Clearance of Hepatitis C Virus (HCV) Is Associated With Improved Outcomes in HCV-Associated Lymphoma.

BACKGROUND: Improved hepatitis C virus (HCV) clearance due to directly acting antiviral agents has led to remarkably improved outcomes of indolent HCV-associated non-Hodgkin lymphoma (NHL). The impact of directly acting antivirals on the outcomes of aggressive NHL is still under investigation. Characteristics of HCV-associated NHL in black patients are not well characterized. We report outcomes of HCV-associated NHL compared to their HCV-negative counterparts in a predominantly black population. PATIENTS AND METHODS: Patients with lymphoma between January 2007 and December 2017 were retrospectively studied. Depending on presence or absence of HCV RNA, patients were grouped into HCV positive (HCV+) and HCV negative (HCV-) cohorts. Depending on virologic clearance (VC), HCV+ were classified into HCV+ with VC and HCV+ without VC. Overall response rate (ORR), complete response, overall survival (OS), and progression-free survival (PFS) of HCV+ patients with and without VC were compared to HCV- patients. RESULTS: Of 397 patients with lymphoma, 40 had HCV. Black comprised 90% of HCV+ patients. Diffuse large B-cell lymphoma was most frequent (47%) in the HCV+ group. HCV+ patients without VC had significantly worse OS and PFS compared to HCV- patients. There were no differences in ORR, complete response, PFS, and OS of HCV+ patients with VC and HCV- patients. These results were consistent in subgroups of diffuse large B-cell lymphoma and aggressive lymphoma. CONCLUSION: HCV clearance is positively associated with lymphoma outcomes in black patients. Patients who clear HCV have noninferior outcomes to HCV- patients, while those who fail to clear HCV have significantly worse outcomes.

Lymphoma survivors have an increased long-term risk of chronic kidney disease.

With improving lymphoma survival, late effects of therapy have emerged. Here, we describe pattern of long-term chronic kidney disease (CKD) in lymphoma survivors. Demographics, comorbidities, lymphoma histology, treatment, and outcome were recorded. Glomerular filtration rate (GFR) was recorded at diagnosis, 1, 2, 5, and 10 years. Rate of GFR decline with time and CKD-free survival were recorded. In 397 patients, median age was 55.3 (18-88), 54% were male, 60% were African Americans, 42% had hypertension (HTN), 15% had DM, 13% had hyperuricemia, 86% received chemotherapy, and 14% had baseline CKD. Total 125 (31%) patients developed CKD in 10 years after lymphoma diagnosis. Probability of CKD development increased significantly with time (23% at 1 year to 41% at 10 years). Rate of GFR decline was 4.6 mL/min/per year. Age, HTN, hyperuricemia, and DM (in young patients) predicted risk of CKD. Thus, lymphoma survivors are at substantial long-term risk of CKD development.

Paraneoplastic frosted branch angiitis as first sign of relapsed Hodgkin lymphoma.

Frosted branch angiitis (FBA) is a rare form of retinal vasculitis with typical perivascular edema taking the shape of frost on a tree branch. It was reported only twice as the initial presentation of Hodgkin lymphoma (HL). Here, we present the first case of paraneoplastic FBA as the initial sign of HL relapse in an elderly female.

A Challenging Case of Pseudohyperkalemia in Chronic Lymphocytic Leukemia.

Pseudohyperkalemia is an uncommon finding in chronic lymphocytic leukemia. It is a misleading condition that could lead to iatrogenic hypokalemia when unwarranted treatment is administered. We describe an interesting case of pseudohyperkalemia in severe leukocytosis and how we identified it.

DA-EPOCH-R for post-transplant lymphoproliferative disorders.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are a potentially fatal group of neoplasms arising in an immunodeficient environment. Although the cornerstone of treatment is reduced immunosuppression (RI), advanced cases often warrant treatment with chemoimmunotherapy. The chemoimmunotherapy regimen of dose-adjusted (DA)-EPOCH-R is superior to R-CHOP in HIV associated aggressive lymphomas, suggesting that it might also be favorable in the setting of PTLD. METHODS: We performed a retrospective analysis of patients with advanced monomorphic PTLD treated with first line DA-EPOCH-R in addition to RI at our institution from 2003-2016. RESULTS: Seven patients were included. Mean age was 51 and mean time from transplant to diagnosis was 71 months. Six of the seven patients received a kidney transplant, six had stage III or IV disease, six had tumors that were EBV positive, and six completed therapy. All six patients who completed therapy achieved a complete response. Mean PFS and OS were 46.6 and 52.6 months, respectively. Treatment was well-tolerated with no significant treatment related morbidity or mortality. CONCLUSIONS: Our findings support several observations in the literature that DA-EPOCH-R is efficacious and well-tolerated for the treatment of advanced, monomorphic PTLD.

Treatment of refractory delayed onset heparin-induced thrombocytopenia after thoracic endovascular aortic repair with intravenous immunoglobulin (IVIG).

Delayed onset heparin induced thrombocytopenia (HIT), is characterized by a late nadir due to persistent platelet-activating IgG antibodies. It typically begins or worsens 5 or more days after heparin is discontinued with complications such as thrombosis up to 3 weeks after exposure to heparin.1-3 In 50% of cases, the platelet count can decrease to very low numbers (<20 000/µL), which is not usual for typical HIT. Here we report 2 cases of post-operative delayed onset HIT manifesting as severe thrombocytopenia that persisted despite cessation of heparin and initiation of argatroban. Key Clinical Question: Is intravenous immunoglulin beneficial in severe refractory delayed-onset HIT?

Clinical and biological predictors of outcome following relapse of CML post-allo-SCT.

Although there are now fewer allo-SCTs performed for CML, leukemic relapse post transplant remains a persistent problem. To better define clinical and biological parameters determining postrelapse outcome, we studied 59 patients with CML relapsing after HLA-identical sibling allo-SCT between 1993 and 2008. Eighteen (30.5%) were transplanted in advanced phase and 41 (69.5%) in chronic phase. With a median follow-up from relapse of 7.9 years, 5-year post relapse survival (PRS) was 62%. Multivariate analysis found disease status at transplant, time to diagnosis of relapse from transplant and pretransplant tyrosine kinase inhibitor (TKI) use as significant factors associated with PRS. Analysis of BCR-ABL transcript expression in the hematopoietic progenitor compartment was performed in 36 patients (22 relapsed, 8 non-relapsed and 6 TKI alone controls). Patients with BCR-ABL expression in their early hematopoietic stem cell compartment (Lineage(-)CD34(+)CD38(-)CD90(+)) had worse survival irrespective of the disease status. We conclude that disease status remains the strongest clinical prognostic factor for PRS in CML following allo-SCT. The persistence of BCR-ABL expression in the progenitor cell compartment in some patients after SCT emphasizes the need to target CML-leukemia stem cells.

Post-transfusion purpura in an African-American man due to human platelet antigen-5b alloantibody: a case report.

INTRODUCTION: Post-transfusion purpura is a rare immunohematological disorder characterized by severe thrombocytopenia following transfusion of blood components and induced by an alloantibody against a donor platelet antigen. It occurs primarily in women sensitized by pregnancy and is most commonly caused by anti-human platelet antigen-1a antibodies. Here, we describe what we believe to be the first documented case of an African-American man who developed post-transfusion purpura due to an anti-human platelet antigen-5b alloantibody after receiving multiple blood products. CASE PRESENTATION: A 68-year-old African-American man initially admitted with atrial flutter was started on anticoagulation treatment, which was complicated by severe hematemesis. On days 4 and 5 of hospitalization, he received six units of packed red blood cells, and on days 4, 13 and 14 he received plasma. His platelet count began to drop on day 25 and on day 32 reached a nadir of 7 × 109/L. His platelet count increased after receiving intravenous immune globulin. An antibody with reactivity to human platelet antigen-5b was detected by a solid-phase enzyme-linked immunoassay. Our patient was homozygous for human platelet antigen-5a. CONCLUSION: This case emphasizes the importance of including post-transfusion purpura in the differential diagnosis for both men and women with acute onset of thrombocytopenia following transfusion of blood products. The prompt recognition of this entity is crucial for initiation of the appropriate management.

Obesity in adult lymphoma survivors.

As a result of therapeutic advances, survivors of lymphoma are now living longer. However, their mortality is higher when compared to the general population, probably due to multiple factors. Survivors of childhood leukemia and lymphoma appear to have an increased prevalence of obesity. The objectives of this retrospective study were to analyze weight change after lymphoma treatment in an adult population and determine factors predictive of weight gain. Data were collected from 219 patients and analyzed sequentially at the initial visit and at 6, 12 and 18 months. There was a progressive increase in weight from the initial visit to 6 months (1.5% increase of initial body weight), 12 months (4.5%) and 18 months (6.4%). More than 9% of patients experienced weight gain greater than 20% during follow-up. There was a statistically significant association between the percentage of increase in weight and age, B symptoms and body mass index (BMI) at presentation. Younger patients, those with B symptoms or those with lower BMI manifested more weight gain (p = 0.0008, p = 0.0440 and p = 0.0009, respectively). Other assessed factors had no effect on weight gain including sex, race, lymphoma histology, disease outcome, radiation therapy, number of treatment regimens and use of steroids. Further studies are needed to explore long-term weight trends and their impact on the health of lymphoma survivors.

Primary lymphoma of bone: an institutional experience.

A retrospective analysis of factors influencing survival in patients with primary lymphoma of bone (PLB) treated at a single institution was performed. The records of 30 eligible patients were evaluated for overall survival (OS) as related to age, sex, stage, International Prognostic Index (IPI) score, number of sites involved and type of treatment. There was a significant difference in OS in patients with IPI scores of low (L) and low intermediate (LI) versus high intermediate (HI) (P = 0.0035), regardless of stage. Sex, age, stage and number of sites did not have a significant influence on OS. There was a statistically significant difference in OS favouring use of combined chemotherapy (with or without rituximab) and radiation compared with either modality alone (P = 0.02). The addition of rituximab resulted in a non-significant trend towards improved OS (P = 0.11). With a median follow up of 49 months, 73% of patients are alive 5 years from diagnosis.

Lyme disease mimicking central nervous system lymphoma.

A 33-year-old male presented with a complaint of intermittently blurred vision and right facial weakness. MRI of the brain and orbits revealed numerous cranial nerve abnormalities. There were no focal brain or spinal cord lesions. Cerebral spinal fluid flow cytometry revealed a monoclonal population of B-lymphoid cells. No other evidence of disease was found. Serum Lyme antibody was reported to be IgM positive. Therapy with ceftriaxone, was followed by improvement in his symptoms. Although flow cytometry is a useful tool in distinguishing malignancy from inflammatory disorders it does not always establish the diagnosis of malignancy by itself.

PF4 ENHANCED assay for the diagnosis of heparin-induced thrombocytopenia in complex medical and surgical patients.

OBJECTIVE: To evaluate the sensitivity and specificity of the PF4 ENHANCED (GTI Diagnostics, Waukesha, WI) enzyme-linked immunosorbent assay for heparin-induced thrombocytopenia using the carbon-14 serotonin-release assay as the reference method. DESIGN: A total of 34 patients were prospectively enrolled with a variety of diagnoses and suspected heparin-induced thrombocytopenia. They were clinically scored and underwent testing with the (14)C-serotonin-release assay. Enzyme-linked immunosorbent assay and (14)C-serotonin-release assay results were also available from 21 medical and surgical patients who had previously been tested. MAIN RESULTS: With the (14)C-serotonin-release assay as the reference method, the sensitivity and specificity of the enzyme-linked immunosorbent assay were 93% and 65%, respectively. There was only one false-negative enzyme-linked immunosorbent assay. The clinical scores were frequently misleading, largely because of difficulty excluding other causes of thrombocytopenia. CONCLUSION: Because of its high sensitivity, we believe the PF4 ENHANCED enzyme-linked immunosorbent assay should be used to identify heparin-induced thrombocytopenia in patients with multiple potential causes of thrombocytopenia, although false-positive results will not be uncommon.

Hodgkin lymphoma in temporal association with growth hormone replacement.

The association between growth hormone (GH) replacement and malignancy has long been debated. We report a case of Hodgkin lymphoma that developed in temporal association with the initiation of GH replacement in a 57-year-old woman with panhypopituitarism secondary to a non-secretory pituitary macroadenoma. Treatment of her pituitary tumor included transphenoidal surgery, external beam radiation, Bromocriptine and Cabergaline therapy. In addition to replacement steroid, thyroid and sex hormones, she insisted on GH replacement. Approximately 2 years after GH initiation, the diagnosis of Hodgkin lymphoma was made. Although the exact contribution of GH to the development of Hodgkin disease in our patient is unclear and a causal effect cannot be concluded, the temporal association is suggestive, and warrants reporting as part of ongoing surveillance for potential complications of GH replacement.

Recombinant activated factor VII (rFVIIa) as salvage treatment for intractable hemorrhage.

BACKGROUND: Recently, there has been an increased use of recombinant activated factor VII (rFVIIa) to promote hemostasis in various hemorrhagic conditions. The objective of this study was to determine the outcome of patients treated with rFVIIa who had intractable bleeding associated with cardiac surgery (CSP) or as a result of other causes (OBP). METHODS: The medical records of 40 consecutive patients treated with rFVIIa were retrospectively reviewed for blood product use before and after treatment. In all patients, rFVIIa was given only after all other measures to stop bleeding had failed. The number of transfused units of red cells (R), platelets (P), fresh frozen plasma (F), and cryoprecipitate (C) were determined both before and after administration of rFVIIa, and the results compared. Mortality at 4 hours and 30 days was assessed. Patients dying within 4 hours of rFVIIa administration were not evaluable for response. Patient characteristics were also assessed as risk factors for mortality. RESULTS: Twelve of 24 CSP survived for more than 4 hours. These 12 patients required an average of 17 units (U) of R, 18 U of P, 18 U of F and 15 U of C pre-treatment compared to an average of 6 U, 10 U, 9 U and 4 U of R, P, F and C respectively, post-treatment. These differences were statistically significant. For the OBP, 11 of 16 survived more than four hours. These 11 patients required an average of 10 U of R, 11 U of P, 14 U of F and 10 U of C pretreatment compared to an average of 1 U, 2 U, 2 U and 0 U of R, P, F, and C respectively, post-treatment. With the exception of C, there was a statistically significant decrease in blood product use following treatment with rFVIIa. Of the survivors in each group, 6 of 12 CSP and 2 of 11 OBP died between 3 and 30 days post-treatment from causes other than bleeding. Mortality at 30 days for CSP and OBP survivors was 50% and 18% respectively, whereas overall 30 day mortality was 75% for CSP and 44% for OBP. CONCLUSIONS: rFVIIa is effective in decreasing blood product use and promoting hemostasis in patients with intractable bleeding associated with cardiac surgery and a variety of other causes.