Eyelid Myeloid Sarcoma: Ominous Presentation of Acute Myelogenous Leukemia.
Orbit. 2014 Jul 24;:1-3
Authors: Phelps PO, Marcet MM, Hong AR, Nichols JW
Abstract A 19 year-old African American man presented to our clinic for a second opinion about a right upper eyelid mass which had been recalcitrant to treatment for nonspecific orbital inflammation by an outside facility. Examination for systemic causes of the patients eyelid lesion led to a diagnosis of acute myelogenous leukemia (AML) FAB subtype M1. A subsequent biopsy of the eyelid tumor confirmed the diagnosis of a myeloid sarcoma. The patient succumbed to complications from his leukemia within 13 months of presentation. This case report is the first, to our knowledge, of an eyelid myeloid sarcoma as the presenting sign of AML and demonstrates the poor prognosis of this lesion.
PMID: 25058666 [PubMed - as supplied by publisher]
Unusual T-lymphoblastic blast phase of chronic myelogenous leukemia.
Case Rep Hematol. 2014;2014:304359
Authors: Xu J, Li S
T-lymphoblastic leukemia/lymphoma (T-ALL) presenting as blast phase of chronic myelogenous leukemia (CML-BP) is rare. In patients without history of CML, it is difficult to differentiate between CML-BP or de novo T-ALL. Here we reported 2 unusual cases of T-ALL presenting as CML-BP. Case 1 was a 24-year-old female with leukocytosis. Besides T-lymphoblasts (32%), her marrow exhibited some morphologic features of CML. Multiple remission or relapsing marrow had never demonstrated morphologic features of CML. Despite of imatinib treatment and stem cell transplant, she died 2.5 years later. Case 2, a 66-year-old male with diffuse lymphadenopathy, showed T-ALL in a lymph node and concurrent CML chronic phase (CML-CP) in his marrow. Same BCR-ABL1 fusion transcript with minor breakpoint was present in both the lymph node and marrow specimens. Although both cases did not have a history of CML, both cases represented T-lymphoblastic CML-BP with unusual features: Case 1 is unusual in that it presented as T-ALL with some CML morphologic feature but never showed CML-CP in her subsequent marrows biopsies; Case 2 is the first reported case of T-lymphoblastic CML-BP harboring BCR-ABL1 transcript with a minor breakpoint.
PMID: 25057418 [PubMed]
Moving towards patient-centered decision-making in chronic myeloid leukemia: assessment of quality of life and symptom burden.
Haematologica. 2014 Feb;99(2):205-8
Authors: Baccarani M, Efficace F, Rosti G
PMID: 24497557 [PubMed - indexed for MEDLINE]
Allogeneic T cells: maestro in the co-ordination of the immune response after hematopoietic stem cell transplantation.
Haematologica. 2014 Feb;99(2):203-5
Authors: Saudemont A, Madrigal JA
PMID: 24497556 [PubMed - indexed for MEDLINE]
Chronic myeloid leukemia (CML): association of treatment satisfaction, negative medication experience and treatment restrictions with health outcomes, from the patient’s perspective.
Health Qual Life Outcomes. 2013;11:167
Authors: Hirji I, Gupta S, Goren A, Chirovsky DR, Moadel AB, Olavarria E, Victor TW, Davis CC
BACKGROUND: The availability of the tyrosine-kinase inhibitor (TKI), imatinib, and later introduction of second generation TKIs, dasatinib and nilotinib, have not only improved clinical outcomes of patients with chronic myeloid leukemia (CML), but also provide multiple therapeutic options for CML patients. Despite the widespread use of these oral therapies, little is known about the impact of different treatment regimens on patient-reported outcomes (PROs) among CML patients. The objective of this study was to assess the impact of patient-reported treatment restrictions and negative medication experiences (NMEs) on satisfaction and other health outcomes among patients with CML treated with oral TKIs.
METHODS: Participants recruited from survey panels and patient networks in the United States (US) and Europe completed an online questionnaire. Respondents included adults (? 18 years) with chronic-phase CML currently on TKI treatment. Study variables included treatment difficulty (i.e., difficulty in following treatment regimens), CML dietary/dosing requirements, NMEs, and validated PROs assessing treatment satisfaction, health-related quality of life (HRQoL), activity impairment, and non-adherence. Structural equation models assessed associations among variables, controlling for covariates.
RESULTS: 303 patients with CML (US n=152; Europe n=151; mean age 51.5 years; 46.2% male) completed the questionnaire. Approximately 30% of patients reported treatment difficulties; treatment difficulty was higher among nilotinib (63.3%) than among dasatinib (2.6%) or imatinib (19.2%) treated patients (p<0.0001). Non-adherence was generally low; however, patients on nilotinib vs. imatinib reported missing doses more often (p<0.05). Treatment satisfaction was associated with significantly increased HRQoL (p<0.05) and lower activity impairment (p<0.01). NMEs were associated with decreased treatment satisfaction (p<0.01) and HRQoL (p<0.05), and greater activity impairment (p<0.01). Higher overall treatment restrictions were associated with greater treatment difficulty (p<0.001), which correlated with non-adherence (p<0.01).
CONCLUSIONS: Treatment satisfaction and NMEs are important factors associated with HRQoL among patients with CML. Increased treatment restrictions and associated difficulty may affect adherence with TKIs. Choosing a CML treatment regimen that is simple and conveniently adaptable in patients’ normal routine can be an important determinant of HRQoL and adherence.
PMID: 24099272 [PubMed - indexed for MEDLINE]
Development of a coordinated allo T cell and auto B cell response against autosomal PTK2B after allogeneic hematopoietic stem cell transplantation.
Haematologica. 2014 Feb;99(2):365-9
Authors: Kremer AN, van der Griendt JC, van der Meijden ED, Honders MW, Ayoglu B, Schwenk JM, Nilsson P, Falkenburg JH, Griffioen M
It is well known that allo-reactive T cells play a crucial role in graft-versus-leukemia and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (alloSCT). Allo-reactive CD4(+) T cells can mediate direct cytolysis, but may also stimulate production of IgG antibodies as helper cells. Immune complexes may subsequently be processed and presented by professional antigen presenting cells and stimulate induction of specific CD8(+) T cells. As such, proteins targeted in coordinated T- and B-cell responses may represent a class of immunodominant antigens in clinical responses after alloSCT. We previously identified LB-PTK2B-1T as HLA class II restricted polymorphic antigen in a patient treated with donor lymphocyte infusion for relapsed chronic myeloid leukemia after HLA-matched alloSCT. Since PTK2B has also been described as antibody target, we here investigated whether a coordinated T- and B-cell response against PTK2B was induced. Patient serum before and after alloSCT and donor lymphocyte infusion (DLI) was screened for antibodies, and we indeed observed development of a humoral immune response against PTK2B. Antibodies against PTK2B were only found after DLI and, in contrast to the CD4(+) T cells, recognized a monomorphic region of the protein. To our knowledge, this is the first description of a coordinated allo-reactive CD4(+) T-cell and auto-reactive antibody response against an autosomal antigen.
PMID: 24097630 [PubMed - indexed for MEDLINE]
The impact of molecular biology techniques on the management of newly diagnosed chronic myeloid leukemia patients in chronic phase. A review.
Transfus Apher Sci. 2013 Oct;49(2):116-9
Authors: Lewalle P, Martiat P
Since the introduction of tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML), the management of this disease has completely changed. The aim has been first to bring to the patient a maximal response and to identify at different time-points what could be considered an optimal response (which is to render the progression free survival as important as possible). To achieve this, new molecular tools were needed, the most important being the real time quantitative PCR (RT-qPCR), to measure the number of remaining transcripts after several period of treatment. The second important tool was the sequencing of the BCR-ABL kinase domain to identify potential mutations giving rise to resistance to imatinib first and next to second generation TKIs. This technique, much more sensitive than cytogenetics, has allowed the definition of important levels of transcripts (the major molecular response i.e. a three log reduction and the complete molecular response i.e. a 4.5 log reduction) the first ensuring a long term PFS on treatment, the second allowing the birth of studies looking at whether it would be possible to discontinue the treatment in this group of patients.
PMID: 24007867 [PubMed - indexed for MEDLINE]
Veterans and Agent Orange: Update 2002
Authors: Institute of Medicine (US) Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Fourth Biennial Update)
This report concentrates on the evidence published after the completion of work on Veterans and Agent Orange: Update 2000 (IOM, 2001) and Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans (IOM, 2002). For each health outcome, the new evidence is reviewed in detail. Conclusions, however, are based on the totality of accumulated evidence, not just on recently published studies. That is, new evidence is interpreted not alone but in the context of evidence addressed in previous reports.
Veterans and Agent Orange: Herbicide/Dioxin Exposure and Acute Myelogenous Leukemia in the Children of Vietnam Veterans
Authors: Institute of Medicine (US) Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Third Biennial Update)
This report begins with a brief overview of the study methodology and the considerations underlying the assessment of research reviewed. This is followed by an evaluation of the epidemiologic evidence, which includes background on the scientific data reviewed in VAO, Update 1996, Update 1998, and Update 2000 and a more thorough discussion of the new information and their interpretation. The reader is referred to relevant sections of the previous reports for additional detail and explanation.
[Reversible pulmonary arterial hypertension related to dasatinib in the treatment for chronic myelogenous leukemia: a case report and literature review.]
Zhonghua Xue Ye Xue Za Zhi. 2014 Jul 14;35(7):581-586
Authors: Liu B, Wang Y, Mi Y, Wang J
OBJECTIVE: To study the clinical features and prognosis of pulmonary arterial hypertension associated with dasatinib.
METHODS: To present a case of pulmonary arterial hypertension (PAH) associated with long-term exposure to dasatinib and review the related literatures.
RESULTS: A 23-year-old female with chronic myelogenous leukemia was treated with dasatinib at a dosage of 140 mg/d after failure of imatinib treatment and achieved complete cytogenetic response. The patient was presented with exertional dyspnea after 35 months of administration with dasatinib. The electrocardiogram showed right ventricular hypertrophy and right axis deviation; transthoracic Doppler echocardiography documented a reduction in diameters of left heart chambers with normal systolic left ventricular function, right heart chambers and pulmonary trunk dilatation, an estimated pulmonary arterial pressure of 114 mmHg; Computed tomography showed thickened pulmonary artery. PAH related to dasatinib was diagnosed and dasatinib was permanently discontinued. The symptom of dyspnea disappeared quickly after withdrawal of dasatinib. The heart structure and pulmonary arterial pressure completely recovered after 7 months of dasatinib discontinuation.
CONCLUSION: PAH is a rare adverse effect of dasatinib treatment. Echocardiograhpy, as a non-invasive screening test for PAH, should be performed before starting dasatinib treatment and repeated during the administration with dasatinib. Dasatinib should be withdrawn permanently in patients with PAH.
PMID: 25052596 [PubMed - as supplied by publisher]
Spontaneously resolved exudative retinal detachment caused by orbital cellulitis in an immunocompromised adult.
Eye (Lond). 2014 Jan;28(1):109-10
Authors: Farah E, Kalantzis G, Papaefthimiou I, Koutsandrea C, Georgalas I
PMID: 24232314 [PubMed - indexed for MEDLINE]
Evaluation of meisoindigo, an indirubin derivative: in vitro antileukemic activity and in vivo pharmacokinetics.
Int J Oncol. 2014 Jul 21;
Authors: Huang M, Lin HS, Lee YS, Ho PC
Meisoindigo has been a routine therapeutic agent in the clinical treatment of chronic myelogenous leukemia (CML) in China since the 1980s. In the present study, the in vitro antileukemic activity of meisoindigo was investigated in acute promyelocytic leukemia (APL) cells, acute myeloid leukemia (AML) cells, and myelomonocytic leukemia cells (NB4, NB4.007/6, HL-60 and U937) comprising both retinoic acid-sensitive and retinoic acid-resistant cells. We found that meisoindigo effectively inhibited the growth and/or proliferation of these four cell types at µM levels. The effects of meisoindigo in these cells are related to its proliferation inhibition and apoptosis induction, and are independent of cell cycle arrest, indicating that meisoindigo could be possible in the treatment of APL, AML and retinoic acid resistant APL. The in vivo pharmacokinetics of meisoindigo and its major circulatory metabolites in rat plasma were then investigated by a newly developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The profiles of plasma concentration versus time were plotted and the relevant pharmacokinetic parameters were calculated for meisoindigo and its reductive metabolites. The plasma concentrations of meisoindigo after oral administration were much lower than the in vitro IC50s determined in the leukemic cells. The contradicting poor pharmacokinetic characteristics and the established clinical efficacy of meisoindigo could indicate the presence of active metabolites in vivo.
PMID: 25050545 [PubMed - as supplied by publisher]
Phase 1b Study of New Posaconazole Tablet for the Prevention of Invasive Fungal Infections in High-Risk Patients With Neutropenia.
Antimicrob Agents Chemother. 2014 Jul 21;
Authors: Duarte RF, López-Jiménez J, Cornely OA, Laverdiere M, Helfgott D, Haider S, Chandrasekar P, Langston A, Perfect J, Ma L, van Iersel ML, Connelly N, Kartsonis N, Waskin H
Posaconazole tablet, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia/myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea/vomiting/chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablet and to identify the dose of posaconazole tablet that would provide exposure within a predefined range of exposures (steady state average concentration [area under the concentration-time curve/24 h] ?500 ng/ml and ?2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: posaconazole 200 mg once daily (n = 20) and 300 mg once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ?28 days. Exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking posaconazole 200 mg once daily and in 31 of 32 (97%) patients taking posaconazole 300 mg once daily; posaconazole 300 mg once daily achieved the desired exposure target. Posaconazole tablet was generally well tolerated in high-risk neutropenic patients. (ClinicalTrials.gov identifier: NCT01777763, PO5615).
PMID: 25049247 [PubMed - as supplied by publisher]
Single-cell gene expression analysis reveals clonal architecture of blast-phase chronic myeloid leukaemia.
Br J Haematol. 2014 May;165(3):414-6
Authors: Nukina A, Kagoya Y, Watanabe-Okochi N, Arai S, Ueda K, Yoshimi A, Nannya Y, Kurokawa M
PMID: 24401018 [PubMed - indexed for MEDLINE]
Restoration of INK4a/ARF gene inhibits cell growth and cooperates with imatinib mesylate in Philadelphia chromosome-positive leukemias.
Oncol Res. 2013;21(1):23-31
Authors: Bai Y, Lu Z, Lin Y, Sun B, Wang S, Wang G
VSV-G-pseudotyped lentiviral vectors expressing p16(INK4a) or p14(ARF) were used to infect at high-efficiency Philadelphia chromosome (Ph)-positive leukemia cell lines lacking endogenous transcripts. Restoration of p16(INK4a) accumulated cells in the G0/G1 phase of cell cycle and restoration of p14(ARF) induced their apoptosis, followed by significant growth inhibition. Transduction of primary blast cells from chronic myeloid leukemia in blast crisis (CML-BC) and Ph-positive acute lymphoblastic leukemia (ALL) with p16(INK4a) or p14(ARF) virus also resulted in cell growth inhibition and/or apoptosis with a patient-to-patient variation, whereas clonal growth and differentiation of cord blood progenitor cells were not affected by enforced expression of INK4a/ARF. Furthermore, upon viral transduction at low multiplicity of infection, INK4a/ARF potentiated the effect of imatinib mesylate on Ph-positive leukemia cell lines in an additive but not synergistic manner. These results suggest that INK4a/ARF protein-mimetic agents may be promising options for Ph-positive leukemias in combination with imatinib mesylate.
PMID: 24330849 [PubMed - indexed for MEDLINE]
Detection of BCR-ABL using one step reverse transcriptase- polymerase chain reaction and microchip electrophoresis.
Methods. 2013 Dec 15;64(3):250-4
Authors: Lin X, Wu J, Liu W, Li H, Wang Z, Lin JM
One-step reverse transcriptase polymerase chain reaction (RT-PCR) coupled with microchip electrophoresis (MCE) was established to analyze BCR-ABL fusion gene. The use of one-step RT-PCR could simplify the RT-PCR procedure and thus reduced the risk of contamination and sample consumption. This method also enhanced the sensitivity for amplified target DNA and dramatically shorted the analysis time. Moreover, this assay can simultaneously identify b2a2 and b3a2. Orthogonal array design, which can investigated mutual effects of PCR parameters, was used to optimize the reaction system. This approach was highly effective, reproducible and sensitive, and would be suitable for the determination of BCR-ABL in clinic diagnosis.
PMID: 23748110 [PubMed - indexed for MEDLINE]
Optic Coherence Tomography of Foveal Hemorrhage Associated With Chronic Myelogenous Leukemia.
Retina. 2014 Jul 18;
Authors: Hori S, Yamamoto K
PMID: 25046396 [PubMed - as supplied by publisher]
Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations.
Patient Prefer Adherence. 2014;8:981-6
Authors: Sweet K, Pinilla-Ibarz J, Zhang L
The treatment for chronic myeloid leukemia has changed significantly over the past 15 years, and as of now, there are five BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1) tyrosine kinase inhibitors that have gained approval for treatment of this disease. All five are very effective drugs, and the decision surrounding which to use in specific patients is based on numerous factors. Bosutinib is one of the newer tyrosine kinase inhibitors to gain approval, and has been studied in the first-line setting as well as after failure of other tyrosine kinase inhibitors. It is an SRC-ABL1 (steroid receptor co-activator-ABL1) inhibitor that works in the presence of most kinase domain mutations. The primary side effects of bosutinib are gastrointestinal upsets. In the appropriate clinical setting, bosutinib can be considered a valuable addition to the armamentarium of treatments available for chronic myeloid leukemia.
PMID: 25045255 [PubMed]
5-(2-carboxyethenyl) isatin derivative induces G2/M cell cycle arrest and apoptosis in human leukemia K562 cells.
Biochem Biophys Res Commun. 2014 Jul 17;
Authors: Zhou Y, Zhao HY, Han KL, Yang Y, Song BB, Guo QN, Fan ZC, Zhang YM, Teng YO, Yu P
Our previous study successfully identified that the novel isatin derivative (E)-methyl 3-(1-(4-methoxybenzyl)-2,3-dioxoindolin-5-yl) acrylate (HKL 2H) acts as an anticancer agent at an inhibitory concentration (IC50) level of 3 nM. In this study, the molecular mechanism how HKL 2H induces cytotoxic activity in the human chronic myelogenous leukemia K562 cells was investigated. Flow cytometric analysis showed that the cells were arrested in the G2/M phase and accumulated subsequently in the sub-G1 phase in the presence of HKL 2H. HKL 2H treatment down-regulated the expressions of CDK1 and cyclin B but up-reguated the level of phosphorylated CDK1. Annexin-V staining and the classic DNA ladder studies showed that HKL 2H induced the apoptosis of K562 cells. Our study further showed that HKL 2H treatment caused the dissipation of mitochondrial membrane potential, activated caspase-3 and lowered the Bcl-2/Bax ratio in K562 cells, suggesting that the HKL 2H-causing programmed cell death of K562 cells was caused via the mitochondrial apoptotic pathway. Taken together, our data demonstrated that HKL 2H, a 5-(2-Carboxyethenyl) isatin derivative, notably induces G2/M cell cycle arrest and mitochondrial-mediated apoptosis in K562 cells, indicating that this compound could be a promising anticancer candidate for further investigation.
PMID: 25044115 [PubMed - as supplied by publisher]
Diabetes Insipidus in Myelodysplastic Syndrome: What We learnt from A Case Regarding Its Diagnosis, Pathophysiology, and Management.
Leuk Lymphoma. 2014 Jul 21;:1-9
Authors: Chuang C, Parnerkar V, Radulescu A, Hunt MA, Cayci Z, Ustun C
PMID: 25039352 [PubMed - as supplied by publisher]