Allogeneic Hematopoietic Stem Cell Transplant for Diffuse Large B-Cell Lymphoma: Evolving Role in the Era of CAR T-Cell Therapy.

PURPOSE OF REVIEW: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma in adults. Although curable in the majority of cases, a substantial portion of patients will experience disease relapse and will die from their lymphoma. This review is aimed at summarizing the role of allogeneic hematopoietic stem cell transplant (allo-HSCT) in patients with relapsed DLBCL with a focus on its role in the era of CAR T-cell therapy RECENT FINDINGS: Allo-HSCT is primarily reserved for patients who experience disease progression or relapse after CAR T-cell therapy, largely due to the high non-relapse mortality (NRM) associated with the procedure. Disease status at the time of allo-HSCT is prognostic with complete remission (CR) associated with better outcomes. Reduced-intensity conditioning (RIC) is likely as effective as myeloablative conditioning (MAC) with less toxicity. In patients with multiply relapsed disease, including after auto-HSCT and CAR T-cell therapy, approximately one-third can be cured with allo-HSCT. Allo-HSCT should be considered a treatment modality for fit adults without major comorbid conditions whose disease can be controlled with emerging treatment modalities (e.g., bispecifics, antibody-drug conjugates).

Mortality and glycemic control among patients with acute and chronic myeloid leukemia and diabetes: a case-control study.

AIM: We examined the association between diabetes and survival in patients with acute and chronic myeloid leukemia and the association of leukemia with glycemic control. PATIENTS & METHODS: Patients with leukemia with and without diabetes (2007-2015) were retrospectively identified and matched 1:1 (n = 70 per group). Overall survival was estimated by the Kaplan-Meier method. Hemoglobin A1c and glucose levels the year after leukemia diagnosis were compared by mixed models. RESULTS: Among 25 of 70 patients with diabetes, mean hemoglobin A1c during the year after leukemia diagnosis was 6.8%. Kaplan-Meier-estimated 3-year survival was 46% for diabetes patients versus 45% for controls (p = 0.79). CONCLUSION: No associations were found between leukemia, diabetes, survival and glycemic control.

The Role of Maintenance Strategies in Metastatic Colorectal Cancer: A Systematic Review and Network Meta-analysis of Randomized Clinical Trials.

Importance: In metastatic colorectal cancer, induction combination chemotherapy with a targeted agent is considered the mainstay of treatment. Multiple randomized clinical trials have examined different strategies of continuing cytotoxic therapy until progression compared with a period of either observation or the use of various maintenance agents. However, those randomized clinical trials have shown inconsistent efficacy results that make it challenging to draw any conclusion on which strategy is preferred. Therefore, a network meta-analysis is helpful to compare different agents across randomized clinical trials. Objective: To evaluate the comparative effectiveness of different treatment strategies for patients with metastatic colorectal cancer. Evidence Review: MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials evaluating different strategies for patients with previously untreated metastatic colorectal cancer. Trials of interest included those including patients with metastatic colorectal cancer who were treated with an initial period of cytotoxic chemotherapy (with or without a biologic) and then switched to one of the following strategies: observation; maintenance with bevacizumab (Bev), fluoropyrimidine (FP), or both (FP + Bev); or continuing the induction regimen until progression. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random-effects model. Network meta-analysis was conducted using a random-effects consistency model to pool evidence from direct and indirect comparisons. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores correspond to greater efficacy. Initial analysis was performed on December 18, 2018. An updated search was performed in April 2019, and no additional studies were added. Findings: Twelve trials at low risk of bias (5540 patients; age range, 23-85 years; 64.4 % male) were included. Network meta-analysis showed no benefit of continuing full cytotoxic chemotherapy until progression vs observation in terms of PFS (hazard ratio, 0.71; 95% CI, 0.46-1.09) and OS (hazard ratio, 0.95; 95% CI, 0.85-1.07). Compared with observation, maintenance therapy showed a PFS benefit (hazard ratio, 0.58; 95% CI, 0.43-0.77) but not an OS benefit (hazard ratio, 0.91; 95% CI, 0.83-1.01). All maintenance strategies (FP, FP + Bev, and Bev) showed significant improvement in PFS vs observation. On SUCRA analysis, maintenance treatment (FP or FP + Bev) had the highest likelihood of achieving improved PFS (67.1% for FP, 99.8% for FP + Bev, and 36.5% for Bev) and OS (81.3% for FP, 73.2% for FP + Bev, and 32.6% for Bev). Conclusions and Relevance: For patients with metastatic colorectal cancer, there is no benefit to continuing the full induction regimen until progression, without a period of either observation or maintenance treatment. A maintenance strategy with a fluoropyrimidine, with or without the addition of bevacizumab, is preferred. However, given the lack of a clear OS benefit, shared decision-making should include observation as an acceptable alternative.

Expanding the Spectrum of Radiation Necrosis After Stereotactic Radiosurgery (SRS) for Intracranial Metastases From Lung Cancer: A Retrospective Review.

OBJECTIVE: Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN. METHODS: We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes. RESULTS: Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality. CONCLUSIONS: This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.

Atrio-Esophageal Fistula: A Case Series and Literature Review.

BACKGROUND Percutaneous catheter radiofrequency ablation (RFA) and cryoablation of the left atrium and pulmonary vein ostia have become successful therapeutic modalities in the management of atrial fibrillation. Atrio-esophageal fistula is a rare complication. Awareness of complication risk is imperative because without prompt diagnosis and urgent surgical intervention, the outcome is often fatal. We present 3 cases of atrio-esophageal fistula following percutaneous catheter radiofrequency ablation (RFA). CASE REPORT Case 1: A 72-year old white male presented 27 days after percutaneous RFA for atrial fibrillation with fever, altered mental status, and melena. Esophagogastroduodenoscopy (EGD) revealed a 1-cm defect in the mid-esophagus. Upon thoracotomy, severe hemorrhage ensued from a concomitant injury to the left atrium. Multiple attempts to repair the left atrial perforation were unsuccessful and the patient died. Case 2: A 71-year old white male presented 29 days after percutaneous RFA for atrial fibrillation with fever and tonic-clonic seizure. Recognition of possible atrio-esophageal fistula was considered and confirmed on thoracotomy. Surgical fixation of the left atria and esophagus were performed. The patient survived and was discharged to a skilled care facility. Case 3: A 75-year old white male presented 24 days after percutaneous RFA for atrial fibrillation with chest pain. An echocardiogram revealed a large pericardial effusion and pericardiocentesis was performed. Despite aggressive measures, the patient died. The autopsy demonstrated a communicating esophageal fistula with the right pulmonary vein. CONCLUSIONS Clinicians tending to patients who have recently undergone atrial ablation need to be aware of atrio-esophageal fistula as a rare but highly fatal complication.