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 ...
TY - JOUR. T1 - Characteristics and survival of BCR/ABL negative chronic myeloid leukemia. T2 - A retrospective analysis of the Surveillance, Epidemiology and End Results database. AU - Giri, Smith. AU - Pathak, Ranjan. AU - Martin, Mike G.. AU - Bhatt, Vijaya Raj. PY - 2015/12. Y1 - 2015/12. UR - http://www.scopus.com/inward/record.url?scp=84993736220&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84993736220&partnerID=8YFLogxK. U2 - 10.1177/2040620715607416. DO - 10.1177/2040620715607416. M3 - Letter. C2 - 26622999. AN - SCOPUS:84993736220. VL - 6. SP - 308. EP - 312. JO - Therapeutic Advances in Hematology. JF - Therapeutic Advances in Hematology. SN - 2040-6207. IS - 6. ER - ...
Free, official coding info for 2021 ICD-10-CM C92.2 - includes detailed rules, notes, synonyms, ICD-9-CM conversion, index and annotation crosswalks, DRG grouping and more.
TY - JOUR. T1 - DETECTION OF REARRANGEMENT WITHIN THE BREAKPOINT CLUSTER REGION OF CHROMOSOME 22 IN THE DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA. AU - HUTCHINS, C.. AU - CASEY, G.. AU - White, Deborah. AU - MOORE, S.. AU - RUDZKI, Z.. AU - KIMBER, R.. PY - 1989/1/1. Y1 - 1989/1/1. N2 - Chronic myeloid leukemia (CML) is characterised by the presence of a Philadelphia (Ph) chromosome in approximately 95% of patients. Molecular analysis has shown that the Ph chromosome translocation breakpoints are clustered within 5.8kb on chromosome 22 (breakpoint cluster region or bcr). This has facilitated the diagnosis of CML by nucleic acid hybridisation using probes specific for the bcr to detect DNA rearrangement in this region. Forty patients diagnosed with CML, including four with variant Ph chromosome translocations and three with normal karyotypes were analysed for rearrangement within the bcr. All except one patient with Ph negative CML had rearrangement within the bcr. In contrast, none of the patients ...
Description: 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. Multiple transcript variants encoding different isoforms have been found for this gene ...
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 ...
Outcomes of acute lymphoblastic leukemia (ALL) in older adults treated with chemotherapy are poor. The CD19/CD3 bispecific T-cell engager (BiTE) antibody blinatumomab is approved for refractory, relapsed or minimal/measurable residual disease (MRD)-positive B-cell ALL, but there is little experience in the upfront setting, including in older patients. We retrospectively analyzed outcomes of blinatumomab monotherapy in five newly diagnosed Philadelphia chromosome-negative B-cell ALL patients over 70 years. Three had cytokine release syndrome, treated with dexamethasone and/or tocilizumab, and four patients had neurotoxicity, treated with dexamethasone, without blinatumomab interruption. All five achieved complete remission (CR) after cycle one, three with undetectable MRD. All five were alive at 8 to 15 months. Three remained in MRD-negative CR. Two relapsed after cycle 3, one with extramedullary disease. In our small cohort of patients over 70 years, blinatumomab was safe initial therapy and ...
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.
Wang SA, Hasserjian RP, Fox PS, Rogers HJ, Geyer JT, Chabot-Richards D, Weinzierl E, Hatem J, Jaso J, Kanagal-Shamanna R, Stingo FC, Patel KP, Mehrotra M, Bueso-Ramos C, Young KH, Dinardo CD, Verstovsek S, Tiu RV, Bagg A, Hsi ED, Arber DA, Foucar K, Luthra R, Orazi A. Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms. Blood. 2014 Apr 24; 123(17):2645-51 ...
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 ...
PRIMARY OBJECTIVES: I. To evaluate the 3-year survival rate in elderly patients with newly diagnosed Philadelphia (Ph)-negative acute
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].
Based on assessments of ropeginterferon alpha-2b in a real-world setting, researchers highlighted the safety, tolerance, and efficacy of the treatment in Philadelphia-negative myeloproliferative neoplasm (MPNs).
TY - JOUR. T1 - Monosomal karyotype in Philadelphia chromosome-negative acute lymphoblastic leukemia. AU - Kenderian, S. S.. AU - Al-Kali, A.. AU - Gangat, N.. AU - Letendre, L.. AU - Hogan, W. J.. AU - Litzow, M. R.. AU - Patnaik, M. M.. N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.. PY - 2013/7. Y1 - 2013/7. UR - http://www.scopus.com/inward/record.url?scp=84880877717&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84880877717&partnerID=8YFLogxK. U2 - 10.1038/bcj.2013.21. DO - 10.1038/bcj.2013.21. M3 - Letter. C2 - 23832069. AN - SCOPUS:84880877717. VL - 3. JO - Blood Cancer Journal. JF - Blood Cancer Journal. SN - 2044-5385. IS - 7. ER - ...
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 - ...
TY - JOUR. T1 - Unbiased pro-thrombotic features at diagnosis in 977 thrombocythemic patients with Philadelphia-negative chronic myeloproliferative neoplasms. AU - Gugliotta, Luigi. AU - Iurlo, Alessandra. AU - Gugliotta, Gabriele. AU - Tieghi, Alessia. AU - Specchia, Giorgina. AU - Gaidano, Gianluca. AU - Scalzulli, Potito Rosario. AU - Rumi, Elisa. AU - Dragani, A.. AU - Martinelli, Vincenzo. AU - Santoro, Cristina. AU - Randi, M. L.. AU - Tagariello, G.. AU - Candoni, Anna. AU - Cattaneo, Daniele. AU - Ricco, Alessandra. AU - Palmieri, Raffaele. AU - Liberati, M.. AU - Langella, Maria. AU - Rago, Angela. AU - Bergamaschi, Micaela. AU - Monari, Paola. AU - Miglio, Rossella. AU - Santoro, Umberto. AU - Cacciola, Rossella R.. AU - Rupoli, Serena. AU - Mastrullo, Lucia. AU - Musto, Pellegrino. AU - Mazzucconi, M. G.. AU - Vignetti, Marco. AU - Cortelezzi, Agostino. AU - Vianelli, Nicola. AU - Martino, Bruno. AU - De Stefano, Valerio. AU - Passamonti, Francesco. AU - Vannucchi, Alessandro ...
Julia E. Maxson, Jason Gotlib, Daniel A. Pollyea, Angela G. Fleischman, Anupriya Agarwal, Christopher A. Eide, Daniel Bottomly, Beth Wilmot, Shannon K. McWeeney, Cristina E. Tognon, J. Blake Pond, Robert H. Collins, Basem Goueli, T. Oh Stephen, W. Deininger Michael, Bill H. Chang, Marc M. Loriaux, Brian J. Druker, Jeffrey W. Tyner ...
Abstract: The major complications of Philadelphia‐negative (Ph‐Negative) myeloproliferative neoplasms (MPNs) are thrombosis, haemorrhage and leukemic transformation. As systemic and haematological diseases, MPNs have the potential to affect many tissues and organs. Some complications lead to the diagnosis of MPNs, but other signs and symptoms are often misdiagnosed or neglected as a sign of MPN disease. […]. ...
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.
Mutations in JAK2, MPL and CALR are highly relevant to the Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs). We performed high resolution melting analysis and Sanger sequencing together with T-A cloning to elucidate the unique mutation profile of these genes, in Chinese patients with MPNs. Peripheral blood DNA samples were obtained from 80 patients with polycythemia vera (PV), 80 patients with essential thrombocytosis (ET) and 50 patients with primary myelofibrosis (PMF). Ten PV patients were identified with diverse JAK2 exon 12 mutations. Five novel JAK2 Exon 12 mutation patterns (M532V/E543G, N533D, M535I/H538Y/K549I, E543G and D544N) were described. JAK2 V617F was detected in 140 samples (66 PV, 45 ET and 29 PMF). JAK2 Exon 12 mutations were prevalent (13%) and variable in the Chinese patients. Compared with PV patients with JAK2 V617F mutations, PV patients with JAK2 exon 12 mutations had an earlier median onset of disease (P = 0.0013). MPL W515L/K mutations were ...
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.. ...
Patients With Relapsed or Refractory ALL - INO-VATE ALL. The safety and efficacy of BESPONSA were evaluated in INO-VATE ALL (NCT01564784) a randomized (1:1), open-label, international, multicenter study in patients with relapsed or refractory ALL. Patients were stratified at randomization based on duration of first remission (, 12 months or ≥ 12 months, salvage treatment (Salvage 1 or 2) and patient age at randomization (, 55 or ≥ 55 years). Eligible patients were ≥ 18 years of age with Philadelphia chromosome-negative or Philadelphia chromosome-positive relapsed or refractory B-cell precursor ALL. All patients were required to have ≥ 5% bone marrow blasts and to have received 1 or 2 previous induction chemotherapy regimens for ALL. Patients with Philadelphia chromosome-positive B-cell precursor ALL were required to have disease that failed treatment with at least 1 tyrosine kinase inhibitor and standard chemotherapy. Table 1 shows the dosing regimen used to treat patients.. Among all ...
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 ...
Epigallocatechin-3-gallate induces apoptosis and cell cycle arrest in Human T-Cell Lymphotrophic Virus type 1 -positive and negative leukemia cells.
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 ...
Background: This study was conducted to evaluate the frequency of JAK2, CALR and MPL mutations in with BCR-ABL myeloproliferative neoplasms and their association with demographic data and hematologic parameters in a referral center, in the Middle East. Methods: Seventy-one patients with BCR-ABL negative myeloproliferative neoplasms were evaluated for JAK2 V617F, CALR type 1, type 2, and MPL by allele-specific PCR and conventional PCR from 2018 to 2019. Results: Twenty three patients were categorized as polycythemia vera and demonstrated JAK2 V617F in 91.3 % of these cases. Thirty-eight patients were classified as essential thrombocythemia and showed JAK2 V617F in 52.6%, CALR type 1 in 18.4%, CALR type 2 in 7.9% and no mutation in 21.1%. Seven patients were recognized as primary myelofibrosis and exhibited JAK2 V617F mutation in 57.1%, CALR type 1 in 14.3 %, CALR type 2 in 14.3% and no mutation in 14.3%. Three patients were diagnosed as MPN, unclassifiable and revealed JAK2 V617F mutation in 33.3% and
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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At its peak in the early 1950s, Philadelphias manufacturing workforce totaled 365,000 people. As we all know, the citys domination declined long ago. Yet manufacturing survives and now manufacturers of all kinds are springing up.
Mayor Nutter said Monday evening that there were no specific threats or threat incidents in Philadelphia. - $author, Philadelphia Daily News
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.