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.

Appendiceal disease in hematopoietic cell transplantation.

Appendiceal diseases are rare reported complications during hematopoietic stem cell transplantation with no guidance on management in the published literature. Medical therapy may be considered in selected patients prior to surgical solutions.

Successful Treatment of Concurrently Diagnosed Multiple Myeloma and Myelodysplastic Syndrome With Isolated Del(5q) With Lenalidomide, Bortezomib, and Dexamethasone.

Lenalidomide is known to be an effective therapy for multiple myeloma and for myelodysplastic syndrome (MDS) with isolated del(5q). We report the case of a patient simultaneously diagnosed with multiple myeloma and myelodysplastic syndrome with isolated del(5q) who was treated successfully with lenalidomide, bortezomib, and dexamethasone. The treatment achieved a stringent complete response of multiple myeloma and a hematologic and cytogenetic response of MDS in three months. Our experience suggests that standard myeloma induction regimens including lenalidomide and a proteasome inhibitor may be considered for treatment of concurrently diagnosed multiple myeloma and MDS with isolated del(5q) and are safe to use in select patients.

Fibrin-Associated Diffuse Large B Cell Lymphoma Found on Revision Arthroplasty of the Knee.

Fibrin-associated diffuse large B cell lymphoma (FA-DLBCL) is a rare Epstein-Barr viruspositive B cell lymphoma that is nonmass-forming, does not directly produce symptoms, and is incidentally discovered on histological examination of tissues excised for other reasons. Despite overlap in morphologic and immunophenotypic features with aggressive B cell neoplasms, FA-DLBCL shows an excellent clinical outcome, even with surgical excision alone. We report an extremely rare occurrence of FA-DLBCL found in association with a metallic implant on revision arthroplasty of the knee. This report also illustrates the need for an integrated multidisciplinary approach for accurate diagnosis and avoidance of overtreatment.

Gamma-Delta T-Cell Lymphoma Following Allogeneic Stem Cell Transplant for Primary Myelofibrosis.

Primary myelofibrosis (PMF) is a disease that affects the bone marrow. It presents with cytopenias, hepatospleomegaly accompanied with extramedullary hematopoiesis, and often with constitutional symptoms. Cytotoxic gamma-delta T-cells are considered a distinct hepatosplenic lymohoma. This is a case presentation of a 43-year-old male with an initial diagnosis of PMF who underwent allogeneic stem cell transplantation complicated by primary graft failure. He subsequently underwent a partial splenic embolization; however, he quickly developed a fulminant hepatosplenic gamma-delta T-cell lymphoma which led to his death that was diagnosed posthumously. PMF has been known to transform into an acute myeloid leukemia, but there has been no established link with gamma-delta T-cell lymphoma.

Essential Thrombocythemia Complicated by Occlusive Thrombosis of the Abdominal Aorta.

INTRODUCTION: Essential thrombocythemia (ET) is a myeloproliferative neoplasm of excessive platelet production complicated by thrombohemorrhagic events. Thrombosis typically occurs in small to medium vessels; thrombosis of large vessels is rare. CASE PRESENTATION: A 75-year-old woman with ET complicated by bilateral retinal vein occlusion was evaluated for fatigue, early satiety, and unintentional weight loss. Her hypertension was well controlled, and her chronic lower extremity claudication from peripheral artery disease was stable. She reported adherence to aspirin 81 mg and hydroxyurea 1000 mg daily, and her platelets (375 × 109/L) were at goal. Bone marrow biopsy was consistent with ET without progression to myelofibrosis or leukemia. CT abdomen demonstrated complete occlusion of the infrarenal aorta, extending into the common iliac arteries, with reconstitution of flow distally via collaterals. The addition of clopidogrel, for platelet inhibition, and cilostazol, for claudication, caused symptom improvement without further thrombosis or bleeding. DISCUSSION: There are few published reports of ET complicated by aortic thrombosis. To our knowledge, this is the first report of aortic thrombosis occurring in an ET patient with normal platelet count on antiplatelet and cytoreductive therapies. There is limited evidence to guide treatment, but medical management with triple antiplatelet therapy may be effective in selected patients.

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.

Implementing a Multidisciplinary Approach to Enhance Compliance With Guideline-Recommended Prechemotherapy Pneumococcal Vaccination in a Military-Based Medical Oncology Practice.

PURPOSE: Patients with cancer are at increased risk for invasive pneumococcal disease, including community-acquired pneumonia. Current Advisory Committee on Immunization Practices and National Cancer Comprehensive Network guidelines recommend pneumococcal vaccination for immunocompromised patients, including patients with cancer. METHODS: We conducted a quality improvement (QI) project to enhance compliance with pneumococcal vaccination in patients before their chemotherapy. Baseline pneumococcal vaccination rates were gathered from July 2013 to June 2014. We reviewed the current guidelines for pneumococcal vaccinations in patients with cancer with physicians and encouraged them to prescribe the pneumococcal vaccination to patients before therapy. We also recruited our clinic nurse practitioner, who meets all patients for chemotherapy teaching, to prescribe the vaccine to patients younger than 65 years of age. RESULTS: During the baseline period, of the 110 patients younger than 65 years who received chemotherapy, seven (6.4%) received the pneumococcal vaccine. Of the 90 patients (median age, 60 years; range, 20 to 86 years) who received chemotherapy during the study period, 58 were younger than 65 years, of whom three patients were already vaccinated before their diagnosis. Twenty-five (45.5%) patients were vaccinated through our QI project. We have improved our compliance with pneumococcal vaccination by 39% ( P < .001). CONCLUSION: We have improved compliance with pneumococcal vaccination in patients with cancer receiving chemotherapy in our clinic through a QI project. We found that screening is best accomplished by a single person who is able to screen all patients. This practice is now a standard of care in our clinic.

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.

Acute pain transfusion reaction.

A 34-year-old woman with a diagnosis of hemophagocytic lymphohistocytosis (HLH) received a double umbilical cord blood transplantation following a myeloablative chemotherapy preparative regimen with busulfan and cyclophosphamide. HLH is a rare, potentially fatal hematologic disorder characterized by the overactivation of histocytes and T lymphocytes, leading to organ infiltration and acute illness. On day 25 post-transplantation, the patient required a platelet transfusion for a platelet count of 6,000 per ml (normal range = 150,000-450,000 per ml). The patient's blood type prior to the cord blood transplantation was B positive and, although both umbilical cord blood donors were O positive, the patient was still B positive per blood bank testing on that day. Although the recipient of an allogenic stem cell transplantation will eventually become the blood type of the donor, the time for this process to occur varies for each person. That process must be monitored by the blood bank for the purpose of cross-matching blood products to decrease hemolysis as much as possible. The patient was premedicated with the facility's standard for platelet transfusions: acetaminophen 650 mg and diphenhydramine 25 mg about 30 minutes prior to the platelet transfusion.

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.

Patterns of care in a population-based sample of soft tissue sarcoma patients in the United States.

BACKGROUND: Soft tissue sarcomas (STS) are relatively uncommon tumors. Data regarding the patterns of care of patients with STS and its consistency with available guidelines are relatively sparse. The authors conducted a detailed analysis of STS patients diagnosed in 2002 and sampled from the Surveillance, Epidemiology, and End Results registries. METHODS: The authors sampled 1369 patients with invasive sarcomas. Hospital records were reabstracted, and treating physicians were contacted to verify the therapy provided to each patient. RESULTS: The median age of patients was 60 years. There was a slight male predominance among the patients with nongynecologic sarcomas. Fifty percent of the patients had localized stage sarcoma. Most patients received surgery, but negative margins were obtained in only 50% of patients. Complete resection was less frequent in patients >or=50 years old. Radiation therapy was used in 53% of patients with extremity sarcomas but in only 20% to 30% of the patients with sarcomas at other sites. About 27% of all patients received chemotherapy. Tumor grade was significantly associated with the use of radiation and chemotherapy. Surgical resection, tumor grade, tumor size, use of radiation therapy, and age significantly influenced survival. CONCLUSIONS: Patterns of care of STS differ based on the site of the tumor. The patterns of care for extremity sarcomas are fairly consistent with the available recommendations, but the patterns of care for other sites are less consistent. In addition to certain tumor characteristics, age of the patient was significantly associated with therapy and patient outcome.

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.

Treatment of a population based sample of men diagnosed with testicular cancer in the United States.

OBJECTIVES: Testicular cancer is the most common cancer in men age 25 to 35 years. We examined therapy, compliance with guidelines, and survival in a population based sample of men newly diagnosed with testicular cancer. MATERIALS AND METHODS: We analyzed the National Cancer Institute's (NCI) patterns of care data on 702 men diagnosed with testicular cancer in 1999. These studies supplement routine data collection by verifying therapy with the patients' treating physicians. Follow-up for vital status was available through December 31, 2004. RESULTS: The majority of the men with seminoma were diagnosed while their cancer was localized and more than 80% of received orchiectomy with radiation. For men with seminoma and nonseminoma germ cell tumors (NSGCT), the percent receiving chemotherapy increased markedly as stage increased. More than 90% of men with regional and distant NSGCT received chemotherapy. Less than 25% of men with localized NSGCT received orchiectomy and retroperitoneal lymph node dissection (RPLND), about 40% had surveillance following an orchiectomy alone, and 30% received orchiectomy and chemotherapy. CONCLUSIONS: The majority of these patients received therapy consistent with guidelines. While there was no significant difference in the use of RPLND in men with localized NSGCT by geographic region, chemotherapy use varied widely. Over 90% of men with localized or regional disease diagnosed in 1999 were alive at the end of 2004. The excellent survival rates point to the need to monitor for late effects of therapy.

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.