Pembrolizumab with R-CHOP in previously untreated diffuse large B-cell lymphoma: potential for biomarker driven therapy

Tumor programmed death-ligand 1 (PD-L1) expression in diffuse large B-cell lymphoma (DLBCL) is associated with inferior outcomes. The first-line immunologically-replete setting may be an opportune time for PD-1 inhibition. We evaluated pembrolizumab in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in untreated patients with DLBCL. Eligible patients were age 18 or older, had adequate organ function, and had DLBCL requiring full-course therapy. Patients received pembrolizumab 200 mg/cycle with R-CHOP, primarily to assess toxicity. Response assessment utilized standard criteria, and PD-L1 staining was performed at a validated central laboratory. Among 30 patients, toxicity was comparable to standard R-CHOP but with two grade ≥3 immune related adverse events (rash, pneumonitis). The overall and complete response rate was 90% and 77%. With 25·5 months of median follow-up, 2-year progression-free survival (PFS) is 83%. PD-L1 expression was associated with non-GCB subtype, and improved PFS and survival. Pembrolizumab can safely be added to R-CHOP, and is associated with a high CR rate and 2-year PFS. Improved PFS with PR-CHOP in PD-L1 expressing tumors contradicts historical data in R-CHOP treated patients, supporting evaluation of PD-L1 as a biomarker to identify DLBCL patients who may benefit from this first-line strategy.     

A phase II trial evaluating the efficacy of high-dose Radioiodinated Tositumomab (Anti-CD20) antibody,etoposide and cyclophosphamide followed by autologous transplantation,for high-risk relapsed or refractory non-hodgkin lymphoma

Radiation is the most effective treatment for localized lymphoma, but treatment of multifocal disease is limited by toxicity. Radioimmunotherapy (RIT) delivers tumoricidal radiation to multifocal sites, further augmenting response by dose-escalation. This phase II trial evaluated high-dose RIT and chemotherapy prior to autologous stem-cell transplant (ASCT) for high-risk, relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity, and tolerability. Patients age < 60 years with R/R NHL expressing CD20 were eligible. Mantle cell lymphoma (MCL) patients could proceed to transplant in first remission. Patients received I-131-tositumomab delivered at ≤25Gy to critical normal organs, followed by etoposide, cyclophosphamide and ASCT. A group of 107 patients were treated including aggressive lymphoma (N = 29), indolent lymphoma (N = 45), and MCL (N = 33). After a median follow-up of 10.1 years, the 10-year PFS for the aggressive, indolent, and MCL groups were 62%, 64%, 43% respectively. The 10-year OS for the aggressive, indolent, and MCL groups were 61%, 71%, 48% respectively. Toxicities were similar to standard conditioning regimens and non-relapse mortality at 100 days was 2.8%. Late myeloid malignancies were seen in 6% of patients. High-dose I-131-tositumomab, etoposide and cyclophosphamide followed by ASCT appeared feasible, safe, and effective in treating NHL, with estimated PFS at 10-years of 43%-64%. In light of novel cellular therapies for R/R NHL, high-dose RIT-containing regimens yield comparable efficacy and safety and could be prospectively compared.     

Therapeutic effects of proprioceptive exercise on functional capacity,anxiety, and depression in patients with diabetic neuropathy: a 2-month prospective study

Clinical Rheumatology - Diabetic neuropathy (DN) is a common and serious complication of diabetes. DN patients are suffering from anxiety, depression, and impairment of functional capacity. Rare...     

Implementation and impact of a multidisciplinary coagulation factor stewardship program at an academic medical center

Journal of Thrombosis and Thrombolysis -     

Round Pendant Around the Neck–Thyroid. A Review

The rare situation of thyroid stone is discussed with literature review and case report. A case of isolated solitary stone of the thyroid is documented here. There are incidences of calcification in the thyroid gland commonly associated with carcinoma thyroid and multinodular goiter. But solitary stone of thyroid is reported rarely and one such case is reported from India. The possibility of malignancy is high, in case of calcification of thyroid swellings. Hence, isolated calcification should be surgically treated even if fine needle aspiration cytology is negative for malignancy.     

Pre-transplant co-infusion of donor-adipose tissue derived mesenchymal stem cells and hematopoietic stem cells may help in achieving tolerance in living donor renal transplantation

Transplantation tolerance is still a Utopian dream for many transplanters. Mesenchymal stem cells (MSC) have shown immuno-modulatory and tolerogenic effects in experimental models. We present a 29-year-old male with end stage renal disease (ESRD) who was transplanted with HLA 4/6 matched kidney from 51-year-old father in June 2010 preceded by co-infusion of donor-adipose tissue derived mesenchymal stem cells (AD-MSC) and bone marrow derived hematopoietic stem cells (BM-HSC) under non-myeloablative conditioning for deleting rejecting T and B-cells. He has maintained fairly stable graft function with serum creatinine (SCr) between 1.5 and 1.8?mg/dL at 3 years post-transplant with absence of donor specific antibodies (DSA), normal protocol graft biopsy, and peripheral T-regulatory cell levels (pTregs) (CD127^low/?CD25^highCD4⁺) of 4.57% on zero immunosuppression since 6 months.     

A pediatric case series of abdominal epilepsy

Background

Abdominal epilepsy (AE) is an infrequent cause of recurrent abdominal pain in children. It is characterized by paroxysmal episodes of abdominal pain, a variety of other abdominal complaints, electroencephalogram abnormalities, and response to anti-epileptic agents. We described the clinical profile of six patients with AE.

Methods

We conducted a retrospective survey of AE in children from the records of the hospital. The diagnosis of AE was dependent on recurrent abdominal symptoms, subtle central nervous system abnormalities, electroencephalogram abnormalities and response to anticonvulsant agents.

Results

The six patients were diagnosed with AE. The incidence of the disease was 0.07% in all admissions to the pediatric ward. Recurrent pain was common in all patients except two who had additional recurrent vomiting. In this series, the boy to girl ratio (1:2) was unequal.

Conclusion

High suspicion is required for the diagnosis of AE after exclusion of other possible causes.     

Color Doppler Visualization of Intramyocardial Coronary Arteries Using a New Echo System: Effect of Contrast Enhancement and Vasodilation

Utilizing a new echocardiographic system, intramyocardial coronary arteries could be demonstrated by color Doppler in a small number of open chest animals. Both intravenous and intracoronary injections of a contrast agent (Levovist) resulted in significant enhancement of color flow signals with an increase in the length, width, and the number of these vessels. Similar results were obtained with intravenous infusion and direct intracoronary injections of a vasodilator (adenosine).