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Annals of Hematology Oct 2002We report the successful administration of interleukin-11 (IL-11 or oprelvekin), a promoter of megakaryocyte maturation, to a 54-year-old male Jehovah's Witness with...
We report the successful administration of interleukin-11 (IL-11 or oprelvekin), a promoter of megakaryocyte maturation, to a 54-year-old male Jehovah's Witness with hepatic cirrhosis and hypersplenic thrombocytopenia requiring surgery for symptomatic interstitial cystitis. This observation suggests that oprelvekin might be crucial in the acute management of certain types of hypersplenic thrombocytopenias.
Topics: Cystitis, Interstitial; Humans; Hypersplenism; Interleukin-11; Jehovah's Witnesses; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Thrombocytopenia; Treatment Refusal
PubMed: 12424546
DOI: 10.1007/s00277-002-0507-y -
Stem Cells (Dayton, Ohio) 1998This paper discusses background information and the body of clinical data that has been accumulated to demonstrate the efficacy and safety of NEUMEGA (recombinant human... (Review)
Review
This paper discusses background information and the body of clinical data that has been accumulated to demonstrate the efficacy and safety of NEUMEGA (recombinant human interleukin 11) when used to prevent severe chemotherapy-induced thrombocytopenia and reduce the need for platelet transfusions in patients with nonmyeloid malignancies. NEUMEGA is recommended to be used at a dose of 50 microg/kg s.c. once daily starting the day after chemotherapy ends until a platelet count of 50,000 cells/microl is achieved after the expected nadir.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Interleukin-11; Neoplasms; Recombinant Proteins; Thrombocytopenia; United States; United States Food and Drug Administration
PubMed: 11012193
DOI: 10.1002/stem.5530160724 -
Journal of the American Pharmaceutical... 1998
Topics: Biotechnology; Drug Approval; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Hirudins; Interleukin-11; Recombinant Proteins; United States; United States Food and Drug Administration
PubMed: 9707962
DOI: 10.1016/s1086-5802(16)30366-7 -
Annals of Palliative Medicine Aug 2022Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing...
BACKGROUND
Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing treatment costs, reducing chemotherapy effectiveness and affecting prognosis. Based on real-world data, this study analyzed the safety, efficacy, and economic of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of CIT in hematological tumors from the perspective of the health care system.
METHODS
We retrospectively collected the data of hematological tumor patients treated with rhTPO and rhIL-11 due to thrombocytopenia caused by chemotherapy. The propensity score matching (PSM) method was used to balance the baseline information of the two groups and they were further stratified according to the degree of thrombocytopenia (grade I-II and grade III-IV). The platelet compliance rate at 2 weeks of treatment was used as the efficacy evaluation index, and the cost-effectiveness method was used to evaluate the economic value of the two drugs in the treatment of thrombocytopenia based on drug effectiveness. Univariate and probabilistic sensitivity analyses were performed.
RESULTS
A total of 1,571 patients met the inclusion and exclusion criteria, and 476 patients were included after 1:1 PSM. For patients with grade I-II thrombocytopenia, no significant difference in the platelet compliance rate was found between the two groups after 1 and 2 weeks of treatment. The platelet compliance rate in the rhTPO group was higher than that in the rhIL-11 group for patients with grade III-IV thrombocytopenia. Cost-effectiveness analysis (CEA) showed that the incremental cost-effectiveness ratio (ICER) for the rhTPO and rhIL-11 groups was 226,615.8. The ICER value was sensitive to the platelet compliance rate of the two groups, the cost of rhTPO, the cost of platelet transfusion in the rhTPO group. Probabilistic sensitivity analysis showed that when willingness to pay was less than approximately 220,000 yuan, rhIL-11 economy presented 100% better than that of rhTPO.
CONCLUSIONS
In CIT treatment for hematological tumors, rhTPO yielded a higher platelet compliance rate than rhIL-11 treatment, especially for patients with grade III-IV thrombocytopenia. However, whether rhTPO has economic advantages still requires further exploration.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Hematologic Neoplasms; Humans; Interleukin-11; Platelet Count; Recombinant Proteins; Retrospective Studies; Thrombocytopenia; Thrombopoietin
PubMed: 36064361
DOI: 10.21037/apm-22-880 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2022To explore the intervention effect of recombinant human interleukin-11 (rhIL-11) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the duration...
OBJECTIVE
To explore the intervention effect of recombinant human interleukin-11 (rhIL-11) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the duration and severity of agranulocytosis in patients with hematological malignancies after chemotherapy, and to analyze the influencing factors.
METHODS
The data of hematological malignancy patients treated with rhIL-11 and rhG-CSF after chemotherapy in the hematology department of The First Hospital of Lanzhou University from July 2017 to July 2020 were collected retrospectively. The duration and differences of agranulocytosis in differeent groups were compared by univariate analysis, and the influencing factors of agranulocytosis duration were further analyzed by multiple regression analysis.
RESULTS
The duration of agranulocytosis in 97 patients was 6.47±2.93 days. The results of univariate analysis showed that there were no statistical differences in the duration of agranulocytosis among patients with different sex, age, height, weight, body surface area, body mass index (BMI), dose of rhG-CSF, dose of rhIL-11, spontaneous bleeding after administration of rhG-CSF and rhIL-11, and the duration of agranulocytosis in patients with different red blood cell count (RBC), hemoglobin(HGB) level, platelet count (PLT) and absolute neutrophil count (ANC), before administration of rhG-CSF and rhIL-11. There were significant differences in agranulocytosis time among patients with different disease types, chemotherapy cycle, fever after rhG-CSF and rhIL-11 administration, and different white blood cell count (WBC) baseline level before rhG-CSF and rhIL-11 administration (P<0.05). Compared with patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), patients with acute myeloid leukemia (AML) had the longest duration of agranulocytosis, which was 7.07±3.05 d. Compared with patients with chemotherapy cycles of 4-6 and ≥7, patients with total chemotherapy cycle of 1-3 had the shortest duration of agranulocytosis, which was 5.25±2.48 d. Compared with patients without fever, patients with fever within 1 day after administration of cytokines and patients with fever within 2-5 days after administration of cytokines, the duration of agranulocytosis was the longest in patients with fever 6 days after administration of cytokines, which was 8.85±2.85 d. Compared with patients with WBC baseline <1.0×10/L, (1.0-1.9)×10/L and (2.0-3.9)×10/L, patients with WBC baseline ≥4.0×10/L had the shortest duration of agranulocytosis, which was 4.50±2.56 d. Multiple linear regression analysis showed that chemotherapy cycle, different fever after administration of rhG-CSF and rhIL-11, diagnosis of ALL and NHL, and WBC baseline level before administration of rhG-CSF and rhIL-11 were the influencing factors of the duration of agranulocytosis (P<0.001).
CONCLUSION
The risk of prolonged agranulocytosis is higher in patients diagnosed with AML, with more chemotherapy cycles, lower WBC baseline before cytokines administration and fever later after cytokines administration, which should be paid more attention to.
Topics: Agranulocytosis; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Humans; Interleukin-11; Lymphoma, Non-Hodgkin; Recombinant Proteins; Retrospective Studies
PubMed: 35680829
DOI: 10.19746/j.cnki.issn.1009-2137.2022.03.043 -
Biochemical and Biophysical Research... Feb 2011Recombinant human interleukin-11 (rhIL-11) has been shown to increase platelet counts in animals and humans and is the only drug approved for its use in...
Recombinant human interleukin-11 (rhIL-11) has been shown to increase platelet counts in animals and humans and is the only drug approved for its use in chemotherapy-induced thrombocytopenia (CIT). However, due to its serious side effects, its clinical use has been limited. The current work presents significantly improved efficacy of rhIL-11 via knowledge based re-designing process. The interleukin-11 mutein (mIL-11) was found to endure chemical and proteolytic stresses, while retaining the biological activity of rhIL-11. The improved efficacy of mIL-11 was evident after subcutaneous administration of mIL-11 and rhIL-11 in the rodent and primate models. More than three-fold increase in maximum plasma concentration (Cmax) and area-under-the curve (AUC) was observed. Furthermore, three-fold higher increase in the platelet counts was obtained after seven consecutive daily subcutaneous mIL-11 injections than that with rhIL-11. The mIL-11 demonstrated not only improved stability but also enhanced efficacy over the currently used rhIL-11 regimen, thereby suggesting less toxicity.
Topics: Amino Acid Sequence; Animals; Haplorhini; Humans; Interleukin-11; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Stability; Rats; Recombinant Proteins
PubMed: 21238428
DOI: 10.1016/j.bbrc.2011.01.041 -
Stem Cells Translational Medicine Apr 2015Megakaryocytes (MKs) are rare hematopoietic cells in the adult bone marrow and produce platelets that are critical to vascular hemostasis and wound healing. Ex vivo...
Megakaryocytes (MKs) are rare hematopoietic cells in the adult bone marrow and produce platelets that are critical to vascular hemostasis and wound healing. Ex vivo generation of MKs from human induced pluripotent stem cells (hiPSCs) provides a renewable cell source of platelets for treating thrombocytopenic patients and allows a better understanding of MK/platelet biology. The key requirements in this approach include developing a robust and consistent method to produce functional progeny cells, such as MKs from hiPSCs, and minimizing the risk and variation from the animal-derived products in cell cultures. In this study, we developed an efficient system to generate MKs from hiPSCs under a feeder-free and xeno-free condition, in which all animal-derived products were eliminated. Several crucial reagents were evaluated and replaced with Food and Drug Administration-approved pharmacological reagents, including romiplostim (Nplate, a thrombopoietin analog), oprelvekin (recombinant interleukin-11), and Plasbumin (human albumin). We used this method to induce MK generation from hiPSCs derived from 23 individuals in two steps: generation of CD34(+)CD45(+) hematopoietic progenitor cells (HPCs) for 14 days; and generation and expansion of CD41(+)CD42a(+) MKs from HPCs for an additional 5 days. After 19 days, we observed abundant CD41(+)CD42a(+) MKs that also expressed the MK markers CD42b and CD61 and displayed polyploidy (≥16% of derived cells with DNA contents >4N). Transcriptome analysis by RNA sequencing revealed that megakaryocytic-related genes were highly expressed. Additional maturation and investigation of hiPSC-derived MKs should provide insights into MK biology and lead to the generation of large numbers of platelets ex vivo.
Topics: Albumins; Blood Platelets; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Megakaryocytes; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin; Transcriptome; United States; United States Food and Drug Administration; Wound Healing
PubMed: 25713465
DOI: 10.5966/sctm.2014-0183 -
The Journal of Infectious Diseases Oct 1998The therapeutic potential of recombinant human interleukin-11 (rhIL-11) was tested in a neutropenic rat model that mimics the clinical consequences of myelosuppressive...
The therapeutic potential of recombinant human interleukin-11 (rhIL-11) was tested in a neutropenic rat model that mimics the clinical consequences of myelosuppressive chemotherapy complicated by Pseudomonas aeruginosa sepsis. rhIL-11-treated animals (150 micrograms/kg intravenously every 24 h for 3 days) had reduced endotoxin levels (P < .05) and less pulmonary edema fluid (P < .001) and were protected (P < .01) against thinning and necrosis of the intestinal mucosa compared with the control group. The survival rate in rhIL-11-treated animals was 40% (19/47), whereas it was 0 (0 of 19) in the control group (P < .01). The addition of ciprofloxacin (10 mg/kg every 12 h) resulted in a survival rate of 9 (60%) of 15, while the combination of rhIL-11 and ciprofloxacin resulted in 100% survival (15/15; P < .05). These results indicate that rhIL-11 supports mucous membrane integrity of the alimentary tract and decreases the systemic inflammatory response to experimental gram-negative infection in immunocompromised animals.
Topics: Animals; Anti-Infective Agents; Bacteremia; Ciprofloxacin; Disease Models, Animal; Drug Therapy, Combination; Humans; Immunocompromised Host; Interleukin-11; Neutropenia; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Sepsis
PubMed: 9806062
DOI: 10.1086/515686 -
American Journal of Hematology Mar 2001The objective of this research was to determine whether rhuIL-11 is an effective treatment in patients with refractory immune thrombocytopenic purpura (ITP). Platelet... (Clinical Trial)
Clinical Trial
The objective of this research was to determine whether rhuIL-11 is an effective treatment in patients with refractory immune thrombocytopenic purpura (ITP). Platelet production is decreased in certain cases of refractory ITP. IL-11 stimulates megakaryocytopoiesis in vitro and was licensed for its clinical effects to ameliorate chemotherapy-induced thrombocytopenia. A pilot study was initiated, intending to enroll 12 patients with ITP. These patients were to receive rhuIL-11 (Neumega) at a dose of 50 microg/kg subcutaneously daily for 21 consecutive days and be observed afterward for 21 additional days. CBC with platelets were obtained twice weekly with visits and physical examinations weekly. The study was terminated after 7 patients were enrolled because of toxicity and lack of efficacy. All 7 patients had had ITP for >9 years and had failed splenectomy, intravenous gammaglobulin, corticosteroids, and a variety of other treatments. The patients at entry all had platelet counts <20,000/microl; 5 of 7 had counts <10,000/microl. The maximal median increase for any day of the study was 6,000/microl. No patient achieved a count of 30,000/microl, and only 3 patients achieved (once each) a platelet count >20,000/microl. Substantial toxicity was seen. The nadir hemoglobin decrease was a mean of 2 g/dl. rhuIL-11 was not effective at increasing the platelet count in any of these patients with refractory ITP. Toxicity was substantial. The lack of platelet response to rhuIL-11 in this study does not exclude the possibility of better effects at other doses and/or in less refractory patients.
Topics: Adolescent; Adult; Hematopoiesis; Hemoglobins; Humans; Immunoglobulins, Intravenous; Interleukin-11; Megakaryocytes; Middle Aged; Pilot Projects; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Treatment Outcome
PubMed: 11279623
DOI: 10.1002/1096-8652(200103)66:3<172::aid-ajh1041>3.0.co;2-q -
Nature Biotechnology Jan 1998
Topics: Antineoplastic Agents; Drug Approval; Humans; Interleukin-11; Recombinant Proteins; Thrombocytopenia; United States; United States Food and Drug Administration
PubMed: 9447578
DOI: 10.1038/nbt0198-7