romiplostim for radiation

Platelet responses at weeks 105 and 157 were maintained in 10 patients who received 3 to 20 g/kg once weekly, and erythroid and neutrophil responses were observed in nine and five patients, respectively. B cells secreting anti-GPIb or anti-GPIIb/IIIa antibodies have been detected in plasma and are a hallmark of patients with ITP.51 These antibodies to GPIb, among other mechanisms, can also lead to neuraminidase-mediated desialylation. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Key Clinical Studies of Romiplostim in Various Clinical Disorders Other Than ITP. Porcelijn L, Huiskes E, Oldert G, Schipperus M, Zwaginga JJ, de Haas M. Detection of platelet autoantibodies to identify immune thrombocytopenia: state of the art. Conversely, TPO binds to MPL receptors on circulating platelets in the blood when platelet levels are high. We have discussed the latest FDA-approved agent, romiplostim, as a treatment modality for H-ARS. The individual has been acutely exposed to myelosuppressive doses of radiation . Christakopoulas GE, DeFor TE, Hage SM, et al. ). External Radiation Source: . and transmitted securely. It is used in: Adults with chronic immune thrombocytopenia (ITP), a condition in which platelets are destroyed by the immune system. 15. Romiplostim to Determine Its Safety and Efficacy in Children With Immune Thrombocytopenia," Blood, 2011, 118(1):2836. Fominykh M, Voloshin S, Schmidt A, et al. Romiplostim (Nplate) for injection is available as 125 mcg, 250 mcg or 500 mcg of deliverable romiplostim as a lyophilized powder in single-dose vials. It is possible that the (single) Fc domain could contribute to the rate at which romiplostim results in a treatment-free response. When engraftment is delayed, the use of a TPO mimetic may successfully increase platelet counts. Thrombopoietin (TPO) is a critical component of platelet production pathways, and TPO receptor agonists (TPO-RAs) are important for the management of ITP by increasing platelet production and reducing the need for other treatments. Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents. NPLATE (ROMIPOSTIM) NPLATE is a prescription medicine used to treat low blood platelet counts (thrombocytopenia). Identification of 146 Metagenome-assembled Genomes from the Rumen Microbiome of Cattle in Japan. See cytokines page and romiplostim FDA drug label. Romiplostim injection is also used to treat acute radiation syndrome in patients who have been exposed to high levels (myelosuppressive doses) of radiation. Fanale M, Stiff P, Noonan K, McCoy J, Rutstein M, Moskowitz C. Safety of romiplostim for treatment of severe chemotherapy induced thrombocytopenia (CIT) in patients with lymphoma receiving multi-cycle chemotherapy: results from an open-label dose- and schedule-finding study, Romiplostim treatment of chemotherapy-induced thrombocytopenia, Study of romiplostim for chemotherapy-induced thrombocytopenia in adult subjects with non-small cell lung cancer (NSCLC), ovarian cancer, or breast cancer (NCT03937154), {"type":"clinical-trial","attrs":{"text":"NCT03937154","term_id":"NCT03937154"}}, Study of romiplostim for chemotherapy induced thrombocytopenia (NCT02052882), {"type":"clinical-trial","attrs":{"text":"NCT02052882","term_id":"NCT02052882"}}, Study of romiplostim for chemo-induced thrombocytopenia in adults subjects with gastrointestinal or colorectal cancer (NCT03362177), {"type":"clinical-trial","attrs":{"text":"NCT03362177","term_id":"NCT03362177"}}. Romiplostim is a TPO-RA that has been used in adults with chronic ITP for more than 11 years. nplate mechanism of action radiation. It should not be used to treat thrombocytopenia caused by other conditions and may worsen pre-existing blood cancers or myelodysplastic syndrome (MDS). A more recent phase 2 study explored the effect of eltrombopag in 23 evaluable patients with expanded types of inherited thrombocytopenia (ie, MYH9-RD, ankyrin repeat domain-containing protein 26 [ANKRD26]related thrombocytopenia, WiskottAldrich syndrome/X-linked thrombocytopenia, monoallelic Bernard-Soulier syndrome, or integrin beta-3 [ITGB3]related thrombocytopenia). The Spanish Group of HSCT retrospectively evaluated the safety and efficacy of TPO-RAs, either romiplostim or eltrombopag, in 86 patients with posttransplant thrombocytopenia.162 The overall response rate for platelet recovery 50 109/L was 72% (median [range] response at 66 [2247] days; median [range] treatment duration 62 [7700] days), which was sustained in 81% of the responding patients after treatment discontinuation.162 A prospective French phase 1/2 study enrolled 24 patients (10 with primary and 14 with secondary thrombocytopenia) providing weekly treatment with romiplostim (starting dose 1 g/kg, escalating up to a maximum dose of 10 g/kg).169 Response, defined as platelet count >50 109/L free of platelet transfusion, was achieved in 18 patients at a median (interquartile range [IQR]) time of 45 (2941) days (range, 2177 days), with a median (IQR) dose of 5 (46.8) g/kg (range, 111 g/kg); such a response was sustained in 16/18 patients for 8 consecutive weeks, independent of platelet transfusions.169 Mahat et al170 reviewed 12 studies (six case series and six case reports) involving the use of romiplostim for prolonged post-HSCT thrombocytopenia (primary thrombocytopenia in 17 patients and secondary in 32 patients); a platelet response of >50 109/L free of platelet transfusion was observed in 40 out of the 49 patients (82%) overall. Alvarado LJ, Andreoni A, Huntsman HD, Cheng H, Knutson JR, Larochelle A. Heterodimerization of TPO and IFN impairs human hematopoietic stem/progenitor cell signaling and survival in chronic inflammation. the convention on the rights of the child; yarp direct forwarding; primary key not found entity framework core Battipaglia G, Ruggeri A, Brissot E, et al. Patterson AM, Vemula S, Plett PA, Sampson CH, Chua HL, Fisher A, Wu T, Sellamuthu R, Feng H, Katz BP, DesRosiers CM, Pelus LM, Cox GN, MacVittie TJ, Orschell CM. No further survival benefit was seen with higher (100 g/kg) or more frequent dosing (3 or 5 once daily doses at 30 g/kg) of romiplostim or combined treatment with pegfilgrastim. 1979]. The use of TPO-RA may allow additional time to delay the second graft request from donors and possibly observe platelet recovery without it. Nationwide survey in France on the use of romiplostim in patients with refractory severe aplastic anemia. Among patients who received romiplostim, the rate of bone marrow events was 1.3 (18 cases) per 100 patient-years and 3.6 (6 cases) per 100 patient-years among patients on the highest dose (>10 g/kg).89 However, in a pooled analysis of adult patients from 13 studies treated for up to 5.4 years, the rate of increased bone marrow reticulin with romiplostim was low: 0.4/100 patient-years in splenectomized and 0.6/100 patient-years in nonsplenectomized patients.76 The overall consensus of the studies is that an increase in reticulin in some patients with ITP treated with romiplostim occurs. Thrombopoietin receptor agonists for severe thrombocytopenia after allogeneic stem cell transplantation: experience of the Spanish Group of hematopoietic stem cell transplant. Pharmacodynamic analysis revealed that the platelet nadir was not as low and recovery was faster in the irradiated mice treated with romiplostim when compared with irradiated control animals (Day 8 versus 10 nadir; Day 22 versus 29 recovery to near baseline). In addition, TPO alters hematopoietic stem cell lineage differentiation via metabolic regulation. The .gov means its official. Ghadaki et al found nine of 31 patients (29%) with ITP had sustained remissions, six of whom (19%) received romiplostim; in most of these cases, once platelet response was achieved, the medication was slowly tapered until it was successfully discontinued.85 In a case series reported by Mingot-Castellano et al, four patients achieved sustained response (two of whom had chronic ITP), with the time to romiplostim taper and discontinuation ranging from 1 to 52 weeks and 14 weeks to 18 months, respectively.86 Carpenedo et al found that 13 of 27 patients (48%, six of whom had chronic ITP) were able to discontinue romiplostim after a mean of 43.3 weeks of therapy; continued treatment-free response was maintained for a mean of 28.8 months.83 In a retrospective analysis, 11 of 46 patients (24%) with relapsed or refractory ITP who received treatment with a TPO-RA were able to discontinue treatment after achieving a platelet response; seven of the 11 patients (64%) received romiplostim for 2 to 36 months with a sustained response 16 to 54 months after discontinuation.84 In their retrospective analysis, Lozano et al found that out of 121 patients who received TPO-RAs, 41 patients (34%) received romiplostim as their only TPO-RA (including 29 patients with chronic ITP).87 Despite the intention of long-term treatment at its initiation, 23 patients (56%) tapered off romiplostim after different durations of treatment and were eligible for assessment of achieving treatment-free response (defined as maintaining a platelet count 50 109/L for at least 6 months without any ITP treatment); out of the 41 patients receiving romiplostim, 21 patients (51%) achieved treatment-free response. A subcutaneous administration of romiplostim (4 mcg/kg/week) had raised the platelet count rapidly and the patient was able to maintain > 100X109/L platelets even after 230 days of romiplostim treatment . Pharmacodynamics-mediated drug disposition (PDMDD) and precursor pool lifespan model for single dose of romiplostim in healthy subjects. WikiZero zgr Ansiklopedi - Wikipedia Okumann En Kolay Yolu . Romiplostim is a prescription medicine also used to treat people including newborns who have been exposed to high levels of radiation (acute radiation syndrome). Coughing up blood. Romiplostim was administered subcutaneously 2, 24, or 48 hours following radiation, in cycle two, cycle three, or both cycles. Romiplostim injection is also used to treat acute radiation syndrome in patients who have been exposed to high levels (myelosuppressive doses) of radiation. Similar to endogenous TPO, romiplostim stimulates growth of megakaryocyte colony-forming cells and increases megakaryocyte number, size, and ploidy.59,60 Studies of platelets suggest that signaling in platelets was similar for romiplostim and eltrombopag; the role of intracellular iron chelation in the effect of eltrombopag is unique, but its clinical impact is not known.3,69 Altogether, these characteristics of romiplostim clarify the reasons why it is a good treatment option for ITP and may be useful in other hematologic conditions that result in thrombocytopenia. Low platelet levels in the blood caused by attacks from the immune system ( immune thrombocytopenic purpura or ITP) Blood problems caused by too much radiation ( hematopoietic syndrome of acute radiation syndrome) Nplate (romiplostim) dosage forms vial 125mcg 250mcg 500mcg Cwirla SE, Balasubramanian P, Duffin DJ, et al. Mason KD, Carpinelli MR, Fletcher JI, et al. Hematopoietic Syndrome of Acute Radiation Syndrome. Clipboard, Search History, and several other advanced features are temporarily unavailable. The full terms of this license are available at. Radiomitigation by Melatonin in C57BL/6 Mice: Possible Implications as Adjuvant in Radiotherapy and Chemotherapy. Introduction. Newly diagnosed patients who received more intensive initial treatment regimens appeared to show improved initial and late response rates,88,9799 which is consistent with the theory that earlier treatment in any disease is potentially more curative than later treatment. The .gov means its official.Federal government websites often end in .gov or .mil. 9. Currao M, Balduini CL, Balduini A, Lin B. romiplostim side effects. Before sharing sensitive information, make sure you're on a federal government site. <span>Purpose: Rapid depletion of white blood cells, platelets, and reticulocytes are hallmarks of hematopoietic injury of acute radiation syndrome (H-ARS) and, if left untreated, can lead to severe health consequences including death. Health Conditions Issues related to neutron and mixed neutron/gamma radiation. Tests were negative on retesting 3 and 6 months later. Vehicle, romiplostim, and/or pegfilgrastim were administered subcutaneously beginning 24 h after TBI for 1-5 days. The antiapoptotic protein Bcl-xL constrains the proapoptotic proteins Bak and Bax to maintain platelet survival; as Bcl-xL degrades, older platelets are primed for cell death.48,49 Genetic inactivation or pharmacologic inhibition of Bcl-xL leads to Bax-/Bak-induced mitochondrial damage and promotes the apoptotic cascade, reducing platelet half-life, and causing thrombocytopenia.48,49 Imbalanced expression of Bcl-xL and Bax has been associated with platelet apoptosis in ITP.50, Another method of platelet clearance appears to involve glycan modifications on platelet surface proteins, which may be triggered by the loss of terminal sialic acid residues on platelet surface glycoproteins as they age. Stem Cell Res Ther. Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. Thrombocytopenia post-HSCT can occur from secondary failure of platelet recovery, defined as a decline in platelet counts to below 20 109/L for 7 consecutive days or requiring transfusion support within 7 days after achieving platelet counts 50 109/L.158 Long-lasting thrombocytopenia could lead to potentially lethal bleeding, thus necessitating the use of prophylactic or therapeutic platelet transfusions. Cines DB, Gernsheimer T, Wasser J, et al. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia, A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia, Clinical overview and practical considerations for optimizing romiplostim therapy in patients with immune thrombocytopenia, Romiplostim treatment in adults with immune thrombocytopenia of varying duration and severity, http://creativecommons.org/licenses/by-nc/3.0/, https://ec.europa.eu/health/documents/community-register/2021/20210122150420/anx_150420_en.pdf, 1 g/kg or at dose received in parent study, Treatment-related serious AEs (Splen versus Nonsplen), Platelet response (ITP 1 year versus >1 year), Treatment-related serious AEs (ITP 1 year versus >1 year), 15, adults, nonhematologic cancer (n=11) and lymphoma (n=4) with postchemotherapy thrombocytopenia. Iraqi M, Perdomo J, Yan F, Choi PY, Chong BH. Romiplostim improves platelet recovery after UCB transplant [abstract no. highcharts stacked column horizontal. Children aged 1 year and older who have had ITP for at least 6 months. 2022 Aug;45(8):558-571. doi: 10.1007/s12272-022-01400-7. Sci Rep. 2022 Aug 5;12(1):13475. doi: 10.1038/s41598-022-17807-7. Postmarket Drug Safety Information for Patients and Providers, Recalls, Market Withdrawals and Safety Alerts, Postmarket Drug Safety Information for Patients and Providers, FDA Drug Safety Communication: Modified Risk Evaluation and Mitigation Strategies (REMS) for Nplate (romiplostim) and Promacta (eltrombopag), FDA announces changes to risk strategy requirements for 2 drugs to treat low platelet counts, FDA Oncologic Drugs Advisory Committee Meeting, 3/12/2008, Nplate (romiplostim) Prescribing and Labeling Information. Development of Romiplostim for Treatment of Primary Immune Thrombocytopenia From a Pharmacokinetic and Pharmacodynamic Perspective. Upon exogenous TPO stimulation, HSCs differentiate to megakaryocytes. Can immune thrombocytopenia be cured with medical therapy? In turn, these functions may affect the outcome of TPO-MPL signaling in hematopoietic stem cells,11 areas in which TPO-RAs have unique and distinct effects.11 Along with increasing platelet production, TPO-RAs also appear to transiently extend their circulating life span, potentially via signaling through the AKT pathway and reducing sensitivity to apoptotic stimuli.21. J Clin Oncol. Another area of interest is bone marrow reticulin, which has been shown to be increased in pediatric and adult patients receiving TPO-RAs.92 In a pooled analysis of 13 studies, one of which included pediatric patients, 12 patients (1.8%) in the romiplostim group experienced bone marrow reticulin (1.3 events per 100 patient-years); all had received high doses of romiplostim (818 g/kg/wk).93 In another pooled analysis that included pediatric, adult, and geriatric patients, 17 cases of bone marrow reticulin and one case of collagen were reported among those receiving romiplostim compared with one case of reticulin in placebo recipients. The response rate is significantly lower in patients with a decreased number of megakaryocytes before treatment.162 No large prospective definitive studies have yet been reported. Thrombopoietin receptor agonists: ten years later, Romiplostim summary of product characteristics, Recombinant human thrombopoietin: basic biology and evaluation of clinical studies. The effectiveness of romiplostim for this use was only studied in animals, because it could not be studied in people. Yamanouchi J, Hato T, Kunishima S, Niiya T, Nakamura H, Yasukawa M. A novel MYH9 mutation in a patient with MYH9 disorders and platelet size-specific effect of romiplostim on macrothrombocytopenia, Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim, Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin, Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. The pharmacokinetics and pharmacodynamics of romiplostim have been evaluated by Wang et al.58,70 In brief, among healthy volunteers, platelet counts increased 1 to 3 days after intravenous administration and 4 to 9 days after subcutaneous administration, peaking on days 12 to 16.58 Pharmacokinetics of romiplostim dosing is nonlinear and dependent on the dose administered and baseline platelet counts.58,70 After subcutaneous administration at doses ranging from 3 to 15 g/kg (an early upper limit of ITP dosing), peak serum concentrations of romiplostim occurred at approximately 7 to 50 hours posttreatment (median, 14 hours), and the half-life was approximately 1 to 34 days (median, 3.5 days).5 Models suggest that romiplostim activity is driven by saturation of receptor occupancy on platelets and megakaryocytes rather than the romiplostim serum concentration.71, A large body of evidence supports the use of romiplostim to safely and effectively increase platelet counts in adults and children with ITP. This interesting finding definitely opens a new therapeutic option for treating thrombocytopenia in dengue. absorbed whole body radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time . Protection of the hematopoietic system against radiation-induced damage: drugs, mechanisms, and developments. Share on Facebook . This is particularly relevant in the posttransplant setting when the risk of hemorrhagic events is often increased by diffuse endothelial damage. Only one patient later experienced relapse at week 67 after about 30 weeks withholding romiplostim. nplate administration. Medical countermeasures for unwanted CBRN exposures: part II radiological and nuclear threats with review of recent countermeasure patents. MeSH Romiplostim 1/6. Romiplostim is a TPO-RA approved for use in patients with ITP in the United States, European Union, Australia, and several countries in Africa and Asia, as well as for use in patients with refractory aplastic anemia in Japan and Korea. For example, romiplostim activates the extracellular domain of the TPO-R, whereas eltrombopag and avatrombopag activate the transmembrane portion of the TPO-R (Figure 4),),33 which could lead to different levels of activity of the TPO-R and hence different responses within the stem cell and megakaryocyte compartments. Adult and pediatric dosage In the settings of accelerated platelet destruction and reduced platelet production, which are typical of advanced liver disease, this contributes substantially to the degree of thrombocytopenia.151,185 Two TPO agents, avatrombopag and lusutrombopag, have been approved in the United States specifically to increase the platelet count in patients with thrombocytopenia and liver disease undergoing a procedure;186,187 eltrombopag was previously approved to treat thrombocytopenia in patients with hepatitis C with liver disease to allow for the initiation and maintenance of interferon-based therapy.129 Treatment with romiplostim was shown to improve platelet counts in a patient with hepatocellular carcinoma188 and in patients with hepatitis C virus,151 allowing most of these patients to undergo planned surgical procedures.

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