Prednisone Research Articles

Emergency treatment of adrenal crisis with prednisone suppositories: a bioequivalence study in female patients with Addison's disease.

ObjectivePatients with adrenal insufficiency (AI) need to adapt their glucocorticoid replacement under stressful conditions to prevent adrenal crisis (AC). Prednisone (PN) suppositories are used for emergency treatment. Pharmacokinetics of 100 mg PN suppositories after vaginal or rectal administration was evaluated.DesignSingle-center, open-label, sequence-randomized, cross-over, bioequivalence study.MethodsTwelve females with primary AI were included. Comparison of pharmacokinetics after vaginal and rectal administration of 100 mg PN suppositories. Main outcome measures: bioequivalence (Cmax: maximum plasma concentration of prednisolone; AUC0 –360: area under the plasma concentration curve of prednisolone from administration to 360 min), adrenocorticotropin (ACTH) levels, safety and tolerability. Comparison of ACTH-suppressive effect with subcutaneous and intramuscular administration of 100 mg hydrocortisone.ResultsVaginal administration of PN suppositories was not bioequivalent to rectal administration: Cmax and AUC0–360 were significantly lower after vaginal compared to rectal administration: 22 ng/mL (109%) vs 161 ng/mL (28%), P < 0.001; 4390 ng/mL * min (116%) vs 40,302 ng/mL * min (26%), P < 0.001; (mean (coefficient of variation), respectively). A suppression of ACTH by >50% of baseline values was observed 149 min (32%) after rectal PN administration; after vaginal PN administration, the maximum decrease within 360 min was only 44%. Adverse events were more frequent after vaginal administration and mainly attributable to the glucocorticoid deficit due to inadequate vaginal absorption. The ACTH-suppressive effect was more pronounced after parenteral hydrocortisone compared to rectal or vaginal PN.ConclusionVaginal administration of PN suppositories in the available form is not useful for prevention of AC. Pharmacokinetics after rectal use of PN show inferiority compared to available data on parenteral glucocorticoids. In adrenal emergencies, hydrocortisone injection should be the first choice.

A randomized phase II study comparing cabazitaxel/prednisone to cabazitaxel alone in docetaxel-pretreated men with metastatic castration resistant prostate cancer (mCRPC): The CABACARE trial.

TPS345 Background: In the TROPIC trial, cabazitaxel (CAB) plus daily prednisone (PDN) was associated with a significant advantage in OS and PFS in docetaxel (DOC)-pretreated patients (Pts). Whether daily PDN may significantly contribute to CAB efficacy or improve its safety profile is unknown. In the CHARTEED trial, DOC was administered without daily PDN with no concerns about the lack of efficacy or greater toxicity. Safety data about CAB without PDN are scarce. Corticosteroids present multiple biological effects, which may potentially be either positive, such as those mediated by adrenal androgen and cytokine suppression, or detrimental, such as those associated with the activation of the glucocorticoid receptor (GR) and of the androgen receptor (AR). Furthermore, PDN is a CYP3A4 inducer and can potentially negatively affect CAB clearance. Finally, AR-V7 positivity in circulating tumor cells and retinoblastoma (RB) loss/inactivation have been identified as potential mechanisms of resistance to hormonal and chemotherapy treatments in prostate cancer. For this reason, we also aim to evaluate if CAB activity is related to such biomarkers. Methods: CABACARE (EudraCT 2016-005251-25) is a randomized, phase II, open label, multi-center study comparing CAB at 25 mg/m2 q21 plus daily PDN (10 mg) vs CAB at 25 mg/m2 q21 alone in mCRPC pts progressed during or after DOC treatment. The study is designed to test non inferiority in terms of PFS, according PCWG-2, of CAB alone vs CAB plus PDN assuming that the two arms are equally effective (non-inferiority HR = 1.4). Main secondary objectives are: safety, QoL, pain assessment, overall response rate (ORR), PSA response, time to PSA progression, Time to radiological progression; OS; time to skeletal related events . The influence of AR-V7 and RB status measured in circulating epithelial cells at baseline on CAB activity will also be evaluated. A total of 35 Italian centers have started / will start recruiting pts in the CABACARE trial. Of the 220 pts required by the trial design, 43 pts have been enrolled since 30th Nov , 2017 until 2nd Oct, 2018 in 10 different Italian Institutions. Clinical trial information: 2016-005251-25.

Sarcoidosis with hypercalcemic and mediastinal lymphadenectasis: A case report

Hypercalcemia is an abnormal calcium metabolism, which can be caused by many diseases. Hypercalcemia caused by sarcoidosis is unusual. Sarcoidosis is a systemic granulomatous disease, it is lack of specificity in initial manifestations and easy to be misdiagnosed. In this paper, we report a patient with hypercalcemia and mediastinal lymphadenectasis, which the first diagnosis was misdiagnosed as tumour. Finally, sarcoidosis was diagnosed by mediastinal lymph node biopsy, and the patient was subsequently treated with glucocorticoid. Prednisone treatment improved symptoms of sarcoidosis, normalised serum calcium and mediastinal lymph nodes were diminished. This case suggests that clinicians need to raise awareness of sarcoidosis to identify and diagnose it correctly. Key words: Hypercalcemic; Mediastinal lymphadenectasis; Sarcoidosis

Primary testicular diffuse large B-cell lymphoma: a single center experience

Objective To review the experience of the clinical diagnosis and treatment of primary testicular diffuse large B-cell lymphoma. Methods A review was made who were treated in the Tumor Hospital of Zhengzhou University from January 2011 to November 2018. The average age of the patients was 58 years old, with 4 cases in left side and 8 cases in right side. All patients were admitted to hospital with painless testicle mass. Solid mass of testis were detected by ultrasound with no abnormality in tumor markers. All patients underwent orchiectomy and followed by chemotherapy. Results Twelve primary testicular lymphoma (PTL) were identified by pathology, with 8 cases in phase I, 2 cases in phase II, 1 case in phase III , and 1 case in phase IV. The mean follow-up was 31 months. Inguinal orchiectomy was recommended as a diagnositc and initial therapy. All patients underwent R-CHOP/CHOP chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisone with or without rituximab, including 6 cases with R-CHOP and 6 cases with CHOP. Nine of 12 patients underwent intrathecal prophylatic chemotherapy and 6 of 12 patients underwent contralateral testicle radiotherapy. Relapse occured in 2 patient with CHOP in central nervous system and died of the disease. One case with CHOP relapsed in abdominal cavity. No contralateral testicle relapse was observed. Conclusions PTL is a rare extranodal lymphoma. Painless testicle tumor in men over 50 years old should suspect of this disease. Inguinal orchiectomy is an important part of the treatment, which combines systemic chemotherapy and prophylactic modalities such as radiotherapy of contralateral testis and/or central nervous system (CNS) prophylaxis. Key words: Lymphoma, B cell; Testis; Treatment; Prognosis

Dose-Adjusted Intensive Chemotherapy Is Safe and Tolerable in Older Patients with Ph-Negative ACUTE Lymphoblastic Leukemia

Topic Significance & Study Purpose/Background/Rationale Outcomes of older adults with acute lymphoblastic leukemia (ALL) remain poor [PMID 19897583, 28419558, 22409379, 10653870]. PEG-Asparaginase (PEG-Asp) is a key component of the chemotherapeutic regimens for treatment of pediatric and younger adult ALL [PMID 29450465]. Older patients with Ph-negative ALL are often not offered PEG-Asp containing regimen due to concerns related to tolerability and safety [PMID 28355969]. Methods, Intervention, & Analysis The Adult Leukemia Program at Mount Sinai Hospital developed an age-based, dose-adjusted pediatric chemotherapy regimen for adults (≥40 years) with diagnosis of Ph-negative ALL. For patients up to 60 years, prednisone (PRD) dose was reduced to 40 mg/m2/day, and PEG-Asp to 1000 units/m2. For patients aged ≥61 years, PRD was further reduced to 25 mg/m2/day. A PEG-Asp oriented supportive care plan was developed to prevent and treat Asp-related adverse effects (AE) based on Antithrombin III (ATIII) and fibrinogen levels. Findings & Interpretation Fourteen patients with median age 60 years (45 – 76) were evaluable, and three patients were ≥ 70 years. Eleven patients had significant co-morbidities at diagnosis, including diabetes, hypertension, previous history of cancer, coronary artery disease, obesity, alcohol related chronic pancreatitis, and chronic diarrhea. Eleven patients (79%) attained a complete remission (CR) at the end of induction (EOI), four of them with detectable minimal residual disease (MRD). Five patients underwent allogeneic hematopoietic stem cell transplantation (HCT) while in CR (age range 46 – 60), four remain in CR at last follow up (median 563 days, range 259 – 883), and one died of relapsed disease 67 days post-HCT. The other eight patients who are receiving chemotherapy are in remission at last follow up (median 317 days, range 63 – 714). Observed PEG-Asp related AE were asymptomatic hypofibrinogenemia and low ATIII levels (n=10), severe hyperbilirubinemia (n=1), and non-life-threatening venous thrombosis (n=1). No patient experienced early death, severe allergic reaction or clinical pancreatitis. Discussion & Implications This dose-adjusted PEG-Asp containing regimen was associated with an encouraging CR rate and with tolerable and manageable AE in this patient population with significant co-morbidities. Treatment related mortality was 0%. Twelve of the 14 patients are currently in sustained remission (median follow-up 399 days, range 63-883). Further prospective evaluation is under way.

Efficacy of oral prednisone acetate for prevention of esophageal stenosis after endoscopic submucosal dissection

Objective To investigate efficacy and safety of oral prednisone acetate for prevention of esophageal stenosis after endoscopic submucosal dissection (ESD) for patients with esophageal precancerous lesions or early esophageal carcinoma. Methods A retrospective analysis was performed on data of 56 patients who underwent circumferential or semi-circumferential (more than three quarters but not a complete circular) ESD for esophageal precancerous lesions or early cancer in Nanjing Drum Tower Hospital from October 2014 to October 2017. The patients were divided into the study group (n=26, prednisolone oral administration after ESD) and the control group (n=30, without prednisolone oral administration after ESD). Endoscopic dilatation was performed whenever patients experienced persistent dysphagia to solids. Clinical data, stricture rate, numbers of endoscopic dilatation, and adverse events were compared between the two groups. Results There were no differences in age, gender, location and length of lesions, endoscopic findings, depths of tumor invasion, and pathological subtypes between the two groups (all P>0.05). The proportion of circumferential esophageal lesions in the study group was higher than that in the control group[53.85% (14/26) VS 23.33% (7/30), χ2=5.53, P=0.02]. The rata of post-procedural esophageal stricture in the study group was significantly lower than that in the control group[30.77% (8/26) VS 60.00% (18/30), χ2=4.78, P=0.03], and the number of endoscopic dilatation was lesser in the study group than the control group (3.85±2.57 VS 9.83±5.82, t=7.22, P=0.00). There were no adverse events related to oral prednisone, and no treatment-related mortality. Conclusion Prednisone acetate oral administration is safe and effective to prevent esophageal stenosis after complete or semi-circular ESD for patients with esophageal precancerous lesions or early esophageal carcinoma. Key words: Esophageal neoplasms; Esophageal stenosis, postoperative; Prednisone; Protective agents; Endoscopic submucosal dissection

Effect of Predniso(lo)ne Induction Dose on Remission in Autoimmune Hepatitis

Typically, patients presenting with autoimmune hepatitis (AIH) are initially treated with predniso(lo)ne (PRED) to rapidly induce remission. However,

Melkersson Rosenthal Syndrome: a case report and review of the literature

Melkersson Rosenthal Syndrome (MRS) is a rare neurological disorder characterized by swelling of the face, particularly one or both lips (granulomatous cheilitis), facial muscle weakness (palsy) and a fissured tongue. We present a patient with Melkersson Rosenthal Syndrome, highlighting the clinical triad of symptoms and management. A74-year-old Nigerian male presented to the Oral Medicine Clinic of the University of Benin Teaching Hospital for evaluation of right-sided facial numbness, inability to close the right eye, left facial deviation suggestive of a lower motor neuron type facial palsy of 4 days, and painless swelling of the upper and lower lips for seven days. On examination, he was found to have swelling of the upper and lower lips, multiple fissures on the tongue, right facial paresthesia, and an isolated right-sided facial nerve paralysis. He was empirically managed with 50mg prednisone daily for seven days, which was tapered over two weeks and neurobion 1 tablet daily for a month. This resulted in remission of lip swelling, however fissured tongue remained. Two months later, facial deviation had become less apparent. Patient is being followed up in the outpatient clinic. Melkersson Rosenthal Syndrome is a rare disorder with features of facial swelling, facial nerve palsy and fissured tongue. Some affected individuals may have all three of these features and others may have only one or two. The diagnosis of MRS can be made clinically when there is a complete triad of symptoms as reported in our patient.Keywords: Melkersson Rosenthal Syndrome, clinical symptoms, management

Multiple keratoacanthoma centrifugum marginatum—a case report and systematic review

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma (KA). Although many cases and reviews of solitary KCM have been reported, few studies have been published on multiple KCM. This article describes a typical case of multiple KCM, and summarizes the clinical characteristics, especially the treatment and prognosis of patients with multiple KCM. We systemically searched for “keratoacanthoma centrifugum marginatum” in the MEDLINE, EMBASE, Cochrane, and SinoMed databases, without time limitation. Sixty-five KCM records were found. After the selection process, ten available articles on multiple KCM were included. We present the case of a female patient with multiple progressive lesions, which are typical of KCM, on the face, a site where few KCM lesions have been observed. Multiple KCM is more common in males; the male-to-female ratio is 7:2 based on the cases that have been reported to date. KCM occurs mostly on the limbs, but lesions on the face and buttocks have also been reported. Both oral and topical (iso)retinoid treatments for multiple KCM were shown to be effective. In patients who are unresponsive to retinoid treatment, methotrexate and prednisone can be used as second-line treatments. Multiple KCM has characteristic clinical features. Although it progresses rapidly without treatment, proper treatment, including retinoids, immunosuppressants, corticosteroids, and excisional surgery, often leads to a favorable outcome.

Homocysteine levels are independently associated with damage accrual in systemic lupus erythematosus patients from a Latin-American cohort.

To determine the impact of homocysteine levels on damage accrual in systemic lupus erythematosus (SLE) patients. This longitudinal study was conducted in consecutive patients seen every 6months at our Rheumatology Department since 2012. Patients with available homocysteine levels and who had at least one subsequent visit were included. Univariable and multivariable Cox regression models were done to determine if homocysteine levels were predictive of damage accrual as per the SLICC Damage Index (SDI). The multivariable model was adjusted for pertinent variables (age at diagnosis, gender, socioeconomic status, disease duration, disease activity (SLEDAI), Framingham score, antimalarial and immunosuppressive drug use, average daily dose, and exposure time to prednisone (PDN)). One hundred forty-five patients were included; their mean (SD) age at diagnosis was 43.70 (12.09) years, 136 (93.8%) were female, and nearly all were Mestizo. At baseline, disease duration was 7.55 (6.73) years; patients were followed for 3.54 (1.27) years. The SLEDAI was 5.60 (4.34), and the SDI 0.97 (1.35). The average daily PDN dose was 7.30 (5.78) mg/day and the time of PDN exposure was 7.36 (6.73) years. Mean homocysteine levels were 10.07 (3.71) μmol/L. The highest tertile of homocysteine levels predicted new damage accrual in the univariable and multivariable models [HR 1.78 (95% CI, 1.042-3.039); p = 0.035 and HR 2.045 (95% CI, 1.077-3.883); p = 0.029, respectively]. Increased levels (> 15μmol/L) were found in 12 (8.3%) patients; 75 (51.7%) patients increased ≥ 1 SDI point. In SLE patients, homocysteine levels predicted damage accrual independently of other well-known risk factors for such occurrence.

Comparative study of dissolution profiles of prednisone 20 mg tablets marketed in Peru

El estudio tuvo como finalidad comparar los perfiles de disolucion de tabletas de prednisona 20 mg comercializados en Peru. Se realizo un estudio cuantitativo comparativo con diseno no experimental, que incluyo doce tabletas para cada formulacion a evaluar (referente y multifuente), bajo condiciones similares de trabajo, en tres medios de disolucion: buffer acido clorhidrico pH 1,2; buffer acetato pH 4,5 y buffer fosfato pH 6,8. Los porcentajes temporales disueltos de prednisona fueron evaluados mediante el orden cinetico cero, uno, Higuchi, raiz cubica y Weibull para el modelo dependiente; mientras que el factor de similitud (f2), tiempo medio de disolucion y eficiencia de disolucion fueron utilizados para el modelo independiente. En el modelo dependiente, la liberacion de prednisona; se ajusto a la cinetica de funcion de Weibull; evaluada mediante el criterio de informacion de Akaike. En el modelo independiente, los valores de f2 en todos los medios de disolucion cumplieron con el rango 50 – 100 establecida por la Food and Drug Adminstration, para indicar similitud in vitro entre los perfiles de disolucion. Asimismo, se evidencio que no existe diferencia estadisticamente significativa entre las formulaciones, respecto al tiempo medio de disolucion y la eficiencia de disolucion. Las tabletas de prednisona 20 mg referente y multifuente comercializados en Peru son similares, con base en pruebas de perfiles de disolucion in vitro .

Dose-Adjusted Intensive Chemotherapy Is Safe and Tolerable in Older Patients with Ph-Negative Acute Lymphoblastic Leukemia

BackgroundThe outcomes of older adults with acute lymphoblastic leukemia (ALL) remain poor when compared to younger ALL patients [PMID 19897583, 28419558, 22409379, 10653870]. Asparaginase (Asp) induces death of human lymphoblasts, and effective asparagine depletion is associated with improved outcomes in ALL. PEG-Asparaginase (PEG-Asp), which has a longer half-life than Asp, is a key component of the intensive chemotherapeutic regimens utilized for treatment of pediatric and younger adult ALL [PMID 29450465]. Frequently, older patients with Ph-negative ALL are not offered PEG-Asp containing pediatric chemotherapy regimen because of concerns related to tolerability and safety in this population [PMID 28355969].MethodsThe Adult Leukemia Program at Mount Sinai Hospital developed an age-based, dose-adjusted, CALGB 10403 based intensive chemotherapy regimen for adults (≥40 years) with a diagnosis of Ph-negative ALL. For patients up to 60 years, prednisone (PRD) dose was reduced from 60 to 40 mg/m2/day from D1 to D28, and PEG-Asp reduced from 2500 to 1000 units/m2 (D4). For patients aged 61 years and above, PRD was further reduced to 25 mg/m2/day, and PEG-Asp to 1000 units/m2 on D4. In CD20+ ALL, rituximab x 8 doses were added to the regimen. CNS-prophylaxis consisted of intrathecal methotrexate at D1, D8 and D29 during induction, and during subsequent courses of chemotherapy based on the CALGB 10403 protocol. A PEG-Asp oriented supportive care plan was developed to prevent and treat Asp-related adverse effects. After the administration of PEG-Asp, Antithrombin III (ATIII) and fibrinogen levels were monitored on the same day, twice a week, for at least two weeks. If ATIII levels were < 70% and/or fibrinogen levels < 120 mg/dL, levels were corrected with the administration of ATIII concentrate and/or cryoprecipitate, respectively.ResultsTwelve patients with a median age of 58 years (45 - 76) were evaluable, and three patients were ≥ 70 years. Nine patients had B-cell ALL and three T-cell ALL. Three patients had a white blood cell count > 30 x103/µL at diagnosis. An ECOG status ≤ 2 at diagnosis was described in all patients, and all of them had multiple complex cytogenetic and molecular abnormalities. Ten patients had significant co-morbidities at diagnosis, including diabetes, hypertension, previous history of cancer, coronary artery disease, obesity, alcohol related chronic pancreatitis, and chronic diarrhea. Nine out of the twelve patients (75%) attained a bone marrow morphological complete remission (CR) at the end of induction (EOI), three of them with detectable minimal residual disease (MRD) that became undetectable after completing course II. Of the three patients who had ≥5% bone marrow blasts at EOI, one attained a CR with undetectable MRD at the end of course IA and another when switched to blinatumomab, and the third one died of progressive disease. No patient experienced early death. Five patients underwent allogeneic hematopoietic stem cell transplantation (HCT) while in CR (age range 46 to 60 years) and four remain in CR at last follow up (median 489 days, range 181 - 841), and one died of relapsed disease 67 days post-HCT. The other six patients who are receiving chemotherapy are alive and in remission at last follow up (median 272 days, range 52 - 639).The common adverse effects associated with PEG-Asp administration in this older group of patients were asymptomatic hypofibrinogenemia and depleted ATIII levels requiring supplementation (n=8), severe hyperbilirubinemia (n=1), and non-life-threatening venous thrombosis (n=1). Severe allergic reaction, clinical pancreatitis and cognitive impairment were not observed.ConclusionThis age-based dose-adjusted PEG-Asp containing regimen was associated with an encouraging CR rate and a tolerable and manageable adverse event profile in this older patient population with significant co-morbidities. Treatment related mortality was 0%. Ten of 12 patients are currently in sustained remission, either with chemotherapy alone or following allogeneic HCT (median follow up 422 days, range 52 to 841 days). Treatment optimization for older patients with ALL utilizing an intensified, age-adjusted PEG-Asp containing induction and consolidation therapy regimen is associated with favorable outcomes and provides an effective bridge to potentially curative therapies such as HCT. Further prospective evaluation is under way. DisclosuresKremyanskaya:Incyte: Research Funding. Mascarenhas:Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Promedior: Research Funding; Janssen: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding.

Clinical analysis on granulocyte colony stimulating factor mobilized allogenetic peripheral blood mononuclear cell transfusion for one patient with primary myelofibrosis in fibrosis stage

Objective To investigate the safety and efficacy of granulocyte colony stimulating factor mobilized allogenetic peripheral blood mononuclear cell (G-PBMNC) in treatment of patient with primary myelofibrosis (PMF) in fibrosis stage with high risk and unsuitable for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods In March 2016, a case of male PMF patient (age: 70 years old)in fibrosis stage with high risk admitted to Department of Hematology, Affiliated Hospital of Panzhihua University was selected as a research subject. Laboratory and imaging examinations were performed to determine the stage and risk of the disease, combined with his medical history and outpatient examination results. After admission, the patient was treated with danazol, thalidomide and prednisone orally, deep intramuscular injection of deferoxamine, subcutaneous injection of erythropoietin (EPO), and suspended red blood cell infusion. In April 2016, the patient received G-PBMNC from his daughter. General condition and treatment safety of patient were observed, and the blood routine test results, transfusion volume of suspended red blood cell and spleen size were monitored. Relevant examination results, diagnosis, treatment and curative effect of this patient were analyzed retrospectively, and related literature was reviewed. This study protocol was approved by the Ethics Committee of Affiliated Hospital of Panzhihua College (No. 11 of the Ethics Examination in 2015), and informed consent was obtained from participant. Results ① After admitted, results of blood routine examination showed that white blood cell count was 2.0×109/L, red blood cell count was 1.5×1012/L, hemoglobin (Hb) value was 39.0 g/L, platelet count was 23.0×109/L, ratio of primitive cells in peripheral blood was 2%. Serum EPO value was more than 774 mIU/mL, and ferritin value was more than 2 250 μg/L. No specimens were taken from the bone marrow puncture. Result of bone X ray radiography showed bone sclerosis. Result of upper abdomen color Doppler ultrasound showed splenomegaly and slight hepatomegaly. The patient was diagnosed as PMF in fibrosis stage with high risk. ② A total of 140 mL of G-PBMNC suspension was isolated from the donor, and transfused to the patient after separation and counting. Number of mononuclear cell (MNC) and CD34+ cell were 3.0×108/kg and 1.6×106/kg, respectively, and acute graft versus host disease (aGVHD) did not develop 1 months after G-PBMNC infusion. ③ Most of the blood routine examination indexes of the patient showed an upward trend after G-PBMNC infusion. 1 and 11 months after G-PBMNC infusion, median white blood cell counts of the patient were 4.0×109/L (3.1×109/L-4.6×109/L) and 3.6×109/L (2.7×109/L-4.0×109/L), and were higher than that of 1.8×109/L (1.3×109/L-2.3×109/L) before G-PBMNC infusion. 8 and 13 months after infusion, median values of Hb were 69.7 g/L (59.2-82.5 g/L) and 70.5 g/L (61.3-84.1 g/L), and were higher than that of 46.8 g/L (33.5-60.3 g/L) before infusion. 6, 11 and 12 months after infusion, median platelet count were 36.5×109/L (22.6×109/L-43.6×109/L), 41.0 ×109/L (29.9 ×109/L-56.7 ×109/L) and 39.0×109/L (25.7×109/L-50.3×109/L), and were also higher than that of 14.0×109/L (7.2×109/L-18.5×109/L) before infusion . ④ Within one month before G-PBMNC infusion, a total of 12 U of suspended red blood cells were transfused; while one month after G-PBMNC infusion, amount of suspended red blood cell infusion decreased to 6.5 U. 3-4 months after infusion, transfusion volume of suspended red blood cell decreased to 1.5 U. 11 months after G-PBMNC infusion, transfusion volume of suspended red blood cell was only 3.5 U, and the patient did not receive blood transfusion for one month. ⑤ There was no progressive enlargement of spleen after infusion of G-PBMNC. Conclusions G-PBMNC could safely improve the routine blood test indexes of PMF patients in fibrosis stage with high risk and reduce the dependence of blood transfusion, so G-PBMNC could be a safe and effective treatment option for fibrotic PMF patients in no condition to allo-HSCT. But this conclusion is limited to the clinical analysis of a single case, and it requires large sample, multi-center, randomized controlled trials for further study and verification. Key words: Allogeneic cells; Transplantation, homologous; Hematopoietic stem cells; Primary myelofibrosis; Therapeutics

Interaction of prednisone with dsDNA at silver nanoparticles/poly(glyoxal-bis(2-hydroxyanil))/dsDNA modified electrode and its analytical application

This paper reports the fabrication of an electrochemical DNA biosensor for the electrochemical determination of prednisone (PRD), which is a synthetic corticosteroid. For this purpose, silver nanoparticles (AgNPs) and a new polymer film poly(glyoxal-bis(2-hydroxyanil)) (P(GBHA)) were electrochemically deposited on a glassy carbon electrode (GCE), respectively. Then, an electrochemical DNA biosensor was prepared onto this electrode surface (GCE/AgNPs/P(GBHA)) by the immobilization of dsDNA using a chronoamperometry method. The proposed electrode was characterized by FESEM, XPS, and cyclic voltammetry (CV). The interaction between the PRD and dsDNA immobilized on the GCE/AgNPs/P(GBHA) electrode was investigated via a differential pulse voltammetry (DPV) method and UV–Vis spectrophotometry. The experimental factors affecting the interaction between the PRD concentration and dsDNA were optimized. The fabricated biosensor showed a wide linear response in a PRD concentration range of 1.0–50.0 μg mL−1 depending on both the adenine and guanine base signals. The detection limit based on the guanine and adenine signals was 0.3 μg mL−1 and 0.25 μg mL−1, respectively. The sensor exhibited excellent anti-interferential ability, good stability and reproducibility and was satisfactorily employed for the electrochemical assay of PRD in serum samples. The new DNA biosensor can be utilized for the sensitive, accurate and rapid analysis of PRD.

Prednisone Reduces the Risk for TB-Associated IRIS

Throughout the world, tuberculosis (TB) remains the most common opportunistic infection at HIV diagnosis; many patients with this coinfection present

Changes of microparticle levels before and after daunorubicin-based chemotherapy in patients with acute leukemia

Objective To observe the serum levels of endothelial microparticles (EMP) and tissue factor-bearing microparticles (TF+ MP) in patients with acute leukemia before and after daunorubicin-based chemotherapy. Methods From July 2012 to February 2013, 15 patients with newly diagnosed acute leukemia in Peking Union Medical College Hospital received DA (daunorubicin + cytarabine) regimen or VDCLP (vincristine + daunorubicin + cyclophosphamide + L-asparaginase + prednisone) regimen chemotherapy. There were 8 males and 7 females, and the median age of patients was 44 years old. Eleven patients were acute myeloid leukemia (M0 1 case, M1 1 case, M2 9 cases), and 4 were acute lymphocytic leukemia. The peripheral blood samples were taken before induction chemotherapy and after 3 days of daunorubicin. Levels of EMP and TF+ MP were assessed using flow cytometry. Results The serum EMP and TF+ MP levels were significantly higher after 3-day daunorubicin infusions than those before induction chemotherapy (28.94/μl vs. 10.74/μl, P = 0.001; 64.24/μl vs. 43.80/μl, P = 0.02). Conclusion Daunorubicin-based chemotherapy may cause increased numbers of EMP and TF+ MP in patients with acute leukemia. Key words: Leukemia, acute; Antineoplastic combined chemotherapy protocols; Daunorubicin; Endothelial particles; Tissue factor-bearing microparticles

Study on the effect of Huangqi-Gegen decoction and Peiyuan-Guben powder on autoimmune myasthenia gravis rats

Objective Experimental model of experimental autoimmune Myasthenia Gravis (EAMG) were established to explore the effect of Zini-Huangqi-Gegen decoction and Peiyuan-Guben powder on EAMG rats model. Methods Experimental animals were randomly divided into the control group (n=10) and the model group (n=30). The model rats were induced by murine AChR-α97-116 peptide immunostaining for EAMG rats model. After the first immunization, the general condictions and body weight of rats were observed, and the Lennon score was used to evaluate the rats. The second immunization was performed on the 11th day after the first immunization. On the 15th day after the first immunization, the rats were randomly divided into the model group(n=8), Huangqi-Gegen decoction and Peiyuan-Guben powder group (abbreviated Huangpei group, n=8) and Prednisone group (n=8) according to the Lennon score. Huangpi group rats were treated with Huangqi-Gegen decoction (21.5 g/kg) combined with Peiyuan-Guben powder (0.8 g/kg), prednisone group with 0.005 4 g/kg prednisone aqueous solution, the control group and the model group oral volume of distilled water. The rats were administered with a body weight of 10 ml/kg once a day for a total of 56 days. At the 70th day after the first immunization, serum was extracted from the rats. The Anti-AChR-α97-116 IgG and its subtype in serum were detected by ELISA. The IL-4, IL-10, IL-17 in serum were detected by ELISA. Results Compared with the model group, the weight of the rats in the Huangpei group and the prednisone group significantly increased after the 28th day of the first immunization (P<0.05). After the 36nd day of the first immunization, the Lennon score of the Huangpei group significantly decreased (P<0.05). At the end of the administration, the amplitude of EMG amplitude attenuation (41.83% ± 7.45% vs. 67.76% ± 4.32%) in the Huangpei group significantly decreased (P<0.05), and the serum IgG (1.15 ± 0.07 vs. 1.24 ± 0.08), IgG1 (0.17 ± 0.01 vs. 0.25 ± 0.03), IL-4 (16.54 ± 1.66 pg/ml vs. 25.64 ± 1.74 pg/ml), IL-10 ( 113.65 ± 12.87 pg/ml vs. 121.54 ± 10.44 pg/ml), IL-17 (43.58 ± 3.54 pg/ml vs. 65.76 ± 3.59 pg/ml) in the rat serum significantly decreased (P<0.05). Conclusions Huangqi-Gegen decoction and Peiyuan-Guben powder can increase the body weight of rats, decrease the concentration of AChR-Ab in serum, the concentrations of IL-4, IL-10 and IL-17 in serum, and effectively improve the symptoms of EAMG rats. Key words: Myasthenia gravis, autoimmune, experimental; Huangqi-Gegen decoction and Peiyuan-Guben powder; Inflammation; Rats

Prognostic value of interim and end-of-treatment 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma

Objective To compare the value of interim and end-of-treatment 18F-fluorodeoxyglucose (FDG) PET/CT for the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Methods A total of 116 DLBCL patients (male∶female=1∶1.32, average age: (57.87±15.89) years) whose initial treatment was rituximab+ cyclophosphamide+ doxorubicin+ vincristine+ prednisone(R-CHOP), were enrolled from 2008 to 2016. All patients underwent pre-treatment, interim and end-of-treatment 18F-FDG PET/CT. End points were progression-free survival (PFS) and overall survival (OS). Correlation between metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), Deauville score (DS), ΔSUVmax, ΔMTV, ΔTLG in the interim PET/CT and those in the end-of-treatment PET/CT was analyzed with Pearson correlation analysis. The ability of metabolic parameters to assess the prognosis was evaluated by receiver operating characteristic(ROC) curve analysis. The survival was analyzed by Kaplan-Meier method and hazard ratio (HR) was calculated by Cox regression model. Results The r values for ΔSUVmax, ΔMTV, ΔTLG of interim and end-of-treatment PET/CT were 0.630, 0.912, 0.955, respectively (all P<0.01). One hundred and four cases (89.7%, 104/116)had the same DS in the interim and end-of-treatment PET/CT, and the r value for DS between two PET/CT scans was 0.733 (P<0.01). The interim metabolic parameters were superior to that at the end of treatment in evaluating the progression. The 5-year PFS(83.1% vs 35.9%, P<0.01; HR=5.969, P<0.01) and OS (95.7% vs 75.5%, P<0.01; HR=8.161, P<0.05) rates were significantly higher in DS 1-3 group than those in DS 4-5 group. Conclusions Interim PET/CT is effective for the prediction of prognosis in DLBCL patients with R-CHOP treatment. Patients with complete remission in the interim can omit the end-of-treatment PET/CT. Key words: Lymphoma, large B cell, diffuse; Prognosis; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Clinical analysis of blastic plasmacytoid dendritic cell neoplasm

Objective To investigate the clinical features, diagnosis, treatment and efficacy of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in order to improve the understanding of BPDCN. Methods On 21 August 2017, a case of BPDCN patient admitted in Hematology Department of Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University, was included in this study. This patient was diagnosed as BPDCN in other hospital in November 2016, and then received 5 courses of CHOP (cyclophosphamide+ doxorubicin+ vincristine+ prednisone)-21 regimen for chemotherapy. After partial remission (PR), the patient relapsed in June 2017, and was admitted in Hematology Department of our hospital for further treatment. After admission, combined with the patient′s medical history, diagnosis was made according to the clinical manifestations, bone marrow examination and relevant laboratory examination results. On 25 August 2017, the patient received 3 courses of VDCP (vindesine+ daunorubicin+ cyclophosphamide+ dexamethasone) regimen for chemotherapy. Vindesine 4 mg/d, d1, 8, 15, 22; doxorubicin 60 mg/d, d4-5, 80 mg/d, d6, 60 mg/d, d15-16; cyclophosphamide 1.7 g/d, d4, 15; and dexamethasone 17 mg/d, d1-7 were applied. The laboratory test results, further diagnosis and assesement of disease, and curative effects of this patient were analyzed retrospectively, and related literature was reviewed to explore the research progress of BPDCN diagnosis and treatment. Results ① After admission, flow cytometry test results of the patients′ bone marrow cells showed abnormal cell population within original cell distribution area, accounting for about 9.4%. Abnormal cell expressed human leukocyte antigen (HLA)-DR, CD4, CD38, CD56 and CD123, and some expressed CD33. Results of morphological examination of bone marrow cells showed that proliferation of bone marrow cells was significantly active. Proportion of granulocyte was 38.0%, proportion of erythroid was 24.0%, and ratio of granulocyte and erythroid was 1.58∶1. Megakaryotic cells and heteromorphic lymphoid cells could be seen. Ratio of primitive cells was 27.0%, and was BPDCN bone marrow invasion. Bone marrow cell immunohistochemical test results showed CD4 (+ ), CD56 (+ ), CD123 (+ ), CD68 (+ ), CD235 (erythroid+ ), myeloperoxidase (MPO) (granulocyte+ ), terminal deoxynucleotidyl transferase (TdT) (-), CD117 (<1%), CD3 (-), CD20 (-), CD23 (-), T cell intracellular antigen (TIA)-1 (+ ), granzyme B (-). Results of scalp biopsy showed that tumor cells were diffuse in dermal layer of the skin without involving the epidermis. Immunohistochemical results showed that CD4 (+ ), CD43 (+ ), CD56 (+ ), CD123 (weak+ ), TdT (scattered+ ), CD117 (-), CD3 (-), CD23 (-), TIA-1 (-), granzyme B (-), and CD68 (scattered+ ). ② The patient was diagnosed with BPDCN, and was comprehensively evaluated as progressive disease (PD) at admission. ③ After the treatment with VDCP regimen, all rashes on the scalp, face and trunk of the patient were eliminated. The granulocyte count returned to the normal reference range. Bone marrow smear results showed that bone marrow hyperplasia was significantly active, with 50.0% granulocytes and 36.5% erythroid. Ratio of granulocytes and red line cells was 1.37∶1. Proportion of primitive granulocytes and abnormal lymphocytes were 0.5% and 3.5%, respectively. The comprehensive evaluation was complete remission (CR). The patient refused to continue treatment and died 20 months after the onset (February 2018). Conclusion BPDCN is a rare and highly aggressive disease with poor prognosis, and standard treatment protocols for BPDCN has not been established currently. Key words: Dendritic cells; Killer cells, natural; Drug therapy; Prognosis; Blastic plasmacytoid dendritic cell neoplasm

Metformin prolonged the survival of diffuse large B-cell lymphoma and grade 3b follicular lymphoma patients responding to first-line treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone: a prospective phase II clinical trial

Background: With the addition of rituximab to chemotherapy, the response rates of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma grade 3b (FL3b) have been significantly improved. However, recurrence remains to be the hinder of long survival of the patients. Metformin is a widely used anti-diabetic agent and has an anti-lymphoma effect through adenosine monophosphate (AMP)-activated protein kinase activation in vitro and in vivo. Methods: We conducted a single center, prospective, single-arm phase II clinical trial of metformin for maintenance therapy in patients with DLBCL or FL3b who achieved complete remission after the first-line treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and analyzed the efficacies of metformin maintenance. Results: The patients received metformin maintenance had significantly better overall survival (OS) than those without metformin maintenance, especially for the diabetic patients. Patients with age >60, elevated serum lactate dehydrogenase (LDH), or International Prognostic Index (IPI) score ≥2 were benefit from metformin maintenance, as well as those with tumor cell expressing Ki67 ≥80%, or with non-germinal center B-cell-like (non-GCB) subtype. In multivariate analysis, age >60, elevated serum LDH and diabetic patients without metformin maintenance were the three independent unfavorable prognostic factors for OS. Conclusions: Metformin could thus be a safe and economic maintenance agent for elderly and high-risk patients not suitable for transplantation.