Therapy-Related Acute Promyelocytic Leukemia Developed During Pembrolizumab Therapy.

A 75-year-old male was diagnosed with carcinoma in-situ of the bladder. He failed standard therapy and was started on pembrolizumab to prevent the need for cystectomy. His malignancy recurred, and he was treated with intravesical valrubicin and gemcitabine/docetaxel. Three years after starting pembrolizumab, he developed severe neutropenia and thrombocytopenia. He was treated for suspected auto-immune cytopenias but was later found to have acute promyelocytic leukemia on peripheral blood smear and cytometry. He was hospitalized, treated with all-trans retinoic acid and arsenic trioxide, and is currently in molecular remission. This case describes therapy-related acute promyelocytic leukemia (t-APL) diagnosed while on pembrolizumab. Pembrolizumab is an immune checkpoint inhibitor that exhibits anti-tumor effects. Development of hematologic malignancies after immune checkpoint inhibitor therapy is rare. The definitive etiology of our patient's t-APL is uncertain; however, it is more likely that he developed de novo acute promyelocytic leukemia (APL), which was suppressed by pembrolizumab and later revealed when pembrolizumab was discontinued.

Salvage extracorporeal membrane oxygenation in induction-associated acute respiratory distress syndrome in acute leukemia patients: A case series.

BACKGROUND:: The prognosis of hematologic malignancies has improved over the past three decades. However, the prognosis in hematologic malignancies with severe acute respiratory distress syndrome has remained poor. Initial reports regarding the utility of extracorporeal membrane oxygenation in hematologic malignancies have been controversial, with limited evaluations of acute leukemia patients supported by extracorporeal membrane oxygenation. METHODS:: We conducted a retrospective review of patients with acute leukemia who developed acute respiratory distress syndrome requiring veno-venous extracorporeal membrane oxygenation support at our facility from July 2015 through August 2017. RESULTS:: Four cases of acute myelogenous leukemia with respiratory failure and acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation while undergoing induction chemotherapy were identified. All patients completed induction therapy with addition of extracorporeal membrane oxygenation support, with two patients dying secondary to their acute leukemia and the other two surviving to allogeneic hematopoietic stem cell transplant. Overall, 75% (three of four) survived to decannulation with a 1-year survival rate following extracorporeal membrane oxygenation of 50% (two of four). CONCLUSION:: Currently, the use of extracorporeal membrane oxygenation in patients with hematologic malignancies who develop severe acute respiratory distress syndrome remains controversial. Although extracorporeal membrane oxygenation in post-allogeneic hematopoietic stem cell transplant is associated with poorer outcomes, our data suggest that salvage extracorporeal membrane oxygenation support is a viable option to manage moderate to severe acute respiratory distress syndrome while completing therapeutic chemotherapy and following in the peri-induction phase of acute leukemia.

Peripheral Smear Review and Bone Marrow Biopsy Correlation.

INTRODUCTION: Peripheral Blood Smear (PBS) interpretation is a useful skill for Haematology/Oncology Clinicians (HOC). AIM: To explore practice patterns of PBS utilization for all benign haematology diagnosis in a non-simulated environment and to evaluate how it may guide the HOC in determining further work up and whether or not to perform a Bone Marrow Biopsy (BMB). MATERIALS AND METHODS: A retrospective review was conducted on 451 outpatient referrals for benign haematology diagnosis. Patient demographics and diagnostic tests were recorded. We further analysed cases in which a blood smear was ordered or reviewed. In cases with PBS review, we recorded testing ordered by the HOC. RESULTS: Records of 451 patients met inclusion criteria. The median age was 55 with males representing 51.9% of the cohort. Distribution of disorders were 50.6% (n = 228) erythrocyte (RBC), 25.5% (n = 114) leukocyte (WBC), 11.3% (n = 51) platelet (PLT), and 12.8% (n = 58) "other." A CBC was ordered in 82.7% of cases (373/451). A PBS was ordered in 47.4% of CBCs obtained (177/373, p<0.001). Of these, documentation occurred in 49.2% (87/177) which led to further testing 41.4% of cases (36/87). A BMB was performed in 11.5% (10/87) of cases in which a PBS was reviewed compared to 4.3% (16/373) of cases where BMB was performed without PBS review (p=.019). Of the 36 cases in which PBS review led to testing, 10 BMBs (27.8%) were performed-all of which led to specific haematologic diagnosis. A specific diagnosis was found in 43.8% (7/16) BMBs performed without prior PBS review. CONCLUSION: PBS interpretation is an important skill for HOCs. Haematology/Oncology (H/O) training programs should continue to teach this skill to increase proficiency in order to help guide diagnostic evaluation of various haematologic disorders.

Everolimus Implicated in Case of Severe Gastrointestinal Hemorrhage.

Breast cancer remains the leading cause of cancer and the third leading cause of cancer related deaths among our population with an estimated number of 246,660 new cases and 40,450 deaths in 2016. With treatment advancements, including targeted agents such as Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, survivability and quality of life continue to improve. However, with the use of these agents come adverse effects, some of which are still being characterized. Our case demonstrates recurrent episodes of gastrointestinal bleeding in a 60-year-old woman being treated with Everolimus for progressive metastatic breast cancer. On endoscopy, bleeding was secondary to erosive gastritis. Previous case reports have described bleeding due to gastric antral vascular ectasia (GAVE), which was described in two prior reported cases. In our case, bleeding also occurred on a reduced dose of Everolimus compared to what is previously reported (5 mg versus 10 mg). As a result of her gastrointestinal bleeding, she required multiple endoscopic interventions including argon plasma coagulation and multipolar heater probe to achieve hemostasis. This is the first case reported of gastrointestinal bleeding not consistent with GAVE and occurring while being on a reduced dose of Everolimus. It is important to document our case so that the Gastroenterology and Hematology communities can be educated and made aware for their patient populations on Everolimus.

Rates of Microbiologically Diagnosed Infection and Pathogen Detection in Hematopoietic Stem Cell Transplant Patients.

Infections remain a significant cause of mortality in hematopoietic stem cell transplant patients. Evaluations of causes of infection are often unrevealing, and at some sites, increasing rates of antimicrobial resistance have been noticed. We performed a retrospective analysis of infection rates and microbiologic testing yield, or percent of tests ordered to diagnose an infection, in the first 100 days of 30 allogeneic and 56 autologous stem cell transplants performed at San Antonio Military Medical Center from July 2011 to April 2014. Blood stream infections were diagnosed in 11.6% with a yield of 6%. Urinary tract infections were diagnosed in 2.3% with a yield of 3%. Clostridium difficile infections were diagnosed in 9.3% and testing yield was 6%. Incidence of respiratory viruses was 5.8% with 4 rhinoviruses/enteroviruses and 1 influenza virus identified. One Proteus mirabilis urinary isolate was an extended spectrum beta-lactamase producer. Five patients, 13% of allogeneic and 4% of autologous patients, died within the first 100 days post-transplantation. History of bacteremia was present in 60% of patients who died; however, only one died due to a microbiologically diagnosed infection. Improved diagnostic tests and methods are needed to increase yield of detection of infection in hematopoietic stem cell transplant patients.

Review of Commonly Used Serum Tumor Markers and Their Relevance for Image Interpretation.

Serum tumor markers are firmly entrenched as one of the primary tools in an oncologist's armamentarium. They can be implemented in a broad range of applications from diagnostic assistance, assessing prognosis, or guiding therapeutic decisions. However, tumor markers also have limitations, which significantly impact how they should be used. Radiologists should be familiar with the following most prevalent tumor markers, which will all be discussed here: prostate-specific antigen (prostate), carcinoembryonic antigen (colon), α-fetoprotein (hepatocellular and testicular), carbohydrate antigen 19.9 (pancreas), cancer antigen 125 (ovarian), human chorionic gonadotropin/lactic dehydrogenase (testicular), and chromogranin A (neuroendocrine). This knowledge should avoid needless intervention, enhance image interpretation, and ultimately provide optimal patient care.

Ectopic breasts: familial functional axillary breasts and breast cancer arising in an axillary breast.

Supernumerary breasts and nipples are not uncommon and have familial and syndrome associations. Although usually of only cosmetic concern, hormonal changes and inflammatory or neoplastic conditions that affect primary breast tissue also may occur in areas of ectopic breast tissue. We describe cases of familial functional axillary breasts and primary carcinoma of the breast arising in ectopic axillary breast tissue.

Pasteurella multocida epiglottitis: A review and report of a new case with associated chronic lymphocytic leukemia.

Pasteurella multocida is a gram-negative coccobacillus that primarily affects animals. P multocida infections in humans are usually associated with animal contact. To the best of our knowledge, only 7 cases of P multocida epiglottitis have been previously reported in the English-language literature; none of these cases occurred in a patient with chronic lymphocytic leukemia. We describe what we believe is the first reported case of P multocida epiglottitis in a patient with chronic lymphocytic leukemia, and we review the previous reports of this rare entity.

The use of higher dose clofarabine in adults with relapsed acute lymphoblastic leukemia.

The standard dose of clofarabine is 52 mg/m2 for pediatrics and 40 mg/m2 in adults. Clofarabine dosed at 52 mg/m2 was used in adult patients with refractory ALL to maximize response before allo-HSCT. All patients had a significant response to therapy. Published pharmacokinetic analysis revealed no difference in peak plasma or intracellular concentrations at clofarabine dosed above 40 mg/m2, yet inhibition of replication in leukemia cells was only sustained over 24 hr at 55 mg/m2. Despite this, there have been no reports of high dose clofarabine used in this setting. Our experience implies that there may be a niche role for clofarabine in reducing disease burden before allo-HSCT for adults with relapsed ALL.

Pulmonary cutaneous metastasis: a case report and review of common cutaneous metastases.

The literature on cutaneous metastatic disease can be difficult to interpret because of inconsistent study design and analysis among authors. Furthermore, one should be careful when reviewing the statistics in the literature, as reported patient populations tend to vary and are not representative of the whole population. However, certain trends are notable and should be reported. Diagnosis of cutaneous metastatic disease carries a grave prognosis. We describe a patient with pulmonary cutaneous metastasis and provide a review of the literature on nonmelanomatous solid tumor malignancies that most commonly have cutaneous metastases. The review will focus on epidemiology, clinical presentation, histology and immunohistochemical staining, and prognosis and management. The most common cutaneous metastasizing carcinomas--breast, lung, and colorectal cancer--also are discussed.

Comparison of cancer diagnosis and treatment in Medicare fee-for-service and managed care plans.

OBJECTIVE: To compare the Medicare managed care (MC) and fee-for-service (FFS) sectors on stage at diagnosis and treatment patterns for prostate, female breast, and colorectal cancers, and to examine patterns across MC plans. DATA: Surveillance, Epidemiology, and End Results-Medicare linked data. METHODS: Among cases diagnosed at ages 65-79 between 1998 and 2002, we selected all MC enrollees (n = 42,467) and beneficiaries in FFS (n = 82,998) who resided in the same counties. MC and FFS samples were compared using logistic regression, adjusting for demographic, geographic, and clinical covariates. RESULTS: The percentage of late stage cases was similar in MC and FFS for prostate and colorectal cancers; there were slightly fewer late stage breast cancer cases in MC after adjustment (7.3% vs. 8.5%, P < 0.001). Within MC, radical prostatectomy was performed less frequently for clinically localized prostate cancer (18.3% vs. 22.4%, P < 0.0001), and 12 or more lymph nodes were examined less often for resected colon cancer cases (40.9% vs. 43.0%, P < 0.05). Treatment patterns for early stage breast cancer were similar in MC and FFS. Analyses of treatment patterns at the individual plan level revealed significant variation among plans, as well as within the FFS sector, for all 3 types of cancer. CONCLUSIONS: On average, there are few significant differences in cancer diagnosis and treatment between MC and FFS. Such comparisons, however, mask the wide variability among MC plans, as well as FFS providers. Observed variation in patterns of care may be related to patient selection, but can potentially lead to outcome differences. These findings support the need for quality measures to evaluate plan practices and performance.

Neoadjuvant therapy before radical prostatectomy for clinical T3/T4 carcinoma of the prostate: 5-year followup, Phase II Southwest Oncology Group Study 9109.

PURPOSE: Several investigators have examined the role of hormonal therapy before definitive local therapy for locally advanced prostate cancer to improve outcome. We evaluated the resectability rate and clinical response rate to 16 weeks of total androgen blockage therapy for clinically locally prostate cancer before radical prostatectomy, and progression-free survival in this multi-institutional study. MATERIALS AND METHODS: Southwest Oncology Group 9109 was a phase II feasibility study designed to treat patients with clinical stage C prostate cancer (T3, T4, N0 and M0). Cases were classified by stage T3 versus T4 and bulky (greater than 4 cm.) versus nonbulky (or less 4 cm.) disease. The neoadjuvant agents used were goserelin and flutamide before radical prostatectomy. RESULTS: A total of 62 patients were accrued to the study and 1 patient was ineligible. There were 2 protocol deviations and these patients refused to undergo prostatectomy after hormonal therapy. Four patients went off protocol treatment because they were not considered surgical candidates. The racial distribution was 72% white, 20% black, 7% Hispanic and 2% Asian. Clinical stage at diagnosis was T3 in 97% and T4 in 3% of cases. Of the patients 39% were diagnosed with bulky disease. Of the 61 eligible patients 55 (90%) underwent a prostatectomy. The 5-year progression-free survival estimate was 70% (24 of 61 cases failed) and the 5-year survival estimate was 90% (11 of 61 deaths). Most of the patients in this trial would have been considered inoperable and referred to radiation oncology. CONCLUSIONS: Neoadjuvant hormonal therapy followed by radical prostatectomy is reasonable and appropriate for clinical stage T3 prostate cancer. A progression-free and overall 5-year survival of 70% and 90%, respectively, compares favorably to Radiation Therapy Oncology Group neoadjuvant trial outcomes for this stage of prostate cancer.