively at 10 years follow-up, median PFS was 17.5 months ([IQR]: 4.5-43.5 months) (p=0.011) and median OS was 33.5 months (IQR: 19.5-84 months) (p=0.007). CONCLUSIONS: Early recognition of symptoms, specialist care, and proper planning can decrease treatment-related complications that result in abandonment.

Cytogenetics in the management of mature B-cell non-Hodgkin lymphomas: Guidelines from the Groupe Francophone de Cytogénétique Hematologique (GFCH).

Non-Hodgkin lymphomas (NHL) consist of a wide range of clinically, phenotypically and genetically distinct neoplasms. The accurate diagnosis of mature B-cell non-Hodgkin lymphoma relies on a multidisciplinary approach that integrates morphological, phenotypical and genetic characteristics together with clinical features. Cytogenetic analyses remain an essential part of the diagnostic workup for mature B-cell lymphomas. Karyotyping is particularly useful to identify hallmark translocations, typical cytogenetic signatures as well as complex karyotypes, all bringing valuable diagnostic and/or prognostic information. Besides the well-known recurrent chromosomal abnormalities such as, for example, t(14;18)(q32;q21)/IGH::BCL2 in follicular lymphoma, recent evidences support a prognostic significance of complex karyotype in mantle cell lymphoma and Waldenström macroglobulinemia. Fluorescence In Situ Hybridization is also a key analysis playing a central role in disease identification, especially in genetically-defined entities, but also in predicting transformation risk or prognostication. This can be exemplified by the pivotal role of MYC, BCL2 and/or BCL6 rearrangements in the diagnostic of aggressive or large B-cell lymphomas. This work relies on the World Health Organization and the International Consensus Classification of hematolymphoid tumors together with the recent cytogenetic advances. Here, we review the various chromosomal abnormalities that delineate well-established mature B-cell non-Hodgkin lymphoma entities as well as newly recognized genetic subtypes and provide cytogenetic guidelines for the diagnostic management of mature B-cell lymphomas.

The salvage role of allogeneic hematopoietic stem-cell transplantation in relapsed/refractory diffuse large B cell lymphoma.

To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.

Recent advances in CAR T-cell therapy for lymphoma in China

Lymphoma is a hematologic malignancy which mainly consists of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Although systemic chemotherapy, radiotherapy, and other advanced therapeutics, including rituximab or immune checkpoint inhibitors, have improved the prognosis in recent decades, there are still a number of patients with relapsed or refractory (R/R) lymphoma with a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy has provided a curative option for patients with relapsed or refractory lymphoma. Numerous clinical trials have been conducted worldwide and presented inspiring results that give insight into this breakthrough therapy. The development of cancer cell therapy in China has been rapid in the past years and dominates the field with the USA. This review aims to summarize the published results of CAR T-cell therapy alone or in combination with other therapies in mainland China, both in R/R NHL and R/R HL (AU)