Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo-HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD. Investigators reported 20 deaths, 60% of which were GVHD-related. The overall mortality risk with GVHD is 11%. In this group, investigators noted an objective response rate (ORR) in 68% of patients, with complete remission (CR) in 47%, partial remission (PR) in 21%, and stable disease in 11%. Among the patients who received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and 9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease stabilization in 5%. After careful evaluation of collective data, we found that CPI use both before and after allo-HSCT can be highly effective, but exposure can lead to a significantly increased risk of GVHD-related morbidity and mortality in this patient population. Despite limited availability of data, there is need for extreme caution while making decisions regarding the use of CPIs. Detailed discussions and prospective well-designed clinical trials are needed to explore this issue further.

Blinatumomab and donor lymphocyte infusion (DLI) combination is a promising cancer therapy, whereby blinatumomab might achieve an initial reduction in leukemic-cell burden using T cells, and after tumor clearance, DLI can potentially stimulate the donor immune system to achieve longer lasting remission. Here, we present a 51-year-old female with mixed phenotype acute leukemia who had a hematologic relapse 3 months after she received total body irradiation-based myeloablative allogeneic hematopoietic stem cell transplantation from an unrelated human leukocyte antigen matched (10/10) donor and achieved complete remission with minimal residual disease negativity by multi-parameter flow cytometry using the combination of blinatumomab and DLI. To the best of our knowledge, this is the first report to describe the use of blinatumomab and DLI combination therapy in the treatment of B/myeloid mixed phenotype acute leukemia.

R-CHOP has been the standard of care for diffuse large B cell lymphoma (DLBCL), curing approximately 60% of patients for more than 2 decades. However, the optimal treatment of patients who are too frail to tolerate this regimen and/or are not candidates for anthracycline therapy continues to be debated. MInT and GELA trials established addition of rituximab to CHOP in DLBCL but excluded patients older than 80 years. Multiple regimens have been tried with varying success in the very elderly, including R-mini-CHOP, R-mini CEOP, R-split CHOP, pre-phase strategies, and R-GCVP. However, there has not been a randomized trial among these strategies. Although addition of novel agents including ibrutinib, brentuximab vedotin, lenalidomide, and many others on the horizon holds promise in this population, none have been tested in a randomized setting or have results awaited. There is also a lack of a validated and easy to use clinical tool in this population to predict patients who will not tolerate R-CHOP. Identifying patients who will not tolerate R-CHOP early with the help of tools like CGA, along with integrating biology-based treatment (ibrutinib, lenalidomide in activated B cell type DLBCL) is being investigated in this population.

Multiple Myeloma (MM) is primarily a disease of old age with a median age of sixty-nine years at diagnosis. The development of novel therapies for induction and use of autologous stem cell transplantation has resulted in improved clinical outcomes and better quality of life for MM patients. Elderly patients, comprising the majority of MM population, have a higher incidence of age-related comorbidities, frailty and organ dysfunction which complicates the coordination of treatment and limits the selection of therapies. Even in the era of multiple chemotherapeutic options, the clinical heterogeneity of the myeloma patients' demands personalized treatments which often require dose-adjustments or dose delays. The use of reduced-dose regimens and various comorbidity indices has improved clinical outcome and regimen tolerability in MM patients with renal, neurological and bone abnormalities. We focus on advancements in the treatment of multiple myeloma with the goal to guide clinicians towards patient-specific management.

BackgroundDiabetic foot ulcers (DFUs) cause significant morbidity and put great economic burden on patient and healthcare facilities. Infection is the main driving force behind admissions related to DFU. Culture of soft tissue or bone is invaluable in diagnosing infection but is time consuming. Inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) are rapid, simple, and inexpensive laboratory tests that can aid in early diagnosis of diabetic foot infection (DFI) and monitor response to treatment. We did a meta-analysis to compare diagnostic performance of inflammatory markers for detecting DFI.MethodsWe searched PubMed, Embase, and Cochrane databases from their inception to December 2017. This meta-analysis was performed according to PRISMA guidelines. We included studies based on following inclusion criteria: (1) at least one of the biomarkers (ESR, CRP, PCT) was evaluated; (2) both sensitivity and specificity were measured as outcomes; and (3) sufficient data were available to construct 2 × 2 contingency table. We used bivariate random effect regression model to pool the sensitivity and specificity of the targeted biomarkers.ResultsA comprehensive literature search identified a total of 73 studies. Twelve studies met our inclusion criteria. Number of studies reporting data on each individual biomarker was as follows: 11 for ESR, seven for CRP, and five for PCT. Pooled sensitivity and specificity for ESR were calculated to be 0.84 (95% CI 0.76–0.89) and 0.82 (95% CI 0.73–0.89) with area under receiver operating characteristic curve (AUROC) of 0.90 (95% CI 0.87–0.92). Pooled sensitivity and specificity for CRP were found to be 0.64 (95% CI 0.46–0.80) and 0.87 (95% CI 0.75–0.93) with AUROC of 0.85 (95% CI0.82–0.88). Pooled sensitivity and specificity for PCT were 0.74 (95% CI 0.62–0.83) with AUROC of 0.84 (95% CI 0.81–0.87).ConclusionESR could be beneficial in ruling out infection in persons who have low suspicion of disease. For those who have high suspicion of disease, PCT could be helpful in ruling in infection. Clinicians should avoid ordering both ESR and CRP because role of CRP is limited. All inflammatory markers need standardization of threshold levels for detecting infection. Disclosures All authors: No reported disclosures.