Adult Lymphoma Research Articles

P134 A RARE CASE OF CARDIAC DIFFUSE LARGE CELL B LYMPHOMA: ECHOCARDIOGRAPHIC RESPONSE TO CHEMOTHERAPY

Abstract Introduction Diffuse large B–cell lymphoma (DLBCL) is the most common subtype of non–Hodgkin‘s lymphoma in adults. Rituximab and Anthracycline–based chemotherapy are the standard treatment, complete remission (CR) is achived in approximately 67% of patients. About one third of patients have refractory disease or relapse after standard therapy, mostly within 5 years of achieving CR. Clinical Case A 62–year–old patient, current smoker, without previous cardiovascular diseases presented to our ER for dyspnea and asthenia. Medical history showed GBC–DLBCL at third stage that achieved CR with R–CHOP therapy and intrathecal prophylaxis. The ECG documented sinus tachycardia with normal ventricular repolarization. Arterial blood gas analysis showed a condition of respiratory distress (pO2 71 mmHg, pCO2 27 mmHg). For suspicion of pulmonary embolism, chest CT with contrast was done showing a bulky mass extending from the right atrium to the right ventricle, also involving the pericardial sac (image 1). Transthoracic echocardiography showed a bulky mass (area 31 cm2) occupying almost the entire right atrium (5.9 x 4.4 cm) and extended, through the tricuspid valve, into the right ventricle, displacing the interventricular septum (image 2). Endomyocardial biopsy confirmed the diagnosis of GBC–DLBCL cardiac recurrence. Assumed the good systolic function of the left ventricle and the age of the patient, chemotherapy debulking was performed with Gemcitabine, followed by R–CHOP and MTX. One month after therapy post–treatment Total Body CT shows a good response with no evidence on echocardiogram of pathological tissue in the right ventricle (image 3). Conclusions Cardiac DLBCL is a rare tumor with few cases reported in the literature. There is currently no standard therapy, particularly for those who are unsuitable for high–dose chemotherapy a/o autologous stem cell transplantation. The multidisciplinary cardiological and hematological approach has proved to be fundamental these patient‘s therapeutic management.

Identification of molecular subtypes and a novel prognostic model of diffuse large B-cell lymphoma based on a metabolism-associated gene signature

BackgroundDiffuse large B cell lymphoma (DLBCL) is the most common lymphoma in adults. Metabolic reprogramming in tumors is closely related to the immune microenvironment. This study aimed to explore the interactions between metabolism-associated genes (MAGs) and DLBCL prognosis and their potential associations with the immune microenvironment.MethodsGene expression and clinical data on DLBCL patients were obtained from the GEO database. Metabolism-associated molecular subtypes were identified by consensus clustering. A prognostic risk model containing 14 MAGs was established using Lasso-Cox regression in the GEO training cohort. It was then validated in the GEO internal testing cohort and TCGA external validation cohort. GO, KEGG and GSVA were used to explore the differences in enriched pathways between high- and low-risk groups. ESTIMATE, CIBERSORT, and ssGSEA analyses were used to assess the immune microenvironment. Finally, WGCNA analysis was used to identify two hub genes among the 14 model MAGs, and they were preliminarily verified in our tissue microarray (TMA) using multiple fluorescence immunohistochemistry (mIHC).ResultsConsensus clustering divided DLBCL patients into two metabolic subtypes with significant differences in prognosis and the immune microenvironment. Poor prognosis was associated with an immunosuppressive microenvironment. A prognostic risk model was constructed based on 14 MAGs and it was used to classify the patients into two risk groups; the high-risk group had poorer prognosis and an immunosuppressive microenvironment characterized by low immune score, low immune status, high abundance of immunosuppressive cells, and high expression of immune checkpoints. Cox regression, ROC curve analysis, and a nomogram indicated that the risk model was an independent prognostic factor and had a better prognostic value than the International Prognostic Index (IPI) score. The risk model underwent multiple validations and the verification of the two hub genes in TMA indicated consistent results with the bioinformatics analyses.ConclusionsThe molecular subtypes and a risk model based on MAGs proposed in our study are both promising prognostic classifications in DLBCL, which may provide novel insights for developing accurate targeted cancer therapies.

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting

IntroductionChimeric antigen receptor T-cell therapy (CAR T) is a revolutionary adoptive immunotherapy approach in lymphoma; however, substantial resources are necessary for administration and care of these patients. Our institution has administered tisagenlecleucel primarily in an outpatient setting, and here we report our clinical outcomes. Patients and MethodsWe conducted a single institution, retrospective study investigating outcomes of adult lymphoma patients treated with commercial tisagenlecleucel between 10/2017 and 12/2020. We analyzed patient characteristics and outcomes of efficacy and safety including overall response rate, progression-free survival, overall survival and cytokine-release syndrome, neurotoxicity, and hospitalizations. ResultsSeventy-two patients with relapsed or refractory non-Hodgkin lymphoma (NHL) who received commercial tisagenlecleucel were identified; 68 (94.4%) patients received outpatient tisagenlecleucel. The overall response rate was 43% with a complete response observed in 25 patients (34.7%). At a median follow-up of 9.1 months, the median progression-free survival was 3.3 months. Grade 3-4 cytokine release syndrome was not observed in the study group and two patients had grade 3-4 neurotoxicity. Twenty-six patients (36.1%) were admitted within 30 days after infusion with a median length of stay of 5 days. Fourteen patients (19.4%) were admitted within 72 hours of infusion. No patient died of CAR T cell-related toxicity. ConclusionOur experience affirms treatment with tisagenlecleucel in the outpatient setting is safe and feasible with close supervision and adequate institutional experience. After infusion, adverse events were manageable and the majority of patients did not require hospitalization.

Cost-effectiveness analysis of axicabtagene ciloleucel vs. salvage chemotherapy for relapsed or refractory adult diffuse large B-cell lymphoma in China.

Axicabtagene ciloleucel (Axi-Cel, 2 × 106 CAR-T cells/kg, single intravenous injection) is a chimeric antigen receptor cell immunotherapy that exhibits favorable clinical efficacy and safety in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). However, this treatment is expensive in China. This study aimed to evaluate the cost-effectiveness of Axi-Cel versus salvage chemotherapy for the treatment of R/R DLBCL from the perspective of the Chinese healthcare system. A decision analysis model containing a short-term decision tree and long-term semi-Markov partitioned survival model was developed. The time horizon was 40years and the period from 10 to 40years was included in sensitivity analysis. The model was developed based on data from the ZUMA-1 and SCHOLAR-1 trials. Life years, quality-adjusted life years (QALYs), overall costs, and the incremental cost-effectiveness ratio (ICER) were estimated at a willingness to pay (WTP) threshold of US $31,320 per QALY, which is three times the gross domestic product per capita. The base case analysis revealed that treatment with Axi-Cel is associated with an increased overall cost of US $175,380 and improved effectiveness of 3.43 LYs and 2.61 QALYs compared to salvage chemotherapy, leading to an ICER of US $51,190 per LY and US $67,250 per QALY. The developed model is sensitive to the discount rate, utility of progression-free survival (PFS), and cost of Axi-Cel. The ICER of Axi-Cel was greater than the WTP threshold in the sensitivity and scenario analyses. To achieve cost-effectiveness, the price of Axi-Cel must be reduced by 59.19% to US $71,000. At its current price, Axi-Cel is not likely to be a cost-effective option compared to salvage chemotherapy for adult patients with R/R DLBCL.

A case of B Cell Lymphoma, NOS – A Manifestation in the Labial Mucosa

<h3>Introduction</h3> Non-Hodgkin's lymphoma of B cell lineage is the third most common malignancy of the maxillofacial region. DLBCL, NOS constitutes 25% - 35% of the adult non-Hodgkin's lymphomas and is more common in elderly individuals, as well as more prevalent in males than in females. The etiology of DLBCL, NOS remains unknown. Underlying immunodeficiency is a significant risk factor. <h3>Materials and Methods</h3> We report a case of a 78-year old female patient who presented with a lump in the upper labial mucosa since two weeks, there were no symptoms prior to the stated time duration. The soft tissue mass was located approximately 4mm from the vermillion border, adjacent to the incisal edges of teeth #10 and 11 (left maxillary lateral incisor and canine), measured around 1cm in diameter and was firm on palpation. The clinical differential included benign salivary gland neoplasms, lipoma and a mucocele. The patient had a past medical history of diffuse large B cell lymphoma three years ago. <h3>Results</h3> Microscopic examination showed an atypical lymphoid proliferation involving the soft tissue with infiltration into the adjacent skeletal muscles. A few residual ductular/glandular elements were also noted. The biopsy was composed of a monotonous infiltrate of medium sized cells with round to irregular nuclei, one or more prominent nucleoli and scant cytoplasm. A polymorphous inflammatory background was not observed, and the cells diffusely infiltrated in to the soft tissue. Immunohistochemistry revealed that the atypical cells were positive for CD20 and BCL2 while negative for CD10, BCL6 and c-Myc. Ki-67 proliferation index was moderate to high. <h3>Conclusions</h3> In summary, the overall features were consistent with a B-cell lymphoma that was difficult to further classify due to limited sampling. Based on the relatively high proliferative rate, the lesion was likely consistent with recurrence of the previously diagnosed diffuse large B-cell lymphoma.

Monocyte-to-Lymphocyte Ratio in the Diagnosis of Lymphoma in Adult Patients.

BackgroundLymphomas, including Hodgkin lymphoma and non-Hodgkin lymphoma, are one of the differentials for peripheral lymphadenopathy and are difficult to diagnose clinically. Biopsy is essential for diagnosing lymphoma, although it is invasive. Non-invasive methods are required to identify patients with suspected lymphoma who should undergo a biopsy. The relevance of the monocyte-to-lymphocyte ratio has recently been reported to be a useful diagnostic marker in children with lymphoma and a prognostic marker of various other diseases. This study aimed to determine the relevance of the monocyte-to-lymphocyte ratio in the diagnosis of lymphoma in adults.MethodsThe study included 246 adult outpatients (median age of 49.0 years) presenting with peripheral lymphadenopathy. The final diagnosis was determined by reviewing the medical records. We categorized all patients into either the lymphoma group or the non-lymphoma group. The lymphoma group included patients who underwent biopsy and were diagnosed with lymphoma by histopathology, while the non-lymphoma group included those diagnosed with disease excluding lymphoma. The monocyte-to-lymphocyte ratios were compared between the two groups.ResultsOf the participants, 33 (13.4%) were assigned to the lymphoma group. The median age of the lymphoma and non-lymphoma groups were 67.0 years (interquartile range [IQR] 55.5–75.5 years) and 46.0 years (IQR 36.0–61.0 years), respectively. The lymphocyte and monocyte levels showed no significant differences between the two groups individually. Nonetheless, the monocyte-to-lymphocyte ratio was significantly higher in the lymphoma group (median, 0.36; IQR, 0.24–0.73) than in the non-lymphoma group (median, 0.29; IQR, 0.21–0.43; P = 0.022), independent of lymph node diameter ≥ 1 cm and C-reactive protein levels.ConclusionThis study suggests that the monocyte-to-lymphocyte ratio can be a helpful diagnostic marker for lymphoma in adults with peripheral lymphadenopathy when the etiology is unclear even after a medical interview and physical examination.

Dual-energy CT perfusion imaging for differentiating invasive thymomas, thymic carcinomas, and lymphomas in adults

To evaluate the role of dual-energy computed tomography perfusion (DECTP) imaging in differentiating invasive thymomas (ITs), thymic cancers (TCs), and lymphomas in adults. Ninety-five patients with solid masses in the prevascular mediastinum who underwent DECTP examinations were enrolled in this study. The perfusion parameters (blood flow, BF; blood volume, BV; mean transit time, MTT; permeability surface, PS) and spectral parameters (water concentration, WC; iodine concentration, IC; normalised iodine concentration, NIC; the slope of spectral radiodensity [Hounsfield units] curve, λHU) of the lesions were analysed. There were no differences in the MTT or WC values among ITs, TCs, and lymphomas (all p>0.05). The IC, NIC, and λHU values in the optimal arterial and venous phases and PS values of TCs were higher than those of ITs and lymphomas (all p<0.05), and there were no differences between ITs and lymphomas (all p>0.05). The BF and BV values of lymphomas were lower than those of ITs and TCs (all p<0.05), and there were no differences between ITs and TCs (all p>0.05). The cut-off values for BF and BV used to differentiate lymphomas from ITs and TCs were 42.83 ml/min/100 g and 4.66 ml/100 g, respectively (area under the receiver operating characteristic curve: 0.847 and 0.839; sensitivity, 80.6% and 82.1%; specificity, 75% and 71.4%; accuracy, 78.9% and 81.1%). The perfusion and spectral parameters of DECTP imaging help to identify ITs, TCs, and lymphomas, and BF and BV values help to differentiate lymphomas from ITs and TCs.

Treatment of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin’s lymphoma (gray zone lymphoma) in children and young adults: a case series

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin’s lymphoma (cHL) is a rare malignant disease that develops from mature B cells. This disease was first recognized as a distinct entity in 2008. It is most common in the 20 to 40 age group and rare in children. Currently, there are no clear criteria for diagnosis and standard therapy for such patients. According to the literature, it is possible to use treatment regimens applied for both aggressive B-cell lymphomas and Hodgkin's lymphoma. The addition of anti-CD20/CD30 targeted agent to standard therapy may be effective, given the expression of these markers by tumor cells. In this article, we present the clinical and morphological characteristics of patients with unclassifiable B-cell lymphoma with features intermediate between DLBCL and cHL, diagnosed at our center, including 4 patients at the onset of the disease in childhood. Patients and/or their legal representatives have consented to the use of information, including photographs, in scientific research and publications.

Burkitt lymphoma – no impact of HIV status on outcomes with rituximab-based chemoimmunotherapy

We analyzed the prognostic factors for treatment outcomes amongst 34 patients with adult Burkitt lymphoma (BL) who received rituximab with standard first-line chemotherapy. Seven patients had human immunodeficiency virus (HIV)-associated BL. Overall, we observed a complete remission (CR) rate of 91.2%, and 10-year progression-free survival (PFS) and overall survival (OS) was 84.8 and 88.2%, respectively. In patients with concomitant HIV, the prognosis was not different with 10-year PFS of 100% and OS of 88.2%. The majority (71.4%) of HIV-associated BL patients received dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) and had excellent outcomes with 100% CR and no relapses. Central nervous system (CNS) disease, bone marrow involvement and elevated serum lactate dehydrogenase (LDH) levels more than 3 times upper limit of normal (ULN) were associated with poorer survival outcomes. Patients with refractory disease, whilst uncommon (n = 4), had dismal outcomes. Patients with adult BL, including HIV-related cases, harbor generally good prognosis in the modern era.

Lived Experiences of Young Adults With Lymphoma During Acute Survivorship.

Hodgkin lymphoma and non-Hodgkin lymphoma are hematologic malignancies of the lymphatic system with increased prevalence in young adults. Numerous studies have examined the health-related quality of life dimensions in young adults with lymphoma; yet, limited research has investigated the experiences of this population. This study aimed to explore the lived experiences of young adults with Hodgkin lymphoma and non-Hodgkin lymphoma ( n = 8) receiving acute treatment from one National Cancer Institute-Designated Cancer Center in the Northeastern United States. A qualitative interpretive phenomenological study design and method was applied to explore the lived experiences of young adults with lymphoma during acute survivorship. The participants lived experiences were shaped by the diagnostic challenges and impediments of cancer and lymphoma in young adults. Through postdiagnosis, they were determined to safeguard parents and close family members from the burden of cancer. The bonds between medical oncologists and nurses offered the participants a dynamic structure to endure acute survivorship. Cancer was challenging to diagnose in this sample of young adults with lymphoma. The presence of nurses was shown to be deeply impactful for young adults with lymphoma. More research is necessary to understand the experiences of young adults with lymphoma through extended or long-term survivorship. Healthcare providers require additional education regarding the diagnostic guidelines in young adult patients with lymphoma. This study underscores the importance of well-defined and structured postdiagnosis survivorship care in young adults with lymphoma.

Acute left ventricular insufficiency in a Burkitt Lymphoma patient with myocardial involvement and extensive local tumor cell lysis: a case report

BackgroundBurkitt lymphoma (BL) is a rare disease with the sporadic variant accounting for less than 1% of adult non-Hodgkin lymphomas. BL usually presents with an abdominal bulk, but extranodal disease affecting the bone marrow and central nervous system is common. Cardiac manifestations, however, are exceedingly rare, with less than 30 cases reported in the literature.Case presentationWe report on a 54-year-old male patient with a six week-long history of paranasal sinus swelling, fatigue and dyspnea on exertion. Stage IV sporadic BL with extensive lymphonodal and cardiovascular involvement was diagnosed. Manifestations included supra- and infradiaphragmatic lymphadenopathy as well as infiltration of the aortic root, the pericardium, the right atrium and the right ventricle. EBV-reactivation was detected, which is uncommon in the sporadic subtype. After initial full-dose chemotherapy with very good BL control, the patient developed acute, but fully reversible cardiac insufficiency. Myocardial lymphoma involvement receded completely during the following two therapy cycles, while cardiac function periodically deteriorated shortly after chemotherapy administration and quickly recovered thereafter. Interestingly, the decline in cardiac function lessened with decreasing myocardial lymphoma manifestation. Once the cardiovascular BL infiltration was resolved, cardiac function remained stable throughout further treatment. Following seven cycles of chemotherapy and mediastinal radiation, the patient is now in continued complete remission.ConclusionsAlthough rare, cardiac involvement in BL can quickly become life-threatening due to rapid lymphoma doubling time and should therefore be considered at initial diagnosis. This case suggests an association between myocardial infiltration, chemotherapy associated tumor cell lysis and transient deterioration of cardiac function until the damage caused by the underlying lymphoma could be restored. While additional studies are needed to further elucidate the mechanisms of acute cardiac insufficiency due to lymphoma lysis in the infiltrated structures, prompt BL control and full recovery of the patient supports courageous treatment start despite extensive cardiovascular involvement.

The Alternative RelB NF-kB Subunit Exerts a Critical Survival Function upon Metabolic Stress in Diffuse Large B-Cell Lymphoma-Derived Cells.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma in adults and reveals distinct genetic and metabolic signatures. NF-κB transcription factor family is involved in diverse biological processes enabling tumor development and resistance to anticancer-therapy through activation of its two main pathways, the canonical and the alternative NF-κB pathways, the main actor of the latter being the RelB NF-kB subunit. RelB DNA binding activity is frequently activated in DLBCL patients and cell lines. RelB activation defines a new DLBCL subgroup with dismal outcome upon immunochemotherapy, and RelB confers DLBCL cell resistance to DNA damage. However, whether RelB can impact on DLBCL cell metabolism and survival upon metabolic stress is unknown. Here, we reveal that RelB controls DLBCL oxidative energetic metabolism. Accordingly, RelB inhibition reduce DLBCL mitochondrial ATP production, and sensitizes DLBCL cells to apoptosis induced by Metformin and L-asparaginase (®Kidrolase), two FDA approved antimetabolic drugs targeting mitochondrial metabolism. RelB also confers DLBCL cell resistance to glutamine deprivation, an essential amino acid that feeds the TCA cycle. Taken together, our findings uncover a new role for RelB in the regulation of DLBCL cell metabolism and DLBCL cell survival upon metabolic stress.

The role of the surgery in the treatment of B-cell lymphomas with small-bowel affectation

Background: Diffuse large cell B lymphoma represents 30% of all adult lymphomas with predominant involvement of individuals in the sixth decade of life. It is a neoplasm with an aggressive course but with cure rates of 50% of the patients.

The physical exam's role in determining dose-limiting toxicity prior to immunochemotherapy administration in lymphoma.

The COVID-19 pandemic has introduced new challenges to healthcare access and delivery. It is critical to identify areas for innovation within oncologic clinical practice to maintain high quality care. We evaluated the potential utility of telemedicine initiatives for patients with lymphoma undergoing immunochemotherapy. We conducted a retrospective review of adult lymphoma patients receiving R-CHOP + /- R, R-ICE, R-GEMOX, and R-DHAP at our institution in the last three years (2017-2019) and identified cycles for which dose modifications were required. We reviewed 1290 total treatment cycles in 301 unique patients, 1102 cycles (85.4%) were R-CHOP + /- R, 105 (8.1%) were R-ICE, 71 (5.5%) were R-GEMOX, and 12 (0.9%) were R-DHAP. We identified that 144 cycles (11.2%) were subject to dosing adjustments. We retrospectively reviewed laboratory results, patient history, and/or physical exam findings that informed dose modifications. Of the 144 dose adjustments, 11% of cycles contained dose increases due to a well-tolerated previous dose noted in the clinical assessment. The remaining 128 modified cycles were dose reductions. Notably, only 7/128 dose reductions were based on physical exam findings alone, due solely to a change in patient body weight. As patients are routinely weighed immediately prior to chemotherapy administration, effectively no dose modifications (0/144) were exclusively based on abnormal physical exam finding during a pre-infusion assessment. These findings suggest that pre-infusion assessments may be amenable to virtual visits for lymphoma patients undergoing immunochemotherapy.

Frequency of Diffuse Large B- Cell Lymphoma, Activated B- Cell Type

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogenous neoplasm of lymphoid series cells constituting 30%–40% of non-Hodgkin lymphoma in adults. DLBCL presents significant heterogeneity Aim: To determine the frequency of activated B-cell subtype of DLBCL by using Hans algorithm. Methods: It was designed as a cross sectional study conducted in a duration of six months (5th Jun 2018 to 7th January 2019). All data was collected by using a Performa. The clinical parameters like age and gender were recorded. The histopathological method used was paraffin embedding and hematoxylin–eosin staining. The immunohistochemical technique used on serial sections was immune-enzymatic soluble complex method. SPSS version 23 was used for data entry and analysis. Mean and standard deviation was determined for quantitative variables like age and tumor size. Calculation of qualitative variables like gender, tumor site (nodal as well as extra-nodal) and immunohistochemical staining was done in the form of frequencies and percentages. The mean age of the patients was 48.55±15.41 years. Majority of them were male with frequency of 69(71.9%) and female were 27(28.1%). Mean size of lymphoma was 12.44±4.24cm in the patients. Most of the cells were nodal with frequency of 58(60.4%) and a few extra nodal with frequency of 38(39.6%). It was noticed that germinal centre B-cell type was in 53(55.2%) and activated B-cell type lymphoma was present in 43(44.8%). Conclusion: It is observed that frequency of the activated B–cell type lymphoma are less common in patients with lymphoma. Keyword: Lymphoma, Germinal, carcinoma

Lymphoma for GPs across the cancer continuum

Lymphomas are a diverse and relatively common cancer type in the UK. Early diagnosis of lymphoma is vital for improving patient outcomes. The majority of patients diagnosed with lymphoma have a life expectancy of more than 5 years. Lymphoma treatments can have long-term health consequences, and patients with a history of lymphoma have a higher risk of subsequently developing other cancers. More robust evidence for the early diagnosis of lymphoma in primary care has been published in recent years, and the classification of lymphoma has recently been updated by the World Health Organisation. This article focuses on the diagnosis of lymphoma in adolescents and adults and the on-going care needs of patients who are being treated for lymphoma or have survived a diagnosis of lymphoma. Further information about lymphoma and other cancers in children can be found in the InnovAiT article by Dr Jennifer Kelly published in 2017.

Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma

Background. Diffuse large B-cell lymphoma (DLBCL) amounts for 30-40 % of all adult non-Hodgkin's lymphomas. After R-CHOP immunochemotherapy 40 % of patients develop early relapsed or therapy-refractory disease. The conventional prognostic parameters in DLBCL are not always effective. Therefore, exploring further predictors of disease course remains an issue. Aim. To assess the prognostic value of pAKT1 and рSy&lt; expression in DLBCL. Materials &amp; Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cutoff of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher's exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test). Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index &gt; 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk&lt; expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49-10.9; p &lt; 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54-7.30; p = 0.002). Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk&lt; markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.

Prognostic values of myeloid differentiation factor 88 (MYD88) and transducin (β)-like receptor 1 (TBLR1) expression in tissues of diffuse large B-cell non-Hodgkin lymphoma patients - an immunohistochemical study.

IntroductionDiffuse large B-cell non- Hodgkin lymphoma (DLBCL) is the largest common category of adult lymphoma. Recurrence and treatment resistance occurs in one-third of cases, triggering them to the progressive stage of DLBCL after treatment. Detection of novel predictive and prognostic biomarkers leads to improvement of its treatment and prognosis.Aim of the studyTo assess the prognostic roles of protein expression of myeloid differentiation factor 88 (MYD88) and transducin (β)-like receptor 1 (TBLR1) in tissues of DLBCL patients.Material and methodsIn the current study we included tissues from 100 cases of DLBCL. For immunohistochemistry, tissues were stained with MYD88 and TBLR1. We followed patients for about 3 years, and then we correlated their expression with clinicopathological and prognostic parameters.ResultsHigher MYD88 and TBLR1 expressions were associated with presence of B symptoms, fever, night sweat, advanced stage, bone marrow involvement and bulky nodal size, presence of extra-nodal extension, unfavourable relapse-free survival, and unfavourable overall survival rates (p < 0.001).Conclusionsoverexpression of MYD88 and TBLR1 expression was present in DLBCL patients and was associated with unfavourable clinicopathological and prognostic parameters.

Treatment of adult Burkitt lymphoma with the CALGB 1002 protocol: a single center experience in Jordan.

BackgroundThe treatment of adult Burkitt lymphoma with pediatric-based chemotherapy protocols usually results in high cure rates, although with significant toxicity. We report our experience with the Cancer and Leukemia Group B1002 (CALGB 1002) protocol.MethodsThe files of adult patients diagnosed with Burkitt lymphoma and treated with the CALGB 1002 protocol at King Hussein Cancer Center between 2008 and 2017 were reviewed. Baseline demographics, clinical laboratory features, treatment details, and responses were collected. The correlations between clinical and laboratory variables with event-free survival (EFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. EFS and OS were plotted using Kaplan‒Meier curves.ResultsThis study included 19 patients with a median age of 33 years (range, 19‒65). Eleven (58%) and two (10.5%) patients had advanced-stage and central nervous system disease, respectively. Among 106 administered cycles, the median interval between cycles was 23 days (range, 19‒84 days). Sixteen patients (84%) achieved a complete response. After a median follow-up of 40.8 months, the 3-year EFS and OS rates were 78.95%. Patients with a low-risk International Prognostic Index (IPI) had better survival than those with intermediate-or high-risk IPI. Grade III‒IV hematological toxicities occurred in 88% of patients, while 73% had grade III‒IV mucositis.ConclusionIn adult Burkitt lymphoma, the CALGB 1002 protocol provides high cure rates and can be administered promptly, but is associated with significant toxicity. Risk-adapted approaches and other, less toxic, chemotherapeutic regimens should be considered.

Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients

Chimeric antigen receptor (CAR) T cells targeting the CD19 antigen are effective in treating adults and children with B-cell malignancies. Place-of-care manufacturing may improve performance and accessibility by obviating the need to cryopreserve and transport cells to centralized facilities. Here we develop an anti-CD19 CAR (CAR19) comprised of the 4-1BB co-stimulatory and TNFRSF19 transmembrane domains, showing anti-tumor efficacy in an in vivo xenograft lymphoma model. CAR19 T cells are manufactured under current good manufacturing practices (cGMP) at two disparate clinical sites, Moscow (Russia) and Cleveland (USA). The CAR19 T-cells is used to treat patients with relapsed/refractory pediatric B-cell Acute Lymphocytic Leukemia (ALL; n = 31) or adult B-cell Lymphoma (NHL; n = 23) in two independently conducted phase I clinical trials with safety as the primary outcome (NCT03467256 and NCT03434769, respectively). Probability of measurable residual disease-negative remission was also a primary outcome in the ALL study. Secondary outcomes include complete remission (CR) rates, overall survival and median duration of response. CR rates are 89% (ALL) and 73% (NHL). After a median follow-up of 17 months, one-year survival rate of ALL complete responders is 79.2% (95%CI 64.5‒97.2%) and median duration of response is 10.2 months. For NHL complete responders one-year survival is 92.9%, and median duration of response has not been reached. Place-of-care manufacturing produces consistent CAR-T cell products at multiple sites that are effective for the treatment of patients with B-cell malignancies.