Traditional Chinese medicine for treating aplastic anemia.

Aplastic anemia (AA) is a bone marrow failure disease caused by T cell hyperfunction. Although the overall response rate has been improved by immunosuppressive therapy (IST) plus Eltrombopag, 30% of patients have either no response or relapse. We therefore attempted to find other ways to improve the outcomes of AA patients. Traditional Chinese medicine has the advantages of low cost, reasonable effects, and few side effects. More and more clinical studies have confirmed that traditional Chinese medicine has a beneficial role in treating AA patients. This article reviews the potential mechanism of traditional Chinese medicine or its active ingredients in the treatment of AA. These include improving the bone marrow microenvironment, regulating immunity, and affecting the fate of hematopoietic stem cells. This provides useful information for further treatment of AA with integration of traditional Chinese and Western medicine and the development of new treatment strategies.

Network pharmacology and experimental verification of the potential mechanism of Er-Xian decoction in aplastic anemia.

To investigate the potential mechanism of Er-Xian decoction (EXD) in treating aplastic anemia (AA), the active components of EXD were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the targets of the components were predicted by the Swiss Target Prediction database. AA targets were collected from the GeneCards, OMIM, DisGeNET, PharmGKB, DrugBank, and TTD databases, the intersection of AA targets and EXD targets was calculated, and an herb-component-target network was constructed by Cytoscape 3.7.2 software. The STRING database was used for protein‒protein interaction (PPI) analysis, and Cytoscape 3.7.2 software was used to construct a PPI network and perform topology analysis. The core targets were imported into the DAVID database for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The molecular docking software AutoDock was used to measure the affinity between active components and key targets. Finally, we established a mouse model of AA and verified the key targets and signaling pathways of EXD by RT‒PCR, ELISA and Western blot analysis. A total of 53 active components were screened from EXD, 2516 AA-related targets were collected, and 195 common targets were obtained. An herb-component-target network and a PPI network were successfully constructed, and 36 core targets were selected from the PPI network. The main active components of EXD include luteolin, kaempferol, berberine, etc., and key targets include PIK3CA, AKT1, STAT3, etc. GO functional enrichment analysis showed that cell components, molecular functions and biological processes with significant correlations were macromolecular complexes, protein serine/threonine/tyrosine kinase activity and protein phosphorylation, respectively. KEGG pathway analysis showed that the pathways with significant correlations included the PI3K-Akt signaling pathway and JAK-STAT signaling pathway. Molecular docking results showed that the tested key targets had good affinity for the corresponding active components. In AA mice, we found that EXD significantly increased white blood cell count, red blood cell count, platelet count and hemoglobin levels, increased mRNA levels of PIK3CA, PIK3CD, AKT1, JAK2, STAT3 and MAPK1, and promoted phosphorylation of PI3K, AKT, ERK1/2 and STAT3. In summary, EXD acts on PI3K, AKT, STAT3 and other targets through berberine, luteolin, quercetin and other components to regulate the PI3K-Akt pathway, JAK-STAT pathway and other pathways, thus exerting its therapeutic effect on AA. This study explained the Chinese medicine theory of treating AA with EXD by tonifying kidney-yang and provides a scientific basis for the use of EXD in treating AA.

Clinical study on combined "lanzhou prescription" for the treatment of "syndrome of heat-toxin congestion and excessiveness" in children with acute aplastic anemias.

Purpose: The clinical efficacy of "Lanzhou prescription" plus or minus combined with western medicine in the treatment of children with acute aplastic anemia, 'excessive accumulation of heat toxin', was comprehensively and objectively evaluated. Methods: Sixty children diagnosed with acute aplastic anemia, 'excessive accumulation of heat toxin' were divided into observation group (lanzhou prescription plus or minus combined with immunosuppressive therapy) and control group (immunosuppressive therapy alone). The relief degree of clinical symptoms and signs and the change of laboratory indicators were taken as the evaluation criteria. Results: (1) After treatment, the results of remission rate of two groups treated by western medicine shows that the remission rate of the observation group was significantly higher than the control group (P< 0.05). (2) the 'cure rate' of the observation group treated for 6 months was significantly higher than treated for 3 months (P<0.05). (3) After treated for 6 months, the indexes of CD34+ cells and FOXP3+ regulatory cells in bone marrow of observation group increased, while the CD8+ cells and B cells decreased significantly, and the indexes of CD3+ cells, CD4+ cells and NK cells decreased somewhat(P<0.05). Conclusion: Compared with immunosuppressive therapy, lanzhou prescription plus or minus combined with immunosuppressive therapy can alleviate the clinical symptoms and signs of children more effectively, obviously improve the Traditional Chinese Medicine symptoms of children, and help bone marrow hematopoietic stem cells gradually restore hematopoietic function.

Dose of deferasirox correlates with its effects, which differ between low-risk myelodysplastic syndrome and aplastic anaemia.

WHAT IS KNOWN AND OBJECTIVE: Patients with low-risk myelodysplastic syndrome (MDS) and aplastic anaemia (AA) often need transfusions, which may accelerate iron overload. The aim of this study was to evaluate the efficacy, safety and dose-effect relationships of deferasirox (DFX) in patients with low-risk MDS and AA who were refractory to regular treatment in a real-world setting. METHODS: Patient data were recorded, and dose-effect relationships of DFX were calculated after the first 6 months. Total annual exposure to DFX was calculated after 12 months and expressed as the accumulated exposure time at a dosage of 20 mg/kg/day. RESULTS AND DISCUSSION: Sixty-one patients with low-risk MDS and 51 with AA were enrolled. The minimum dosage of DFX needed for a significant serum ferritin (SF) decrease was 20 mg/kg/day at 6 months, and the minimum accumulation of DFX had to reach 9 months at 20 mg/kg/day by 12 months for patients with low-risk MDS. For patients with AA, the minimum dosage was 10 mg/kg/day at 6 months, and the minimum accumulation had to reach 3 months at 20 mg/kg/day by 12 months. With the same exposure, significant improvements in haematological parameters were also observed in AA. Lower liver enzymes compared with baseline were observed. Gastrointestinal disorders and elevated serum creatinine were the most common side effects. Higher exposure to DFX correlated with longer overall survival (OS). WHAT IS NEW AND CONCLUSION: A significant decrease in SF and an improvement in haematologic parameters, organ function and even OS can be achieved if the accumulated DFX dose reaches a certain level. Patients with low-risk MDS need a higher dose than those with AA.

Integrated Network Pharmacology and Metabolomics Analysis to Reveal the Potential Mechanism of Siwu Paste on Aplastic Anemia Induced by Chemotherapy Drugs.

Purpose: This study aimed to reveal the multicomponent synergy mechanisms of SWP based on network pharmacology and metabolomics for exploring the relationships of active ingredients, biological targets, and crucial metabolic pathways. Materials: Network pharmacology, including TRRUST, GO, and KEGG, enrichment was used to discover the active ingredients and potential regulation mechanisms of SWP. LC-MS and multivariate data analysis method were further applied to analyze serum metabolomics profiling for discovering the potential metabolic mechanisms of SWP on AA induced by Cyclophosphamide (CTX) and 1-Acetyl-2-phenylhydrazine (APH). Results: A total of 27 important bioactive ingredients meeting the ADME (absorption, distribution, metabolism, and excretion) screening criteria from SWP were selected. Interaction networks were constructed and validated based on the 10 associated ingredients with the relevant targets. A total of 125 biomarkers were found by Metabolomics approach, which associated with the development of AA, mainly involved in amino acid metabolism and lipid metabolism. While SWP can reverse the above 12 metabolites changed by AA. Network analysis revealed the synergistic effects of SWP through the 43 crucial pathways, including Sphingolipid signaling pathway, Sphingolipid metabolism, Arginine and proline metabolism, VEGF signaling pathway, Estrogen signaling pathway. Conclusion: The study suggested that SWP is a useful alternative for the treatment of AA induced by CTX + APH. Its potential mechanisms are to improve hematopoietic microenvironment and promote bone marrow hematopoiesis therapies.

Effects of Sodium Chlorophyllin Copper on APO-1 Expression in Bone Marrow Mesenchymal Stem Cells of Rats with Aplastic Anaemia.

Background: Aplastic anaemia (AA) is a highly prevalent blood disorder in the East and Southeast Asian countries, and a proportion of the patients is poorly treated with immunosuppressive agents. This study is aimed at exploring the effects of sodium copper chlorophyllin (SCC) on rats with AA and at providing the theoretical basis for the treatment of AA using traditional Chinese medicine. Methods: A rat model of AA was induced by combining 5-fluorouracil with busulfan, and different groups were treated with 25 mg/kg cyclosporin A (CsA) and low-, medium-, and high-dose SCC (25-, 50-, and 100-mg/kg; L-, M-, and H-SCC, respectively). A comparative analysis of peripheral blood counts, T-cell subsets, cytokine levels, bone marrow pathology, and APO-1 expression in mesenchymal stem cells in each group was conducted. Results: SCC can increase the platelet count and haemoglobin concentration in the peripheral blood of AA rats, whereas bone marrow biopsies revealed that the number of nucleated cells and megakaryocytes of SCC-treated rats increased compared with the model group. This was particularly evident in the H-SCC group. As regards the correction of immune function, unlike CsA, which reduced the absolute CD8+ T-cell count, SCC corrected the imbalanced CD4/CD8 ratio by increasing the absolute CD4+ T-cell count, whereas SCC increased the number of regulatory T-cells and reduced the level of interferon-γ in AA rats. When comparing the expression of APO-1 in the MSCs, results of the reverse-transcriptase polymerase chain reaction and Western blot analysis showed that SCC can increase the expression of APO-1 both at the mRNA and protein levels. Conclusion: We found that SCC can improve haematopoietic function and regress immune disorders in AA rats, which enhanced the expression of APO-1 in bone marrow MSCs. This may be one of the mechanisms of SCC in treating AA.

Long-term eltrombopag for bone marrow failure depletes iron.

Eltrombopag (EPAG) has been approved for the treatment of aplastic anemia and for immune thrombocytopenia, and a subset of patients require long-term therapy. Due to polyvalent cation chelation, prolonged therapy leads to previously underappreciated iron depletion. We conducted a retrospective review of patients treated at the NIH for aplastic anemia, myelodysplastic syndrome, and unilineage cytopenias, comparing those treated with EPAG to a historical cohort treated with immunosuppression without EPAG. We examined iron parameters, duration of therapy, response assessment, relapse rates, and common demographic parameters. We included 521 subjects treated with (n = 315) or without EPAG (n = 206) across 11 studies with multiyear follow-up (3.6 vs. 8.5 years, respectively). Duration of EPAG exposure correlated with ferritin reduction (p = 4 × 10-14 ) regardless of response, maximum dose, or degree of initial iron overload. Clearance followed first-order kinetics with faster clearance (half-life 15.3 months) compared with historical responders (47.5 months, p = 8 × 10-10 ). Risk of iron depletion was dependent upon baseline ferritin and duration of therapy. Baseline ferritin did not correlate with response of marrow failure to EPAG or to relapse risk, and timing of iron clearance did not correlate with disease response. In conclusion, EPAG efficiently chelates total body iron comparable to clinically available chelators. Prolonged use can deplete iron and ultimately lead to iron-deficiency anemia mimicking relapse, responsive to iron supplementation.

Effect of Wuzhi capsules on cyclosporine A concentration in children with aplastic anemia immunotherapy: a single-center observational study.

OBJECTIVE: This research aimed to assess the effect of Wuzhi capsules (WZC) on the blood concentration of cyclosporine A (CsA) in renal aplastic anemia recipients. METHODS: This observational study was carried out at the Hematology Oncology Center, Beijing Children's Hospital between November 2019 and February 2020. A total of 102 Chinese AA recipients receiving CsA (6 mg/kg/d) with or without WZC were included in this study. Baseline data, such as age, therapeutic drug monitoring data, and follow-up information were collected. The promotion concentration of CsA was calculated, and the pharmaceutical economics evaluation with combination of two drugs was also carried out. RESULTS: Dose- and body weight-adjusted trough concentrations (C0/D/W) of CsA in the WZC group were found to be significantly higher than that in the non-WZC group (P < 0.01). The average C0 of CsA increased by (63.27 ± 45.81) ng/mL. The incidence of adverse events was also not statistically significant between the two groups (P > 0.05). CONCLUSION: WZC can increase CsA concentration without increasing adverse drug reactions. Efficient and convenient immunosuppressive effects on AA recipients can be achieved via immunosuppressant therapy in combination with WZC.

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study.

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION: The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

Panaxdiol Saponins Component Promotes Hematopoiesis and Modulates T Lymphocyte Dysregulation in Aplastic Anemia Model Mice.

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C) in the treatment of aplastic anemia (AA) model mice. METHODS: Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C (20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine (40 mg/kg), and andriol (25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and FoxP3 proteins were detected by flow cytometry and Western blot. RESULTS: The peripheral blood of white blood cell (WBC), platelet, neutrophil counts and hemoglobin (Hb) concentration were significantly decreased in the model group compared with the normal group (all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group (all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers (all P<0.01). Furthermore, PDS-C therapy increased peripheral blood CD3+ and CD3+CD4+ cells and reduced CD3+CD8+ cells (P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium- and high doses groups also increased CD4+CD25+FoxP3+ cells, downregulated T-bet protein expression, and upregulated GATA-3 and FoxP3 protein expressions in spleen cells (P<0.05). CONCLUSION: PDS-C possesses dual activities, promoting proliferation hematopoietic progenitor cells and modulating T lymphocyte immune functions in the treatment of AA model mice.

Saponins from Panax notoginseng leaves improve the symptoms of aplastic anemia and aberrant immunity in mice.

Aplastic anemia (AA) is usually treated with immunosuppressive agents, but their efficacy and safety are not satisfactory. Panax notoginseng saponins (PNS) promote the proliferation of hematopoietic stem/progenitor cells. This study aimed to examine the effects of leaf PNS (LPNS) on hematopoiesis and T cells in mouse models of AA. The experiments were performed in normal mice and AA mice (controls, cyclosporine, and low, medium, and high doses of LPNS). Hematopoietic cells were counted using colony formation assays. The proportions of T cells were measured by flow cytometry. The ERK1/2, T-bet, GATA-3, FOXP3, and RORγ proteins were assessed by western blotting. Cytokines were measured using a cytometric bead array. AA mice showed impaired hematopoiesis, high activation of T cells, and decreased expression of T-bet, GATA-3, and FOXP3. LPNS attenuated the inflammation observed in AA mice, and significantly increased the number of hematopoietic progenitor cells. The proportions of Th2 and regulatory T cells and the protein levels of P-ERK1/2, GATA-3, and FOXP3 were increased in the AA + LPNS mice compared with the AA mice. In contrast, LPNS decreased the proportions of Th1 and Th17 cells and the protein expression of T-bet. LPNS and cyclosporine had similar effects, but of different amplitudes. These results suggest that LPNS have dual activities in AA: 1) promoting the proliferation of hematopoietic progenitor cells; and 2) modulating T cell immune functions, an activity similar to that of cyclosporine. Additional studies are necessary to confirm those results before clinical use.

The herbal decoction modified Danggui Buxue Tang attenuates immune-mediated bone marrow failure by regulating the differentiation of T lymphocytes in an immune-induced aplastic anemia mouse model.

Angelicae Sinensis, Radix Astragali and Rhizoma Coptidis are all herbs of modified Danggui Buxue Tang (DGBX) and are extensively applied herbs in traditional Chinese medicine for the treatment of anemia and inflammation. In this study, immune-induced AA mice were used as an animal model, and the immunosuppressive agent, Ciclosporin A (CsA), was used as a positive control. Multiple pro-inflammatory cytokines were examined by bead-based multiplex flow cytometry. The T-cell subsets were assessed using a fluorescence-activated cell sorter (FACS). Western blot analysis was used to estimate the protein expression levels of specific transcription factors for T helper cells (Th1, Th2 and Th17) and key molecules of the Janus-activated kinase (Jak)/signal transducer and activator of transcription (Stat3) signaling pathway. DGBX treatment could significantly increase the production of whole blood cells in peripheral blood (PB); inhibit the expansion of Th1 and Th17 cells; increase the differentiation of Th2 and Tregs cells; regulate the expression levels of T-bet, GATA-3, RORγ and proinflammatory cytokines; and decrease the expression levels of key molecules in the Jak/Stat signaling pathway. These results indicate that DGBX can regulate the differentiation of T lymphocytes, resulting in immunosuppressive and hematogenic functions on AA mice. DGBX might be a good candidate for inclusion in a randomized study for AA with more data on the possible side effects and doses used in humans. Ultimately, it may be used for applications of traditional medicine against AA in modern complementary and alternative immunosuppressive therapeutics.

Efficacy and advantages of modified Traditional Chinese Medicine treatments based on "kidney reinforcing" for chronic aplastic anemia: a randomized controlled clinical trial.

OBJECTIVE: To compare the efficacy of modified treatments based on "kidney reinforcing" in the management of chronic aplastic anemia (CAA), and explore their advantages and specialties. METHODS: One hundred and eleven patients with CAA were randomly divided into three groups: kidney reinforcing alone (KA), "kidney reinforcing and Qi tonifying" (KQ), and "kidney reinforcing and blood circulation invigorating" (KC). Normal and positive control groups were also formed. All patients were treated for 6 months (two courses). Hemograms, Traditional Chinese Medicine (TCM) syndrome scores, and therapeutic effects were assessed, and changes in T-lymphocyte subsets, regulatory T cells and cytokines were detected. RESULTS: The KQ and KC groups had lower TCM syndrome scores than the positive control group after 6 months (P < 0.05). The KQ group had a higher overall efficacy than the positive control group after 3 months (P < 0.05), while platelet counts increased in the KC group after 6 months (P < 0.05). CD3+ T-lymphocyte ratios decreased only in the KQ group, while CD3 + CD4 + CD8 − Tlymphocytes increased only in the KC group after 6 months (P < 0.05). Levels of interferon-γ, tumor necrosis factor tor-α, interleukin (IL)-2 and IL-6 decreased and levels of IL-4 and IL-10 increased in all treated groups after 6 months. Levels of IL-6 in the KQ and KC groups were lower than those in the positive control group (P < 0.05). CONCLUSION: Treatments based on kidney reinforcing have a rebalancing effect on cytotoxic and T helper cells, and regulate expression of interferon- γ, IL-2, IL-6 and IL-4. KQ may be more effective in treating CAA, and KC may have an advantage in platelet recovery.

Clinical study of pai-neng-da capsule in the treatment of chronic aplastic anemia.

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (panaxadiol saponins component, PND), a new Chinese patent medicine, on patients with chronic aplastic anemia (CAA) and to explore the optimal therapeutic regimen for CAA. METHOD: A total of 36 patients with CAA were enrolled and divided into three groups: the AP group (20 cases, andriol 120 mg/day + PND 240 mg/day), the ACP group (13 cases, andriol 120 mg/day + cyclosporine 3-6 mg kd(-1) day(-1) + PND 240 mg/day), and the PND group (3 cases, PND 240 mg/day). All patients were treated and followed up for 6 months. Peripheral blood counts, renal and hepatic function and Chinese medical (CM) symptoms of patients were assessed and all indices were gathered at the beginning and end of the study. RESULT: In the AP group, no significant hematologic difference was observed at the end of 6-month treatment comparing with the beginning. In the ACP group, the blood counts were maintained at the same level after the 6-month treatment. In the PND group, trilineage hematologic improvement was displayed at the end of 6-month treatment comparing with the beginning. No significant difference was showed in renal and hepatic function in all patients. All patients' clinical symptom improved according to CM symptom score. The effective rates were 95%, 73% and 100%, respectively. CONCLUSION: PND improved the efficacy and decreased side effects by cutting down the dosage of andriol, and it could also improve patients' clinical symptom and quality of life. PND were effective and safe in the treatment of CAA, it could be used alone or in combination with pharmacological agents such as andriol and cyclosporine.

Eltrombopag interference in routine chemistry testing.

BACKGROUND: High doses of Eltrombopag have been previously reported to cause bilirubin interference. Following receipt of a sample from a patient receiving high-dose Eltrombopag therapy, the laboratory decided to investigate the effect of this drug on routine chemistry testing. METHODS: Interference studies were performed by spiking Eltrombopag into aliquots of a serum pool to give concentrations ranging from 0 to 500 µg/mL. The following analytes, namely albumin, alkaline phosphatase, alanine transaminase, aspartate transaminase, Urea, total calcium, cholesterol, triglycerides, glucose, high-density lipoprotein cholesterol, iron, magnesium, inorganic phosphate, creatinine, bicarbonate, transferrin, ferritin, electrolytes, total and direct bilirubin and serum indices (hemolysis, icterus and lipaemia) were then measured on the Roche Cobas 6000 chemistry analyzer (Roche, Indianapolis, USA). RESULTS: Eltrombopag interference (>10% change of the baseline value) was observed for total cholesterol, triglycerides, inorganic phosphate and high-density lipoprotein cholesterol. Clinical significant interference was observed for total cholesterol, inorganic phosphate and high-density lipoprotein cholesterol CONCLUSIONS: Presence of high Eltrombopag concentrations in blood samples has been demonstrated to cause interference in the measurement of certain spectrophotometric-based assays on the Roche Cobas 6000 analyzer.

Deferasirox Decreases Liver Iron Concentration in Iron-Overloaded Patients with Myelodysplastic Syndromes, Aplastic Anemia and Other Rare Anemias.

Iron overload in transfusion-dependent patients with rare anemias can be managed with chelation therapy. This study evaluated deferasirox efficacy and safety in patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemias. A 1-year, open-label, multicenter, single-arm, phase II trial was performed with deferasirox (10­40 mg/kg/day, based on transfusion frequency and therapeutic goals), including an optional 1-year extension. The primary end point was a change in liver iron concentration (LIC) after 1 year. Secondary end points included changes in efficacy and safety parameters (including ophthalmologic assessments) overall as well as in a Japanese subpopulation. Overall, 102 patients (42 with MDS, 29 with AA and 31 with other rare anemias) were enrolled; 57 continued into the extension. Mean absolute change in LIC was ­10.9 mg Fe/g dry weight (d.w.) after 1 year (baseline: 24.5 mg Fe/g d.w.) and ­13.5 mg Fe/g d.w. after 2 years. The most common drug-related adverse event was increased serum creatinine (23.5%), predominantly in MDS patients. Four patients had suspected drug-related ophthalmologic abnormalities. Outcomes in Japanese patients were generally consistent with the overall population. Results confirm deferasirox efficacy in patients with rare anemias, including a Japanese subpopulation. The safety profile was consistent with previous studies and ophthalmologic parameters generally agreed with baseline values (EUDRACT 2006-003337-32).

Effects of the total saponins from Dioscorea nipponica on immunoregulation in aplastic anemia mice.

Dioscorea nipponica Makino, a popular folk medicine, exerts anti-inflammation properties. The present study investigated the therapeutic effect of the total saponins from Dioscorea nipponica Makino (TSDN) on aplastic anemia (AA) and possible immune regulation mechanisms. Using a mouse model of AA, three different doses of TSDN were orally administrated for 14 consecutive days. We first demonstrated that TSDN was found to be effective in alleviating pancytopenia with a hypocellular bone marrow as compared with AA model group. Moreover, gastrogavage administration of a medium dose of TSDN was found to dramatically increase the percentage of CD4(+) cells in bone marrow nucleated cells (BMNC) and restore the CD4(+)/CD8(+) ratio. The pro-inflammatory cytokine concentrations of IL-2 and IFN-γ were significantly decreased, and anti-inflammatory cytokine IL-4 was significantly increased in culture supernatant of BMNC. Further investigations showed that TSDN obviously inhibited Fas-FasL-induced BMNC apoptosis as well as effectively suppressed intracellular apoptosis protein of caspase-3 and -8 expressions. Taken together, these findings suggested that TSDN could alleviate AA by elevating the CD4(+)/CD8(+) T-cell ratio, inhibiting inflammatory Th1-cytokines, and exerting anti-apoptosis effects.

Use of Chamomilla recutita in the Prevention and Treatment of Oral Mucositis in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Randomized, Controlled, Phase II Clinical Trial.

BACKGROUND: Oral mucositis is a common inflammatory complication among patients undergoing hematopoietic stem cell transplantation (HSCT). Among its therapeutic properties, Chamomilla recutita has anti-inflammatory effects. OBJECTIVE: The aim of this study was to identify the dosage of the liquid extract of C recutita in mouthwash that is needed to reduce the incidence and intensity of oral mucositis in adult patients undergoing allogenic HSCT. METHODS: In a randomized phase II clinical trial, 40 patients were randomized to receive routine care plus mouthwash containing a liquid extract of C recutita at 0.5%, 1%, or 2% (experimental groups) or standard care alone (control group). Daily evaluation was performed using the measurement scale for oral toxicity defined by the World Health Organization. Statistical analysis was performed, in which the incidence, intensity, and duration of oral mucositis were compared between each experimental group and the control group. RESULTS: The experimental group at the 1% dosage demonstrated reduced incidence, intensity, and duration of oral mucositis compared with the control group. The formulation was well tolerated by patients and was safe, as no moderate or severe adverse effects were identified. CONCLUSIONS: In this study, the use of mouthwash containing 1% C recutita extract can be associated with reduced incidence, intensity, and duration of mucositis in adults patients undergoing allogenic HSCT. IMPLICATIONS FOR PRACTICE: The results of this investigation will help nurses and other professionals in selecting the C recutita dosage used to manage oral mucositis in patients undergoing HSCT.