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- Large Granules in the Peripheral Blood Smear and Bone Marrow Aspirate of a 3-Year-Old Male With Lymphadenopathy and Fever. [JOURNAL ARTICLE]
- Lab Med 2014; 45(3):244-247.
A 3-year-old male with oculocutaneous albinism presented with lymphadenopathy and fever. Serological testing revealed Epstein-Barr virus (EBV)-specific immunoglobulin M (IgM) and a diagnosis of infectious mononucleosis was made. A complete blood count and peripheral blood smear demonstrated mild anemia, thrombocytopenia, and neutropenia with leukocytes that contained large azurophilic and eosinophilic granules. Bone marrow examination demonstrated increased hemophagocytic histiocytes along with granulocytes that contained large eosinophilic granules. In addition to hemophagocytic lymphohistiocytosis, presumably due to acute EBV infection, the patient was diagnosed with Chediak-Higashi syndrome based on the pathognomonic granules within peripheral leukocytes and precursors. The differential diagnosis of a young patient with oculocutaneous albinism presenting with an acute viral infection includes a relatively narrow range of genetic syndromes based solely on the history of albinism. This case demonstrates the application of clinical laboratory data to presumptively diagnose Chediak-Higashi syndrome in the midst of a presentation of hemophagocytic lymphohistiocytosis secondary to acute EBV infection.
- Semi-physiological pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation of 5-fluorouracil for thrombocytopenia in rats. [JOURNAL ARTICLE]
- Xenobiotica 2014 Jul 22.:1-10.
Abstract 1. The aim of this study was to develop a simple pharmacokinetic-pharmacodynamic (PK-PD) model that could characterize the complete time-course of alterations in platelet counts to predict the onset and degree of thrombocytopenia, which severely limits the use of the anticancer agent 5-fluorouracil (5-FU), in rats. 2. Platelet counts were measured in rats following the intravenous administration of various doses of 5-FU for 4 days to obtain data for an analysis of the PK-PD model. Our PK-PD model consisted of a two-compartment PK model, with three compartments for the PD model and 10 structural PK-PD model parameters. 3. After the 5-FU treatment, platelet counts transiently decreased to a nadir level, showed a rebound to above the baseline level before recovering to baseline levels. Nadir platelet counts and rebounds varied with the AUC0-∞ level. The final PK-PD model effectively characterized platelet count data and final PD parameters were estimated with high certainty. 4. This PK-PD model and simulation may represent a valuable tool for quantifying and predicting the complete time-course of alterations in blood cell counts, and could contribute to the development of therapeutic strategies with 5-FU and assessments of various novel anticancer agents that are difficult to examine in humans.
- Phase II Study of Avatrombopag in Thrombocytopenic Patients with Cirrhosis Undergoing an Elective Procedure. [JOURNAL ARTICLE]
- J Hepatol 2014 Jul 15.
This is a Phase II multicenter study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis.Adults with cirrhosis and platelet counts ⩾10 to ⩽50(∗)x10(9)/L were randomized to placebo or avatrombopag in 2 sequential cohorts. Cohort A: Placebo versus one of 3 different doses, (100 mg loading dose followed by 20, 40, or 80 mg/day on Days 2-7) of a first-generation avatrombopag formulation. Cohort B: Placebo versus one of 2 different doses (80 mg loading dose followed by 10mg/day for Days 2-7, or 20 mg/day for Days 2-4) of a second-generation avatrombopag formulation. Primary endpoint was achievement of a platelet increase of ⩾20x10(9)/L from baseline and >50x10(9)/L at least once during Days 4-8.A total of 130 patients were randomized: 93 patients (51, Cohort A; 42, Cohort B) to avatrombopag and 37 (16, Cohort A; 21 Cohort B) to placebo. The primary endpoint was achieved by 49.0% of treated patients in Cohort A and 47.6% in Cohort B compared to 6.3% and 9.5% of controls and a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p<0.01), except for the 100/40 mg group in Cohort A (p=0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avathrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up.In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.
- Prognostic significance of CD20 expression and Epstein-Barr virus (EBV) association in classical Hodgkin lymphoma in Japan: A clinicopathologic study. [Journal Article]
- Pathol Int 2014 Jul; 64(7):336-45.
To investigate the clinicopathological significance of CD20 expression and Epstein-Barr virus (EBV) association in Hodgkin and Reed-Sterberg cells of classical Hodgkin lymphoma (CHL), CD20 expression and EBV positivity (by EBER in situ hybridization) were investigated in 389 CHL patients in Japan. They included 74 CD20-positive cases (19%) and 315 CD20-negative cases (81%). CD20-positive cases showed significantly older age at onset (P = 0.018) and higher association with EBV (P = 0.002). Multivariate analysis identified EBV-positivity (but not CD20-positivity), presence of B symptoms, thrombocytopenia, elevated serum lactate dehydrogenase and performance status >1 as poor prognostic factors for overall survival (OS). We constructed a new prognostic model with these five factors classifying patients into three groups: low risk, 0-1 adverse factor; intermediate risk, 2-3 factors; high risk, 4-5 factors. This prognostic model could stratify the prognosis of CHL patients (P < 0.0001). For 144 patients (58%) classified into the low-risk group, the 5-year OS was 91%. For 92 patients (37%) in the intermediate group, the 5-year OS was 66%; for 11 patients (5%) in the high-risk group, the 5-year OS was 36%. In conclusion, EBV is identified as an independent poor prognostic factor for CHL patients. Therefore, examination of EBV association in CHL is recommended as routine pathologic practice especially in countries where EBV infection prevails.
- Monovalent H1N1 influenza vaccine safety in pregnant women, risks for acute adverse events. [JOURNAL ARTICLE]
- Vaccine 2014 Jul 18.
To assess risks for acute adverse events and pregnancy complications in pregnant women following monovalent 2009 H1N1 inactivated influenza (MIV) vaccination.Within the Vaccine Safety Datalink, we compared rates of pre-specified medically attended events (MAE) occurring within 42 days of MIV vaccination to those occurring in matched cohorts that at the same gestational age were either unvaccinated or received seasonal trivalent inactivated influenza (TIV) vaccine. Using generalized estimating equation method, with a Poisson distribution and log link, we calculated adjusted incident rate ratios (AIRR).Among 9349 women receiving MIV in any trimester, only one MAE occurred 0-3 days following MIV, an allergic reaction. No cases of Guillain-Barré syndrome, Bell's palsy, or transverse myelitis occurred 1-42 days after MIV. Compared to women receiving TIV and to unvaccinated women, risks for acute MAEs were not increased following MIV for any outcome. Hyperemesis was the most common adverse event in the MIV, TIV, and unvaccinated groups, occurring at a rate of about 4% over a 42-day period in all groups. Over a 42-day window, among all groups, incident gestational diabetes occurred at a rate of 3% and thrombocytopenia occurred at a rate of approximately 0.3%. Among women receiving MIV during pregnancy, increased risks for these and other less common obstetric events were not detected.In this large cohort of pregnant women no acute safety signals were identified within 6 weeks of receipt of MIV.
- Her-2 positive gastric cancer presented with thrombocytopenia and skin involvement: a case report. [Journal Article]
- Case Rep Oncol Med 2014.:194636.
Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM) and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2) is positive in gastric cancer at a rate of 7-34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG) involvement except bone metastases.
- Thrombocytopenia in Plasmodium vivax Malaria: How Significant? [Journal Article]
- J Trop Med 2014.:567469.
Introduction.Thrombocytopenia is frequently noticed with P. falciparum malaria but is less reported and studied with P. vivax. Materials and Methods. The study was conducted in the Department of Medicine, SBKS MI & RC, Pipariya. We included patients who were diagnosed with vivax malaria. The data regarding their clinical and hematological profile was collected and analysed. Result. A total of 66 patients were included. 42 (63%) had platelet count <100000/mm(3). Mean platelet count was 1,18,650, range being 8000/mm(3)-6,10,000/mm(3). Amongst those with thrombocytopenia, 16 (38.09%) had anemia, 14 (33.33%) had serum creatinine >1.2 gm/dL, 15 (35.71%) had jaundice (s. bilirubin > 1.2), 2 (4.76%) had altered sensorium, 6 (14.28%) had ARDS, 2 needed ventilator support, and 1 expired. Amongst those with normal platelet count, 5 (20.83%) had anemia and 1 had jaundice whereas none had elevated s. creatinine, altered sensorium, or lung involvement.
Conclusion.Thrombocytopenia is now being seen more commonly with vivax malaria. Patients with platelet count <1 lac/cumm have more severe disease.
- Toxicity profile of temozolomide in the treatment of 300 malignant glioma patients in Korea. [Journal Article]
- J Korean Med Sci 2014 Jul; 29(7):980-4.
This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.
- Gain-of-Function mutation in STIM1 (p.R304W) is Associated with Stormorken Syndrome. [JOURNAL ARTICLE]
- Hum Mutat 2014 Jul 18.
Stormorken syndrome is a rare autosomal dominant disorder characterized by a phenotype that includes miosis, thrombocytopenia/thrombocytopathy with bleeding time diathesis, intellectual disability, mild hypocalcaemia, muscle fatigue, asplenia and ichthyosis. Using targeted sequencing and whole exome sequencing, we identified the c.910C>T transition in a STIM1 allele (p.R304W) only in patients and not in their unaffected family members. STIM1 encodes Stromal interaction molecule 1 protein (STIM1) which is a finely tuned endoplasmic reticulum (ER) Ca(2+) sensor. The effect of the mutation on the structure of STIM1 was investigated by molecular modeling, and its effect on function was explored by calcium imaging experiments. Results obtained from calcium imaging experiments using transfected cells together with fibroblasts from one patient are in agreement with impairment of calcium homeostasis. We show that the STIM1 p.R304W variant may affect the conformation of the inhibitory helix and unlock the inhibitory state of STIM1. The p.R304W mutation causes a gain of function effect associated with increase of both resting Ca(2+) levels and store operated calcium entry. Our study provides evidence that Stormorken syndrome may result from a single-gene defect which is consistent with Mendelian dominant inheritance. This article is protected by copyright. All rights reserved.
- FCR and bevacizumab treatment in patients with relapsed chronic lymphocytic leukemia. [JOURNAL ARTICLE]
- Cancer 2014 Jul 15.
Patients with relapsed chronic lymphocytic leukemia (CLL) often achieve response with chemoimmunotherapy but have short remission durations. Studies have shown that patients with CLL have increased angiogenesis in the microenvironment; levels of proangiogenic growth factors such as VEGF and/or angiopoietin-2 are also elevated. Increased angiogenesis correlates with poor outcome in CLL. Bevacizumab (B) is a humanized monoclonal antibody targeting VEGF-A.In this study, we analyzed whether a combination of bevacizumab with fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy (FCR-B) could improve outcomes in patients with relapsed CLL. Sixty-two patients were enrolled. The median age of the patients was 60 years (range, 31-84 years) and 40% had received >1 prior therapy for CLL. Sixty-one patients were evaluable for toxicity, and 57 were evaluable for response. Six cycles were planned; 36 patients (59%) completed ≥4-6 cycles of the regimen.The overall response rate was 79%, with 13 (23%) complete remissions (CRs), 8 nodular partial remissions (14%), and 24 partial remissions (43%). The median progression-free survival and overall survival rates were 13.5 and 45 months, respectively. Grade 3 or 4 toxicities included febrile neutropenia (n = 40), infections (n = 21), thrombocytopenia (n = 18) and anemia (n = 9).Results with FCR-B were similar to those observed with an historical cohort of relapsed patients treated with FCR. Cancer 2014. © 2014 American Cancer Society.