[The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia].

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) µg/L, and 54% (14/26) of these patients had SF levels of ≥100 µg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) µg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 µg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

[Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy].

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).

[Characteristics of bone marrow compensatory erythropoiesis in hereditary spherocytosis].

Objective: To reveal the compensatory features of bone marrow (BM) erythropoiesis in hereditary spherocytosis (HS) and to explore the effect of diferent hemoglobin levels on this compensation. Methods: Clinical and laboratory data of patients with HS were collected, and the peripheral blood absolute reticulocytes counts value was taken as the surrogate parameter to evaluate the ability of erythropoiesis compensation. BM erythropoiesis compensation in HS with diferent degrees of anemia were evaluated. Results: ①Three hundred and two patients were enrolled, including 115 with compensated hemolytic disease, 74 with mild anemia, 90 with moderate anemia, and 23 with severe anemia. ②Hemoglobin (HGB) was negatively correlated with serum erythropoietin in the decompensated hemolytic anemia group (EPO; rs=-0.585, P<0.001) . ③The median absolute reticulocyte count (ARC) of HS patients was 0.34 (0.27, 0.44) ×10(12)/L, up to 4.25 times that of normal people. The maximum ARC was 0.81×10(12)/L, about 10 times that of normal people. The median ARC of patients with compensated hemolytic disease was 0.29 (0.22, 0.38) ×10(12)/L, up to 3.63 times that of normal people. The median ARC of patients with hemolytic anemia was 0.38 (0.30, 0.46) ×10(12)/L, which was significantly higher than the patients with compensated hemolytic disease, up to 4.75 times that of normal people (z=4.999, P=0.003) . ④ ARC was negatively correlated with HGB in the compensated hemolytic disease group (rs=-0.177, P=0.002) and positively correlated with HGB in the decompensated hemolytic anemia group (rs=0.191, P=0.009) . There was no significant difference in the ARC among patients with mild, moderate, and severe anemia (χ(2)=4.588, P=0.101) . ⑤The median immature reticulocyte production index of the mild, moderate, and severe anemia groups was 13.1% (9.1%, 18.4%) , 17.0% (13.4%, 20.8%) , and 17.8% (14.6%, 21.8%) , respectively; the mild anemia group had lower index values than the moderate and severe anemia groups (P(adj) values were both<0.05) , but there was no significant difference between the latter groups (P(adj)=1.000) . The median immature reticulocyte count of patients in the mild, moderate, and severe groups was 5.09 (2.60, 7.74) ×10(10)/L, 6.24 (4.34, 8.83) ×10(10)/L, and 7.00 (3.07, 8.22) ×10(10)/L, respectively; there was no significant difference among the groups (χ(2)=3.081, P=0.214) . Conclusion: HGB can be maintained at a normal level through bone marrow erythropoiesis, while red blood cells are reduced in HS. However, once anemia develops, the bone marrow exerts its maximum erythropoiesis capacity and does not increase, regardless of anemia aggravation or serum EPO increase.

[Effect of iron deficiency level on oral iron absorption].

Objective: To study the effect of iron deficiency level for oral iron absorption in iron deficient patients. Methods: 37 non-pregnant female patients who were diagnosed with iron deficiency and 13 healthy females who completed their physical examination at the outpatient department of the Anemia Center of the Institute of Hematology & Blood Diseases Hospital from July 2018 to June 2020 were included. Hepcidin and C2-C0 of oral iron absorption test were analyzed in different iron deficiency and serum ferritin level. Results: The median of Hepcidin in IDA, ID/IDE and healthy control group were 4.9 (2.17-32.86) , 26.98 (11.02-49.71) and 69.89 (42.23-138.96) µg/L (P<0.001) , respectively. Hepcidin level of IDA group was lower than that of ID/IDE group (adjusted P=0.005) and healthy control (adjusted P<0.001) . Hepcidin level of ID/IDE group had no significant difference compared with healthy control (adjusted P=0.22) . The mean of C2-C0 in IDA, ID/IDE and healthy control group were (35.30±21.68) , (37.90±14.06) and (23.57±10.14) µmol/L (P=0.130) , respectively. Multilinear regression analysis showed C0, SF, sTFR and HGB were independent factors for Hepcidin in iron deficient patients, with an equation of Hepcidin=-31.842-0.642*C0+2.239*SF+1.778*sTFR+0.365*HGB-0.274*RET-HB. We didn't find independent factor of C2-C0. Conclusion: The degree of iron deficiency had an effect on oral iron absorption. Patients of ID/IDE group absorbed iron more slowly than patients of IDA group. Iron deficient patients with normal gastrointestinal function absorbed more iron by oral administration when they were in a more serious iron deficient stage. Hepcidin was a better parameter to distinguish iron absorption level among different iron deficient patients than C2-C0 of oral iron absorption test.

[Expression of iron-regulating erythroid factors in different types of erythropoiesis disorders].

Objective: To investigate the expression of iron-regulating erythroid factors in different types of erythropoiesis disorders. Methods: From January 2016 to November 2019, the plasma concentrations of iron-regulating erythroid factors were measured by ELISA methods in 47 patients with different types of erythropoiesis disorders. The adaptation orientation of iron-regulating erythroid factor expression with bone marrow erythropoiesis activities (represented by bone marrow-nucleated erythrocytes ratio) was analyzed. Results: The median plasma growth differentiation factor (GDF) 15 levels in patients with polycythemia vera (PV) , pure red cell aplasia (PRCA) , autoimmune hemolytic anemia (AIHA) , and myelodysplastic syndrome (MDS) were 266.01 ng/L (112.40, 452.37) , 110.63 ng/L (81.41, 220.42) , 52.11 ng/L (32.61, 171.66) , and 276.53 (132.16, 525.70) ng/L, respectively, which were significantly higher than those in normal patients with 37.45 (19.65, 57.72) ng/L (all P < 0.01) . The plasma TWSG1 expression levels were not significantly different in patients with PV, PRCA, AIHA, and MDS from those of normal patients (P>0.05) . The median plasma GDF11 level in PV was 74.75 (10.95, 121.32) ng/L, which was significantly higher than 36.90 (3.38, 98.34) ng/L in normal control subjects (P<0.01) . However, no statistical differences were observed in the other three subjects (P>0.05) . The median plasma erythroferrone (ERFE) levels in AIHA and PV were 121.76 ng/L (68.12, 343.11) and 129.63 (47.02, 170.03) ng/L, respectively, with the highest level in AIHA in all the studied types of erythropoiesis disorders. The bone marrow-nucleated erythrocytes ratio was significantly and positively correlated with ERFE (r=0.458, P=0.001) but not with GDF15 (r=-0.163, P=0.274) , GDF11 (r=0.120, P=0.421) , and TWSG1 (r=-0.166, P=0.269) . Conclusion: The expression profile of iron-regulating erythroid factors is not exactly the same in different types of erythropoiesis disorders. ERFE demonstrated the highest correlation with erythropoiesis activities.

[Efficacy and safety of eltrombopag in aplastic anemia: A multi-center survey in China].

Objective: To evaluate the safety and efficacy of eltrombopag combined with immunosuppressive therapy in patients with aplastic anemia (AA) in China. Methods: We investigated and analyzed the clinical data of AA patients from 14 hematological treatment centers who were treated with oral eltrombopag for at least 3 mon. Results: We enrolled 56 AA patients, including 19 treatment-naïve patients and 37 IST-refractory patients. The median administration period for eltrombopag was 7 (3-31) months, and the median maximum stable dosage was 75 mg/d (50-150 mg/d) . The 3-month hematological response (HR) rate was 60%, and the complete response (CR) rate was 30% in 10 SAA patients who were treated with first-line eltrombopag and standard IST (ATG+CsA) . Eight of 9 eltrombopag and CsA ± androgen first-line treated SAA patients responded (8/9, 89%) and 4 (44%) gave CR. The overall HR and CR rates were 79% and 52.6%, respectively, among these 19 patients by the end of the follow-up period. Of the 19 AA patients who were refractory to CsA ± androgen, 11 achieved HR (57.9%) at 3 mon, and the best HR rate was 44% in standard IST (ATG+CsA) refractory 18 patients after eltrombopag treatment. Fifty-one percent of the patients experienced mild or moderate adverse events, and gastrointestinal discomfort was the most common adverse effect reported by the study subjects. Conclusion: Adding Eltrombopag in first-line IST can accelerate the acquisition and improve the quality of hematological responses in AA patients. AA with relatively more residual hematopoietic cells may be well treated with eltrombopag and non-ATG IST. Eltrombopag can be used as salvage therapy for CsA±androgen refractory patients. Eltrombopag was generally safe and well tolerated by AA patients in China.

[Evaluation of the efficacy and safety of iron therapy in patients with paroxysmal nocturnal hemoglobinuria complicated with iron deficiency anemia].

Objective: To evaluate the efficacy and safety of iron supplement in patients who have paroxysmal nocturnal hemoglobinuria (PNH) with iron deficiency. Methods: We performed analyses on the clinical data of 48 patients who accepted oral and/or intravenous iron treatment. Forty-eight consecutive PNH patients with iron deficiency who visited our hospital between November 2011 and August 2018 were enrolled in the study. Results: Total 30 patients received oral iron; 18 patients received intravenous iron supplements, including 6 who did not respond to oral iron. The median PNH clone size was 90.2% (38.5%-99.9%) in the granulocytes and 69.7% (27.6%-98.1%) in the red blood cells. The response rate was 56% (20/36) in patients who received oral iron, and the hemoglobin concentration increased 21 (10-52) g/L compared to that at baseline. Sixteen out of eighteen (89%) patients responded to intravenous iron; 6 patients who did not respond to oral iron received intravenous iron, and the hemoglobin level of 5 patients increased. Patients exhibited increased LDH levels and deepen urine after iron supplementation; however, no severe adverse events, such as thrombosis and iron-related adverse effects, were noted. Conclusion: Iron treatment is safe and effective in increasing the hemoglobin level in PNH patients with iron deficiency; those who did not respond to oral iron could benefit from intravenous iron supplement.

[Clinical and laboratory analysis of 17 patients with γδT-cell large granular lymphocyte leukemia].

Objective: To compare the difference of the clinical and laboratory characteristics between γδ T-cell large granular lymphocyte leukemia (γδT-LGLL) and αß T-cell large granular lymphocyte leukemia (αßT-LGLL) . Methods: The clinical and laboratory characteristics of 17 patients with γδT-LGLL and 91 patients with αßT-LGLL in the department of therapeutic center of anemia of enrolled in our hospital from January 2009 to January 2019 were retrospectively analyzed. Results: The median age of the 17 patients with γδT-LGLL was 54 years (range, 25-73 years) , the most common presenting symptom was anemia. In comparison with αßT-LGLL patients, splenomegaly was common (41% and 44%, respectively) , whereas hepatomegaly (12% and 5%, respectively) and lymphadenopathy (6% and 8%, respectively) were rare. The positive rates of antinuclear antibody (59% and 45%, respectively) were high, whereas the positive rates of rheumatoid factor (6% and 10%, respectively) were rare for both groups. There were no differences on peripheral blood counts between the two groups. However, γδT-LGLL patients were found to be predominantly expressed a CD4(-)/CD8(-) phenotype. Steroid therapy with prednisone was used alone as first-line therapy for 1 patient. Cyclosporin A (CsA) was used alone as first-line therapy for 3 patients. CsA in combination with steroids were administered in 13 patients. After 4 months treatment, 2 patients acquired complete response, 4 patients acquired partial response, the overall response was 35%. Conclusion: γδT-LGLL is a rare mature T-lymphocyte proliferative disease. Clinical and laboratory characteristics were quite similar for γδT-LGLL in compare with αßT-LGLL. γδT-LGLL predominantly expressed a CD4(-)/CD8(-) phenotype. The data presented here indicate the CsA is an effective option for the first-line treatment of γδT-LGLL.

[Red blood cell lifespan detected by endogenous carbon monoxide breath test in patients with polycythemia vera].

Objective: To detect the red blood cell lifespan in patients with polycythemia vera (PV), and explore the influencing factors. Methods: From February 2017 to December 2018, 27 patients with PV at Blood Diseases Hospital, Chinese Academy of Medical Science and 18 normal controls were recruited. Red blood cell lifespan was detected by endogenous carbon monoxide (CO) breath test. The related factors were analyzed. Results: The average red blood cell lifespan of 27 PV patients was 80 (range, 35-120) days (d), which was significantly shorter than that of the normal controls [110.5(69-166) d, P<0.05], namely 35.3 d shorter. The red blood cell lifespan of ten newly diagnosed patients and 17 patients who were treated with hydroxyurea and/or interferon were 98 (35-117) d and 69 (45-120) d, respectively, which were both shorter than that of the normal control (P=0.010, 0.000). Correlation analysis showed that red blood cell lifespan of patients with newly diagnosed PV was associated with JAK2 mutation allele burden (r=0.900, P=0.037), peripheral blood lymphocyte count (r=-0.742, P=0.014) and the level of serum vitamin B(12) (r=-0.821, P=0.023). Conclusion: The lifespan of red blood cells in patients with PV is about one-third shorter than normal, and is related to JAK2 mutation allele burden, absolute lymphocyte count, and serum vitamin B(12) level.

Tetramethylpyrazine supplementation reduced Salmonella Typhimurium load and inflammatory response in broilers.

The present study tested whether tetramethylpyrazine (TMP) supplementation could influence the growth performance, Salmonella Typhimurium (S. Typhimurium) load, inflammasomes, cytokines, and chemokines in broilers. Treatments were a 2 × 2 factorial design, including negative control (NC), S. Typhimurium challenge (SC), and NC/SC + TMP (150 mg/kg of diet). The trial lasted for 28 D, and S. Typhimurium subclinical challenge was occurred on day 8. The results showed that S. Typhimurium challenge worsened (P < 0.05) growth performance, S. Typhimurium load in intestinal digesta and visceral tissues, intestinal inflammatory responses, and permeability compared to the NC treatment. TMP supplementation increased (P < 0.05) feed intake, weight gain, and feed efficiency by 4.3 to 12.0%, but decreased (P < 0.05) S. Typhimurium load by 5.4 to 45.8%, inflammasomes (caspase-1/3/9, gasdermin A/E, and nod-like receptor protein 3) by 25.0 to 59.0%, chemokines (C-C motif ligand 2 and C-X-C motif 10) by 40.2 to 47.2%, intestinal permeability by 28.2% compared to the SC treatment. The TMP also reduced inflammatory response by influencing tumor necrosis factor α, interleukin 1ß/4/6. Factorial analysis indicated that TMP and SC were interactive (P < 0.05) on most parameters due to the more pronounced TMP effect in S. Typhimurium challenge groups. It is concluded that TMP can promote growth and mitigate S. Typhimurium infection by reducing the S. Typhimurium load and inflammatory response in broilers.

[Tolerance and pharmacodynamics phase â clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma].

Objective: To evaluate the tolerance and safety of a human-mouse chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients achieved objective response with CD20(+) B-cell non-Hodgkin's lymphoma (NHL). Methods: Nine patients with CD20(+) B-cell NHL received dose-escalating IBI301 infusions (250 mg/m(2), n=3; 375 mg/m(2), n=3; 500 mg/m(2), n=3, respectively). The data of all patients were collected for safety analyses. The median exposures of 125 mg/m(2), 375 mg/m(2), 500 mg/m(2) dose groups were 243, 690 and 980 mg, respectively. Safety and tolerability were evaluated by monitoring adverse events (AE). The ratios of CD19(+), CD20(+) B cells and the levels IgG and IgM were detected to evaluate the pharmacodynamics. Results: Totally 52 events of AE were observed, including 18 events of AE in 125 mg/m(2) group, 14 events of AE in 375 mg/m(2) group and 20 events of AE in 500 mg/m(2) group, respectively. There were 26 adverse reactions of 52 cases of AE, 22 reactions were judged to be probably related to IBI301, and 4 reactions were not probably related to IBI301, all disappeared or returned to baseline levels. Common AE in this study included decreased WBC, upper respiratory infection, decreased neutrophil count, dyspepsia, hyperuricemia, paresthesia, oral mucositis and dizziness. No patients quitted or trial discontinued. No severe AE (SAE) were reported. No dose-limiting toxicity (DLT) events were observed in the study. The ratio of CD20(+) and CD19(+) B cells decreased in all subjects. There was no significant changes of the levels of IgG and IgM. Conclusions: The single dose of IBI301 injection was well tolerated, and the AE occurred in the patients recovered. No SAE were reported, No DLT events were observed in the study. The IBI301 caused an elimination of the peripheral CD20-expressing B cells in all patients. Clinical trial registration: Chinadrugtrials, CTR20140762.

[Evaluation of efficacy of immunosuppressive therapy plus recombinant human thrombopoietin for children with severe aplastic anemia].

Objective: To evaluate the therapeutic efficacy and safety of immunosuppressive therapy (IST) combined with recombinant human thrombopoietin (rhTPO) for severe aplastic anemia (SAA) in pediatric patients. Method: A retrospective case-control study was conducted and the clinical data of 45 pediatric patients with de novo SAA admitted to the Anemia Diagnosis and Treatment Center of Chinese Academy of Medical Sciences & Blood Disease Hospital during the period from December 2009 to December 2014 were analyzed. Among them, 15 patients were treated with the regimen of IST together with rhTPO and 30 patients were given IST treatment only. The variation characteristics of the peripheral blood routine as well as the transfusion of blood products was dynamically observed, and the therapeutic efficacy was assessed respectively after 3, 6 and 12 months after the treatment. In the meantime, adverse effects related to rhTPO application were recorded. Thereafter, the statistics of the two groups were compared by non-parametric rank sum test. Result: Among 45 pediatric patients, there were 26 male and 19 female, and the median age was 11 years (6-14). The number of patients received good hematological response(complete remission (CR) plus good partial response (GPR)) in the combinatory group versus vs. the IST group was 6 vs. 3 patients (χ(2)=3.906, P=0.048) at the 3rd month, 7 vs. 7 patients (χ(2)=1.568, P=0.210) at the 6th month, and 13 vs. 14 patients (χ(2)=6.667, P=0.01) at the 12th month respectively. For those achieved good hematological response at the 3rd month, the amount of platelets transfusion and red blood cells transfusion of the combined group were both less than that of the IST group during the period from the 10th to the 12th weeks (platelets transfusion: 1.4 U vs. 2.9 U, t=-3.523, P=0.002; red blood cells transfusion: 0.8 U vs. 2.6 U, t=-2.392, P=0.026). No serious adverse effect related to rhTPO application was observed in the IST combined with rhTPO group. Conclusion: Application of rhTPO can improve the short-term therapeutic efficacy of IST for pediatric SAA, alleviate transfusion dependence, and has a good safety profile.

[Analysis of clinical efficacy of recombinant activated factor â ¦ on bleeding in patients with hematologic disorders].

Objective: To investigate the treatment efficacy of recombinant activated factor Ⅶ (rFⅦa) for bleeding among patients with hematologic disorders. Methods: A total of 38 times of bleeding in 31 patients with hematological disease treated with rFⅦa were analyzed retrospectively. Results: The clinical effective rate of rFⅦa for bleeding management in acquired hemophilia A (AHA) patients/hemophilia patients with inhibitor, acute promyelocytic leukemia (APL) patients and patients with non-APL leukemia was 90% (9/10) , 71.4% (5/7) and 60.0% (3/5) , respectively, which was higher than that in patients following HSCT (30.8%) . The clinical effective rate of rFⅦa for patients with bleeding score of 2 (100.0%) was higher than that with 3 (66.7%) and 4 (54.1%) . The effective rate of rFⅦa was 25.0% (2/5) in 5 patients with cerebral hemorrhage, 66.7% (6/9) in 9 patients with hematuria and 41.7% in 12 patients with gastrointestinal hemorrhage. The curative effect for 3 patients with joints and muscle bleeding and 5 patients with skin, nasal, pharyngeal and gum bleeding was excellent. Following HSCT, among patients with bleeding score of 4 points, high dose and repeated use of rFⅦa did not necessarily achieve a good effect. Among AHA/hemophilia patients with inhibitors and patients with acute leukemia who had bleeding score of 4 points, the use of low dose FⅦa could achieve good therapeutic effect, however the efficacy of lowest dose (22.5 µg/kg) rFⅦa was poor. Conclusions: The hemostasis efficacy of rFⅦa is affected by various factors such as diseases, bleeding sites, bleeding score and so on. The use of rFⅦa can achieve good efficacy for bleeding management in AHA patients/hemophilia patients with inhibitor, APL patients and patients with non-APL leukemia. However the efficacy of rFⅦa for bleeding of patients after HSCT is poor. Early use of rFⅦa is important for successful hemostatic treatment. Management of underlying condition is as important as hemostatic treatment.

[Comparison of efficacy and safety of two different dose of recombinant human thrombopoietin regimens in severe aplastic anemia patients with immunosuppressive therapy].

OBJECTIVE: To compare the short-term therapeutic effect of different regimens combining recombinant human thrombopoietin (rhTPO) with immunosuppressive therapy (IST) applied in severe aplastic anemia (SAA). METHODS: The clinical data of newly diagnosed adult SAA patients treated with first-line IST, including 18 patients with rhTPO daily and 43 patients with rhTPO every other day, was analyzed retrospectively. RESULTS: There was no significant difference between the basic clinical characteristics of the patients classified in different groups. The therapeutic effect was assessed 3 months and 6 months after IST. The statistical data revealed that the overall responses (OR) were not significantly different in daily group and every other day group (3 months: 50.0% vs 51.2%, P=0.934; 6 months: 77.8% vs 69.8%, P=0.525), while the good hematological response (CR+GPR) in SAA treated with rhTPO daily was significantly higher than that of patients treated with rhTPO every other day at 3 month after IST (38.9% vs 9.3%,P=0.011). RBC transfusion independence were not significantly different between the two groups after 4 weeks as well as 8 weeks treatment(4 weeks: 22.2% vs 18.6%,P=0.736; 8 weeks: 55.6% vs 46.5%,P=0.519), while platelet transfusion independence in rhTPO daily treated group was significantly higher than that in every other day group (88.9% vs 48.8%,P=0.003). In addition, there were no more adverse events observed in rhTPO daily group. CONCLUSIONS: It's more effective to promote hematopoietic recovery and reduce platelet transfusion dependence when rhTPO was daily used other than used every other day.

Elevated expression of CX3C chemokine receptor 1 mediates recruitment of T cells into bone marrow of patients with acquired aplastic anaemia.

OBJECTIVE: Acquired aplastic anaemia (AA) is a T-cell-mediated, organ-specific autoimmune disease characterized by haematopoietic stem cell destruction in the bone marrow. The exact molecular mechanism of T-cell trafficking into the bone marrow is unclear in AA. Very late activation antigen-4 (VLA-4) and CX3C chemokine receptor 1 (CX3CR1) play active roles in many autoimmune diseases. Therefore, we investigated whether VLA-4 and CX3CR1 also contribute to T-cell migration into the bone marrow in acquired AA. DESIGN, SETTING AND SUBJECTS: Expression levels of CX3CR1 and VLA-4 and their ligands [fractalkine (CX3CL1) and vascular cell adhesion molecule-1 (VCAM-1)] were examined in 63 patients with AA and 21 healthy control subjects. T-cell chemotaxis and adhesion were analysed in 17 patients with severe AA. We also prospectively evaluated the expression pattern of CX3CR1 during treatment with antithymocyte globulin plus cyclosporine in 11 patients with severe AA. RESULTS: The proportion of peripheral and bone marrow CD4(+) and CD8(+) T cells expressing CX3CR1 and the level of CX3CL1 was increased in patients with AA. However, there was no significant difference in VLA-4 expression or VCAM-1 levels. Functional studies demonstrated that chemotaxis towards autologous bone marrow plasma or soluble CX3CL1 was significantly higher in T cells from AA patients and could be blocked by CX3CR1 inhibitors. CX3CR1-mediated T-cell adhesion was also upregulated in these patients. The expression of CX3CR1 was associated with the efficacy of immunosuppressive therapy. CONCLUSION: The present findings demonstrate that CX3CR1 plays a pivotal role in recruitment of T cells into the bone marrow in acquired AA and is a potential therapeutic target for treatment of this disorder.