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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 -
Cancer Jun 2003Previous research has shown oprelvekin (recombinant human interleukin-11 [rhIL-11]) to be effective in reducing the requirements for platelet transfusions after... (Comparative Study)
Comparative Study
BACKGROUND
Previous research has shown oprelvekin (recombinant human interleukin-11 [rhIL-11]) to be effective in reducing the requirements for platelet transfusions after myelosuppressive chemotherapy in patients who have previously experienced thrombocytopenia. The economic consequences of the routine use of this platelet growth factor and the usual standard of platelet transfusions for prophylaxis of severe chemotherapy-induced thrombocytopenia have not been compared.
METHODS
The authors constructed a decision-analytic model to compare the alternatives of rhIL-11 versus usual care using probability, outcome, and cost data from previously published clinical trials and their own institutional sources. They incorporated the costs of platelet transfusions and adverse events from rhIL-11 into the analysis. Quality-of-life outcomes were not considered. The pharmacoeconomic analysis was based on the criterion of cost minimization from the payer's perspective.
RESULTS
The expected cost of the usual care strategy for prophylaxis of severe thrombocytopenia (transfusion when platelets < 20000 microL(-1)) was US dollars 3495 for a 3-week cycle of chemotherapy. The prophylactic rhIL-11 strategy was more expensive, with an expected cost of US dollars 5328 over the same time period. Nonetheless, it was associated with fewer platelet transfusions, avoiding an average of 6.7 U compared with usual care. The savings from avoidance of platelet transfusion and adverse reactions to transfusion from the use of rhIL-11 were not offset by the substantial cost of the pharmaceutical. The greater expected costs from the rhIL-11 strategy were relatively insensitive to the unit price and efficacy of rhIL-11 and the costs of platelet transfusions and monitoring.
CONCLUSIONS
From the payer's perspective, rhIL-11 cannot be considered a cost-saving clinical strategy compared with routine platelet transfusions for patients with severe chemotherapy-induced thrombocytopenia.
Topics: Antineoplastic Agents; Costs and Cost Analysis; Humans; Interleukin-11; Models, Theoretical; Platelet Transfusion; Recombinant Proteins; Thrombocytopenia
PubMed: 12784347
DOI: 10.1002/cncr.11447 -
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 -
Medicine Apr 2019This study evaluated the effectiveness of recombinant human interleukin-11 (rhIL-11) in the treatment of immune thrombocytopenia (ITP) and determined whether clinical...
Platelet and peripheral white blood cell counts at diagnosis predict the response of adult immune thrombocytopenia to recombinant human interleukin-11: A retrospective, single-center, case-control study.
This study evaluated the effectiveness of recombinant human interleukin-11 (rhIL-11) in the treatment of immune thrombocytopenia (ITP) and determined whether clinical and laboratory findings predicted the treatment response.This retrospective, single-center, case-control study included 103 adult patients with ITP treated between July 2010 and April 2014 at Jiangxi Province People's Hospital. About 49 patients in the pred+IL group received prednisone (conventional dose) combined with an rhIL-11 regimen, and 54 patients in the pred alone group received prednisone (conventional dose) alone. Demographic data, initial and follow-up platelet counts, proportions of patients achieving platelet counts ≥30 × 10/L (response) and ≥100 × 10/L (complete response) at different time points, and adverse reactions were compared between groups.Complete response rates were similar between groups overall but higher in the pred+IL group than in the pred alone group for newly diagnosed patients and those with severe ITP (P < .05). Proportions of patients achieving response or complete response at different time points were similar between groups overall but higher in the pred+IL group than in the pred alone group for newly diagnosed patients and those with severe ITP (P < .05). Posttreatment platelet count correlated negatively with platelet count at diagnosis and white blood cell (WBC) count at diagnosis in patients with newly diagnosed ITP (r = -0.337, P = .073 and r = -0.367, P = .050, respectively) or ITP with bleeding-related episodes (r = -0.357, P = .020 and r = -0.434, P = .004, respectively). No immediate or postinfusion severe adverse reactions were observed.rhIL-11 increased CR and improved hemostasis in patients with newly diagnosed or severe ITP. Platelet and WBC counts at diagnosis can predict the response to rhIL-11.
Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Female; Humans; Interleukin-11; Leukocyte Count; Male; Middle Aged; Platelet Count; Prednisone; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Retrospective Studies; Young Adult
PubMed: 31008943
DOI: 10.1097/MD.0000000000015195 -
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 -
Blood May 1996We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels... (Clinical Trial)
Clinical Trial
We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cohort Studies; Female; Humans; Injections, Subcutaneous; Interleukin-11; Middle Aged; Recombinant Proteins; Thrombocytopenia
PubMed: 8611685
DOI: No ID Found -
Arthritis Research 2001Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis.
Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints. The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed. This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 microg/kg of rhIL-11 or placebo twice per week or 5 or 15 microg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug. Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 microg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response. The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site.
Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Subcutaneous; Interleukin-11; Joints; Male; Middle Aged; Recombinant Proteins; Treatment Outcome
PubMed: 11438043
DOI: 10.1186/ar309 -
Thrombosis and Haemostasis Feb 2013Desmopressin (DDAVP) is the treatment of choice in those with mild von Willebrand disease (VWD), yet 20% are unresponsive to DDAVP, and among the 80% who respond, the...
Desmopressin (DDAVP) is the treatment of choice in those with mild von Willebrand disease (VWD), yet 20% are unresponsive to DDAVP, and among the 80% who respond, the response is transient, as endothelial stores are depleted after three days. We, therefore, conducted a single-center Phase II clinical trial to determine safety and biologic efficacy of recombinant interleukin-11 (rhIL-11, Neumega®) in patients with VWD unresponsive or allergic to DDAVP, or mild or moderate haemophilia A (HA). Increases in VWF:RCo wer e observed by 48 hours after rhIL-11, with a 1.54-fold increase by Day 4, 1.30-fold in VWD and 1.73-fold in HA. Similarly, by 48 hours, increases in VIII:C were observed, with a 1.65-fold increase by Day 4, 1.86-fold in VWD and 1.48-fold in HA. Platelet VWFmRNA expression by qPCR increased 0.81-fold but did not correlate with plasma VWF:Ag responses. rhIL-11 was well tolerated, with grade 1 or less fluid retention, flushing, conjunctival erythema, except for transient grade 3 hyponatraemia in one subject after excess fluid intake for diabetic hyperglycaemia, which resolved with fluid restriction. In summary, rhIL-11 increases VWF levels in two of four DDAVP-unresponsive or allergic VWD and F.VIII levels in four of five mild or moderate haemophilia A subjects, suggesting its potential use in treatment of these disorders.
Topics: Adult; Biomarkers; Deamino Arginine Vasopressin; Drug Resistance; Factor VIII; Female; Hemophilia A; Hemostatics; Humans; Interleukin-11; Male; Middle Aged; Pennsylvania; Prospective Studies; Protein Multimerization; RNA, Messenger; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult; von Willebrand Diseases; von Willebrand Factor
PubMed: 23238591
DOI: 10.1160/TH12-06-0447