BACKGROUND: Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients. METHODS: This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events. RESULTS: At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated. CONCLUSIONS: Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high. REGISTRATION ClinicalTrials.gov, NCT04214951.
Adult ; Humans ; Purpura, Thrombocytopenic, Idiopathic ; Thrombopoietin/adverse effects* ; Prospective Studies ; Recombinant Fusion Proteins ; Receptors, Fc/therapeutic use* ; Receptors, Thrombopoietin/therapeutic use* ; Thrombocytopenia/chemically induced* ; Benzoates/adverse effects* ; Hydrazines/adverse effects*

To explore influence of platelet donation on donor's megakaryocytopoiesis, platelet counts and plasma concentrations of thrombopoietin (TPO), interleukin-3 (IL-3), IL-6 and nitric oxide (NO) were determined in 42 frequent platelet donors (undergoing plateletpheresis more than once a month for 24 months and their mean platelet yield of collection was 2.5 x 10(11)), in 62 limited platelet donors (undergoing plateletpheresis less than once a month for 24 months) after a donation-free period of > 5 weeks and in 40 whole blood donors who never undergoing plateletpheresis after a donation-free period of > 6 months. The results showed that the TPO levels was significantly lower in frequent platelet donors than in limited platelet donors (P < 0.01) and whole blood donors (P < 0.01). There were no significant differences between three groups in platelet counts, IL-3, IL-6 and NO. These findings suggest that the number of megakarocytes significantly increased in frequent platelet donors.
Adult ; Blood Donors ; Humans ; Interleukin-3 ; blood ; Interleukin-6 ; blood ; Megakaryocytes ; cytology ; Platelet Count ; Plateletpheresis ; adverse effects ; Thrombopoiesis ; Thrombopoietin ; blood

In autoimmune thrombocytopenic purpura (AITP) specific autoantibodies bind platelet GP via their Fab fragments. Both splenic CD5+ B and CD5- B cells produce platelet glycoprotein-specific antibodies. There is limited number of antigenic determinants, and the GP-specific autoantibodies are derived from a restricted number of B-cell clones in chronic AITP. Blocking co-stimulatory signals could induce platelet-specific T cell anergy. MMF could be used as a second line agent for the treatment of steroid-resistant AITP. Detection of plasma thrombopoietin levels play an important role in the differentiation of thrombocytopenic states caused by platelet destruction or due to bone marrow hypoplasia. Endogenous TPO level is also important on the differential diagnosis of ET and RT. Quinine- or heparin-dependent antibodies could induce thrombocytopenia. PCR-SSP is useful for the genotyping of the platelet-specific alloantigen HPA. Biotinylated platelets have an impaired response to agonists as evidenced by in vitro platelet aggregation tests.
Antigens, Human Platelet ; immunology ; Blood Platelets ; immunology ; Heparin ; adverse effects ; Humans ; Platelet Membrane Glycoproteins ; immunology ; Purpura, Thrombocytopenic, Idiopathic ; etiology ; immunology ; Thrombopoietin ; blood

OBJECTIVETo explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with high-dose dexamethasone (DXM) in the treatment of children with refractory immune thrombocytopenic purpura (ITP).

METHODSFifty-eight ITP children who had failed first-line therapy were randomly divided into two groups: DXM treatment (n=27) and rhTPO + DXM treatment (n=31). The DXM treatment group received two continuous cycles of DXM treatment; in each cycle, patients received high-dose DXM (0.6 mg/kg daily) by intravenous drip for 4 days every 28 days. The rhTPO group received subcutaneous injection of rhTPO (300 U/kg daily) for 14 days additional to DXM treatment. The overall response rate (marked response rate + slight response rate) and adverse reactions were evaluated after 3, 7, and 14 days and 1, 2, and 3 months of treatment.

RESULTSAfter 7 and 14 days and 1 month of treatment, the rhTPO + DXM treatment group had a significantly higher marked response rate and a significantly higher overall response rate than the DXM treatment group (P<0.05). After 2 months of treatment, the rhTPO + DXM treatment group had a significantly higher overall response rate than the DXM group (P<0.05). One patient in the DXM treatment group had liver damage during the first week of treatment. There was no hypertension, fever, rash, allergy, or weakness in the two groups.

CONCLUSIONSrhTPO combined with high-dose DXM is an effective and safe approach for treating refractory ITP.

Child ; Child, Preschool ; Dexamethasone ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Female ; Humans ; Infant ; Male ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; administration & dosage ; Thrombopoietin ; administration & dosage ; adverse effects ; Treatment Outcome

OBJECTIVETo evaluate the efficacy of short-term intermittent prophylactic use of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe thrombocytopenia in lung cancer patients.

METHODS24 advanced non-small cell lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U×kg(-1)×d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet count was monitored and compared with that in the previous treatment cycle (control cycle, CC).

RESULTSThe lowest platelet count in the prophylactic rhTPO cycle was significantly higher than that in control cycle [(56 ± 16) × 10(9)/L vs. (28 ± 13) × 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also shortened by the prophylactic rhTPO [(8 ± 2) d vs. (12 ± 3) d, P < 0.001]. The area under curve (AUC) of platelet count (21 days) was significantly increased [(3517 ± 685) × 10(9)/L vs. (2063 ± 436) × 10(9)/L, P < 0.001]. The time to platelet nadir and peak was not affected.

CONCLUSIONProphylactic use of rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced thrombocytopenia in lung cancer patients.

Adenocarcinoma ; blood ; drug therapy ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Area Under Curve ; Carboplatin ; administration & dosage ; adverse effects ; Cisplatin ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Dizziness ; chemically induced ; Female ; Fever ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Platelet Count ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; blood ; chemically induced ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use

Application of ex vivo expanded megakaryocytic progenitor cells (MKPC) is a strategy for the treatment of thrombocytopenia after hematopoietic stem cell transplantation. Some growth factors including thrombopoietin (TPO), megakaryocyte growth and development factor (MGDF), interleukin (IL)-1, IL-3, IL-6, IL-11, platelet-derived growth factor (PDGF), and serotonin (5-HT) have been demonstrated to play an important role on the regulation of megakaryocyte/platelet development, the efficient conditions for the expansion of the megakaryocyte (MK) progenitors from hematopoietic stem/progenitor cells were discussed in this review article. TPO alone produced a high proportion of MK progenitors but a low total cell count. The addition of IL-1 beta, IL-3, IL-6 and Flt-3L improved the expansion outcome. The combination of three to five cytokines produced more efficient expansions of hematopoietic stem and MK progenitors. PDGF also enhanced the ex vivo expansion of CD61+ CD41+ cells and CD34+ cells in combination with TPO, IL-1 beta, IL-3, IL-6 and Flt-3L. PDGF is a suitable growth factor to improve the ex vivo expansion of MKPC without promoting their in vitro maturation. More importantly, PDGF also enhanced the engraftment of human stem and progenitor cells in NOD/SCID mice. It has been reported that MKPC can be safely administered to autologous peripheral blood progenitor cell transplant recipients. In short, MKPC can be expanded ex vivo and safely applied to autologous transplant.
Cells, Cultured ; Hematopoietic Stem Cells ; cytology ; Humans ; Megakaryocytes ; cytology ; Peripheral Blood Stem Cell Transplantation ; adverse effects ; methods ; Platelet-Derived Growth Factor ; pharmacology ; Serotonin ; pharmacology ; Thrombocytopenia ; prevention & control ; Thrombopoietin ; pharmacology

BACKGROUNDThe management of patients with refractory immune thrombocytopenia (ITP) is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin (rhTPO) in combination with cyclosporin A (CsA) for the management of patients with corticosteroid-resistant primary ITP.

METHODSThirty-six patients with corticosteroid-resistant ITP were randomly divided into an observation group and control group. In the observation group, 19 patients received subcutaneous injection of rhTPO at a dose of 1 µg/kg (300 U/kg) once daily up to day 14. Simultaneously they also received oral CsA at a dose of 1.5-2.0 mg/kg twice daily for three months. In the control group, rhTPO alone was administered subcutaneously at 1 µg/kg once daily in the other 17 ITP patients for 14 consecutive days and then the treatment was withdrawn.

RESULTSThere was no significant difference in the response rate at the end of the first week after treatment initiation between the observation group and the control group (63.2% vs. 58.8%, P > 0.05), neither was there at the end of the second week (89.5% vs. 94.1%, P > 0.05). However, the relapse rate in the observation group was significantly lower than that in control group at the end of the first (17.7% vs. 50.0%, P < 0.05), second (29.4% vs. 68.8%, P < 0.05) and the third month (29.4% vs. 87.5%, P < 0.01). In addition, rhTPO plus CsA were well tolerated and adverse events recorded were mild.

CONCLUSIONSCombination therapy with rhTPO and CsA was effective in the management of patients with corticosteroidresistant ITP, with a relatively short time to response and low recurrence rate. It might be considered as a potential secondline treatment regimen for ITP.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Adult ; Aged ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Resistance ; Female ; Humans ; Male ; Middle Aged ; Recombinant Proteins ; therapeutic use ; Thrombocytopenia ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo assess the efficacy of prophylactic treatment with recombinant human thrombopoietin (rhTPO) on chemotherapy-induced thrombocytopenia in tumor patients.

METHODSIn this randomized cross-over self-controlled clinical trial, 24 patients with malignant neoplasms were randomized group A (12 cases) and group B (12 cases). All the patients underwent two identical cycles of chemotherapy. In group A, RhTPO (1.0 µg/kg) was administered subcutaneously on a daily basis 3 days before the second chemotherapy cycle for 7 consecutive days, and in group B, RhTPO was administered daily 6-24 h after the second chemotherapy cycle for 7 days. In both groups, RhTPO was not administered in the first chemotherapy cycle, which served as the control cycle.

RESULTSIn both the groups, platelet count was significantly higher in the second cycle than in the control cycle, and the duration of thrombocytopenia was significantly shortened in the second cycle. Compared with group B, the patients in group A showed a significantly higher platelet count in the second cycle and a significantly shorter duration of thrombocytopenia in the second cycle.

CONCLUSIONProphylactic administration of rhTPO can significantly reduce the severity and duration of thrombocytopenia and promote platelet recovery in patients undergoing chemotherapy for malignant tumors.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Cross-Over Studies ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; drug therapy ; Platelet Count ; Recombinant Proteins ; therapeutic use ; Thrombocytopenia ; chemically induced ; prevention & control ; Thrombopoietin ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treatment for chemotherapy-induced thrombocytopenia in patients with lung cancer.

METHODSFifty-one lung cancer patients with platelet count < 100 x 10(9)/L after chemotherapy were enrolled into this study. They were divided into three groups: mild, moderate and severe thrombocytopenia groups according to the platelet count. rhTPO was subcutaneously administered at a dosage of 300 microg kg(-1) d(-1) until the platelet count >or= 100 x 10(9)/L or absolute value of platelet count >or= 50 x 10(9)/L. Laboratory tests included routine blood count, serum biochemistry, and blood coagulation test.

RESULTSThe duration of the chemotherapy-induced thrombocytopenia was significantly shorter in the mild group than that in the moderate and severe groups (P < 0.01). After administration of rhTPO, the time of declined platelet count beginning to recover was also significantly shorter in the mild group than that in the moderate and severe groups (P < 0.01). There was a statistically significant difference in platelet transfusion needed among the three groups (P < 0.01). However, no significant difference was found among the three groups in the time of rhTPO treatment (P > 0.05) and platelet count improvement (P > 0.05).

CONCLUSIONRecombinant human thrombopoietin can be effectively and safely administered to deal with grade III/IV chemotherapy-induced thrombocytopenia in lung cancer patients with mild adverse effects.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Dizziness ; chemically induced ; Female ; Fever ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Platelet Count ; Platelet Transfusion ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; chemically induced ; drug therapy ; therapy ; Thrombopoietin ; adverse effects ; therapeutic use

OBJECTIVETo evaluate the efficacy and safety of domestically manufactured recombinant human thrombopoietin (rhTPO) in the treatment for chemotherapy-induced thrombocytopenia in patients with solid tumors.

METHODSA non-randomized controlled study was conducted. Seventy-two patients with platelet count < 75 x 10(9)/L after chemotherapy were enrolled into this study according to the standard criteria of NCI-CTC toxicity stratification. Thirty-five patients in the treatment-group received subcutaneous injection of rhTPO at a dose of 15,000 U/d, another 37 patients in the control group received subcutaneous injection of rhIL-11a at a dose of 3 mg/d as the paralleled control.

RESULTSThe mean minimal platelet count after rhTPO treatment was (46.2 +/- 20.3) x 10(9)/L in the treatment-group versus (37.2 +/- 16.7) x 10(9)/L in the control-group (P < 0.05), while the mean maximal platelet count was (250.2 +/- 159.0) x 10(9)/L versus (160.5 +/- 96.4) x 10(9)/L (P < 0.05). The incidence rate of adverse effects and duration of grade III and IV thrombocytopenia in the treatment-group was also significantly lower than those in the control-group. Furthermore, the patients receiving platelet transfusion were 4/35 in the treatment-group versus 11/37 in the control-group (P > 0.05). The side-effect rate in the treatment-group was significantly lower than that in the control-group (11.4% versus 78.4%, P < 0.01).

CONCLUSIONCompared with rhIL-11, administration of rhTPO after chemotherapy is safe and effective with mild adverse effects in reducing the degree and duration of thrombocytopenia.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; blood ; drug therapy ; Female ; Fever ; chemically induced ; Headache ; chemically induced ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Platelet Count ; Recombinant Proteins ; adverse effects ; therapeutic use ; Thrombocytopenia ; chemically induced ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use