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Pediatric Radiology Jul 2003Interleukin-11 (Oprelvekin, Neumega) is a newly introduced thrombopoietic growth factor that stimulates production, differentiation, and maturation of megakaryocytes and...
Interleukin-11 (Oprelvekin, Neumega) is a newly introduced thrombopoietic growth factor that stimulates production, differentiation, and maturation of megakaryocytes and platelets. Reversible periostitis has been reported as the side effect of the drug in primates and in the phase I/II trials. We report our experience with 5 cases of periostitis, occurring in thrombocytopenic children with three non-malignant and two malignant conditions, out of 24 pediatric patients treated with IL-11 at 75 micro g/kg per day for a median of 17 days. The findings were noted in the clavicle or the proximal humerus. Two patients also had forearm and lower-extremity long-bone involvement. All patients had normal bones before IL-11 was given, changes occurred in both non-malignant and malignant diseases, and periostitis disappeared after use of the drug was discontinued. The distribution and appearance of the changes are similar to prostaglandin E1 and hypervitaminosis A. The changes are reversible after termination of treatment and are most noted in younger patients. The exact mechanism is not clear. The detection of periostitis makes it essential for the radiologists to inquire as to what medications patients are receiving. The pediatric doses (75 g/kg/d) are above those recommended for adult patients (50 g/kg/d) and this may account for the pediatric bone changes of periostitis.
Topics: Antineoplastic Agents; Child; Child, Preschool; Humans; Interleukin-11; Periostitis; Radiography; Recombinant Proteins; Retrospective Studies; Thrombocytopenia; Time Factors
PubMed: 12728286
DOI: 10.1007/s00247-003-0893-x -
Clinical Journal of Oncology Nursing Apr 1999Oprelvekin (Neumega, Genetic Institute Co., Cambridge, MA) is a thrombopoietic growth factor approved by the U.S. Food and Drug Administration for the prevention of...
Oprelvekin (Neumega, Genetic Institute Co., Cambridge, MA) is a thrombopoietic growth factor approved by the U.S. Food and Drug Administration for the prevention of severe thrombocytopenia following myelosuppressive chemotherapy in patients with nonmyeloid malignancies. The most common side effects are edema, dyspnea, tachycardia, and conjunctival redness. Patient-care concerns include appropriate timing of administration, patient selection, dosing and administration issues, and the early identification and management of side effects.
Topics: Antineoplastic Agents; Female; Humans; Interleukin-11; Middle Aged; Patient Care Planning; Patient Education as Topic; Patient Selection; Recombinant Proteins; Thrombocytopenia; United States; United States Food and Drug Administration
PubMed: 10633612
DOI: No ID Found -
Expert Review of Hematology May 2021: Chemotherapy-induced thrombocytop enia (CIT) is a common complication of cancer treatment causing chemotherapy delays, dose reductions, and treatment discontinuation,... (Review)
Review
: Chemotherapy-induced thrombocytop enia (CIT) is a common complication of cancer treatment causing chemotherapy delays, dose reductions, and treatment discontinuation, negatively impacting treatment outcomes and putting patients at risk for bleeding complications. There is no FDA-approved agent available to manage CIT.: This article covers the diagnosis, definitions, and clinical challenges of CIT, and then focuses on the therapeutics developed to manage CIT. The first-generation thrombopoietic agents (oprelvekin and recombinant human thrombopoietins) are reviewed for critical background and context, followed by a detailed discussion of the data for the thrombopoietin receptor agonists (TPO-RAs) to manage CIT. Efficacy of TPO-RAs in treatment and prevention of CIT, as well as safety concerns such as the risk of thromboembolic complications, are reviewed in detail. For this review, a PubMed/MEDLINE literature search was undertaken for relevant articles published from 1995-2021.: After over two decades of drug development for CIT, multiple clinical trials and observational studies have found TPO-RAs, in particular romiplostim, to be safe and effective agents to manage patients with CIT, although no agent is yet FDA-approved for this indication. Active management of CIT with TPO-RAs is likely to improve oncologic outcomes, although additional data are needed. Phase 3 trials are ongoing.
Topics: Antineoplastic Agents; Benzoates; Humans; Neoplasms; Purpura, Thrombocytopenic, Idiopathic; Receptors, Fc; Receptors, Thrombopoietin; Recombinant Fusion Proteins; Thrombocytopenia
PubMed: 33926362
DOI: 10.1080/17474086.2021.1924053 -
Drug Safety Nov 2014Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection,... (Review)
Review
Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection, inflammation and malignancy. Key to understanding their function is recognition of their pleiotropism and often overlapping and functional redundancies. Classified here into 9 main families, most of the 20 approved cytokine preparations (18 different cytokines; 3 pegylated), all in recombinant human (rh) form, are grouped in the hematopoietic growth factor, interferon, platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) families. In the hematopoietin family, approved cytokines are aldesleukin (rhIL-2), oprelvekin (rhIL-11), filgrastim and tbo-filgrastim (rhG-CSF), sargramostim (rhGM-CSF), metreleptin (rh-leptin) and the rh-erythropoietins, epoetin and darbepoietin alfa. Anakinra, a recombinant receptor antagonist for IL-1, is in the IL-1 family; recombinant interferons alfa-1, alfa-2, beta-1 and gamma-1 make up the interferon family; palifermin (rhKGF) and becaplermin (rhPDGF) are in the PDGF family; and rhBMP-2 and rhBMP-7 represent the TGFβ family. The main physicochemical features, FDA-approved indications, modes of action and side effects of these approved cytokines are presented. Underlying each adverse events profile is their pleiotropism, potency and capacity to release other cytokines producing cytokine 'cocktails'. Side effects, some serious, occur despite cytokines being endogenous proteins, and this therefore demands caution in attempts to introduce individual members into the clinic. This caution is reflected in the relatively small number of cytokines currently approved by regulatory agencies and by the fact that 14 of the FDA-approved preparations carry warnings, with 10 being black box warnings.
Topics: Cytokines; Drug Approval; Humans; Recombinant Proteins
PubMed: 25270293
DOI: 10.1007/s40264-014-0226-z -
Oncology (Williston Park, N.Y.) Nov 1998The outcomes of thrombocytopenia are clinically serious (hemorrhage), costly to prevent and treat (platelet transfusions and hospitalization), and may result in delay of... (Review)
Review
The outcomes of thrombocytopenia are clinically serious (hemorrhage), costly to prevent and treat (platelet transfusions and hospitalization), and may result in delay of the subsequent cycle of chemotherapy. Oprelvekin, the first commercially available platelet growth factor, has been shown to be safe and effective in reducing the need for platelet transfusions. In placebo-controlled trials of patients with solid tumors receiving dose-intensive chemotherapy, 68% of oprelvekin recipients escaped transfusion altogether, compared with only 41% of those who received a placebo. Side effects are generally mild, reversible, and related to fluid retention. Although clinical trials provide evidence about how many patients, on average, can be expected to benefit from agents such as oprelvekin, the trials provide little information about which patients in the general oncology population will benefit. Guidelines based on clinical trial data are limited by this approach. An alternative approach is to develop a clinical profile or model of patients at high risk of developing serious clinical outcomes and target platelet growth factors to these patients through the use of guidelines. Other important components of the guideline development process include a thorough evaluation of the costs of treatments and side effects as well as a careful evaluation of patient's preferences for alternative treatment strategies. Guidelines limiting growth factor use to only those patients who are most likely to benefit provide an opportunity to use expensive new agents in a cost-effective, evidence-based fashion.
Topics: Antineoplastic Agents; Humans; Interleukin-11; Neoplasms; Practice Guidelines as Topic; Thrombocytopenia; Treatment Outcome
PubMed: 10028521
DOI: No ID Found -
Mediterranean Journal of Hematology and... 2017Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct... (Review)
Review
Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues-AMG-51, PEG-TPOmp and AKR-501, recombinant human IL-11 (rhIL-11, Oprelvekin), recombinant human erythropoietin (rhEPO), danazol and L-carnitine have shown promising early result with improving thrombocytopenia. Thrombocytopenia in chronic HCV infection remain a major problem, however the recent change in DAAs without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based anti-viral therapy.
PubMed: 28293407
DOI: 10.4084/MJHID.2017.019 -
Oncology (Williston Park, N.Y.) Sep 2000
Review
Topics: Antineoplastic Agents; Blood Platelets; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Hematopoiesis; Humans; Interleukin-11; Maximum Tolerated Dose; Megakaryocytes; Recombinant Proteins; Thrombocytopenia
PubMed: 11033833
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Sep 2000Thrombocytopenia occurs at various grades of severity in patients with nonmyeloid malignancies undergoing chemotherapy with myelosuppressive agents. Frequently, it is... (Review)
Review
Thrombocytopenia occurs at various grades of severity in patients with nonmyeloid malignancies undergoing chemotherapy with myelosuppressive agents. Frequently, it is the major dose-limiting hematologic toxicity, especially in the treatment of potentially curable malignancies such as leukemia, lymphomas, and pediatric cancers. This is becoming increasingly important given the recent trend toward the use of dose-intensive combination chemotherapy regimens facilitated by supportive hematopoietic colony-stimulating factors to prevent chemotherapy-induced febrile neutropenia. The standard preventive measure against chemotherapy-induced depression of platelets in subsequent treatment cycles has been dose reduction and/or dose delay. However, follow-up data from studies in various populations of patients with cancer suggest a correlation between delivery of lower than intended doses and poor outcomes, including reduced disease-free periods and overall survival. Other consequences of thrombocytopenia include the need for platelet transfusions and subsequent exposure to the risk of numerous complications, including bacterial and viral infections; febrile, nonhemolytic transfusion reactions; and transfusion-induced immunosuppression. Furthermore, a large proportion of multitransfused patients become refractory to subsequent infusions. Refractoriness to platelet transfusions is quickly becoming more prominent. The availability of a platelet growth factor--recombinant human interleukin-11(rhIL-11, also known as oprelvekin [Neumega])--provides an effective means of preventing chemotherapy-induced thrombocytopenia and accelerating platelet recovery, thereby facilitating the administration of full doses of chemotherapy during subsequent cycles and avoiding the need for rescue with platelet transfusions.
Topics: Antineoplastic Agents; Bone Marrow; Colony-Stimulating Factors; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Immunosuppression Therapy; Interleukin-11; Maximum Tolerated Dose; Neoplasms; Opportunistic Infections; Platelet Transfusion; Recombinant Proteins; Survival Rate; Thrombocytopenia
PubMed: 11033835
DOI: No ID Found -
Pharmacotherapy Mar 2000The numerous drugs to which the acutely ill are exposed place these patients at a significant risk of developing drug-induced thrombocytopenia. Such patients tend to... (Review)
Review
The numerous drugs to which the acutely ill are exposed place these patients at a significant risk of developing drug-induced thrombocytopenia. Such patients tend to have preexisting hemostatic defects that place them at additional risk of complications as a result of the drug-induced thrombocytopenia. The clinical challenge is to provide rapid identification and removal of the offending agent before clinically significant bleeding or, in the case of heparin, thrombosis results. Drug-induced thrombocytopenic disorders can be classified into three mechanisms: bone marrow suppression, immune-mediated destruction, and platelet aggregation. Clinical characteristics, preliminary laboratory findings, and drug history specific to the mechanisms can assist clinicians in rapidly isolating the causative drug.
Topics: Acute Disease; Anticoagulants; Antineoplastic Agents; Chondroitin Sulfates; Critical Care; Dermatan Sulfate; Disease Management; Drug Combinations; Fibrinolytic Agents; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Interleukin-11; Recombinant Proteins; Thrombocytopenia; Thrombopoietin
PubMed: 10730685
DOI: 10.1592/phco.20.4.292.34883