Antithymocyte globulin for aplastic anemia secondary to pembrolizumab: a case report and review of literature.

Aplastic anemia is a rare but potentially serious complication of immune checkpoint inhibitor therapy. The authors present a case of pembrolizumab-induced aplastic anemia that was refractory to steroids but had some hematologic response to modified-dosing antithymocyte globulin (ATG). This is the first reported case of hematological response to ATG for immune checkpoint inhibitor-induced aplastic anemia and the first reported case of modified ATG dosing for this indication. Cases of immune checkpoint inhibitor-induced aplastic anemia and management options are also summarized. Given the high morbidity and mortality associated with ICI-induced aplastic anemia, more data is necessary to guide evidence-based management recommendations.

Immune checkpoint inhibitors (ICIs) are a form of anticancer therapy that enlists the body's own immune system to fight cancer cells. Although remarkably effective against some types of cancer, ICIs can also cause the augmented immune system to attack noncancer cells, resulting in unwanted off-target side effects. One rare but potentially serious complication of ICIs is aplastic anemia, where the body stops producing enough new blood cells. There is little known about ICI-induced aplastic anemia. The authors present a case of ICI-induced aplastic anemia that did not improve with standard treatment but had some response to antithymocyte globulin, which has not been previously reported. Previously published cases of ICI-induced aplastic anemia and management options are also summarized.

Delivery of Adjuvant Oxaliplatin for Colon Cancer: Insights From Routine Clinical Practice.

BACKGROUND: Adjuvant oxaliplatin is now a standard treatment option for patients with early-stage colon cancer. However, treatment delivery and outcomes achieved in routine practice are not well described. METHODS: All cases of colon cancer diagnosed in Ontario from 2002 to 2008 were identified using the Ontario Cancer Registry. Pathology reports were obtained for a 25% random sample to identify stage II and III cases; patients treated with adjuvant oxaliplatin were included in this analysis. Treatment records were reviewed to identify oxaliplatin dose reductions or omissions. Modified Poisson regression was used to evaluate factors associated with dose reduction/omission. Cox proportional hazards model was used to explore factors associated with cancer-specific survival (CSS) and overall survival (OS). RESULTS: The study population included 532 patients; 88% (469/532) had stage III disease. The mean/median number of oxaliplatin cycles delivered was 10/12. A dose reduction/omission of oxaliplatin occurred in 54% of cases (288/532), and the dose was subsequently escalated in 34% of these (97/288). Women were more likely than men to have dose reduction/omission (relative risk, 1.29; 95% CI, 1.10-1.51). Dose reduction/omission was not associated with inferior CSS (hazard ratio [HR], 0.76; 95% CI, 0.51-1.14) or OS (HR, 0.81; 95% CI, 0.59-1.13). Five-year CSS and OS of all cases were 77% (95% CI, 72-81) and 72% (95% CI, 68-76), respectively. On-treatment mortality rates were 1% and 3% within 30 and 90 days of oxaliplatin, respectively. CONCLUSIONS: Dose reductions of adjuvant oxaliplatin are common in routine practice but are not associated with inferior survival. Long-term survival achieved in the general population is comparable to the results of clinical trials.

Severe asthma associated with myasthenia gravis.

Severe asthma constitutes a subgroup of approximately 10% of all asthma cases. Approximately one-half of these individuals have a refractory form of the disease in which atopy and T-helper cell 2-skewed immunological response may not be as closely linked to the disease as in other phenotypes of asthma. This suggests that not all asthma is explained by a T-helper cell 2-skewed immunological response, and that other immunological mechanisms may be important in this category of nonatopic asthma. The authors present a case involving a 55-year-old Caucasian man with nonatopic, adult-onset asthma, nonsteroidal anti-inflammatory drug sensitivity and idiopathic urticaria. This individual presented two years following his initial asthma diagnosis with diplopia and mild ptosis, and was subsequently diagnosed with seropositive myasthenia gravis.

Pathway-specific apoptotic gene expression profiling in chronic lymphocytic leukemia and follicular lymphoma.

Defects in the apoptotic pathway are pathogenetically important in chronic lymphocytic leukemia and follicular lymphoma. To further understand these defects, we profiled the apoptotic gene expression of these two neoplasms. Oligonucleotide arrays with 112 apoptotic genes were used, and data analysis was performed on seven chronic lymphocytic leukemia and 10 follicular lymphoma frozen tumor samples from six and seven patients, respectively. The overall gene expression pattern was strikingly similar among all 17 samples, regardless of the type of lymphoma and history of chemotherapy exposure. MCL1, TNFRSF1B and TNFRSF7 were highly expressed in most cases. The apoptotic gene expression between the groups of untreated chronic lymphocytic leukemia (n=3) and untreated follicular lymphoma (n=6) was also similar (Pearson correlation coefficient, 0.94). Comparison between the groups of untreated chronic lymphocytic leukemia (n=3) and postchemotherapy chronic lymphocytic leukemia (n=4) revealed six genes with >2-fold changes, including BIRC5/Survivin that was higher in the postchemotherapy samples. This finding was validated by immunohistochemistry. Similar analysis of follicular lymphoma cases did not identify any significant differences. To conclude, our findings suggest that chronic lymphocytic leukemia and follicular lymphoma share common apoptotic defects, and highlight the importance of MCL1 and the TNF pathway. Upregulation of survivin may be one of the mechanisms by which chronic lymphocytic leukemia becomes desensitized to chemotherapy.