[Consensus on the clinical diagnosis, treatment and prevention of cancer treatment-induced thrombocytopenia in China (2023 edition)].

Cancer treatment-induced thrombocytopenia (CTIT) is a common adverse event during anti-tumor treatment, of which incidence is related to tumor classification, regimens, course of chemotherapy, etc. CTIT may result in a series of events including bleeding, dose intensity reduction, chemotherapy delay, and in severe cases, even the need for platelet transfusion, ultimately affecting the implementation of treatment plan, increasing the cost of treatment, reducing treatment effect and quality of life, and leading to a poor prognosis. The treatment of CTIT should first identify the cause, assess the risk of bleeding, and then adopt treatment strategies according to the cause and severity of CTIT. The main treatments of CTIT include platelet transfusion, application of various types of platelet-producing drugs, and measures to reduce the additional loss of platelets. Among them, platelet-producing drugs mainly refer to platelet-stimulating factors, including recombinant human thrombopoietin (rhTPO), recombinant human interleukin 11(rhIL-11), and thrombopoietin receptor agonists (TPO-RAs). In addition, traditional Chinese medicine also has some assistance in raising platelets. Pharmacological prophylaxis in high-risk patients may help reduce the incidence and severity of CTIT. This consensus aims to support Chinese oncologists in the diagnosis and treatment of CTIT in China, reduce the risk of bleeding and improve the quality of life of patients.

[Analysis of immune inflammation-related proteins in serum of patients with rheumatoid arthritis and the regulatory effect of Xinfeng Capsule on cytokines].

Objective To screen and verify the expression profile of immune inflammatory key proteins in patients with rheumatoid arthritis (RA), and to explore the intervention effect of Xinfeng Capsule (XFC) on it. Methods The differential expressions of key proteins in serum of RA patients and healthy controls were screened by the RayBiotech antibody microarray. The correlation between differential proteins and laboratory indexes [rheumatoid factor (RF), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and anti-cyclic citrullinated peptide (ACCP) antibody] was analyzed by Pearson correlation. Eighty RA patients were randomly divided into XFC group and leflunomide (LEF) group, 40 cases in each group. After 4 weeks of treatment, the clinical efficacy, laboratory indexes, self-perception of patient [Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), short form health survey questionnaire (SF-36)] and the changes of differential proteins were observed. Results Compared with healthy controls, in the RA group there were 24 up-regulated proteins and 9 down-regulated proteins, and IL-2, IL-5, IL-11, IL-17, tumor necrosis factor-ß (TNF-ß), and cytotoxic T lymphocyte-associated protein 4 (CTLA4) expressions were up-regulated, while IL-8, programmed death 1-ligand 2 (PD-L2) and macrophage surface marker CD86 expressions were down-regulated, among which IL-11, IL-17, and PD-L2 were with the most significant difference expressed. IL-11 was positively correlated with hs-CRP (r=0.2412) and ESR (r=0.3799), and IL-17 was positively correlated with hs-CRP (r=0.4667). After treatment, the apparent efficiency of XFC group [62.50% (25/40)] was significantly higher than that of LEF group [25.0% (10/40)]; SAS and SDS were decreased, while PF, VT, and SF were significantly increased in both groups, but there was no significant difference between the two; hs-CRP, ESR, RF, and anti-CCP were significantly decreased in both groups with the XFC group being significantly better in reducing hs-CRP, ESR, and RF compared with the LEF group; IL-11 and IL-17 were significantly decreased, while PD-L2 was significantly increased in both groups with the XFC group being significantly better in reducing IL-11, IL-17, and raising PD-L2 compared with the LEF group. Conclusion In serum of RA patients the expressions of IL-11 and IL-17 are significantly increased, and the expression of PD-L2 is significantly decreased. Patients' health improves with the XFC redressing the imbalance of the expressions of IL-11, IL-17, and PD-L2.

[Therapeutic Efficacy of Multigly-Cosidorum Tripterygium Combined with rhIL-11 for Immune Thrombocytopenia].

OBJECTIVE: To study the therapeutic efficacy of multigly-cosidorum Tripterygium combined with rhIL-11 for treating patients with immune thrombocytopenia (ITP). METHODS: A total of 75 patients with ITP were divided into 2 group: experimental group and control group. The experimental group included 40 patients who had been treated with multigly-cosidorum Tripterygium combined with rhIL-11. Multigly-cosidorum Tripterygium was given at a dose of 1mg/kg·d for 2 months and rhIL-11 was injected at a dose of 16,000,000 units per day. Control group included 35 patients who had been treated with prednisone at a dose of 1 mg/kg·d. Platelet counts were performed every day before platelet counts >30 × 109/L. Peripheral blood T cells were collected before and after treated for 2 months. The ratios of CD4⁺, CD8⁺ T cells in peripheral blood T cells were analyzed by flow cytometry. RESULTS: Totally effective rate in experimental group was 77.5%. Totally effective rate in control group was 82.9%. Totally effective rate showed no statistical difference between these two groups (P > 0.05). The average time of platelet count 30 × 109/L in experimental and control groups were 13.06 ± 6.10 days and 9.76 ± 5.71 days respectively; in experimental group, the ratio of CD4⁺ T cells in peripheral blood was 21.03% before treatment, then rised to 34.49% after treatment for 2 months (P < 0.01); The ratio of CD8⁺ T cells in peripheral blood was 26.35% before treatment, then decreased to 20.18% (P < 0.01). In control group, the ratio of CD4⁺ T cells was 22.30% before treatment, then rised to 25.11% after treatment for 2 months (P < 0.05); The ratio of CD8⁺ T cells in peripheral blood was 27.24% before treatment, then decreased to 21.35% (P < 0.01). CONCLUSION: Multigly-cosidorum tripterygium can correct disorder of T lymphocytes, the combination of multigly-cosidorum triptergium and rhIL-11 can accelerate therapeutic efficacy for treating ITP and with less adverse reaction, so this combination may be effective and safe for treating patients with ITP.

Comparative response of plasma VWF in dogs to up-regulation of VWF mRNA by interleukin-11 versus Weibel-Palade body release by desmopressin (DDAVP).

Recombinant human interleukin-11 (rhIL-11), a glycoprotein 130 (gp130)-signaling cytokine approved for treatment of thrombocytopenia, also raises von Willebrand factor (VWF) and factor VIII (FVIII) by an unknown mechanism. Desmopressin (1-deamino-8-d-arginine vasopressin [DDAVP]) releases stored VWF and FVIII and is used for treatment of VWF and FVIII deficiencies. To compare the effect of these 2 agents, heterozygous von Willebrand disease (VWD) and normal dogs were treated with either rhIL-11 (50 microg/kg/d subcutaneously x 7 days) or DDAVP (5 microg/kg/d intravenously x 7 days). The rhIL-11 produced a gradual and sustained elevation of VWF and FVIII levels in both heterozygous VWD and normal dogs while DDAVP produced a rapid and unsustained increase. Importantly, rhIL-11 treatment produced a 2.5- to 11-fold increase in VWF mRNA in normal canine heart, aorta, and spleen but not in homozygous VWD dogs, thus identifying a mechanism for elevation of plasma VWF in vivo. Moreover, dogs pretreated with rhIL-11 retain a DDAVP-releasable pool of VWF and FVIII, suggesting that rhIL-11 does not significantly alter trafficking of these proteins to or from storage pools. The half-life of infused VWF is unchanged by rhIL-11 in homozygous VWD dogs. These results show that rhIL-11 and DDAVP raise plasma VWF by different mechanisms. Treatment with rhIL-11 with or without DDAVP may provide an alternative to plasma-derived products for some VWD and hemophilia A patients if it is shown safe in clinical trials.

Treatment of lupus-induced thrombocytopenia with recombinant human interleukin-11.

Autoimmune thrombocytopenia can be a serious manifestation of systemic lupus erythematosus (SLE) which necessitates treatment with immunosuppressive agents and platelet transfusions. Interleukin-11 (IL-11) is a unique thrombopoietic growth factor which causes proliferation of megakaryocyte progenitors as well as induces megakaryocytic maturation. To our knowledge, this agent has not been used in the treatment of autoimmune thrombocytopenia, since theoretically there is a danger of IL-11 stimulating the immune system by up-regulating the lymphoid stem cells. We describe a 36-year-old splenectomized woman with known SLE who presented with pulmonary hemorrhage, acute renal failure, change in mental status, and severe thrombocytopenia (platelet count 2,000/mm3). Her pulmonary, renal, and central nervous system complications responded to intensive therapy with intravenous (IV) pulse methylprednisone and cyclophosphamide along with hemodialysis. The thrombocytopenia remained refractory to the above treatment plus daily multiple platelet transfusions and IV immunoglobulin. Treatment with recombinant human IL-11 (25 microg/kg/day subcutaneously) was initiated and continued for 5 days. Her platelet count improved to 25,000/mm3 within 48 hours, and she experienced no adverse effects.

Use of thrombopoietic growth factors in acute leukemia.

Several hematopoietic growth factors have been shown to affect megakaryocyte development, and two, interleukin (IL)-11 and thrombopoietin (TPO) are presently being evaluated for use in patients with thrombocytopenia. In two studies patients who required one or more platelet transfusions during their first course of chemotherapy were found to require fewer platelet transfusions if their second cycle was augmented with IL-11. The drug was generally safe, with cardiovascular compromise the only significant complication occurring in a minority of patients. Although these reports included patients with various malignancies, studies of IL-11 in patients with myeloproliferative disorders have not been presented. In several clinical trials in cancer patients treatment with TPO was safe, and when administered early following a moderately aggressive cytotoxic insult was effective in accelerating platelet recovery. In addition, in both pre-clinical and clinical trials, TPO given to stem cell donors during mobilization lead to accelerated hematopoietic recovery. Finally, TPO appears safe when administered to patients with acute myelogenous leukemia (AML), both with respect to acute toxicity and long-term outcome of the leukemia. However, when used following a 7-day course of standard chemotherapy, the agent does not appear to accelerate platelet recovery. As such, additional clinical trials to test different growth factor regimens are ongoing. A number of studies have suggested that megakaryocytic growth factors may play a role in the biology of myeloproliferative disorders. Given the potential for adversely affecting patients with these disorders, the affects of IL-11 or TPO in patients with AML must continue to be carefully studied.

Recombinant human interleukin-11 in experimental Pseudomonas aeruginosa sepsis in immunocompromised animals.

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.

Trophic effects of interleukin-11 in rats with experimental short bowel syndrome.

Interleukin-11 (IL-11) is a multifunctional cytokine, derived from bone marrow stromal cells, that stimulates proliferation of stem/progenitor precursor cells in the small intestinal crypts and accelerates recovery of intestinal mucosa after cytoablative therapy. This study evaluates whether IL-11 can improve the function and structure of the small intestine and enhance adaptation in an experimental model of short bowel syndrome. After 90% small bowel resection, 32 Sprague-Dawley rats were divided randomly into eight experimental groups of four animals each. Four groups were treated with IL-11 (125 micrograms/kg twice daily, subcutaneously), and the four control groups were treated with a similar volume (0.1%) of bovine serum albumin (BSA). The animals were weighed daily and were killed on day 2, 4, 6, or 8; remnant small bowel was evaluated for villus height and crypt cell mitosis. The body weight of the animals that received IL-11 was significantly greater at the beginning of postoperative day 4 in comparison to that of the BSA groups (P < .01 during days 5 to 7). The rats that had IL-11 also had significantly greater villus height and crypt cell mitotic rates (P < .05). These observations suggest that IL-11 has a trophic effect on the small bowel during the adaptive phase that follows massive bowel resection and may be useful in the treatment of short bowel syndrome.

The biology of interleukin 11.

Interleukin 11 (IL-11) is a multifunctional cytokine which may play a role in regulating the growth and development of cells in both the hematopoietic and lymphoid systems. IL-11 activity was originally detected in the conditioned medium of a primate bone marrow stromal cell line, and the human cDNA was cloned from a human fetal lung fibroblast cell line. The purified protein shows multifunctional activity, influencing lymphohematopoietic stem cell proliferation and differentiation, megakaryocyte progenitor cell proliferation and differentiation, erythroid progenitor cell proliferation, B lymphocyte maturation, activation of hepatocyte acute phase protein synthesis, and adipogenesis. At the molecular level, IL-11 is unique, containing no asparagine-linked glycosylation sites and no cysteine residues. The IL-11 receptor belongs to a family of cytokine receptors which includes the receptors for IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF), which are all capable of interacting with the signal transducing receptor gp130 after ligand binding. IL-11 has demonstrated activity in preclinical models for the treatment of thrombocytopenia and, in some cases, neutropenia; studies are underway to confirm its usefulness in the clinic for treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.