Citations

SummaryThe effects of ibrutinib on the natural history of autoimmune cytopenias (AIC) among chronic lymphocytic leukaemia (CLL) patients treated in routine clinical practice require further investigation. Using the Mayo Clinical CLL Database, 193 CLL patients treated with ibrutinib between November 2013 and January 2017 outside the context of a clinical trial were identified; complete review of their medical records was performed for details of past history of AIC and treatment‐emergent AIC. We identified 29/193 (15%) patients with history of AIC prior to ibrutinib start. Of 12 patients requiring AIC therapy at ibrutinib start, 8 (67%) were able to discontinue or de‐escalate AIC treatment, and no patient had worsening of their AIC after initiating ibrutinib. Eleven (6%) patients developed treatment‐emergent AIC after a median of 59 (range, 6–319) days following the initiation of ibrutinib, 7 of whom (64%) were able to continue ibrutinib. Overall and event‐free survival from time of ibrutinib start were not significantly different between patients with history of AIC and those with no history of AIC. Treatment‐emergent AIC were seen exclusively in patients with unmutated IGHV and were associated with a shorter EFS. These results suggest a low rate of treatment‐emergent AIC and improvement in patients with existing AIC.

SummaryCD38 is expressed on Waldenström macroglobulinaemia (WM) cells, but its role as a therapeutic target remains undefined. With recent approval of the anti‐CD38 monoclonal antibody, daratumumab (Dara), we hypothesized that blocking CD38 would be lethal to WM cells.In vitroDara treatment of WM cells (including ibrutinib‐resistant lines) elicited antibody‐dependent cellular cytotoxicity (ADCC), complement‐dependent cytotoxicity (CDC), antibody‐dependent cell phagocytosis (ADCP) and direct apoptosis.In vivo, Dara treatment was well tolerated and delayed tumour growth in RPCI‐WM1‐xenografted mice. CD38 is reported to augment B‐cell receptor (BCR) signalling; we noted that Dara significantly attenuated phosphorylated SYK, LYN, BTK, PLCγ2, ERK1/2, AKT, mTOR, and S6 levels, and this effect was augmented by cotreatment with ibrutinib. Indeed, WM cells, including ibrutinib‐resistant WM cell lines treated with the ibrutinib + Dara combination, showed significantly more cell death through ADCC, CDC, ADCP and apoptosis relative to single‐agent Dara or ibrutinib. In summary, we are the first to report thein vitroandin vivoanti‐WM activity of Dara. Furthermore, we show a close connection between BCR and CD38 signalling, which can be co‐targeted with ibrutinib + Dara to induce marked WM cell death, irrespective of acquired resistance to ibrutinib.

AbstractIn a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF2 adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl‐2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole‐based CUR–BF2 and CUR compounds and their bis‐thiocyanato derivatives exhibited high anti‐proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI‐8226) with significantly lower IC50 values versus healthy PBMC cells; they also exhibited higher anti‐proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD‐1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).

Abstract BACKGROUND Reducing length of stay (LOS) in a safe manner has the potential to save significant costs for the care of patients undergoing elective lumbar spine surgery. Due to the relative absence on weekends of staff required for discharging patients to rehabilitation or nursing facilities, we hypothesize that patients undergoing lumbar surgery later in the week have a longer LOS than their counterparts. OBJECTIVE To analyze the effect of day of the week for lumbar surgery on LOS. METHODS Patients undergoing surgery for lumbar degenerative disease were prospectively enrolled in the multicenter quality and outcomes database registry. A multivariable proportional odds regression model was built with LOS as the outcome of interest and patient and surgical variables as covariates. RESULTS A total of 11 897 patients were analyzed. Among those discharged home, the regression analysis demonstrated significantly higher odds of longer LOS for patients undergoing surgery on Friday as compared to Monday ( P < .001). Among those discharged to a facility, there were significantly higher odds of longer LOS for patients undergoing surgery on Wednesday ( P < .001), Thursday ( P < .001), and Friday ( P = .002) as compared to Monday. CONCLUSION The findings of this study suggest that lumbar patients undergoing fusions and those discharged to a facility have longer LOS when surgery is later in the week. Scheduling these patients for surgery earlier in the week and ensuring adequate resources for patient disposition on weekends may lead to LOS reduction and cost savings for hospitals, payers, and patients alike.

AbstractHSTCL is a highly aggressive malignancy with a poor prognosis. Case series and accounts have reported the use of different chemotherapy regimens with diverse patient outcomes. Most long‐term survivors had undergone high‐dose chemotherapy with autologous or allogeneic HCT. We describe two pediatric patients with HSTCL who were treated with chemotherapy followed by allogeneic HCT. Both patients are alive and in complete remission 2 and 8 years after therapy. Multiagent chemotherapy followed with allogeneic HCT seems to provide patients who have chemotherapy‐sensitive disease a long‐term disease‐free survival.

Chondrosarcoma is a cancer of cartilage cells, and despite being a common primary bone tumor, tracheal chondrosarcoma is rare with only 18 cases reported in the literature prior to mid-2016. A 60-year-old gentleman presented with progressively increasing cough, severe stridor, and production of phlegm for approximately 2 years. On admission to our tertiary care hospital, he developed complete obstructive apnea within an hour, and was intubated. A tracheal biopsy was performed, followed by resection. Histopathology confirmed chondrosarcoma of the trachea. The patient tolerated the procedure very well and is currently symptom-free on follow-up, with no signs of recurrence.

Key PointsCoexisting psychiatric comorbidities are associated with greater increased health care utilization and cost of care in patients with MM. Clinical complications of MM are seen more frequently in patients with coexisting psychiatric conditions.