Autologous stem cell transplant in fit patients with refractory or early relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy.

Chimeric antigen receptor T-cell therapy is the new standard of care in fit patients with refractory or early relapsed diffuse large B-cell lymphoma (DLBCL). However, there may still be a role for salvage chemotherapy (ST) and autologous stem cell transplant (ASCT) in certain circumstances (e.g., lack of resources for chimeric antigen receptor T-cell therapy, chemosensitive relapses). We retrospectively studied 230 patients with refractory or early relapsed DLBCL who underwent ST and ASCT. The median line of ST was one (range, 1-3). Best response before ASCT was complete response in 106 (46%) and partial response in 124 (54%) patients. The median follow-up after ASCT was 89.4 months. The median progression-free (PFS) and overall survival (OS) were 16.1 and 43.3 months, respectively. Patients relapsing between 6 to 12 months after frontline therapy had a numerically better median PFS (29.6 months) and OS (88.5 months). Patients who required one line of ST, compared to those requiring more than one line, had a better median PFS (37.9 vs. 3.9 months; P=0.0005) and OS (68.3 vs. 12.0 months; P=0.0005). Patients who achieved complete response had a better median PFS (71.1 vs. 6.3 months; P<0.0001) and OS (110.3 vs. 18.9 months; P<0.0001) than those in partial response. Patients who achieved complete response after one line of ST had the most favorable median PFS (88.5 months) and OS (117.2 months). Post-ASCT survival outcomes of patients with refractory or early relapsed DLBCL appeared reasonable and were particularly favorable in those who required only one line of ST to achieve complete response before ASCT, highlighting the role of this procedure in select patients with chemosensitive disease.

Burkitt lymphoma in the modern era: real-world outcomes and prognostication across 30 US cancer centers.

We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P < .001) and without difference based on setting of administration (ie, inpatient vs outpatient). Outcomes were also improved at an academic vs community cancer center (3-year PFS, 67% vs 46%, P = .006; OS, 72% vs 53%, P = .01). In multivariate models, age ≥ 40 years (PFS, hazard ratio [HR] = 1.70, P = .001; OS, HR = 2.09, P < .001), ECOG PS 2 to 4 (PFS, HR = 1.60, P < .001; OS, HR = 1.74, P = .003), lactate dehydrogenase > 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates.

Outcomes of patients with limited-stage plasmablastic lymphoma: A multi-institutional retrospective study.

Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1-196), the 3-year progression-free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3-year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper-CVAD or auto-SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.

Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study.

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.

Discrepancy between treatment goals documentation by oncologists and their understanding among cancer patients under active treatment with chemotherapy.

OBJECTIVE/BACKGROUND: Discussion of treatment goals between oncologists and patients is challenging. Patients frequently misunderstand goals of therapy. There are several methods to document goals of chemotherapy, however, and are frequently not incorporated into patient charts. METHODS/DESIGN: Cancer patients receiving their first cycle of chemotherapy were interviewed. Patients' recall of discussions with their oncologist regarding therapy intent was assessed and compared to documentation. An adjusted McNemar's test was utilised. A one-sample proportion test was used to evaluate whether the overall observed rate of discordance was significantly different from the proposed 33% rate; a rate posited as a threshold too high in the clinical sense. RESULTS: Two hundred and seven eligible patients were interviewed. Oncologist identified treatment goals were not documented in 24.6% of cases and had to be excluded. There was not a significant difference in the directionality of discordance present. Inter-rater agreement between patient and oncologist was found to be adequate (κ = 0.64). The overall rate of discordance (17.29%) was found to be significantly less than the proposed acceptable level of 33% (p < 0.01). Upon univariable analysis, age, gender, marital and employment status were not found to be associated with discordance. CONCLUSIONS: Discordance between treatment goals documentation and their understanding exists, indicating continued miscommunication between the patient and oncologist.

Fatal pulmonary embolism following splenectomy in a patient with Evan's syndrome: case report and review of the literature.

BACKGROUND: Evans syndrome (ES) is a rare disease characterized by simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) with or without immune neutropenia. Splenectomy is one of the treatment options for disease refractory to medical therapy. Venous thromboembolism (VTE) following splenectomy for hematological diseases has an incidence of 10%. CASE PRESENTATION: Here we describe a case report of a young patient hospitalized with severe hemolytic anemia with Hgb 4.8 g/dl. He developed thrombocytopenia with platelet nadir of 52,000/mm3, thus formally diagnosed with ES. He failed standard medical therapy. He underwent splenectomy and had a fatal outcome. Autopsy confirmed the cause of death as pulmonary embolism (PE). CONCLUSIONS: This case report and review of the literature highlight important aspects of the association between VTE, splenectomy, and hemolytic syndromes including the presence of thrombocytopenia. The burden of the disease is reviewed as well as various pathophysiologic mechanisms contributing to thromboembolic events in these patients and current perioperative prophylactic anticoagulation strategies. Despite an advancing body of literature increasing awareness of VTE following splenectomy, morbidity and mortality remains high. Identifying high risk individuals for thromboembolic complications from splenectomy remains a challenge. There are no consensus guidelines for proper perioperative and post-operative anti-coagulation. We encourage future research to determine which factors might be playing a role in increasing the risk for VTE in real time with hope of forming a consensus to guide management.

Evolving treatment patterns and improved outcomes in relapsed/refractory mantle cell lymphoma: a prospective cohort study.

Over the last two decades, the frontline therapy for mantle cell lymphoma (MCL) has evolved. However, the impact of subsequent lines of therapy on survival outcomes has not been well characterized. In this study, we investigated the treatment patterns and survival outcomes in patients with relapsed/refractory (R/R) MCL treated with second-line (2 L) therapy. Adult patients with newly diagnosed MCL from 2002 to 2015 were enrolled in a prospective cohort study. Clinical characteristics, 2 L treatment details, and outcomes were compared between patients who received 2 L treatment between 2003-2009 (Era 1), 2010-2014 (Era 2), and 2015-2021 (Era 3). 2 L treatment was heterogenous in all eras, and there was a substantial shift in the pattern of 2 L therapy over time. The estimated 2-year EFS rate was 21% (95% CI, 13-35), 40% (95% CI, 30-53), and 51% (95% CI, 37-68) in Era 1-3 respectively, and the 5-year OS rate was 31% (95% CI, 21-45), 37% (95% CI, 27-50), and 67% (95% CI, 54-83) in Era 1-3, respectively. These results provide real-world evidence on evolving treatment patterns of 2 L therapy based on the era of relapse. The changes in 2 L treatment correlated with improved EFS and OS, suggesting that treatment advances are associated with improved outcomes in patients with R/R MCL.

Progression-Free Survival at 24 Months as A Landmark After Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B-cell Lymphoma.

Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who achieve progression-free survival (PFS) at 24 months (PFS24) after immunochemotherapy (IC) have excellent overall survival (OS) comparable to that of the age- and sex-matched general population. However, a similar landmark has not been established for patients with relapsed or refractory (RR) DLBCL following frontline IC who are subsequently treated with salvage therapy followed by autologous stem cell transplantation (ASCT). To evaluate the role of PFS24 as a landmark after ASCT in patients with RR DLBCL, we identified patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic between July 2000 and December 2017 and University of Iowa between April 2003 and April 2020 from institutional lymphoma and transplantation databases. Clinical characteristics, treatment information, and outcome data were abstracted. PFS, OS, and post-ASCT relapse survival (PRS) were analyzed using Kaplan-Meier method, and cumulative incidences of relapse versus nonrelapse mortality and different causes of death were compared accounting for competing events. A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow-up of 8.0 years (95% confidence interval [CI], 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, the post-ASCT relapse rate was much higher than the nonrelapse mortality rate (48.1% versus 9.1% at 5 years). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and nonrelapse mortality were similar (14.8% and 12.3% at 5 years). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma-related and -unrelated death rates were similar after achieving PFS24. For all patients who had a post-ASCT relapse, median PRS was 0.7 (95% CI, 0.5-0.9) year, and late relapse (>2 versus ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] versus 0.5 [0.3-0.7] years, P< .001). The study establishes PFS24 as an important landmark associated with post-ASCT outcomes in patients with RR DLBCL after frontline IC.

HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis.

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.

A Retrospective Analysis of the Efficacy of Immunotherapy in Metastatic Soft-Tissue Sarcomas.

Although checkpoint inhibitors have been approved in multiple cancers, they are still under investigation in soft tissue sarcoma (STS). We conducted a retrospective review to report the safety, efficacy, and prognostic factors related to checkpoint inhibitors in STS. A sequential cohort of metastatic STS patients from four institutions treated with checkpoint inhibitors was assembled. Logistic and Cox regression models were applied to determine the effect of patient characteristics, prior treatment, and baseline factors on achieving the best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by the treating physician. Eighty-eight patients with two median prior therapies received checkpoint inhibitors. Treatments included pembrolizumab in 47, nivolumab in 6, ipilimumab in 1, combination ipilimumab/nivolumab in 27, and other combination immunotherapies in 7 patients. Immunotherapy was discontinued in 54 patients-72.2% for progression, 16.7% for toxicity, and 11.1% for other reasons. Median progression-free survival (PFS) was 4.1 months and median overall survival was 19.1 months. One patient with undifferentiated pleomorphic sarcoma (UPS) achieved a CR, while 20 patients had a PR, including 7 UPS, 9 leiomyosarcoma (LMS), and 1 each with alveolar soft part sarcoma, fibroblastic sarcoma, sclerosing epithelioid fibrosarcoma, and myxofibrosarcoma. Forty-five percent (9 of 20) of LMS patients achieved a PR. Twenty-eight patients had SD. Our results confirm the activity and safety of anti-PD-1 therapy in metastatic STS. A notable response rate was observed in UPS and LMS subtypes. This study expands the knowledge base beyond what is currently available from clinical trials involving checkpoint inhibitors in metastatic STS.

Timing of surgery following neoadjuvant chemoradiation in rectal cancer: a retrospective analysis from an academic medical center.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) has been shown to achieve decreased local recurrence (LR) with lower toxicity in rectal cancer patients, but data confirming the optimal timing of surgery following this therapy is less robust. METHODS: The University of Iowa Cancer Registry was queried to identify all patients with stages II-III rectal cancer who received nCRT and surgery from 2000 through 2012. Primary endpoints were time interval to surgery (TI), and overall survival (OS). Secondary endpoints included pathologic outcomes, perioperative morbidities and postoperative complications. Patient characteristics and treatment regimens were compared. Univariate Cox proportional hazard models were used to study the association between TI and OS. Associations of TI with secondary endpoints were tested using Chi-square tests of association. RESULTS: Eighty-seven patients presented with stages II-III rectal cancer. Mean TI was 9.92 weeks. There was no significant association between TI and OS when comparing <8 to ≥8 weeks (P=0.23) or when considering the interval as a continuous variable (P=0.85). Increased LOS [median 7.00 days, P=0.05, HR 1.03 (1.00-1.06)] did correlate with worse survival outcomes. Delaying surgery beyond 8 weeks was associated with increased risk for wound infection (P=0.05). CONCLUSIONS: OS was not influenced by longer intervals between nCRT and surgery. Delaying surgery beyond 8 weeks was associated with increased risk for wound infection.

Expanding pseudoaneurysm compressing the coronary arteries and causing cardiogenic shock.

A 37-year-old man who recently underwent aortic valve replacement after endocarditis presented with cardiogenic shock. A large expansile pseudoaneurysm was subsequently discovered using multiple imaging modalities. Although transesophageal echocardiography is important in diagnosing valve endocarditis, coronary CT angiography of prosthetic valves is feasible and image quality is good. In this case, coronary CT angiography allowed for better understanding of transesophageal echocardiography images and earlier diagnosis of coronary involvement as cause for left ventricular dysfunction.

Coronary artery aneurysms in acute coronary syndrome: case series, review, and proposed management strategy.

Coronary artery aneurysm (CAA) is an uncommon clinical finding, with an incidence varying from 1.5%-4.9% in adults, and is usually considered a variant of coronary artery disease (CAD). CAA identified in the context of acute coronary syndrome (ACS) represents a unique management challenge, particularly if the morphology of the CAA is suspected to have provoked the acute clinical syndrome. CAA is associated with thrombus formation due to abnormal laminar flow, as well as abnormal platelet and endothelial-derived pathophysiologic factors within the CAA. Once formed, mural thrombus may potentiate the deposition of additional thrombus within aneurysmal segments. Percutaneous revascularization of CAA has been associated with complications including distal embolization of thrombus, no-reflow phenomenon, stent malapposition, dissection, and rupture. Presently, there are no formal guidelines to direct the management of CAA in patients presenting with ACS; controversies exist whether conservative, surgical, or catheter-based management should be pursued. In this manuscript, we present an extensive review of the existing literature and associated clinical guidelines, and propose a management algorithm for patients with this complex clinical scenario. Armed with this perspective, therapeutic decisions may be tailored to synthesize patient factors and preferences, individualized clinical assessment, and existing American Heart Association/American College of Cardiology guidelines for management of ACS.