Incidence of chemotherapy-induced peripheral neuropathy within 12 weeks of starting neurotoxic chemotherapy for multiple myeloma or lymphoma: a prospective, single-center, observational study.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) may necessitate chemotherapy dose reduction, delay, or discontinuation. This pilot study tested feasibility of patient enrollment, CIPN screening, and data collection in cancer patients for a future clinical study that will assess the safety and efficacy of an intervention that may prevent CIPN. METHODS: This prospective, observational, single-center, pilot study included adults with newly diagnosed lymphoma or multiple myeloma receiving neurotoxic chemotherapy. Patients were enrolled between September 2016 and February 2017. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire was completed by patients at 3 time points: baseline, week 6, and week 12. The primary outcome was change in the neurotoxicity score between these time points. RESULTS: Of 33 patients approached for consent, 28 (85%) provided consent and were enrolled. The FACT/GOG-Ntx questionnaire was completed by 28 (100%) at baseline, 25 (89%) at week 6, and 24 (86%) at week 12. Average (standard deviation) neurotoxicity scores were 36.5 (6.6) at baseline, 34.0 (8.3) at week 6, and 30.6 (7.6) at week 12. Neurotoxicity scores changed from baseline by - 2.7 points (95% CI - 5.5 to 0.1; p = 0.061) at week 6 and - 6.0 points (95% CI - 5.6 to - 0.8; p = 0.012) at week 12. Clinically meaningful declines (decrease of > 10% from baseline) in neurotoxicity score were detected in 36% (9 of 25) at week 6 and in 67% (16 of 24) at week 12. CONCLUSION: Sixty-seven percent of patients experienced clinically significant CIPN within 12 weeks of starting chemotherapy. Feasibility metrics for enrollment, consent, CIPN assessment, and follow-up were met.

Delayed autologous stem cell transplantation following cardiac transplantation experience in patients with cardiac amyloidosis.

This study sought to retrospectively investigate the outcomes of patients with light-chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1-year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004-2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart-kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8-32.9 months) post-HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart-lung transplantation. A strategy of delayed ASCT 1-year post-HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.

Light Chain Amyloidosis: Epidemiology, Staging, and Prognostication.

Amyloidosis is a disorder of protein misfolding and metabolism in which insoluble fibrils are deposited in various tissues, causing organ dysfunction and eventually death. Out of the 60-plus heterogeneous amyloidogenic proteins that have been identified, approximately 30 are associated with human disease. The unifying feature of these proteins is their tendency to form beta-pleated sheets aligned in an antiparallel fashion. These sheets then form rigid, nonbranching fibrils that resist proteolysis, causing mechanical disruption and local oxidative stress in affected organs such as the heart, liver, kidneys, nervous system, and gastrointestinal tract. Here we review the epidemiology of light chain amyloidosis, the staging, and the concomitant prognostication that is critical in determining the appropriate treatment.

Diffuse Cerebral Edema and Impending Herniation Complicating Hepatic Encephalopathy in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disease characterized by the formation of cutaneous and visceral telangiectasias and arteriovenous malformations (AVM). Multiple organs may be affected, including the nasal mucosa, skin, lungs, gastrointestinal tract, and brain. The following case highlights a unique manifestation of HHT in a patient with a gastrointestinal hemorrhage and epistaxis, resulting in hyperammonemia and diffuse cerebral edema and herniation. Clinicians should be aware of this potential complication in such patients and initiate ammonia-reducing agents early to avoid this devastating consequence.

Establishing a multidisciplinary taskforce to improve anticoagulation safety at a large health system.

PURPOSE: To describe the development of a multidisciplinary anticoagulant safety taskforce (ASTF) to address anticoagulation-related issues across the medication-use system. SUMMARY: Oral and parenteral anticoagulants have been classified as high-alert medications because of their potential for harm. Errors at the point of prescribing, monitoring, and administering therapy have been noted in safety literature. Our hospital system, which includes 1 academic medical center, 6 community hospitals, and 1 long-term care facility, designed a multidisciplinary ASTF to address anticoagulation-related issues. The ASTF used the 2017 Institute for Safe Medication Practices (ISMP) Medication Safety Self-Assessment for Antithrombotic Therapy as the primary tool for reviewing current practices, performing gap analyses, and identifying our greatest areas of opportunity. The top 8 best practice elements related to anticoagulant use were identified for initial efforts of ASTF activity. Meetings were led by a medication safety pharmacist who reviewed process opportunities and actions to address gaps. The hospital chief quality and patient safety officer and the vice president of quality were the executive sponsors of the ASTF. Key stakeholders such as the medication safety committee chair and the president of the medical staff were instrumental in leading the initiative. Recommendations from the ASTF were reviewed and approved by the system medication safety committee and the system pharmacy and therapeutics committee to support system-wide implementation. The ASTF accomplished more than initially planned within its first year. Error mitigation occurred through policy revisions, order set development and modification, and implementation of practice changes to comply with each best practice. The ISMP antithrombotic self-assessment score improved from 67% to 87%, surpassing the initially targeted score of 75%. To overcome implementation barriers with the electronic health record, we enlisted support from our informatics leadership to leverage information technology. Overall, the success of the taskforce was attributed to the teamwork and leadership of key individuals within the organization. CONCLUSION: Leveraging interest from key stakeholders across multiple disciplines with an established assessment tool was key in developing a productive and successful ASTF. The group came together to evaluate anticoagulant-related issues and implement sustainable changes to decrease anticoagulation error potential.

Vancomycin-induced immune thrombocytopenia.

BACKGROUND: Vancomycin has only rarely been implicated as a cause of thrombocytopenia, and there is only limited evidence that this complication is caused by immune mechanisms. We conducted a study to determine whether thrombocytopenia is caused by vancomycin-dependent antibodies in patients being treated with vancomycin. METHODS: We identified and characterized vancomycin-dependent, platelet-reactive antibodies in patients who had been referred for testing during a 5-year period because of a clinical suspicion of vancomycin-induced thrombocytopenia. We obtained clinical information about the patients from their referring physicians. RESULTS: Drug-dependent, platelet-reactive antibodies of the IgG class, the IgM class, or both were identified in 34 patients, and clinical follow-up information was obtained from 29 of these patients. The mean nadir platelet count in these patients was 13,600 per cubic millimeter, and severe bleeding occurred in 10 patients (34%). Platelet levels returned to baseline in all 26 surviving patients after vancomycin was stopped. In 15 patients, the drug was continued for 1 to 14 days while other possible causes of thrombocytopenia were investigated. Vancomycin-dependent antibodies were not found in 25 patients who had been given vancomycin and in whom thrombocytopenia did not develop. CONCLUSIONS: Severe bleeding can occur in patients with vancomycin-induced immune thrombocytopenia. The detection of vancomycin-dependent antiplatelet antibodies in patients receiving the antibiotic in whom thrombocytopenia develops, and the absence of antibodies in patients given the drug in whom platelet counts remain stable, indicate that these antibodies are the cause of the thrombocytopenia.

Hypereosinophilia associated with echinacea use.

Echinacea, believed by herbal practitioners to enhance the immune system, is one of the most widely used herbal supplements in the United States. Like most herbal products, it lacks strict FDA regulation and more information is needed about its potential adverse reactions. Here, we report the case of a patient with eosinophilia of unclear etiology whose condition resolved after cessation of this supplement. We feel this likely represents an IgE-mediated allergic process to echinacea.

Anemia and leukopenia following intravenous colloidal silver infusions-Clinical and hematological features, unique peripheral blood film appearance and effective therapy with supplemental oral copper and apheresis.

Alternative medical therapy with multiple intravenous colloidal silver infusions may cause severe illness, including profound copper deficiency-induced anemia and hepatic toxicity. No chelating agent for silver poisoning exists and effective therapy requires apheresis in combination with continuous administration of oral copper.

Responses to human CD40 ligand/human interleukin-2 autologous cell vaccine in patients with B-cell chronic lymphocytic leukemia.

PURPOSE: Human CD40 ligand activates the malignant B-cell chronic lymphocytic leukemia cells and enhances their capacity to present tumor antigens. Human interleukin-2 further potentiates the immunogenicity of human CD40 ligand in preclinical murine models. EXPERIMENTAL DESIGN: We prepared autologous B-cell chronic lymphocytic leukemia cells that expressed both human CD40 ligand (>90% positive) and human interleukin-2 (median secretion, 1,822 pg/mL/10(6) cells; range, 174-3,604 pg). Nine patients were enrolled in a phase I trial, receiving three to eight s.c. vaccinations. RESULTS: Vaccinations were administered without evidence of significant local or systemic toxicity. A B-cell chronic lymphocytic leukemia-specific T-cell response was detected in seven patients. The mean frequencies of IFN-gamma, granzyme-B, and IL-5 spot-forming cells were 1/1,230, 1/1,450, and 1/4,500, respectively, representing a 43- to 164-fold increase over the frequency before vaccine administration. Three patients produced leukemia-specific immunoglobulins. Three patients had >50% reduction in the size of affected lymph nodes. Nonetheless, the antitumor immune responses were observed only transiently once immunization ceased. High levels of circulating CD4+/CD25+/LAG-3+/FoxP-3+ immunoregulatory T cells were present before, during and after treatment and in vitro removal of these cells increased the antileukemic T-cell reactivity. CONCLUSIONS: These results suggest that immune responses to B-cell chronic lymphocytic leukemia can be obtained with human CD40 ligand/human interleukin-2-expressing s.c. vaccines but that these responses are transient. High levels of circulating regulatory T cells are present, and it will be of interest to see if their removal in vivo augments and prolongs the antitumor immune response.

Use of an Intravascular Warming Catheter during Off-Pump Coronary Artery Bypass Surgery in a Patient with Severe Cold Hemagglutinin Disease.

Cold hemagglutinin disease with broad thermal amplitude and high titers presents challenges in treating cardiac-surgery patients. Careful planning is needed to prevent the activation of cold agglutinins and the agglutination of red blood cells as the patient's temperature drops during surgery. We describe our approach to mitigating cold agglutinin formation in a 77-year-old man with severe cold hemagglutinin disease who underwent off-pump coronary artery bypass surgery without the use of preoperative plasmapheresis. This experience shows that the use of an intravascular warming catheter can maintain normothermia and prevent the activation and subsequent formation of cold agglutinins. To our knowledge, this is the first reported use of this technique in a patient with cold hemagglutinin disease. The chief feature in this approach is the use of optimal thermal maintenance-rather than the more usual decrease in cold-agglutinin content by means of therapeutic plasma exchange.

Role of radiation therapy in a patient with primary pancreatic lymphoma.

Pancreatic lymphoma is an extremely rare disease. The role of radiation therapy as an adjunct to chemotherapy for the treatment of this disease is poorly defined. We present a case of primary pancreatic lymphoma treated with radiation therapy as an adjunct to chemotherapy.

Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a common, often catastrophic, syndrome that produces the most hypercoagulable of states. Emerging therapeutic strategies use alternative anticoagulants; warfarin's place is being reexamined. Early in the course of warfarin therapy, there may be net procoagulant effects because of the inhibition of protein C. With HIT, it has been suggested that unopposed warfarin can precipitate venous limb gangrene. There are also reports of warfarin-induced skin necrosis. We seek to confirm and increase awareness of the risks of warfarin with HIT. METHODS: We describe 6 patients with HIT seen at 3 medical centers in whom frank or impending venous limb gangrene, central skin necrosis, or both were temporally related to warfarin initiation. RESULTS: At warfarin initiation, 5 patients had recognized HIT and 1 had it recognized later. Complications emerged after 2 to 7 days, and consisted of warfarin-induced skin necrosis (n = 5) and venous limb gangrene (n = 2); 1 patient had both. This emerged with unopposed warfarin in 4 patients and as a direct thrombin inhibitor was being withdrawn in 2. All had supratherapeutic international normalized ratios. One patient required leg and breast amputations, and another one died. CONCLUSIONS: Because of the early effects on protein C, warfarin can precipitate venous limb gangrene and/or skin necrosis in the extreme hypercoagulable milieu of HIT. With HIT, unopposed warfarin should be avoided and caution is needed during transition from a direct thrombin inhibitor. Warfarin should be initiated at modest doses in patients with HIT after platelet recovery. Implications extend to warfarin initiation with other thrombotic diatheses.

Laparoscopic splenectomy for chronic recurrent thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a serious hematologic disorder with a high rate of morbidity and mortality when it fails to go into remission. The primary treatment is total plasma exchange. The addition of corticosteroids, chemotherapeutic agents, or antiplatelet agents is of unproven benefit, and splenectomy has been offered as salvage therapy in refractory cases. We performed laparoscopic splenectomy (LS) on two patients with chronic refractory TTP. The early and late postoperative courses, including hematologic data, are presented here. The mean duration of surgery was 113 minutes and the mean estimated blood loss was 35 mL. Mean hospital stay was 1.5 days. The early postoperative platelet count showed an immediate rise in both patients. After 19 months and 16 months of follow-up, respectively, both patients remain in remission without further episodes of TTP. Laparoscopic splenectomy is a safe and effective therapy for patients with chronic relapsing and refractory TTP. The inherent benefits of the minimally invasive approach, its low morbidity, short hospital stay, and faster recovery, are significant advantages for these patients.

The amyloidoses: clinical features, diagnosis and treatment.

Amyloidosis is a rare disorder in which insoluble amyloid proteins are deposited in body organs, causing abnormal protein build-up in tissues and eventually leading to organ dysfunction and death. It affects less than 200,000 people in the United States, classifying it as a rare disease according to the National Institutes of Health. Definitive determination of the underlying protein is critical since prognosis and treatment of amyloidosis can vary widely depending on the responsible protein. The following paper describes the various types and clinical features of amyloidosis and provides an overview of current diagnostic tools and therapies.

Fatal paraneoplastic systemic leukocytoclastic vasculitis as a presenting feature of chronic lymphocytic leukemia.

BACKGROUND: The most common paraneoplastic vasculitis is leukocytoclastic vasculitis (LCV),(1) 75% of which are caused by hematological malignancies. Chronic lymphocytic leukemia (CLL) is associated with a multitude of auto-immune paraneoplastic syndromes. Data on LCV in association with CLL is restricted to isolated case reports,(3,4) none of which had systemic LCV. We present a unique case of fatal paraneoplastic, systemic LCV as an initial presentation of CLL in an elderly male with multiple co-morbidities. CASE: A 71-year-old man presented with a palpable, symmetric, purpuric rash on the lower extremities and an absolute lymphocytosis (white blood cell count 26.9; 23% lymphocytes). His co-morbidities included coronary artery disease, congestive heart failure, and new critical aortic stenosis. Flow cytometry of peripheral blood demonstrated an abnormal population of B-cells, positive for CD5, CD19, and CD23, consistent with CLL. The skin biopsy specimen revealed neutrophilic inflammation in vessel walls indicative of LCV. Acute renal failure (creatinine 2 mg/dL), urinary red cell casts, and hypocomplementemia were concerning for a systemic vasculitis. The antinuclear antibody, cryoglobulin titer, antineutrophil cytoplasmic antibody, serum protein electrophoresis, viral serologies were negative. On hospital day 6, he developed acute hepatocellular injury and acute respiratory failure. Continuous veno-venous hemodialysis was begun for worsening acidemia and hyperkalemia. Two days later he became obtunded on hospital day 8 and had an elevated lactic acid level with generalized abdominal tenderness worrisome for bowel ischemia. The same day he needed intubation with cardiopulmonary resuscitation for a brief episode of asystole. Despite aggressive treatment with high-dose steroids and plasmapheresis, he suffered worsening renal failure and shock. His family sought withdrawal of care on hospital day 11. Autopsy revealed diffuse LCV of the stomach, distal ileum, integument and alveoli with petechial hemorrhages, fibrin thrombi, and gangrenous patchy necrosis. CONCLUSION: Paraneoplastic LCV is a rare syndrome and seldom occurs in association with CLL. This is the first reported case of fatal systemic paraneoplastic LCV from B-cell CLL. Dermatologic involvement is universal with LCV, and may portend systemic disease. More data on its pathogenesis in CLL is warranted.

Epstein-Barr virus-related lymphoproliferative disorder induced by equine anti-thymocyte globulin therapy.

Post-transplant lymphoproliferative disorder (PTLD) is generally caused by an uncontrolled B-cell proliferation induced by Epstein-Barr virus (EBV) in the setting of impaired EBV-specific T-cell immunity. PTLD has been described in allogeneic hematopoietic stem cell transplant (HSCT) and rarely in autologous HSCT. Anti-thymocyte globulin (ATG) is being increasingly utilized for acute rejection in organ transplantation, severe autoimmune diseases and aplastic anemia. Mainly, the use of rabbit ATG has been associated with PTLD, which is considered to be more immunosuppressive than equine ATG. The sole administration of equine ATG has rarely been associated with PTLD. Due to the increased use of these potent and novel immunosuppressive agents, it is paramount to be aware of these complications. We present a 55-year-old man with an autologous HSCT who presented with an unusual case of monoclonal plasmacytic PTLD. His lymphoproliferative disorder occurred 3 years after his HSCT and 1 month after the use of equine ATG administered for severe aplastic anemia. We review current concepts of EBV-PTLD, including risk factors, the potential for preemptive therapy and various management strategies.

Current management of the myeloproliferative disorders: a case-based review.

CONTEXT: Properly managed, the myeloproliferative disorders are generally compatible with prolonged survival. Challenges to the hematologist include knowing when and how best to intervene to prevent and manage complications. The cytoreductive agent of choice for these disorders is currently hydroxyurea, emerging from randomized trials beginning with those of the Polycythemia Vera Study Group. OBJECTIVE: To examine the roles and shortcomings of interventions (including hydroxyurea, antiplatelet agents, anagrelide, interferon, thalidomide, alkylating agents, cell cytopheresis, erythropoietins, splenectomy, bone marrow transplantation, and imatinib) for myeloproliferative disorders. DATA SOURCES: This report uses actual case histories to illustrate the roles and shortcomings of these interventions. CONCLUSIONS: Beyond phlebotomy for polycythemia vera, patients with polycythemia vera and essential thrombocythemia can be stratified by their risk for thrombosis, which guides the institution of cytoreductive therapies. High-risk patients generally benefit from cytoreductive therapy, and hydroxyurea has emerged as the agent of choice, because alkylating agents (and P32) have high leukemogenic potentials. Anagrelide and interferon are second-line agents. The addition of low-dose aspirin is beneficial for most, helping to prevent arterial thrombotic complications. Therapy in any of these disorders should be tailored to the unique characteristics of the individual patient. With myelofibrosis, therapeutic options run the gamut from observation, erythropoietic stimulators, cytotoxic agents, splenectomy, and bone marrow transplantation. Thalidomide and imatinib have shown some utility. Future challenges are the refinement of individualized treatment strategies and the development of targeted therapies based on rapidly expanding understanding of the molecular perturbations in these disorders.