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Infections remain a major concern following bispecific antibody therapy but are not well described in pivotal trials. We present the first well-documented case of a classic but rare opportunistic infection, disseminated Mycobacterium avium complex, in a patient receiving bispecific antibody therapy. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Significant unmet need remains for patients with relapsed/refractory FL after =3 lines of prior therapy. While recent advancements have likely improved the survival of patients with FL, most patients will eventually relapse. The treatment of patients with FL after multiple relapses or those with refractory disease has historically led to lower overall response rates (ORR) and shorter progressionfree survival (PFS) with each subsequent line of therapy. New treatments with high ORR and durable PFS are needed in this setting, particularly in patients that progress within 2 years of first line chemoimmunotherapy (POD24) and/or those refractory chemoimmunotherapy. Chimeric antigen receptor T-cell therapies targeting the B-cell antigen CD-19 have shown to be an efficacious treatment option for both heavily pretreated patients and/or patients with refractory FL, resulting in a high ORR and durable remissions. [ABSTRACT FROM AUTHOR]

STOP-CA was a multicenter, double-blind, randomized, placebo-controlled trial comparing atorvastatin to placebo in treatment-naïve lymphoma patients receiving anthracycline-based chemotherapy. We performed a preplanned subgroup to analyze the impact of atorvastatin on efficacy in patients with diffuse large B-cell lymphoma (DLBCL). Patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at standard doses for six 21-day cycles and were randomly assigned to receive atorvastatin 40 mg daily (n = 55) or placebo (n = 47) for 12 months. The complete response (CR) rate was numerically higher in the atorvastatin arm (95% [52/55] vs. 85% [40/47], p =.18), but this was not statistically significant. Adverse event rates were similar between the atorvastatin and placebo arms. In summary, atorvastatin did not result in a statistically significant improvement in the CR rate or progression-free survival, but both were numerically improved in the atorvastatin arm. These data warrant further investigation into the potential therapeutic role of atorvastatin added to anthracycline-based chemotherapies. [ABSTRACT FROM AUTHOR]

PURPOSE This study investigated the effectiveness of algorithmic testing in hematopathology at the Brigham and Women's Hospital and Dana-Farber Cancer Institute (DFCI). The algorithm was predicated on test selection after an initial pathologic evaluation tomaximize cost-effective testing, especially for expensive molecular and cytogenetic assays. MATERIALS AND METHODS Standard ordering protocols (SOPs) for 17 disease categories were developed and encoded in a decision support application. Six months of retrospective data from application beta testing was obtained and compared with actual testing practices during that timeframe. In addition, 2 years of prospective data were also obtained from patients at one community satellite site. RESULTS A total of 460 retrospective cases (before introduction of algorithmic testing) and 109 prospective cases (following introduction)were analyzed. In the retrospective data, 61.7% of tests (509 of 825) were concordant with the SOPs while 38.3% (316 of 825) were overordered and 30.8%(227 of 736) of SOP-recommended tests were omitted. In the prospective data, 98.8% of testing was concordant (244 of 247 total tests) with only 1.2%overordered tests (3 of 247) and 7.6%omitted tests (20 of 264 SOP-recommended tests; overall P < .001). The cost of overordered tests before implementing SOP indicates a potential annualized saving of $1,347,520 in US dollars (USD) in overordered testing at Brigham and Women's Hospital/DFCI. Only two of 316 overordered tests (0.6%) returned any additional information, both for extremely rare clinical circumstances. CONCLUSION Implementation of SOPs dramatically improved test ordering practices, with a just right number of ancillary tests that minimizes cost and has no significant impact on acquiring key informative test results. [ABSTRACT FROM AUTHOR]

Summary: Data describing outcomes of chimeric antigen receptor (CAR) T‐cell therapy in patients with secondary central nervous system (SCNS) involvement of mantle cell lymphoma (MCL) are limited. We identified 10 patients with MCL and SCNS involvement treated with anti‐CD19 CAR T‐cell therapy at three US academic centres. Frequent objective responses were observed in the CNS (86%) and systemically (90%), and the 1‐year progression‐free survival was 47%. Seven patients developed immune‐effector‐cell‐associated‐neurotoxicity‐syndrome (n = 2 Grade 1, n = 5 Grade 3). Our results suggest that anti‐CD19 CAR T‐cell therapy in this setting is feasible and additional data regarding neurotoxicity in this population may be warranted. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma is the most common subtype of lymphoma. First-line treatment with combination chemoimmunotherapy is successful in about 60% of patients. For those who have relapse, second-line therapy consists of additional chemoimmunotherapy followed by autologous stem cell transplant. But most of these patients do not have good outcomes. The U.S. Food and Drug Administration (FDA) has approved CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) for third-line treatment; CAR-T is also effective for relapsed disease. The study described in this article examines whether CAR-T could be used as second-line therapy. Visual Abstract. Second-Line Chimeric Antigen Receptor T-Cell Therapy in Diffuse Large B-Cell Lymphoma: Diffuse large B-cell lymphoma is the most common subtype of lymphoma. First-line treatment with combination chemoimmunotherapy is successful in about 60% of patients. For those who relapse, second-line therapy consists of additional chemoimmunotherapy followed by autologous stem cell transplant. But most of these patients do not have good outcomes. The U.S. Food and Drug Administration (FDA) has approved CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) for third-line treatment; CAR-T is also effective for relapsed disease. The study described in this article examines whether CAR-T could be used as second-line therapy. Background: First-line treatment of diffuse large B-cell lymphoma (DLBCL) achieves durable remission in approximately 60% of patients. In relapsed or refractory disease, only about 20% achieve durable remission with salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]) and TRANSFORM (lisocabtagene maraleucel [liso-cel]) trials demonstrated superior event-free survival (and, in ZUMA-7, overall survival) in primary-refractory or early-relapsed (high-risk) DLBCL with chimeric antigen receptor T-cell therapy (CAR-T) compared with salvage chemoimmunotherapy and consolidative ASCT; however, list prices for CAR-T exceed $400 000 per infusion. Objective: To determine the cost-effectiveness of second-line CAR-T versus salvage chemoimmunotherapy and consolidative ASCT. Design: State-transition microsimulation model. Data Sources: ZUMA-7, TRANSFORM, other trials, and observational data. Target Population: "High-risk" patients with DLBCL. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Axi-cel or liso-cel versus ASCT. Outcome Measures: Incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB) in 2022 U.S. dollars per quality-adjusted life-year (QALY) for a willingness-to-pay (WTP) threshold of $200 000 per QALY. Results of Base-Case Analysis: The increase in median overall survival was 4 months for axi-cel and 1 month for liso-cel. For axi-cel, the ICER was $684 225 per QALY and the iNMB was −$107 642. For liso-cel, the ICER was $1 171 909 per QALY and the iNMB was −$102 477. Results of Sensitivity Analysis: To be cost-effective with a WTP of $200 000, the cost of CAR-T would have to be reduced to $321 123 for axi-cel and $313 730 for liso-cel. Implementation in high-risk patients would increase U.S. health care spending by approximately $6.8 billion over a 5-year period. Limitation: Differences in preinfusion bridging therapies precluded cross-trial comparisons. Conclusion: Neither second-line axi-cel nor liso-cel was cost-effective at a WTP of $200 000 per QALY. Clinical outcomes improved incrementally, but costs of CAR-T must be lowered substantially to enable cost-effectiveness. Primary Funding Source: No research-specific funding. [ABSTRACT FROM AUTHOR]

Objective: To develop an automated, physiologic metric of immune effector cell‐associated neurotoxicity syndrome among patients undergoing chimeric antigen receptor‐T cell therapy. Methods: We conducted a retrospective observational cohort study from 2016 to 2020 at two tertiary care centers among patients receiving chimeric antigen receptor‐T cell therapy with a CD19 or B‐cell maturation antigen ligand. We determined the daily neurotoxicity grade for each patient during EEG monitoring via chart review and extracted clinical variables and outcomes from the electronic health records. Using quantitative EEG features, we developed a machine learning model to detect the presence and severity of neurotoxicity, known as the EEG immune effector cell‐associated neurotoxicity syndrome score. Results: The EEG immune effector cell‐associated neurotoxicity syndrome score significantly correlated with the grade of neurotoxicity with a median Spearman's R2 of 0.69 (95% CI of 0.59–0.77). The mean area under receiving operator curve was greater than 0.85 for each binary discrimination level. The score also showed significant correlations with maximum ferritin (R2 0.24, p = 0.008), minimum platelets (R2 –0.29, p = 0.001), and dexamethasone usage (R2 0.42, p < 0.0001). The score significantly correlated with duration of neurotoxicity (R2 0.31, p < 0.0001). Interpretation: The EEG immune effector cell‐associated neurotoxicity syndrome score possesses high criterion, construct, and predictive validity, which substantiates its use as a physiologic method to detect the presence and severity of neurotoxicity among patients undergoing chimeric antigen receptor T‐cell therapy. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does 1 year of treatment with atorvastatin, 40 mg/d, started prior to anthracycline-based chemotherapy among patients with lymphoma, reduce the chance of a significant decrease in left ventricular ejection fraction (LVEF) compared with placebo? Findings: In this randomized trial of 300 adult patients with lymphoma, the percentage of patients with a decrease in cardiac function (≥10% absolute decline in LVEF from prior to chemotherapy to a final value of <55% over the 12-month study period), among those randomized to atorvastatin was 9% compared with a rate of 22% among patients randomized to placebo. This difference met statistical significance. Meaning: Atorvastatin reduced cardiac functional impairment in patients with lymphoma treated with anthracyclines. This finding may support the use of atorvastatin in patients with lymphoma at risk of cardiac dysfunction due to anthracycline treatment. Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use. Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022. Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months. Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P =.002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P =.001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P =.26). The number of serious related adverse events was low and similar between groups. Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use. Trial Registration: ClinicalTrials.gov Identifier: NCT02943590 This randomized trial assesses the effect of 12 months of atorvastatin vs placebo on development of cardiac dysfunction among patients with lymphoma undergoing anthracycline-based chemotherapy. [ABSTRACT FROM AUTHOR]

Summary: The use of CD19 chimeric antigen receptor T‐cell (CAR‐T) therapy for relapsed/refractory solid organ transplantation (SOT)‐related post‐transplant lymphoproliferative disorder (PTLD) is not well studied. We conducted a multicentre, retrospective analysis of adults with relapsed/refractory SOT‐associated PTLD. Among 22 relapsed/refractory SOT‐PTLD patients, the pathology was monomorphic B cell. Prior SOTs included 14 kidney (64%), three liver (14%), two heart (9%), one intestinal (5%), one lung (5%), and one pancreas after kidney transplant (5%). The median time from SOT to PTLD diagnosis was 107 months. Pre‐CAR‐T bridging therapy was used in 55% of patients, and immunosuppression was stopped completely before CAR‐T infusion in 64%. Eighteen (82%) patients experienced cytokine release syndrome: one (5%) each grade (G) 3 and G4. The immune effector cell‐associated neurotoxicity syndrome was observed in 16 (73%) patients: six (27%) G3 and two (9%) G4. The overall response rate was 64% (55% complete response). Three patients (14%) experienced allograft rejection after CAR‐T. The two‐year progression‐free survival and overall survival rates were 35% and 58%, respectively. Additionally, the achievement of CR post‐CAR‐T was strongly associated with survival. Collectively, the safety and efficacy of CD19 CAR‐T therapy in relapsed/refractory SOT‐related PTLD appeared similar to pivotal CAR‐T data, including approximately one‐third of patients achieving sustained remission. [ABSTRACT FROM AUTHOR]

Improved biomarkers are needed to guide patient selection for autologous stem cell transplantation (ASCT) and post-ASCT maintenance therapies in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the prognostic value of minimal residual disease (MRD) using immunoglobulin-based high-throughput sequencing (Ig-HTS), we analyzed pre- and post-ASCT peripheral blood and pre-ASCT apheresis stem cell (ASC) samples in 36 cHL patients. A tumor clonotype was detected in only 12 patients (33%). Among these patients, MRD within plasma samples was closely associated with impending relapse. All patients (n = 3) with detectable MRD in any post-ASCT plasma sample relapsed (100% specificity), and MRD was not detected in any patients in remission. MRD testing from cellular specimens (peripheral blood mononuclear cell or ASC samples) was not associated with relapse. In this small cohort, plasma-based MRD testing appeared to be a promising biomarker in cHL, but given low clonotype detection rates with Ig-HTS, alternative MRD approaches should be investigated. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cells (CAR T) are groundbreaking therapies but may cause significant toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. Granulocyte colony-stimulating factor (G-CSF) is often used to mitigate neutropenia after CAR T, but there is no consensus recommended strategy due to hypothesized, but largely unknown risks of exacerbating toxicities. To investigate the impact of G-CSF, we retrospectively analyzed 197 patients treated with anti-CD19 CAR T for lymphoma and 47 patients treated with anti-BCMA CAR T for multiple myeloma. In lymphoma, 140 patients (71%) received prophylactic G-CSF before CAR T (mostly pegylated G-CSF) and were compared with 57 patients (29%) treated with G-CSF after CAR T or not exposed. Prophylactic G-CSF was associated with faster neutrophil recovery (3 vs. 4 days, P < 0.01) but did not reduce recurrent neutropenia later. Prophylactic G-CSF was associated with increased grade ≥2 CRS (HR 2.15, 95% CI 1.11–4.18, P = 0.02), but not ICANS. In multiple myeloma, prophylactic G-CSF was not used; patients were stratified by early G-CSF exposure (≤2 days vs. ≥3 days after CAR T or no exposure), with no significant difference in toxicities. Future trials should clarify the optimal G-CSF strategy to improve outcomes after CAR T. [ABSTRACT FROM AUTHOR]

Summary: ZUMA‐1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi‐cel), an autologous CD19‐directed chimaeric antigen receptor (CAR)‐T cell therapy, in refractory large B‐cell lymphoma. To reduce treatment‐related toxicity, several exploratory safety management cohorts were added to ZUMA‐1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end‐points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days −5 through −3), 2 × 106 CAR‐T cells/kg (day 0) and once‐daily oral dexamethasone [10 mg, day 0 (before axi‐cel) through day 2]. Forty patients received axi‐cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty‐eight per cent of patients did not experience CRS or NEs within 72 h of axi‐cel. With a median follow‐up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population. [ABSTRACT FROM AUTHOR]

The use of circulating tumor DNA (ctDNA) for detecting and monitoring tumors is rapidly increasing in oncology, and has recently been applied to diffuse large B-cell lymphoma (DLBCL) [[1]]. Three patients (10%) did not return to the center for follow-up; complete remission (CR) status at EOT was unknown for these patients and they did not have serial PB samples after EOT. Given our desire to obtain data from as many patients as possible, we attempted to reevaluate our pilot samples which had been transferred to Adaptive, with only 8 of the 13 pilot patients having sufficient tumor sample for NGS-MRD analysis. [Extracted from the article]

Axicabtagene ciloleucel is the first U.S. Food and Drug Administration–approved autologous anti‐CD19 chimeric antigen receptor (CAR) T‐cell therapy for the treatment of patients with relapsed or refractory large B‐cell lymphoma after ≥2 prior systemic therapies. Although axicabtagene ciloleucel is administered only at authorized treatment centers, community oncologists play a critical role in the CAR T‐cell treatment journey, recognizing potentially eligible patients for referral and then, after treatment, closely collaborating with treatment centers to monitor and manage patients long term. ZUMA‐1, the pivotal, multicenter, phase I/II study of 108 patients treated with axicabtagene ciloleucel, resulted in an objective response rate of 83%, including 58% complete responses. With a 27.1‐month median follow‐up, 39% of patients had ongoing responses. CAR T‐cell therapy is associated with the potentially life‐threatening adverse events (AEs) of cytokine release syndrome and neurologic events, which generally occur early after treatment. In ZUMA‐1, cytokine release syndrome and neurologic events were generally reversible and grade ≥3 cytokine release syndrome and neurologic events occurred in 11% and 32% of patients, respectively. Frequent prolonged AEs included hypogammaglobulinemia, B‐cell aplasia, and cytopenias requiring supportive care until recovery of hematopoietic function. Rate of treatment‐related mortality was low, at <2%. With appropriate management of common AEs, axicabtagene ciloleucel offers the potential for long‐term durable responses in patients who otherwise lack curative treatment options. Implications for Practice: Community oncologists should be familiar with key aspects of chimeric antigen receptor (CAR) T‐cell indications and eligibility to help recognize and refer potential patients for this paradigm‐changing treatment option at the appropriate time during the disease course. To ensure optimal long‐term outcomes for patients who have been treated with CAR T‐cell therapy, oncologists must also be familiar with common prolonged AEs and their monitoring and management. This article reviews information relevant to oncologists who are caring for patients who have been treated with CAR T cells or who are considering referring a patient with large B‐cell lymphoma for CAR T‐cell therapy. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy is a revolutionary new form of immunotherapy for the treatment of hematologic malignancies. The two primary toxicities associated with CAR T-cell therapy include cytokine-release syndrome and neurotoxicity. Cytokine-release syndrome is generally self-limited but high-grade toxicities like hypotension and hypoxemia can be managed with agents that block the effects of IL-6, like tocilizumab, and/or corticosteroids. Although CAR T-cell therapy-associated neurotoxicity is a well-described clinical phenomenon, its pathophysiology remains inadequately understood; treatments and preventive strategies remain elusive. Animal models and clinical trial experience suggest the centrality of monocytes, endothelial dysfunction, and the blood-brain barrier in the development of CAR T-cell-associated neurotoxicity. Here we report what is known from preclinical models, clinical trials, and histopathologic studies regarding the pathophysiology of neurotoxicity, predictors of its incidence, and potential targets for the treatment and prevention of neurotoxicity. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cell therapy has become an important tool in the treatment of relapsed and refractory malignancy; however, it is associated with significant neurological toxicity. We characterized the neurological toxicity associated with chimeric antigen receptor T-cell therapy in a consecutive series of 100 patients up to 2 months post transfusion, 28 of whom were obtained from chart review and the others by prospective observation. The underlying neoplasms were lymphoma (74%), myeloma (14%), leukaemia (10%), and sarcoma (2%). The median age of the cohort was 64.5 years old and 39% of patients were female. The most commonly occurring neurological symptoms were encephalopathy (57%), headache (42%), tremor (38%), aphasia (35%) and focal weakness (11%). Focal neurological deficits are frequently observed after chimeric antigen receptor T-cell therapy and are associated with regional EEG abnormalities, FDG-PET hypometabolism, and elevated velocities on transcranial Doppler ultrasound. In contrast, structural imaging was typically normal. As this form of treatment is more widely adopted, recognition of the frequently encountered symptoms will be of increasing importance for the neurologists and oncologists caring for this growing patient population. [ABSTRACT FROM AUTHOR]

Abstract: Background: High‐dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high‐risk lymphoma. However, elderly patients are often not considered ASCT candidates based on age alone. Subjects, Materials, and Methods: A retrospective analysis of patients ≥70 years of age with a diagnosis of Hodgkin or non‐Hodgkin lymphoma receiving ASCT between 2000 and 2016 at two partner institutions was performed. Clinical data were extracted from institutional databases and individual medical records. Multivariate analysis was performed to examine the association of clinical variables with transplant outcomes. Results: One hundred seven patients were identified. Median age at transplant was 72 years (range, 70–79). The most common lymphoma subtype was diffuse large B‐cell (n = 63, 59%). Median time to neutrophil and platelet engraftment were 10 and 12 days, respectively. With a median follow‐up for survivors of 20 months following ASCT (range, 6 months to 13.1 years), estimates for 2‐year progression‐free survival and overall survival were 58% (95% confidence interval [CI], 48%–67%) and 65% (95% CI, 55%–74%), respectively. Two‐year estimate for relapse was 34% (95% CI, 25%–44%) and nonrelapse mortality (NRM) was 7% (95% CI, 3%–14%). Multivariate analysis showed that more recent date of transplant was associated with lower NRM. The Hematopoietic Cell Transplantation‐Comorbidity Index score was not predictive of NRM in this data set (high‐risk vs. low‐risk, hazard ratio 3.45, p = .065). Conclusion: Eligibility for ASCT should be an individualized decision, and age should not be an absolute contraindication to ASCT in healthy elderly patients with lymphoma. Implications for Practice: Although high‐dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high‐risk lymphoma, elderly patients are often not considered candidates due to concern for excess toxicity and mortality. This retrospective study showed favorable transplant outcomes, including survival and toxicity, in a large cohort of lymphoma patients over 70 years of age who underwent ASCT. Eligibility for ASCT should be an individualized decision, and age should not be an absolute contraindication to ASCT in healthy elderly patients with lymphoma. [ABSTRACT FROM AUTHOR]

The article discusses a study on the detection of activating MAP2K1 mutations in patients with atypical hairy cell leukemia and hairy cell leukemia variant (HCLv). The study investigated the cases of patients who also demonstrated the BRAFV600E mutation. The results showed the association of MAP2K1 mutations with preferential usage of the IGHV4-34 variable gene segment.

The treatment landscape for newly diagnosed follicular lymphoma (FL) has dramatically changed over the past decade, first with the advent of rituximab and then with the activity of old and new drugs, like bendamustine and lenalidomide, in this disease. The efficacy and tolerability of rituximab has led to a paradigm shift for the management of patients with low volume FL for many oncologists. Despite the lack of a survival benefit seen with this approach, many now use this single agent in patients who had historically been observed. Likewise, its use as maintenance therapy following successful front-line induction therapy of patients with symptomatic FL, with either rituximab alone or specific chemoimmunotherapy regimens, has improved remission duration and widely been adopted. As newer chemoimmunotherapy regimens, like bendamustine and rituximab, have superior outcomes with improved tolerability, upfront treatment options are redefined and questions emerge: whom do maintenance strategies benefit, and what is the optimal sequencing of therapies? Finally, as newer targeted and potentially better tolerated therapies demonstrate efficacy in the relapsed setting, their use, both in combination with and in place of chemotherapy, is being explored. The promising regimen of lenalidomide with rituximab is being compared with chemoimmunotherapy in a randomized fashion. Cure remains elusive, however, in advanced stage disease and so safety and tolerability, in addition to efficacy, remain important endpoints. [ABSTRACT FROM AUTHOR]

Chemoimmunotherapy followed by autologous stem cell transplantation ( ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma ( MCL). The achievement of complete remission ( CR) and minimal residual disease ( MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine ( RB/ RC). This phase 2 study ( NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13 months, the progression-free survival rate was 96%. Among 15 MRD -evaluable patients who completed treatment, 93% achieved MRD negativity after RB/ RC. In conclusion, RB/ RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/ RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population. [ABSTRACT FROM AUTHOR]

The article focuses on the detection of circulating tumour deoxyribonucleic acid (DNA) in patients with aggressive B-cell non-Hodgkin lymphoma. It states that methods to detect any disease in patients with diffuse large B cell lymphoma (DLBCL) or mediastinal large B-cell lymphoma (MLBCL) rely primarily on imaging methods. It further mentions that these methods are associated with significant cost and radiation exposure.

In the positron emission tomography ( PET) era, traditional prognostic factors may not apply for patients with relapsed/refractory ( R/ R) diffuse large B cell lymphoma ( DLBCL) undergoing autologous stem cell transplantation ( ASCT). Moreover, little is known about prognostic factors in patients transplanted for transformed indolent lymphoma ( TIL). We conducted a retrospective study of 143 patients with R/ R DLBCL and TIL who were transplanted in the last decade and had a post-salvage PET scan. We examined prognostic factors in both groups, and constructed a prognostic score for DLBCL patients. For patients with DLBCL, post-salvage PET response was an important prognostic factor. Advanced age and symptomatic relapse were also significantly associated with outcome. A simple score could stratify patients into three risk groups with 4-year post- ASCT overall survival of 84%, 59%, and 10%, and 4-year progression-free survival of 67%, 41% and 0% ( P < 0·0001 for both). However, none of those factors (including PET response to salvage) appeared relevant for patients with TIL, despite their comparable overall outcome. Our prognostic score for DLBCL patients undergoing ASCT may be useful for prognostication, for stratification in clinical trials, and to motivate the design of new strategies for patients in the high-risk group, who may not derive benefit from standard ASCT. [ABSTRACT FROM AUTHOR]

Patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) are at increased risk for developing Hodgkin's lymphoma (HL), a risk that has not decreased despite the success of combination antiretroviral therapy (cART) in the modern era. HIV-associated HL (HIV-HL) differs from HL in non-HIV-infected patients in that it is nearly always associated with Epstein-Barr virus (EBV) and more often presents with high-risk features of advanced disease, systemic "B" symptoms, and extranodal involvement. Before the introduction of cART, patients with HIV-HL had lower response rates and worse outcomes than non-HIV-infected HL patients treated with conventional chemotherapy. The introduction of cART, however, has allowed for the delivery of full-dose and dose-intensive chemotherapy regimens with improved outcomes that approach those seen in non-HIV infected patients. Despite these significant advances, HIV-HL patients remain at increased risk for treatment-related toxicities and drug-drug interactions which require careful attention and supportive care to insure the safe administration of therapy. This paper will address the modern diagnosis, risk stratification, and therapy of HIV-associated HL. [ABSTRACT FROM AUTHOR]

The article focuses on common transplant complication called post-transplant lymphoproliferative disorder (PTLD), its risk factors and response after solid organ transplantation. It presents several risk factors for the development of PTLD which include the type of organ transplanted, the type and degree of immunosuppresion, and the time from the transplantation. Moreover, it mentions various therapies for PTLD including the reduction in immunosuppression, chemotherapy, and radiation therapy.