Journal of clinical haematology最新文献

{"title":"Moving the Treatment of Acute Myeloid Leukemia to the Outpatient Setting: Current Expert Perspectives and Consensus Findings","authors":"Chetasi Talati, K. Sweet, D. Pollyea, S. Kurtin, J. Eatrides, H. Erba","doi":"10.33696/haematology.2.033","DOIUrl":"https://doi.org/10.33696/haematology.2.033","url":null,"abstract":"Intensive treatments for acute myeloid leukemia (AML) have traditionally been administered on an inpatient basis due in part to chemotherapy regimen infusion requirements, transfusion support, and the need for close monitoring for infectious complications and adverse events. However, hospitalization is a major component of burgeoning healthcare costs and may contribute to impaired quality of life in patients with AML. To help inform the ongoing discussion regarding the merits and challenges of outpatient administration of AML therapy, a multidisciplinary panel of experts were engaged to identify areas of consensus, explore ongoing uncertainties, and develop an algorithm that may help inform discussions on outpatient treatment between healthcare providers and patients. Based on available evidence and clinical experience, inpatient treatment remains appropriate for majority of patients with AML undergoing conventional intensive induction chemotherapy. The more recently introduced liposomal formulation of cytarabine and daunorubicin (CPX-351) has an infusion schedule that is more amenable to outpatient administration. Outpatient administration of CPX-351 for select patients with close daily monitoring has been implemented via a multidisciplinary team-based model. The feasibility of safely managing AML patients receiving outpatient CPX-351 is being prospectively evaluated in an ongoing phase 4 study. Panelists generally agreed that lower-intensity regimens including venetoclax combined with hypomethylating agents or lowdose cytarabine (LDAC), glasdegib plus LDAC, enasidenib, ivosidenib, and gilteritinib can be administered safely in the outpatient setting for most newly diagnosed AML patients. Venetoclax-based combinations are also promising for outpatient administration but may require risk stratification due to the potential for tumor lysis syndrome (TLS). The proposed algorithm developed to inform consideration of outpatient treatment is focused on consideration of patient fitness, the treatment regimen selected, infrastructure in place to support outpatient administration, and patient/caregiver agreement with the outpatient approach. Educational needs for clinicians and recommendations to overcome knowledge gaps regarding outpatient therapy were also formulated. Outpatient administration of AML therapy is feasible in the appropriate clinical setting and patient. However, further research is needed regarding feasibility, logistics, safety, and patient outcomes including quality of life. Abbreviations: AML: Acute Myeloid Leukemia; CIVI: Continuous Intravenous Infusion; CLL: Chronic Lymphocytic Leukemia; COVID-19: Coronavirus Disease 2019; HCT: Hematopoietic Cell Transplantation; HDAC: High-Dose Cytarabine; HMA: Hypomethylating Agent; IPOP: Inpatient/Outpatient; LDAC: Low-Dose Cytarabine; MDS: Myelodysplastic Syndrome; NCCN: National Comprehensive Cancer Network; QoL: Quality of Life; TLS: Tumor Lysis Syndrome; WBC: White Blood Cell Talati C, Sweet ","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47310637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventing Stroke in Sickle Cell Disease: 2021. The Role of Transcranial Doppler Ultrasound (TCD) When the Use of Transfusion is Problematic","authors":"R. Adams","doi":"10.33696/haematology.2.035","DOIUrl":"https://doi.org/10.33696/haematology.2.035","url":null,"abstract":"In 2009, as an invited Commentary to the article: “STOP” ing the Harm: When is State Intervention Justified? [1], I wrote that while TCD is an indicator of risk, not a biopsy diagnosis (such as proof of cancer), at some point in the velocity spectrum the high velocity detected by TCD reaches what many—myself included--believe is an unacceptable risk of stroke [2]. Even at the low end of the intervention window, 200 cm/sec Time Averaged Mean of the Maximum (TAMM), the point where periodic transfusion is recommended based on the STOP Trial [3], the risk is at least 10 times background and it goes up from there. The risk is markedly attenuated (>90%) by transfusion. Stroke by its nature is permanent. While some strokes are minor and survival with recovery is the expected outcome, it is not assured.","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":"18 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41303612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Precision Profiling: The Way Forward for Personalized Medicine","authors":"Lyndsey Flanagan, S. Glavey, T. Chonghaile","doi":"10.33696/haematology.2.031","DOIUrl":"https://doi.org/10.33696/haematology.2.031","url":null,"abstract":"AML: Acute Myeloid Leukemia; BAD: Bcl-2 associated agonist of cell death; BAK: Bcl-2 homologous antagonist killer; BAX: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; Bcl-W: B-cell lymphoma-w; Bcl-xL: B-cell lymphoma-extra-large; Bfl-1: Bcl-2-related gene expressed in fetal liver; BH: Bcl-2 Homology; BIK: Bcl-2 Interacting Killer; BIM: Bcl-2-like protein 11; BMF: Bcl-2 Modifying Factor; CCND1: Cyclin D1; CD: Cluster of Differentiation; CLL: Chronic Lymphocytic Leukemia; FDA: Food and Drug Administration; HRK: Harakiri; JC-1: 1st J-aggregateforming cationic dye; Mcl-1: Myeloid cell leukemia 1; MM: Multiple Myeloma; MOMP: Mitochondrial Outer Membrane Permeabilization; NOXA: Latin for damage; PCL: Plasma Cell Leukemia; PUMA: p53 Upregulated Modulator; sPCL: Secondary Plasma Cell Leukemia; tBID: Truncated BH3 interacting-domain death agonist","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41792537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary Changes of the Cardiovascular System Initiated by Reduced Atmospheric O2 Gave Rise to Mammalian and Avian Endothermy","authors":"G. Soslau","doi":"10.33696/haematology.2.036","DOIUrl":"https://doi.org/10.33696/haematology.2.036","url":null,"abstract":"This commentary will address the salient points explored in a previous publication on the role of the red blood cell and platelet in the evolution of mammalian and avian endothermy [1], include additional concepts associated with the evolution of endothermy, and finally address future directions that may be followed in this area of research. The most simplistic definition of the terms endothermic and ectothermic is the former refers to warmblooded animals that maintain their body temperature by endogenous mechanisms while the latter refers to coldblooded animals that require external sources of heat to warm their bodies. In actuality the ability to maintain body heat is more complex for many animals categorized by these terms since some large-bodied ectotherms can maintain body temperatures by internal mechanisms and some endotherms do not maintain body temperature at selective times, such as when hibernating [2-7]. It was hypothesized that environmental pressures during the Permian/Triassic period when there was a dramatic drop in atmospheric O2 selected for vertebrates with genetic mutations that afforded the animal more efficient pathways to transport O2 to their tissues. Over millennia multiple mutations resulted in genetic and structural changes in the cardiovascular system and the cells within their blood. Structural changes included: the transition to a fourchamber heart that permitted the formation of high-pressure systemic and low-pressure pulmonary circulation [8]; greatly increased density of capillary networks and arterioles to allow for more efficient gas exchange [9]; a pulmonary/systemic differential of blood flow/pressure to enhance gas exchange in lungs; reduced red blood cell size with greater cell surface area/cell to enhance gas exchange at the tissue level, and in the case of mammals the enucleation of both red blood cells and platelets. The initial changes would have been directed by genetic mutations of genes in an ancestor common to Abstract","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46681973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atezolizumab Monotherapy as First-line Treatment in Patients with Advanced BRAFV600 Wild-type Melanoma","authors":"J. Coelho, T. Rebelatto, Rodrigo R. Pereira, P. Liedke, A. B. Zanon, S. Azevedo","doi":"10.33696/haematology.2.034","DOIUrl":"https://doi.org/10.33696/haematology.2.034","url":null,"abstract":"Juliano C. Coelho1,2*, Taiane F. Rebelatto1,2, Rodrigo R. Pereira1,2,3, Pedro E. R. Liedke1,2,3, Andrea B. Zanon1, Sergio J. Azevedo1,2,3 1Unidade de Pesquisa Clínica em Oncologia, Porto Alegre, Brazil 2Oncology Department, Oncoclinicas Group, Porto Alegre, Brazil 3Department of Oncology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil *Correspondence should be addressed to Juliano C. Coelho; juliano.oncologia@gmail.com","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49255835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Severity and Mortality in Acquired Thrombotic Thrombocytopenic Purpura (aTTP). Utility of Clinicalbiological Scores","authors":"C. Pascual-Izquierdo, A. Domingo-González","doi":"10.33696/haematology.2.030","DOIUrl":"https://doi.org/10.33696/haematology.2.030","url":null,"abstract":"C. Pascual-Izquierdo1,2*, A. Domingo-González3,4 1Servicio de Hematología y Hemoterapia. Hospital General Universitario Gregorio Marañón, Madrid, Spain 2Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain 3Servicio de Hematología y Hemoterapia. Hospital Universitario Virgen del Rocío, Sevilla, Spain 4Instituto de Investigación Sanitaria Virgen del Rocío, Sevilla, Spain *Correspondence should be addressed to Cristina Pascual Izquierdo; crisizquierdo3@yahoo.es","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49296226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower 24-Month Relative Survival among Black Patients with Non- Hodgkin's Lymphoma: An Analysis of the SEER Data 1997-2015.","authors":"Maria J Nieto,&nbsp;Zhen Li,&nbsp;Hasan Rehman,&nbsp;Muhammad Wasif Saif","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Recent progress in the therapies used in patients with Non- Hodgkin's lymphoma has improved survival. The incidence has been reported to be decreasing in the last few years, accounting for 4% of all cancers. This study analyzed time trends for incidence, mortality, and prevalence of NHL.</p><p><strong>Methods: </strong>We analyzed the SEER Cancer Database from 1997 to 2015. Join point regression analysis was used to determine age-adjusted incidence rates, 24-month relative survival rate, and to identify racial/ethnic groups with a lower survival.</p><p><strong>Results: </strong>The trend in incidence of NHL decreased between 2008 and 2011 at an annual percentage change rate of 3.74%. The male predominance among NHL patients between 1997-2015 was 57%. The number of male patients affected with NHL has been similar in the last 20 years. Female predominance with NHL was higher in 1998 at 46 %, and lower in 2010 at 42.85%. The 24-month relative survival rate was higher among white patients as compared to black patients with NHL.</p><p><strong>Conclusions: </strong>Our analysis demonstrated that the incidence of Non-Hodgkin's Lymphoma has decreased among minorities; however, the outcomes are inferior in terms of survival. This analysis showed an inferior 24-month relative survival rate among black patients compared with white patients. This analysis demonstrates the need for further research in NHL to determine the biological differences and social factors that influence the lower survival among black patients with NHL.</p>","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":"2 1","pages":"5-13"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25573362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavopiridol (Alvocidib), a Cyclin-dependent Kinases (CDKs) Inhibitor, Found Synergy Effects with Niclosamide in Cutaneous T-cell Lymphoma.","authors":"Xu Hannah Zhang,&nbsp;Jack Hsiang,&nbsp;Steven T Rosen","doi":"10.33696/haematology.2.028","DOIUrl":"https://doi.org/10.33696/haematology.2.028","url":null,"abstract":"<p><p>Flavopiridol (FVP; Alvocidib), a CDKs inhibitor, is currently undergoing clinical trials for treatment of leukemia and other blood cancers. Our studies demonstrated that FVP also inhibited p38 kinases activities with IC₅₀ (μM) for p38α: 1.34; p38 β: 1.82; p38γ: 0.65, and p38δ: 0.45. FVP showed potent cytotoxicity in cutaneous T-cell lymphoma (CTCL) Hut78 cells, with IC₅₀ <100 nM. NMR analysis revealed that FVP bound to p38γ in the ATP binding pocket, causing allosteric perturbation from sites surrounding the ATP binding pocket. Kinomic profiling with the PamGene platform in both cell-based and cell-free analysis further revealed dosage of FVP significantly affects downstream pathways in treated CTCL cells, which suggested a need for development of synergistic drugs with FVP to prevent its clinically adverse effects. It led us discover niclosamide as a synergistic drug of FVP for our future <i>in vivo</i> study.</p>","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":"2 2","pages":"48-61"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39158047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy Promotes Release of Exosomes Which Upregulate Cholesterol Synthesis and Chemoresistance in AML Blasts.","authors":"Chang-Sook Hong,&nbsp;Michael Boyiadzis,&nbsp;Theresa L Whiteside","doi":"10.33696/haematology.2.026","DOIUrl":"https://doi.org/10.33696/haematology.2.026","url":null,"abstract":"Extracellular vesicles (EVs) are emerging as a key mediator of intercellular communication as well as a major mechanism of functional reprogramming of cells in disease [1-2]. All cells produce EVs, which freely circulate and are found in all body fluids. EVs are heterogenous, consisting of subsets of vesicles with different sizes, distinct origins, and various functions (Figure 1). They mediate a broad variety of biological events ranging from cellular activation, inflammation, blood coagulation, angiogenesis, cellular transport, and others. Among these vesicles, a subset of small EVs (30-150 nm in diameter) originating from multivesicular bodies (MVBs) in parent cells and referred to as small extracellular vesicles (sEVs) carry proteomic, genomic and functional signatures that resemble those of parent cells and are, therefore, taken as surrogates of parent cells. In cancer, tumor-derived exosomes (TEX) reflect characteristics of tumor cells and are considered candidates for “liquid tumor biopsy” [3]. Emerging evidence shows that TEX are a major sEV subset in plasma of patients with cancer, including hematologic malignancies [4].","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":"2 2","pages":"36-39"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39211251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoscale Chitosan-Based Hemostasis Membrane","authors":"S. Biranje, P. Madiwale, R. Adivarekar","doi":"10.33696/HAEMATOLOGY.1.013","DOIUrl":"https://doi.org/10.33696/HAEMATOLOGY.1.013","url":null,"abstract":"Excessive bleeding or hemorrhage in traumatic injuries is the leading preventable cause of death in the combat and civilian trauma centers. Nearly 50% of military deaths, 90% of military battlefield casualties, and 33-56% mortalities in civilian’s surgical bleeding are associated with severe bleeding and can be prevented [1]. Hence, significant and rapid hemostasis or bleeding control require innovative strategies with easy to use, stable, and inexpensive processing. Furthermore, the developed hemostatic material should ensure biocompatibility and biodegradability with non-immunogenic properties. To date, a wide variety of hemostatic powders, dressings, and bandages have been investigated as useful materials in reducing hemorrhage. Unfortunately, studies have shown several limitations, especially in managing penetrating injuries, where it is hard to stop bleeding through hemostatic bandages and dressings alone [2]. Also, the most widely used hemostatic powders are still challenging to apply in the wounded area during excessive bleeding [3].","PeriodicalId":87297,"journal":{"name":"Journal of clinical haematology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45865795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}