TY - JOUR. T1 - Preferential sequestration in vitro of BCR/ABL negative hematopoietic progenitor cells among cytokine nonresponsive CML marrow CD34+ cells. AU - Veena, P.. AU - Cornetta, K.. AU - Davidson, A.. AU - Agüero, B.. AU - McMahel, J.. AU - Traycoff, C. M.. AU - Srour, E. F.. PY - 1997/6/2. Y1 - 1997/6/2. N2 - It is believed that long-term cultures of CML marrow cells favor the outgrowth of BCR/ABL negative hematopoietic progenitor cells (HPC) and that this phenomenon may be enhanced with negative hematopoietic regulators which can maintain primitive HPC in a quiescent state. Proliferation of CML marrow CD34+ cells in primary short-term cultures, maintained in the presence or absence of macrophage inhibitory protein-1 alpha (MIP-1α), was tracked with the membrane dye PKH2. After 7 to 10 days it was possible to distinguish between cytokine responsive (CR) CD34+ cells (cells which had divided thus becoming PKH2(dim)) and cytokine nonresponsive (CNR) CD34+ cells (cells which had not ...
The protein encoded by this gene is a component of centriolar satellites, which are electron dense granules scattered around centrosomes. Inhibition studies show that this protein is essential for the correct localization of several centrosomal proteins, and for anchoring microtubules to the centrosome. Chromosomal aberrations involving this gene are associated with papillary thyroid carcinomas and a variety of hematological malignancies, including atypical chronic myeloid leukemia and T-cell lymphoma.
The official nomenclature in this field has gone through many changes over the years and the MeSH tree structure in this area had not been revised, in toto, for a long time. The main authority source used in this revision was the International Classification of Diseases for Oncology (ICD-O), 3d edition, supplemented by recent papers and texts1. Members of some working groups who are advising on the upcoming 4th edition were also consulted.. Many of the leukemia terms have undergone name changes as immunophenotypic and molecular biological techniques have made diagnosis more precise. For instance the old descriptor LEUKEMIA, MYELOID, CHRONIC is now called LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE. The old descriptor LEUKEMIA, MYELOID, PHILADELPHIA-NEGATIVE is now LEUKEMIA, MYELOID, CHRONIC, ATYPICAL, BCR-ABL NEGATIVE.. The old classification system for lymphomas, was discarded for a simpler model. Many old names are now obsolete, though some have been retained as entry terms. This includes ...
To characterize the pharmacokinetics of vincristine in two patient cohorts: Bcr-Abl positive ALL patients treated with the standard protocol with imatinib and Bcr-Abl negative ALL patients treated with the same protocol but without imatinib ...
The FAB group has recently published guidelines for distinguishing chronic granulocytic leukaemia (CGL) from chronic myelomonocytic leukaemia (CMML) and atypical chronic myeloid leukaemia (aCML). Whereas CGL is generally recognized to be a distinct entity, there is debate as to whether CMML and aCML are separate disorders or part of a spectrum of myeloproliferative disorders with dysplastic features. Data are presented on 10 cases who developed features of a CML during the course of their disease but who presented with a normal or a low leucocyte count without a monocytosis and were diagnosed as refractory anaemia. This suggests that, at least in some cases, aCML represents an unusual evolution of MDS, and even though these patients have a uniformly poor prognosis it may be premature to regard aCML as a distinct clinical entity ...
TY - JOUR. T1 - Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome-negative acute lymphoblastic leukemia in the era of minimal residual disease. AU - Issa, Ghayas C.. AU - Kantarjian, Hagop M.. AU - Yin, C. Cameron. AU - Qiao, Wei. AU - Ravandi, Farhad. AU - Thomas, Deborah. AU - Short, Nicholas J.. AU - Sasaki, Koji. AU - Garcia-Manero, Guillermo. AU - Kadia, Tapan M.. AU - Cortes, Jorge E.. AU - Daver, Naval. AU - Borthakur, Gautam. AU - Jain, Nitin. AU - Konopleva, Marina. AU - Khouri, Issa. AU - Kebriaei, Partow. AU - Champlin, Richard E.. AU - Pierce, Sherry. AU - OBrien, Susan M.. AU - Jabbour, Elias. PY - 2017/2/1. Y1 - 2017/2/1. N2 - BACKGROUND: The introduction of novel prognostic factors such as minimal residual disease (MRD) and genomic profiling has led to the reevaluation of the role of cytogenetics and other conventional factors in risk stratification for acute lymphoblastic leukemia (ALL). METHODS: This study assessed the impact of baseline ...
Philadelphia chromosome-negative ALL in the older adult (age ≥40 y): Standard multiagent chemotherapy regimen (eg, CALGB 8811 [daunorubicin, vincristine, prednisone, pegaspargase, cyclophosp... more
1 Schinzel A, Giedion A. A syndrome of severe midface retraction, multiple skull anomalies, clubfeet, and cardiac and renal malformations in sibs. Am J Med Genet 1978; 1: 361-375. 2 Piazza R, Valletta S, Winkelmann N, Redaelli S, Spinelli R, Pirola A et al. Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet 2012; 45: 18-24. 3 Makishima H, Yoshida K, Nguyen N, Sanada M, Okuno Y, Ng KP et al. Somatic mutations in Schinzel-Giedion Syndrome gene SETBP1 determine progression in myeloid malignancies. Blood 2012; 120: 2 (abstract). 4 Damm F, Itzykson R, Kosmider O, Droin N, Renneville A, Chesnais V et al. SETBP1 mutations in 658 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia and secondary acute myeloid leukemias. Leukemia 2013; 27: 1401-1403. 5 Laborde RR, Patnaik MM, Lasho TL, Finke CM, Hanson CA, Knudson RA et al. SETBP1 mutations in 415 patients with primary myelofibrosis or chronic myelomonocytic leukemia (CMML): independent prognostic impact in CMML.
2.1.2 If superiority of blinatumomab in the MRD positive group is shown, to compare the OS of blinatumomab in conjunction with chemotherapy to chemotherapy alone in patients with BCR-ABL-negative B cell precursor ALL who are MRD negative after induction and intensification chemotherapy, based on MFC assessment of residual blasts ...
The high toxicity of current Anti-Retroviral Therapy (ART) regimens has driven a number of studies investigating therapeutic approaches aimed at reducing drug exposure while maintaining the beneficial effects of immune reconstitution. Preliminary observations in HCV/HIV co-infected individuals already support an antiviral effect by Pegylated Interferon-Alpha-2A (Peg-IFN-Alpha-2A:Pegasys®) on HIV-1 replication; however, the ability of Peg-IFN-Alpha-2A (as a single agent) to maintain long-term suppression of HIV-1 replication in patients who interrupt ART after having achieved immune reconstitution remains undetermined. The rationale for addressing two doses of Peg-IFN-Alpha-2A (180 and 90 ug/week) is based on the antiviral activity reported with both doses and the lower incidence of adverse events associated with doses lower than that approved for HCV therapy (90 versus 180ug/week).. The long-range goal of this proposal is to determine if Peg-IFN-Alpha-2A monotherapy can sustain HIV-1 ...
Vincristine Liposome is an anti-cancer chemotherapy drug used in the treatment of Philadelphia chromosome-negative acute lymphoblastic leukemia.
PRIMARY OBJECTIVES:I. To compare the overall survival (OS) of blinatumomab in conjunction with chemotherapy to chemotherapy alone in patients with
Sigma-Aldrich offers abstracts and full-text articles by [Nicholas A Vitanza, Wafik Zaky, Roy Blum, Julia A Meyer, Jinhua Wang, Teena Bhatla, Debra J Morrison, Elizabeth A Raetz, William L Carroll].
On December 3, 2014, blinatumomab (Blincyto) was granted accelerated approval for use in treating Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).1,2. Supporting Trial. Approval was based on results of a single-arm trial in 185 patients showing achievement of durable complete remission/complete remission with partial hematologic recovery. Blinatumomab was administered by continuous infusion for 4 weeks of a 6-week cycle. In the first cycle, the initial dose was 9 µg/d for week 1, then 28 µg/d for the remaining 3 weeks. The target dose of 28 µg/d was administered in cycle 2 and subsequent cycles starting on day 1 of each cycle.. Among treated patients, the median age was 39 years (range, 18-79 years), 34% had undergone hematopoietic stem cell transplantation prior to receiving blinatumomab, and 17% had received more than two prior salvage therapies.. Complete remission/complete remission with partial hematologic recovery within two ...
TY - JOUR. T1 - Philadelphia chromosome‐negative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region. Long term follow‐up results. AU - Cortes, Jorge E.. AU - Talpaz, Moshe. AU - Beran, Miloslav. AU - OBrien, Susan M.. AU - Rios, Mary B.. AU - Stass, Sanford. AU - Kantarjian, Hagop M.. PY - 1995/1/15. Y1 - 1995/1/15. N2 - Background. Five to 10% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia chromosome (Ph), but one‐third of them have rearrangements of the breakpoint cluster region (BCR‐positive). Methods. The authors analyzed the characteristics, treatment response, and prognosis of 23 patients with BCR‐positive, Ph‐negative CML, and compared them with patients with Ph‐positive CML, Ph‐negative BCR‐negative CML and chronic myelomonocytic leukemia (CMML) treated during the same period. Results. Seventeen patients had early chronic phase CML, 3 had late chronic phase, 2 had accelerated phase, and 1 had blastic ...
TY - JOUR. T1 - The colony-Stimulating factor 3 receptor T640N mutation is oncogenic, sensitive toJAKInhibition, and mimics T618i. AU - Maxson, Julia. AU - Luty, Samuel B.. AU - MacManiman, Jason D.. AU - Paik, Jason C.. AU - Gotlib, Jason. AU - Greenberg, Peter. AU - Bahamadi, Swaleh. AU - Savage, Samantha L.. AU - Abel, Melissa L.. AU - Eide, Christopher A.. AU - Loriaux, Marc. AU - Stevens, Emily A.. AU - Tyner, Jeffrey. PY - 2016/2/1. Y1 - 2016/2/1. N2 - Purpose: Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in the majority of chronic neutrophilic leukemia (CNL) and a smaller percentage of atypical chronic myeloid leukemia (aCML) cases. Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. In this study, we assess the importance of the CSF3R T640N mutation as a marker of CNL/aCML and potential therapeutic target. Experimental Design: Sanger sequencing of leukemia samples was ...
TY - JOUR. T1 - Clonal cytogenetic abnormalities and BCL2 rearrangementin interdigitating dendritic cell sarcoma [3]. AU - Nayer, Hassan. AU - Murphy, Kathleen M.. AU - Hawkins, Anita L.. AU - Long, Patricia P.. AU - Gillison, Maura. AU - Borowitz, Michael. AU - Griffin, Constance A.. PY - 2006/12/1. Y1 - 2006/12/1. UR - http://www.scopus.com/inward/record.url?scp=33845572651&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=33845572651&partnerID=8YFLogxK. U2 - 10.1080/10428190600879896. DO - 10.1080/10428190600879896. M3 - Letter. C2 - 17169812. AN - SCOPUS:33845572651. VL - 47. SP - 2651. EP - 2654. JO - Leukemia and Lymphoma. JF - Leukemia and Lymphoma. SN - 1042-8194. IS - 12. ER - ...
SILVER SPRING, Md. - The Food and Drug Administration has approved a new drug for treating a rare type of leukemia, the agency said Thursday.. The FDA approved South San Francisco, Calif.-based Talon Therapeutics Marqibo (vincristine sulfate liposome), an injectable drug for Philadelphia chromosome-negative acute lymphoblasic leukemia, or Ph-negative ALL. The drug, which consists of the widely used anti-cancer drug vincristine encased within a liposome - a drug delivery system made of a material similar to cell membranes - is approved for patients whose leukemia has returned twice or more or has progressed after two or more regimens of therapy.. According to the National Cancer Institute, part of the National Institutes of Health, more than 6,000 people will be diagnosed with ALL this year, and 1,440 will die from it. The disease is a rapidly progressing form of blood and bone marrow cancer more common in children than adults.. ...
Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase 2 trial of B-lineage ALL patients with persistent or relapsed MRD, a T cell-engaging bispecific Ab construct induced an 80% MRD response rate. In the present study, we show that after a median follow-up of 33 months, the hematologic relapse-free survival of the entire evaluable study cohort of 20 patients was 61% (Kaplan-Meier estimate). The hema-tologic relapse-free survival rate of a subgroup of 9 patients who received allogeneic hematopoietic stem cell transplantation after blinatumomab treatment was 65% (Kaplan-Meier estimate). Of the subgroup of 6 Philadelphia chromosome-negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. We conclude that blinatumomab can induce long-lasting complete remission in B-lineage ALL patients with persistent or recurrent MRD. The
Learn more about Marqibo® (vinCRIStine sulfate LIPOSOME injection) at MARQIBO.com. Marqibo® is for the treatment of adult patients with Philadelphia chromosome-negative (Ph‒) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following 2 or more anti-leukemia therapies. This indication is based on overall response rate. Clinical benefit such as improvement in overall survival has not been verified.
We have followed one patient with Philadelphia (Ph)-negative chronic myelogenous leukemia and identified an additional four patients from the literature who showed the rearrangement in the breakpoint cluster region (bcr) on chromosome 22 characteristic of Ph-positive chronic myelogenous leukemia. The clinical course of these five patients was similar to that of Ph-positive patients, with easily controlled leukocyte counts, a prolonged benign phase, and prolonged survival. Furthermore, we have shown, for the first time, that bcr rearrangement in Ph-negative chronic myelogenous leukemia can result in expression of the aberrant 210-kilodalton bcr-abl fusion protein, which has been strongly implicated in Ph-positive leukemogenesis. Research data pertaining to possible cytogenetic mechanisms leading to production of p210bcr-abl in the absence of the Ph chromosome are reviewed. Molecular analysis provides an important tool for classifying and predicting prognosis of some patients with Ph-negative ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Imatinib mesylate (Gleevec; Novartis) has been successfully employed in the treatment of Philadelphia-positive chronic myeloid leukaemia (Ph+ CML) (Deininger et al, 2005). Although imatinib restores a polyclonal haemopoiesis in over 90% of patients, development of clonal chromosome abnormalities in Ph-negative cells (Ph) clonal evolution) occurs in about 15% of cases with a complete cytogenetic remission (CCR). This phenomenon has been very rarely observed in patients treated with interferon-a and/or cytotoxic agents. As the biological and clinical significance of these clones are still unclear, we investigated two cases of CML in chronic phase, not previously treated with genotoxic agents or drugs, in which imatinib therapy lead to the emergence of Ph) clones characterised by an abnormality initially disclosed in the Ph+ cells, a picture found only in two other cases in the literature (Gozzetti et al, 2003; Royer-Pokora et al, 2003). In patient 1, all metaphases at diagnosis carried both the Ph ...
The FDA approved South San Francisco, Calif.-based Talon Therapeutics Marqibo (vincristine sulfate liposome), an injectable drug for Philadelphia chromosome-negative acute lymphoblasic leukemia, or Ph-negative ALL. The drug, which consists of the widely used anti-cancer drug vincristine encased within a liposome - a drug delivery system made of a material similar to cell membranes - is approved for patients whose leukemia has returned twice or more or has progressed after two or more regimens of therapy.. According to the National Cancer Institute, part of the National Institutes of Health, more than 6,000 people will be diagnosed with ALL this year, and 1,440 will die from it. The disease is a rapidly progressing form of blood and bone marrow cancer more common in children than adults.. ...
Class: Biological Therapy. Generic Name: Blinatumomab. Trade Name: Blincyto®. For which conditions is this drug approved? Blincyto is approved for treatment of a certain type of acute lymphoblastic leukemia (ALL): Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute ALL.. What is the mechanism of action? Blincyto is a type of drug known as a monoclonal antibody. Monoclonal antibodies target and attach to cancer cells, which tells the immune system to destroy the cancer. Specifically, Blincyto targets a protein called CD19 thats found on the surface of B-cell leukemia cells. Another protein, CD3, thats found on the surface of T-cell lymphocytes (part of the immune system), then connects with CD19 to destroy the cancer cells.. How is Blincyto typically given (administered)? Blincyto is given by intravenous (IV) infusion into your vein using an infusion pump. One treatment cycle includes a continuous IV infusion for four weeks, followed by a two-week break during which ...
DEERFIELD, Ill., January 15, 2015 - Walgreens today announced that, effective immediately, Walgreens Infusion Services will serve as a limited network home infusion provider for BLINCYTO™ (blinatumomab), a therapy for the treatment of patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). BLINCYTO™ can now be obtained through and administered by Walgreens Infusion Services.. "Through our nationwide, community-based infusion services, we deliver comprehensive and collaborative patient care for those with complex conditions and were pleased to be able to provide home infusion services to appropriate patients requiring immunotherapy to treat this rare form of ALL," said Paul Mastrapa, president, Walgreens Infusion Services.. Walgreens Infusion Services specially trained infusion nurses and pharmacists treat patients with a wide range of acute, chronic and rare conditions. As the nations largest provider of home and ...
Background. Prognosis of acute lymphoblastic leukemia in elderly is poor. The GRAALL-SA1 phase II trial randomly compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients ≥55 years with Philadelphia chromosome-negative ALL. Design and Methods. Sixty patients received either continuous infusion-Doxorubicin (12 mg/m²/d) and continuous infusion-vincristine (0.4 mg/day) on day1-4 or liposomal-Doxorubicin (40 mg/m2;) and standard vincristine (2 mg) on day1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. Endpoints were safety, outcome and prognostic factors. Results. Myelosupression was reduced in the Peg-Dox arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and less erythrocytes transfusions (P=0.04). Grade 3/4 infections and gram-negative bacteremia were reduced in the Peg-Dox arm (P=0.04 and 0.02, respectively). There was a trend toward less ...
Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome. Material and Methods: Pyrosequencing was performed to detect JAK2 (V617F) and MPL (W515K/L) and capillary electrophoresis to identify CALR exon 9.0 mutations in 100.0 samples of Ph-negative MPNs (38.0 PV, 55 ET, 4 PMF, and 3 MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of PV, 74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F) mutant allele burden (mutational load | 50.0%) was predominantly observed
Class: Biological Therapy. Generic Name: Blinatumomab. Trade Name: Blincyto®. For which conditions is this drug approved? Blincyto is approved for treatment of a certain type of acute lymphoblastic leukemia (ALL): Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute ALL.. What is the mechanism of action? Blincyto is a type of drug known as a monoclonal antibody. Monoclonal antibodies target and attach to cancer cells, which tells the immune system to destroy the cancer. Specifically, Blincyto targets a protein called CD19 thats found on the surface of B-cell leukemia cells. Another protein, CD3, thats found on the surface of T-cell lymphocytes (part of the immune system), then connects with CD19 to destroy the cancer cells.. How is Blincyto typically given (administered)? Blincyto is given by intravenous (IV) infusion into your vein using an infusion pump. One treatment cycle includes a continuous IV infusion for four weeks, followed by a two-week break during which ...
The cytokine BAFF is produced by a number of cell types, including monocytes, neutrophils, macrophages, dendritic cells, and some subsets of T cells (17). Receptors for BAFF, however, were initially thought to be restricted to more differentiated B-lineage cells. Therefore, the expression of BAFF receptors on transformed B-lineage lymphocytes in CLL was not entirely unexpected. In contrast, based on BAFF-null and BAFF-R-null mutants as well as other studies, it has been generally accepted that precursor B-lineage cells do not express this receptor. Our studies confirm that there is no expression of this receptor in normal bone marrow pre-B cells. Interestingly, Rodig and colleagues (35) also performed FACS on two pre-B ALL samples and reported that these were negative for expression of BAFF-R. Therefore, the prominent expression of the BAFF-R that we detected on both Ph-positive and Ph-negative ALL samples was unanticipated. In fact, all 12 samples that were tested by us, including original ALL ...
Human leukocyte antigen (HLA) haploidentical stem cell transplantation (haplo-SCT) as a postremission treatment for standard risk Philadelphia chromosome-negative acute lymphoblastic leukemia (SR Ph-ALL) in the first complete remission (CR1) has not been defined. In this multicenter, phase 3 study (NCT02042690), of the 131 consecutive Ph-ALL young adult patients (YA, aged 18-39 years) without high-risk features who achieved CR1, 114 patients without HLA-matched donors received consolidation with an adult chemotherapy regimen (n = 55) or haplo-SCT (n = 59). In the landmark analysis, haplo-SCT resulted in a lower 2-year cumulative incidence of relapse (CIR, 12.8% vs 46.7%, P = 0.0017) and superior 2-year leukemia-free survival (LFS, 80.9% vs 51.1%, P = 0.0116) and 2-year overall survival (OS, 91.2% vs 75.7 [64.8-93.2] %, P = 0.0408) than chemotherapy. In the time-dependent multivariate analysis with propensity score adjustment, postremission treatment (haplo-SCT vs chemotherapy) was an independent risk
In this issue of the Hematology, Transfusion and Cell Therapy Journal, Cacemiro et al. evaluated the plasma cytokine profile of 47 patients with Ph-negative myeloproliferative neoplasms (MPN) [essential thrombocythemia (ET), primary myelofibrosis (PMF), and polycythemia vera (PV)] and of healthy subjects.1 They demonstrated increased levels of pro-inflammatory cytokines in MPN patients and higher levels of interferon (IFN)-γ-induced protein 10 (IP-10) in PMF patients with the JAK2 V617F mutation. They found differences in the cytokine profile among the three MPN disorders, including increased levels of IL-12p70, IL-17A, and RANTES in PMF, showing that MPN, in particular PMF, have altered inflammatory profiles. However, their sample population did not make clinical and prognostic implications of their findings possible.. What is the clinical relevance of the altered cytokine levels in MPN? Are they related to constitutional symptoms, transformation or evolution to fibrosis? Do they have an ...
Key words. Myelofibrosis (MF), including primary myelofibrosis (PMF) and MF secondary to essential thrombocythemia (ET) or polycythemia vera (PV), is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm associated with progressive bone marrow fibrosis.1 Many patients with MF experience new or worsening anemia during disease progression. Varying from study to study, 35% to 54% of patients with PMF have been reported to have anemia (i.e., hemoglobin ,10 g/dL) at the time of diagnosis.2-5 Anemia adversely affects overall survival (OS), and is included as a key negative prognostic factor in validated prognostic scoring systems for patients with PMF, which were developed before the introduction of Janus kinase (JAK) inhibitor therapy.2,3,5 Ruxolitinib, a JAK1/JAK2 inhibitor, improved OS compared with placebo and best available therapy in patients with intermediate-2 or high-risk MF5 in the phase 3 COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT) ...
The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2 V617F and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for ...
BACKGROUND: The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of these mutations has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for these mutations in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms ...
Conclusions:. Essential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms. ...
Expert-reviewed information summary about the treatment of myelodysplastic/myeloproliferative neoplasms including chronic/juvenile myelomonocytic leukemias and atypical CML.
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Brian Patrick Smith MD is a Critical Care Specialist who practices in Philadelphia, PA. Get a full report about this doctors background by clicking here.
The PRV-1 gene has been proposed as a marker of polycythaemia vera (PV). PRV-1 and NB1 are alleles of the polymorphic gene CD177, which belongs to the Ly-6/uPAR superfamily, and their coding regions differ at only four nucleotides. We studied neutrophil CD177 mRNA levels in normal subjects and in 235 patients with Ph-negative chronic myeloproliferative disorders (CMD), including PV, essential thrombocythaemia and myelofibrosis with myeloid metaplasia. Additional disease states were investigated for comparison. Highly variable neutrophil CD177 mRNA levels were observed in normal individuals. Neutrophils isolated from the bone marrow, or from peripheral blood following granulocyte colony-stimulating factor administration showed markedly higher CD177 expression than circulating granulocytes on steady state. Increased neutrophil CD177 mRNA levels were detected in all CMD. Elevated values were also found in reactive conditions and in disorders such as chronic myeloid leukaemia and myelodysplastic ...
... are a group of slow-growing blood cancers in which the bone marrow makes too many abnormal red blood cells, white blood cells, or platelets, which accumulate in the blood. The type of myeloproliferative disorder is based on whether too many red blood cells, white blood cells, or platelets are being made. Sometimes the body will make too many of more than one type of blood cell, but usually one type of blood cell is affected more than the others are ...
Start-up company Micromet owned the intellectual property rights, and when it was acquired these were transferred to Amgen, which now markets Blincyto in the United States following the drugs approval by the FDA. Prof. Thomas Sommer, interim Scientific Director at MDC, says: "The MDCs basic research has borne fruit. The path to drug approval is often a long and difficult one, but the example set by Blinatumomab and other promising MDC projects show that we are on the right track.". Blincyto is used to treat B-cell acute lymphoblastic leukemia (full name: Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia or pre-B-cell ALL). In the U.S., Blincyto was granted breakthrough therapy designation for treating this specific type of leukemia. Patients suffering from the disease usually have a prognosis of only a few months survival time. The drug signifies new hope for these patients. It will be used in situations where conventional treatment will no longer lead to recovery ...
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Principal Investigator:KONDO TAKESHI, Project Period (FY):2013-04-01 - 2016-03-31, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Hematology
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Specialists recommend to start the treatment with a 50 mg daily dose. Take one 50 mg pill, or two 25 mg tablets once a day for five days. If ovulation does not occur after the first course, next time you may increase your dose up to 100 mg of Clomid daily. In this case take 100 mg pill, or two 50 mg pills, or four 25 mg pills once a day.. You may have three fertility treatment courses one by one. Start the next one as early as 30 days after the previous one. Fortunately, most women ovulate and get pregnant after the first course of therapy.. ...
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As the damage increases on this central visual nerve, blind spots emerge in your visual field. The reason behind the nerve deterioration is high eye pressure.. The pressure is from increased aqueous humor that draws to your anterior eye chamber. The process takes place via the tissue where cornea and iris meet. Any form of system failure or overproduction of the fluid leads to pressure buildup.. In addition, there are cases where Glaucoma affects families.. This is due to certain gene conditions that are inherited in the family.. There are various types of Glaucoma that include:. • Open Glaucoma, which is common, compared to other conditions.. • Angle-closure Glaucoma or closed-angle Glaucoma. • Children Glaucoma. • Normal-tension Glaucoma. • Pigmentary Glaucoma. ...
TY - JOUR. T1 - The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph - acute lymphoblastic leukemia cells. AU - Scuto, Anna. AU - Kirschbaum, Mark. AU - Kowolik, Claudia. AU - Kretzner, Leo. AU - Juhasz, Agnes. AU - Atadja, Peter. AU - Pullarkat, Vinod. AU - Bhatia, Ravi. AU - Forman, Stephen. AU - Yen, Yun. AU - Jove, Richard. PY - 2008/5/15. Y1 - 2008/5/15. N2 - We investigated the mechanism of action of LBH589, a novel broad-spectrum HDAC inhibitor belonging to the hydroxamate class, in Philadelphia chromosome-negative (Ph -) acute lymphoblastic leukemia (ALL). Two model human Ph - ALL cell lines (T-cell MOLT-4 and pre-B-cell Reh) were treated with LBH589 and evaluated for biologic and gene expression responses. Low nanomolar concentrations (IC 50:5-20 nM) of LBH589 induced cell-cycle arrest, apoptosis, and histone (H3K9 and H4K8) hyperacetylation. LBH589 treatment increased mRNA levels of proapoptosis, growth arrest, and DNA ...
Disorders which share common features: Polycythemia Vera causes the overproduction of red cells, white cells and platelets; Idiopathic Myelofibrosis has an overproduction of white cells or platelets with anemia and an increase in bone marrow fibrous tissue. Essential Thrombocytosis features an increase in circulating platelets. Also Chronic Neutrophilic Leukemia and Chronic Eosinophilic Leukemia both which may develop into Leukemia.
Research in the Jerry Spivak Lab focuses on chronic myeloproliferative disorders, particularly their molecular mechanisms and methods for distinguishing them diagnostically and interventionally. By analyzing gene expression in polycythemia vera stem cells, we have learned that patients with polycythemia vera can be differentiated from those with erythrocytosis and can be diagnosed as having either aggressive or slow-growing disease. We are also studying the roles played by specific molecular markers in the pathogenesis and diagnosis of polycythemia vera.. Research Areas: stem cells, pathogenesis, polycythemia vera, myeloproliferative disorders ...
Bulgular: leri ya , tan da y ksek l kosit say s JAK2 mutasyon pozitifli i tromboz i in risk fakt r olarak bulunmu tur. Trombosit say m n n 1000x109/L zerinde olmas kanama komplikasyonlar a s ndan risk fakt r d r. Hidroksi re tedavisi l semik d n mle ili kili bulunmam t r. Bu hastalarda: Medyan takip s resi 50 ay (22,2- 81,75 eyrekler) idi. Primer miyelofibrozisli hastalar ET i in 179 ay ve PV i in 231 ay olan ya am s releri ile kar la t r ld nda 137 ay ile en k sa ya am s resine sahip hastalard r. L semik transformasyon, tromboembolik olaylar, 60 ya st olmak ve anemi ya am s resinin etkileyen fakt rler olarak bulunmu tur ...
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Diagnostic Related Group MS-DRG V35.0 MYELOPROLIFERATIVE DISORDERS OR POORLY DIFFERENTIATED NEOPLASMS WITH MAJOR O.R. PROCEDURE WITHOUT CC/MCC
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The Haitian Coalition of Philadelphia, the French International School of Philadelphia, and students of the Girard College in Philadelphia will join forces on Monday, January 20, to pack fully supplied book bags to benefit children of Emmanuel Baptiste de la Saintete. This is one of … Continue reading →. ...
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The Ph chromosome is the most frequent rearrangement in adult ALL. some patients have had both B-cell and myeloid markers . Because of the high frequency of the BCR/ABL rearrangement and its dire clinical consequences, molecular studies using RT-PCR should be routinely performed at diagnosis when clinical suspicion is high and cytogenetic analysis is nondiagnostic.. ...
The Ph chromosome is the most frequent rearrangement in adult ALL. some patients have had both B-cell and myeloid markers . Because of the high frequency of the BCR/ABL rearrangement and its dire clinical consequences, molecular studies using RT-PCR should be routinely performed at diagnosis when clinical suspicion is high and cytogenetic analysis is nondiagnostic.. ...
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Xie, Y. H., Yang, Z. X. & Barreto, D. (2016). The Influence of Particles Aspect Ratio on the Shear Behaviour of Granular Materials. In Springer Proceedings in Physics; Proceedings of the 7th International Conference on Discrete Element Methods, 253-264. doi:10.1007/978-981-10-1926-5_29. ISBN 978-981-10-1925-8; 978-981-10-1926-5. ...
The discovery of the JAK2 V617F mutation has undoubtedly revolutionised the diagnosis of the classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) with the mutation present in greater than 95% of polycythaemia vera (PV) patients, approximately 50% of patients with essential thrombocythaemia (ET) and primary myelofibrosis (PMF) and, to a lesser degree, in a number of other myeloid malignancies such as refractory anaemia with ringed sideroblasts with thrombocytosis, chronic myelomonocytic leukaemia and acute myeloid leukaemia. Detection of this mutation is beneficial in differentiating between a reactive haematological response and a true clonal disorder and can also serve as a target for therapeutic intervention.1 Current guidelines for the diagnosis of PV, ET and PMF maintain the requirement for inclusion and/or exclusion of numerous other clinical and laboratory parameters such as histopathological examination of a bone marrow biopsy.2-4 Molecular testing for the ...