ASCT后罗米司亭与rhTPO对血小板输注总量的调整后关联：多模型加权与敏感性分析

… after high-dose chemotherapy and autologous stem cell transplantation: an unresolved problem and possible approaches to resolve it. J Hematother 1996; 5: 407–414. 10 Pendry K, …

Key Points • There are no prior prospective studies of thrombopoietin receptor agonists to enhance platelet recovery after auto-HCT.• As studied, romiplostim did not shorten the duration and depth of the platelet nadir, but it enhanced platelet recovery after day +15.

Prolonged thrombocytopenia after HSCT is a strong risk factor for transplant related mortality and morbidity, and no standard treatment guideline exists. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, increases the platelet production, and are being increasingly used in various conditions with thrombocytopenia. In this review, we present an overview of these TPO-RAs and review their efficacy and safety in prolonged post HSCT thrombocytopenia. Through a systematic literature search, we identified 25 reports describing their use for this indication. Thirteen reports (8 case series and 5 case reports) described the use of eltrombopag in 78 patients with Prolonged Isolated Thrombocytopenia (PIT) and 43 patients with Secondary Failure of Platelet Recovery (SFPR). A consistent and durable response with the rise in platelet counts above 50 × 10 9/L for 7 consecutive days without platelet transfusion was seen in 85 out of 121 patients (Overall Response Rate, ORR 70%). Amongst the responders, 56 were patients with PIT (ORR for PIT of 72%) versus 29 patients with SFPR (ORR for SFPR of 67%). No serious grade 3 or 4 adverse effects were reported. Similarly, 12 reports (6 case series and 6 case reports) described the use of romiplostim in prolonged post HSCT thrombocytopenia (17 patients with PIT and 32 patients with SFPR). Response with the increment of platelet count was described in 40 out of 49 patients (ORR 82%). Amongst the responders, 10 patients had PIT (ORR for PIT of 59%) versus 30 patients had SFPR (ORR for SFPR of 94%). TPO-RAs have an overall favorable response rate for both PIT and SFPR with a reasonable safety profile. However, given the lack of control groups, study heterogeneity, and the potential publication bias, the results should be interpreted with caution.

… Immune thrombocytopenia following autologous transplantation in solid tumors has not … thrombocytopenia after high-dose chemotherapy and peripheral blood stem cell transplantation …

… , Kutlar A: Autoimmune thrombocytopenia following autologous hematopoietic stem cell transplantation: Review of literature and treatment options. Bone Marrow Transplant 2000;26:925…

… (tandem transplantation)3 … We report the first case of autoimmune thrombocytopenia after tandem transplantation in a patient with a refractory germ cell tumor. A 45-year-old man with no …

Thrombocytopenia following allogeneic hematopoietic stem cell transplantation is a usual complication and can lead to high morbidity and mortality. New strategies, such as the use of another graft versus host-disease prophylaxis, alternative donors, and management of infections, have improved the survival of these patients. The mechanisms are unknown; therefore, the identification of new strategies to manage this potentially serious problem is needed. Thrombopoietin receptor agonists are currently available to stimulate platelet production. Some small retrospective studies have reported their potential efficacy in an allogeneic stem cell transplant setting, confirming good tolerability. Recent studies with higher numbers of patients also support their safety and efficacy in this setting, hence establishing the use of these drugs as a promising strategy for this post-transplant complication. However, prospective trials are needed to confirm these results.

… romiplostim, from the discovery of the underlying pathophysiology of ITP to the isolation and cloning of thrombopoietin and the subsequent availability of romiplostim in the clinic (Fig 1). …

… factors is not thrombopoiesis; thrombopoietin (TPO) is the … Thrombopoietin was identified simultaneously by five groups … , romiplostim competes with TPO for binding of the human Mpl …

… Recombinant human thrombopoietin attenuates carboplatin-induced severe thrombocytopenia and … recombinant human thrombopoietin in patients with delayed platelet recovery after …

“Immune thrombocytopenia” (ITP) is an autoimmune disorder that leads to peripheral destruction, as well as a decreased production of platelets. ITP most commonly presents as mild mucocutaneous bleeding. Though it is rare, the leading cause of mortality in persons with ITP is intracranial hemorrhage and those that do not respond to therapy are at increased risk. Our understanding of the pathophysiology of ITP has evolved immensely, especially over the last 60 years. The discovery of the platelet-production stimulator, thrombopoietin (TPO), lent clarity to an earlier hypothesis that inhibition of platelet production at the level of the megakaryocyte, at least in part, accounts for thrombocytopenia in adults with ITP. This facilitated the development of TPO-based therapies to treat ITP. Thrombopoietin receptor agonists are one of the most recent treatments to enter the landscape. Original production of a recombinant human TPO was halted after clinical trials revealed the untoward effect of autoantibodies to the recombinant human TPO with cross-reactivity to endogenous TPO. Next-step development focused on stimulation of the TPO receptor with fewer immunogenic agents. Currently, two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are licensed in the USA to treat thrombocytopenia in adults with persistent or chronic ITP. Ongoing research will assess their efficacy in other immune-mediated and nonimmune-mediated primary and secondary thrombocytopenias.

This study retrospectively compared the efficacy and safety of romiplostim and recombinant human thrombopoietin (rhTPO) in managing chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours, aiming to provide valuable evidence for clinical practice in CIT management. A retrospective cohort study involving patients with solid tumours who received either romiplostim or rhTPO following anticancer treatment was conducted at Nanjing Second Hospital from January 2024 to May 2025. The primary outcomes assessed were platelet recovery, treatment efficacy, and recovery time, whereas the secondary outcomes included chemotherapy adherence and the incidence of adverse events. A total of 68 patients were included in the analysis, among whom 32 received romiplostim and 36 received rhTPO. Baseline characteristics were comparable between the two groups. Romiplostim demonstrated a higher treatment efficacy (71.9%) than rhTPO (63.9%) ,although this difference was not statistically significant(P = 0.239). The median platelet recovery time was shorter in the romiplostim group (9 days) than in the rhTPO group (12 days) (P = 0.012). Platelet recovery to ≥ 100 × 10⁹/L was achieved by 62.5% of the romiplostim patients versus 44.4% of the rhTPO patients (P = 0.137). Furthermore, a higher proportion of patients in the romiplostim group (90.6% vs. 83.3% with rhTPO) were able to continue scheduled chemotherapy, although this difference did not reach statistical significance (P = 0.376). The incidence of adverse events was similar between the two groups, although it was lower in the romiplostim group. Compared with rhTPO, romiplostim significantly shortened the time to platelet recovery and required fewer administrations. Overall safety was comparable between the two groups, with no new safety concerns identified. Future prospective studies are warranted to confirm long-term outcomes.

Romiplostim, a thrombopoietin (TPO) receptor agonist, is a clinically approved drug that is clearly effective in reconstituting hematopoiesis in refractory aplastic anemia and　idiopathic thrombocytopenic purpura. However, the mechanism underlying its biological effect is unknown, and its differences from other TPO receptor agonists remain unclear. Therefore, we determined the in vitro expansion effect of romiplostim on human CD34 + hematopoietic stem and progenitor cells (HSPCs) versus recombinant human TPO (rhTPO) and another clinically available drug, eltrombopag. We also performed single-cell RNA-seq to determine effects of romiplostim on CD34 + HSPCs at the molecular level. The maximum expansion effect of romiplostim on total CD34 + cells, CD34 + CD38 + progenitor cells, and CD34 + CD38 − immature cells was comparable to that of rhTPO, but higher than that of eltrombopag, particularly on CD34 + CD38 − immature cells. Single-cell RNA-seq analysis revealed that both romiplostim and eltrombopag induced signatures driven by rhTPO, but romiplostim induced molecular changes related to RHOA signaling in the most primitive HSPC subsets that were partially driven or not driven by eltrombopag. Additionally, romiplostim did not induce TFRC expression as was observed with eltrombopag. In conclusion, romiplostim expands and affects human HSPCs similar to rhTPO, but partially different from eltrombopag in terms of induction of gene expression.

… These were full-length glycosylated recombinant human thrombopoietin (rHuTPO) and a … glycol moiety (pegylated recombinant human megakaryocyte growth and development factor, …

… Upon binding of thrombopoietin or romiplostim to the distal HRD-2, the receptor (right) conformation changes and a number of signal transduction pathways are activated that increase …

Delayed platelet engraftment (DPE) is a prevalent complication following umbilical cord blood transplantation (UCBT), accompanied by increased transplant-related mortality. This study aims to evaluate the efficacy, safety, and tolerability of romiplostim and recombinant human thrombopoietin (rhTPO) in enhancing platelet engraftment after UCBT. A total of 19 patients scheduled to receive UCBT were randomly assigned to the romiplostim group (250 µg once weekly from day 5 to platelet engraftment after UCBT, n = 7) or rhTPO group (300 U/kg once daily from days 5 to 18 after UCBT, n = 12). The median time of PLT engraftment was no statistical difference between rhTPO and romiplostim group: 29.5 days (range: 13–43 days) compared to 31 days (range: 23–40 days; P =.269). The median dose of romiplostim was 4 (range: 2–5 doses). Furthermore, the consumption of PLT was equivalent between the Ro group and the rhTPO group: 10 units (range: 7–26 units) and 10 units (range: 3–24 units; P =.694). All patients survived for one year and remained relapse-free. Romiplostim group had a lower incidence of acute graft versus host disease (aGvHD). No severe adverse effects were observed in any of the patients. This study demonstrated that romiplostim and rhTPO are both effective in promoting platelet engraftment after UCBT. Romiplostim was more practical and tolerable due to its cost and labor-saving benefits.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count < 50 × 109/L) received rhTPO (n = 80) or placebo (n = 40) once daily for up to 5 or 7 days. The primary endpoint was the proportion of patients with sustained platelet counts ≥ 50 × 109/L from 24 h before invasive procedure to 7 days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p < 0.0001). Preoperatively, platelet counts ≥ 50 × 109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p < 0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p < 0.0001). The median duration of platelet counts ≥ 50 × 109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0 days, p = 0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Thrombopoietin, the primary regulator of blood platelet production, was postulated to exist in 1958, but was only proven to exist when the cDNA for the hormone was cloned in 1994. Since its initial cloning and characterization, the hormone has revealed many surprises. For example, instead of acting as the postulated differentiation factor for platelet precursors, megakaryocytes, it is the most potent stimulator of megakaryocyte progenitor expansion known. Moreover, it also stimulates the survival, and in combination with stem cell factor leads to the expansion of hematopoietic stem cells. All of these growth-promoting activities have resulted in its clinical use in patients with thrombocytopenia and aplastic anemia, although the clinical development of the native molecule illustrated that “it’s not wise to mess with mother nature”, as a highly engineered version of the native hormone led to autoantibody formation and severe thrombocytopenia. Finally, another unexpected finding was the role of the thrombopoietin receptor in stem cell biology, including the development of myeloproliferative neoplasms, an important disorder of hematopoietic stem cells. Overall, the past 30 years of clinical and basic research has yielded many important insights, which are reviewed in this paper.

Romiplostim is a thrombopoietin receptor agonist (TPO-RA) used for the treatment of adult primary immune thrombocytopenia (ITP). ITP is an autoimmune condition characterized by low platelet counts due to increased destruction and reduced platelet production. First-line interventions include corticosteroids, anti-D, and intravenous immunoglobulins, while second-line therapies comprise splenectomy, rituximab, cyclosporine A, and TPO-RAs. The recognition that compromised platelet production is a critical part of the pathogenesis of ITP prompted the development of therapeutic strategies based on the stimulation of the TPO receptor. TPO-RAs enhance megakaryocyte proliferation, increase platelet production, and lead to a reduction in bleeding episodes in ITP patients. This review will summarize current data on the TPO-RA romiplostim, with a particular focus on its relation to splenectomy.

Background Recombinant human TPO (rhTPO) promotes platelet engraftment in patients after allogeneic HSCT (allo-HSCT). However, the effects of rhTPO on platelet recovery after …

… a platelet transfusion at the first sign of bleeding, rather than prophylactically. Prophylactic platelet transfusion at defined platelet … undergoing autologous stem-cell transplantation and for …

Background Delayed platelet engraftment is a significant complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Objectives This retrospective study evaluates the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, in promoting platelet engraftment post-allo-HSCT. Design Retrospective observational cohort study. Methods A cohort of 133 patients was analyzed, including 68 treated with hetrombopag post-transplant and 65 controls. Cumulative incidence function evaluated platelet engraftment, with propensity score matching and competing risk analysis to strengthen robustness. Factors associated with platelet engraftment were examined using multivariate Cox models with time-dependent coding of hetrombopag exposure. Results Hetrombopag significantly reduced the time to overall response (OR: 15.0 days vs. 20.0 days; p = 0.009) and complete response (CR: 17.5 days vs. 34.0 days; p < 0.001). The cumulative incidence of CR was higher in the hetrombopag group (92.78% vs. 86.58%; p = 0.001), with a significantly shorter median time to CR (19 days vs. 38 days) defined by the cumulative incidence function. Multivariate Cox regression identified hetrombopag as a protective factor for platelet recovery (HR: 2.04; p = 0.004). Competing risk and PSM analyses confirmed hetrombopag’s role in faster platelet engraftment. The treatment was well-tolerated, with manageable mild liver enzyme elevations and hypomagnesemia but no grade 3/4 adverse events. Conclusion Hetrombopag significantly accelerates platelet engraftment and has a favorable safety profile, suggesting its potential as a therapeutic adjunct in managing thrombocytopenia post-allo-HSCT. This study complements and validates findings from prior prospective studies, providing external confirmation in a real-world cohort.

Thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-SCT) can pose significant problems in management of patients. Eltrombopag is a small-molecule thrombopoietin receptor agonist that has been approved for use in immune thrombocytopenic purpura and aplastic anemia; but its use after allo-SCT is limited. Between 2014 and 2017, we treated 13 patients with eltrombopag for poor platelet engraftment without evidence of relapse at the time of initiation, including 6 patients with primary platelet engraftment failure and 7 with secondary platelet engraftment failure. Eltrombopag was started at an initial dose of 25 or 50mg per day, and dose adjustments were made in accordance with the manufacturer's recommendation. The cumulative incidence of platelet recovery to ≥50,000/μL without the need for transfusion for at least 7days was defined as response. The overall response rate was 62% (n = 8). Of the 6 patients with primary isolated platelet failure, 3 (50%) responded, and of the 7 patients with secondary platelet failure, 5 (71%) responded. The median time to response was 33days (range, 11 to 68 days). In addition, no significant differences in platelet recovery were noted in patients with adequate and decreased bone marrow megakaryocytic reserve (60% and 67%, respectively). Although eltrombopag was well tolerated, and no patient discontinued treatment because of adverse events, only 3 patients were alive at the end of the observation period, with relapse and graft-versus-host disease accounting for majority of the deaths. This suggested that despite the relatively good overall response rate to eltrombopag, inadequate platelet engraftment is a harbinger of poor outcome in allo-SCT.

Background: There is no standard treatment to accelerate recovery from melphalan-induced thrombocytopenia in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). Romiplostim, a thrombopoietin receptor agonist, has been developed to upregulate platelet production. Objective: This study aimed to assess the efficacy and safety of romiplostim in reducing platelet transfusions post-ASCT in MM patients. Methods: This was an investigator-initiated, single-center, open-label, comparative pilot study conducted from January to December 2022. We evaluated 18 melphalan-conditioned MM patients treated with pegylated granulocyte colony-stimulating growth factor (GCSF) (6 mg subcutaneously, SC, on day 2) and romiplostim (250 mcg SC on day 3) post-ASCT (romiplostim cohort). We compared them with 56 MM patients who had undergone ASCT and received GCSF alone (conventional or retrospective cohort, enrolled from 2015 to 2021). Efficacy endpoints included the number of mean single donor platelet (SDP) and packed red blood cell (PRBC) transfusions, time to platelet and neutrophil engraftment, and safety and tolerability assessments. Results: In the romiplostim cohort, the average number of SDP transfusions required was significantly lower than that in the conventional cohort (1.39 vs. 3.40, p = 0.0001). Platelet engraftment occurred significantly faster in the romiplostim cohort versus the conventional cohort (9.72 vs. 12.57 days, p = 0.0018). Neutrophil engraftment days and PRBC transfusion requirements were comparable between the two groups. No deaths or major safety concerns were reported. Conclusion: Romiplostim demonstrated an improved efficacy and a favorable safety profile compared to the conventional approach in patients undergoing ASCT.

Abstract Thrombopoietin (TPO) is the major physiological regulator of platelet production. It is produced by the liver at a constant rate and cleared from the circulation by TPO receptors on circulating platelets thereby providing an efficient feedback system regulating platelet production by bone marrow megakaryocytes. When TPO binds the megakaryocyte TPO receptor, signal transduction pathways are activated that promote viability, endomitosis and maturation, and increase platelet production. When TPO is eliminated by genetic manipulation or antibody, megakaryocyte and platelet number decline to about 15% of normal. Humans with TPO deficiency due to liver disease or TPO mutation have thrombocytopenia while TPO overproduction due to genetic mutations produces lifelong thrombocythemia. Early recombinant forms of TPO (rHuTPO and PEG-rHuMGDF) were effective in increasing platelet counts in patients with ITP or undergoing chemotherapy or platelet apheresis. Current clinically available TPO receptor agonists (romiplostim, eltrombopag) increase platelet counts in > 90% of ITP patients with minimal adverse effects and have also been shown to be effective in a wide range of other thrombocytopenic disorders. The TPO receptor agonists avatrombopag and lusutrombopag have been approved for the treatment of thrombocytopenia in adults with chronic liver disease scheduled to undergo a procedure.

ABSTRACT Introduction Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cancer treatment, frequently leading to reduced relative dose intensity, and is associated with reduced survival. Given the lack of FDA-approved therapies for CIT, thrombopoietin receptor agonists (TPO-RAs) have received significant attention for treatment and prevention of CIT. Areas covered This review will summarize the development of prior agents for treatment of CIT, discuss the existing literature investigating the use of TPO-RAs in CIT primarily in patients with solid tumor malignancies, and offer insights on the future direction of TPO-RAs and other therapeutics for CIT. Expert opinion In alignment with NCCN guidelines, we recommend that patients with CIT participate in a clinical trial for consideration of TPO-RA treatment or consider off-label use of romiplostim when participation in clinical trials is not possible. The literature to date supports the use of TPO-RAs for treatment of persistent CIT. Further data is needed to describe the long-term efficacy, safety, and prescribing practices of TPO-RAs in a diverse patient population with a variety of tumor types and chemotherapy regimens in addition to exploring the underlying biology of CIT.

Although development of first-generation thrombopoietic growth factors (recombinant human thrombopoietin [TPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) was stopped due to development of antibodies to PEG-rHuMGDF, nonimmunogenic second-generation thrombopoietic growth factors with unique pharmacologic properties have been developed. TPO peptide mimetics contain TPO receptor-activating peptides inserted into complementarity-determining regions of Fab (Fab 59), attached to the IgG Fc region (AMG 531), or pegylated (Peg-TPOmp). Orally available, TPO nonpeptide mimetics (eltrombopag, AKR-501) bind and activate the TPO receptor by a mechanism different from TPO and may have an additive effect to TPO. TPO agonist antibodies are monoclonal antibodies activating the TPO receptor but modified in size [TPO minibodies; ie, VB22B sc(Fv)2] or immunoglobuln type (domain subclass-converted TPO agonist antibodies; ie, MA01G4G344). All second-generation thrombopoietic growth factors stimulate growth of TPO-dependent cell lines via JAK2/STAT signaling pathways and increase platelet counts in animals. When tested in healthy humans, TPO peptide and nonpeptide mimetics produced a dose-dependent rise in platelet count. AMG 531 and eltrombopag markedly increase platelet counts in patients with immune thrombocytopenic purpura, without significant adverse effects. One or more second-generation thrombopoietic growth factors should soon be clinically available for treating thrombocytopenic disorders.

Collagen activates platelets through a tyrosine kinase-dependent pathway, involving phospholipase Cgamma2. Functional responses such as aggregation and secretion induced by collagen are potentiated by preincubation with thrombopoietin (TPO). In this study, we show that collagen and thrombopoietin activate the phosphatidylinositol 3-kinase (PI 3-kinase) pathway and that this contributes to their respective actions. The structurally distinct inhibitors of PI 3-kinase, wortmannin, and LY294002, completely inhibit formation of phosphatidylinositol 3,4,5-trisphosphate by collagen. This leads to a substantial reduction in the formation of inositol phosphates and phosphatidic acid, 2 indices of PLC activity, and the consequent inhibition of intracellular Ca(++) [Ca(++)](i), aggregation and secretion. Potentiation of the collagen response by TPO is prevented in the presence of wortmannin and LY294002. However, when the 2 PI 3-kinase inhibitors are given after the addition of TPO but before the collagen, recovery of potentiation is observed. This suggests that potentiation is mediated through activation of PI 3-kinase. TPO stimulates aggregation of platelets from a low percentage of donors and this is also blocked by wortmannin. These results suggest that the PI 3-kinase pathway plays an important role in signaling by collagen and in the priming action of TPO.

Antibodies have brought valuable therapeutics in the clinical treatment of various diseases without serious adverse effects through their intrinsic features such as specific binding to the target antigen with high affinity, clinical safety as serum proteins, and long half-life. Agonist antibodies, furthermore, could be expected to maximize the value of therapeutic antibodies. Indeed, several IgG/IgM antibodies have been reported to induce cellular growth/differentiation and apoptosis. These agonist antibodies, however, should be further improved to exert more potent biologic activities and appropriate serum half-life depending upon the disease indications. Here, we report that IgG antibodies against the thrombopoietin receptor (Mpl), which have an absence or very weak agonist activity, can be engineered to be agonist minibodies, which include diabody or sc(Fv)2 as potent as natural ligand. Through this technological development, minibodies have been successfully constructed to bind and activate 2 types of dysfunctional mutant Mpls that cause congenital amegakaryocytic thrombocytopenia (CAMT). This drastic conversion of biologic activities by designing minibodies can be widely applicable to generate agonist minibodies for clinical application, which will constitute a new paradigm in antibody-based therapeutics.

Bone marrow failure is characterized by a disruption of hematopoietic stem cell (HSC) homeostasis and function, which causes decreased blood counts. Germline and somatic mutations within HSCs and immune dysregulation contribute to the pathogenesis of marrow failure. Allogeneic HSC transplant is a potentially curative therapy for marrow failure, although not all patients are candidates for this procedure. Immune suppressive therapy (IST) is an effective treatment for patients with aplastic anemia (AA) and select patients with myelodysplastic syndromes, but some patients fail to respond or relapse after IST. Over the past decade, the oral thrombopoietin receptor agonist eltrombopag has become a therapeutic option for AA in combination with frontline IST, and as a single agent for relapsed and refractory patients after IST. In this review, we highlight current knowledge of thrombopoietin receptor agonist mechanisms of action, and clinical indications and toxicities in patients with marrow failure, including the risk of clonal evolution.

… (hetrombopag) can promote blood count recovery after … We compared baseline data and blood cell recovery … The platelet recovery time in the treatment group was(10.38±1.46) d, which …

Delayed platelet recovery remains a frequent and clinically significant complication following hematopoietic stem cell transplantation (HSCT) in children, contributing to increased transfusion burden, bleeding risk, and prolonged hospitalization. Thrombopoietin receptor agonists (TPO‐RAs), including romiplostim, have demonstrated activity in post‐transplant thrombocytopenia; however, prospective pediatric data on their early post‐transplant use are limited. We evaluated the safety and potential effects of early romiplostim administration on platelet and hematopoietic recovery following pediatric HSCT.

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is pivotal for hematological malignancies but faces challenges in delayed platelet engraftment, poor graft function (PGF), and bleeding risks. Hetrombopag, a thrombopoietin receptor agonist, was evaluated to enhance platelet recovery posttransplant. Patients undergoing allo‐HSCT were randomized on Day 3 Post‐Infusion into low‐dose (2.5 mg/day), high‐dose (5 mg/day) hetrombopag groups, or a control group receiving thrombopoietin (300 U/kg/day). Endpoints included platelet/neutrophil engraftment time, PGF incidence, transfusion needs, and safety. Among 212 analyzed patients, platelet engraftment was faster in hetrombopag groups (median 13 days) versus controls (15 days; p = 0.0022), with no dose‐dependent difference (p = 0.0593). Neutrophil engraftment was also accelerated (13 vs. 15 days; p = 0.0001). PGF incidence was lower in hetrombopag groups (5.04%) versus controls (13.7%; p = 0.027). The experimental group required fewer platelet transfusions (p = 0.002), had reduced gastrointestinal bleeding, and lower costs. Secondary platelet recovery failure showed no intergroup differences. Hetrombopag safely accelerates platelet and neutrophil engraftment, reduces PGF risk, and decreases transfusion dependency post‐allo‐HSCT. Low‐dose hetrombopag demonstrated efficacy equivalent to high‐dose, offering a cost‐effective strategy to improve transplant outcomes.

… , TPO was changed to Nplate in the last … ) engraftment studies with single CB transplants in immune-deficient mice, where we have shown that TPO treatment can improve early platelet …

Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT) accompanied by increased transplant-related complications or death. This study was designed to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) in promoting platelet engraftment after UCBT. A total of 120 patients scheduled to receive UCBT were randomly assigned to the rhTPO group (300 U/kg once daily from days 14 to 28 after UCBT, n = 60) or the control group (n = 60). The primary outcome was the 60-day cumulative incidence of platelet engraftment after single-unit cord blood transplantation. The 60-day cumulative incidence of platelet engraftment (platelet count ≥20 × 109/L) and the 120-day cumulative incidence of platelet recovery (platelet count ≥50 × 109/L) were both significantly higher in the rhTPO group than in the control group (83.1% vs 66.7%, P = .020; and 81.4% vs 65.0%, P = .032, respectively). In addition, the number of required platelet infusions was significantly lower in the rhTPO group than in the control group (6 vs 8 units, respectively; P = .026). The cumulative incidence of neutrophil engraftment and the probability of 2-year overall survival, disease-free survival, and graft-versus-host disease-free relapse-free survival did not differ between the 2 groups. Other transplant-related outcomes and complications did not differ between the 2 groups, and no severe adverse effects were observed in patients receiving rhTPO. This study demonstrated that rhTPO is well tolerated in patients and could effectively promote platelet engraftment after UCBT. This study was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) as ChiCTR-IPR-16009357.

Introduction Thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Underlying mechanisms are poorly known and usually multifactorial. Its treatment is not well defined, mostly based in platelet transfusion. Thus, is important to identify new strategies to manage this important post-SCT complication. Romiplostim and Eltrombopag are currently available thrombopoietin receptor agonists (TPO-RAs) that stimulate platelet production. Some studies with very small number of cases have reported their potential efficacy in the allo-SCT setting. For this reason, the aim of our study is to analyze the efficacy and safety of TPO-RAs for severe and persistent thrombocytopenia after allo-SCT. Patients and methods We performed a retrospective multicenter study including patients from centers of GETH with prolonged isolated thrombocytopenia (PT) or secondary failure of platelet recovery (SFPR) after allo-SCT. PT was defined as the engraftment of all peripheral blood cell lines but with platelet count ≤20000/µL for 7 consecutive days or requirement of transfusion for more than 60 days after allo-SCT. SFPR was defined as a decline of platelet counts to ≤20000/µL for 7 consecutive days or requirement of transfusion after achievement platelets ≥50000/µL without transfusion for 7 days post-SCT. The primary endpoint was platelet recovery to ≥50000/µL. Results Eighty-six patients with thrombocytopenia after allo-SCT were included. The characteristic of the patients, are summarized in table 1. Sixteen (19%) of the patients had PT and 71 (82%) SFPR. TPO-RA was started at a median time of 127 days (27-1177) after allo-SCT (41% Romiplostim / 59% Eltrombopag). Median initial and maximum administered doses were 50 mg/daily (25-150) and 75 (25-150) for Eltrombopag and 1 µg/kg (1-7) and 5 (1-10) for Romiplostin, respectively. Eighteen patients (21%) were previously treated with cell infusion (67% mesenchymal cells and 33% CD34+ boost). Median platelet count before TPO-RA onset was 14000/µL (1000-57000). Platelet recovery to ≥50000/µL was 60% and the response was achieved at a median time of 56 days (2-247). Responses were similar considering all potential causes of thrombocytopenia evaluated. 81% of the patients had decrease number of megakaryocytes prior to treatment showing a worse response to therapy: median time to ≥20000/µL platelets 43 days versus 28 days (p=0.011), with also a lower rate of platelet recovery to ≥50000/µL (62% versus 85% if normal megakaryocytes). In patients treated with Eltrombopag, 27% had neutropenia <1000/µL and 74% achieved >1000/µL after therapy. The median treatment duration was 62 days (7-700) and 62% discontinued TPO-Ra maintaining response. Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the cases. At last follow up with a median of 10 months (1-59), 72% of the patients maintained the response and 61 (71%) were alive. Death rate was significantly lower in responder-patients to TPO-RAs, 15% versus 53% in non-responders (p<0.001). Causes of death were disease progression (28%), infections (48%), graft versus host disease (GvHD) (16%) and others (8%). Conclusion To our knowledge this is the biggest series analyzing the use of TPO-Ra after allo-SCT. Our results support the efficacy and safety in this new setting with responses around 60% and a low number of side effects. Additional studies to identify predictors of response are needed. No relevant conflicts of interest to declare.

ABSTRACT Thrombocytopenia is a common and serious complication that can occur following hematopoietic stem cell transplantation (HSCT), and it contributes to increased morbidity and mortality. The mechanisms of post-HSCT thrombocytopenia are multifactorial and complex. There are no clear consensus and guidelines for managing thrombocytopenia post-HSCT. Recently, there has been promising use of thrombopoietin receptor agonists (TPO-RAs), particularly eltrombopag and romiplostim, as treatments for post-HSCT thrombocytopenia. Notably, that this indication is considered off-label, and data in this use are limited. Based on the existing body of evidence, romiplostim emerges as a safe and effective option for individuals with transfusion-dependent thrombocytopenia after HSCT. In this context, we present a summary of our experience at a single center, where romiplostim was used in the management of post-HSCT thrombocytopenia due to poor graft function. Notably, all four cases responded positively to romiplostim treatment, and no significant adverse events were observed.

Prolonged thrombocytopenia occurs in up to 37% of patients after hematopoietic stem cell transplantation (HSCT) and is associated with adverse prognosis and increased risk of bleeding. Eltrombopag, a thrombopoietin receptor agonist, can increase platelet counts in thrombocytopenic patients. We conducted a phase II study, adaptively randomizing patients at ≥35 days post-HSCT to receive placebo or eltrombopag at a platelet count ≤20,000/µL for 7 days or platelet transfusion-dependent and a neutrophil count ≥1500/µL. Sixty patients were randomized to eltrombopag (n = 42) or placebo (n = 18) and received at least 1 dose. Fifteen patients (36%) in the eltrombopag arm achieved a platelet count of ≥30,000/µL, compared with 5 patients (28%) in the placebo arm, with a posterior probability of 0.75. (The protocol required this probability to be >0.975 to declare a winner; thus, the results are inconclusive.) However, 9 patients (21%) in the eltrombopag arm achieved a platelet count of ≥50,000/µL, compared with no patients in the placebo arm (P = .046). The overall survival, progression-free survival, relapse rate, and nonrelapse mortality were similar in the 2 arms. In conclusion, compared with placebo, treatment with eltrombopag led to a higher percentage of patients achieving a platelet count of ≥50,000/µL in patients with persistent thrombocytopenia after HSCT.

Eltrombopag is a thrombopoietin agonist and has been used in aplastic anemia and post-transplantation thrombocytopenia. The c-MPL receptor is present on hematopoietic stem cells. There are no reports of eltrombopag utilization for improving poor graft function in the post-transplant setting. Here were report a case of a young female with post-transplant poor graft function as evident from the low absolute neutrophil count, anemia, and thrombocytopenia on day 60. Eltrombopag was started on day 72 and resulted in improvement in all 3 cell lines. The counts continued to be stable even after eltrombopag was discontinued. The patient tolerated the drug without significant side effects for 1 year.

… and transfusion utilization at a single transplant center in 505 … engraftment time (Po0.001) and the platelet engraftment time (Po0… such as eltrombopag,23 romiplostim24 or others may be …

… There was a statistically significant improvement in engraftment with … After a single subcutaneous romiplostim dose is administered to healthy volunteers, there is the typical platelet …

Delayed platelet recovery (DPR) is a common and complex complication of hematopoietic stem cell transplantation (HSCT) with unclear mechanisms and poor patient outcomes. Emerging evidence suggests that impaired megakaryogenesis plays a critical role in the development of DPR. In this study, we report remarkable hypermethylation within CG islands of HSCs and megakaryocyte progenitor cells (MKPs) in patients with DPR. Treatment with the hypomethylating agent decitabine reduced methylated CG levels in MKPs and enhanced megakaryocyte production in mice. In addition, we found that DNMT3A negatively regulated megakaryogenesis in megakaryocyte lineages derived from primary HSCs. Transplantation with HSC-overexpressed DNMT3A impeded platelet engraftment following HSCT in mice. We further demonstrated that DNMT3A was directly bound to and methylated ETS1 and RUNX1 during megakaryogenesis. These findings highlight abnormal DNA methylation in DPR and indicate that hypomethylating agents may improve megakaryocyte proliferation and differentiation by targeting DNMT3A-mediated methylation.

CD34+ cell count correlates with engraftment potency after autologous stem cell transplantation. Assessment of CD34+ mainly occurs after apheresis and before cryopreservation with dimethyl sulfoxide (DMSO). The influence of postthaw CD34+ cell numbers over time to engraftment is not well studied, and determination of postthaw CD34+ cell counts is challenging for a variety of reasons. The aim of this retrospective study was to systematically assess the value of postthaw CD34+ cell counts in autologous grafts with and without DMSO removal.

… is frequent after allogeneic hematopoietic cell transplantation, especially after UCB… stem cell homing and engraftment as shown by similar rates of platelet recovery and neutrophil engraft…

BACKGROUND Autologous hematopoietic stem cell transplantation (auto-HSCT) is a cornerstone therapeutic strategy for lymphoma. Slow engraftment after auto-HSCT increases the risks of infection and hemorrhage, prolongs hospital stay, and is therefore a critical determinant of transplant safety and clinical outcomes. To date, clinical evidence on risk factors for slow engraftment after auto-HSCT in patients with lymphoma remains insufficient, particularly regarding the pretransplant immune microenvironment and lymphocyte subsets. AIM To explore clinical and immune risk factors and construct a prediction model for slow engraftment after auto-HSCT in patients with lymphoma. METHODS We retrospectively enrolled 166 patients with lymphoma who underwent auto-HSCT at two Chongqing centers from July 2022 to June 2025. Patients were divided into slow engraftment (neutrophil engraftment &gt; 10 days or platelet engraftment &gt; 12 days, based on the median times) and early engraftment groups. Baseline clinical features, transplantation parameters, pretransplant lymphocyte subsets, and inflammatory cytokines were collected. Univariate and multivariate logistic regression analyses were used to identify independent risk factors, construct a combined predictive model, and assess its performance. RESULTS Multivariate analysis identified advanced age, reinfused CD34+ cell dose &lt; 3.5 × 106/kg, a higher proportion of CD8+ T cells, a lower absolute CD4+ T-cell count, and prolonged peritransplant fever as independent risk factors for slow engraftment after auto-HSCT in lymphoma patients. Patients receiving a high CD34+ cell dose (≥ 3.5 × 106/kg) achieved faster neutrophil and platelet engraftment than those in the low-dose group. Compared with patients with early engraftment, those with slow engraftment showed pretransplant T-cell subset imbalance and elevated interleukin-2 and interferon-γ levels. A prediction model integrating these variables demonstrated good predictive performance and outperformed individual indicators, achieving an area under the curve (AUC) of 0.780 for identifying patients at risk of slow engraftment after auto-HSCT. CONCLUSION Slow engraftment after auto-HSCT is associated with clinical and immune factors. Pretransplant T-cell imbalance predicts delayed engraftment, and a combined model improves risk prediction (AUC = 0.780).

Introduction Currently, no study has determined whether platelet transfusion refractoriness (PTR) post-hematopoietic stem cell transplantation (HSCT) before engraftment in patients with myelodysplastic syndrome (MDS) would impacts clinical outcomes. Methods We performed a MDS-specific retrospective analysis to determine whether PTR in one-month post-HSCT in patients with MDS could influence outcomes. Results and discussion Among the 315 patients enrolled, 110 (34.9 %) had PTR from stem cell infusion to one-month post-HSCT. Baseline characteristics of the PTR and non-PTR groups were similar. We found that patients with PTR had a slower and lower rate of platelet engraftment by day 28, as well as a slower recovery of neutrophils. The median days of neutrophil and platelet engraftment were 14 days (9-23) and 17 days (8-28) in the PTR groups versus 13 days (9-23) and 15 days (7-28) in the non-PTR group (P<0.001). By day 28, 84 of 110 patients (76.4%) with PTR achieved platelet engraftment compared with 181 of 205 patients (88.3%) without PTR achieving platelet engraftment (P=0.007). In addition, patients in the PTR group received significantly more red blood cell (median, 17 units vs. 10 units, P<0.001) and platelet transfusions (median, 13 units vs. 7 units, P<0.001). However, the overall survival was similar between the two groups. PTR in one-month post-HSCT, haploidentical donor, and ferritin level>1041ng/ml (median level) were independent adverse factors of platelet engraftment.

… associated with delayed platelet engrnftnient after both allo-BMT and allo-PBSCT (p<OO I ). … infection and its adverse effect on platelet engraftment. Further study will be needed to …

Background Currently, there are no approved options to prevent or treat chemotherapy-induced thrombocytopenia (CIT). We performed a systematic literature review and meta-analysis on use of thrombopoietic agents for CIT. Patients and methods We searched Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, EMBASE, ClinicalTrials.gov, and health technology assessments from January 1995 to March 2021 for studies evaluating thrombopoietic agents for CIT, including recombinant human thrombopoietin (rhTPO), megakaryocyte growth and development factor (MGDF), romiplostim, and eltrombopag. Random effects meta-analyses were conducted for efficacy and safety endpoints. Results We screened 1503 titles/abstracts, assessed 138 articles, and abstracted data from 39 publications (14 recombinant human thrombopoietin, 7 megakaryocyte growth and development factor, 9 romiplostim, 8 eltrombopag, and 1 romiplostim/eltrombopag). Random effects meta-analyses of data from multiple studies comparing thrombopoietic agents versus control (comparator, placebo, or no treatment) showed that thrombopoietic agents did not significantly improve chemotherapy dose delays and/or reductions (21.1% vs 40.4%, P = 0.364), grade 3/4 thrombocytopenia (39.3% vs 34.8%; P = 0.789), platelet transfusions (16.7% vs 31.7%, P = 0.111), grade ≥ 2 bleeding (6.7% vs 16.5%; P = 0.250), or thrombosis (7.6% vs 12.5%; P = 0.131). However, among individual studies comparing thrombopoietic agents with placebo or no treatment, thrombopoietic agents positively improved outcomes in some studies, including significantly increasing mean peak platelet counts (186 x 109/L with rhTPO vs 122 x 109/L with no treatment; P < 0.05) in one study and significantly increasing platelet count at nadir (56 x 109/L with rhTPO vs 28 x 109/L with not treatment; P < 0.05) in another study. Safety findings included thrombosis (n = 23 studies) and bleeding (n = 11), with no evidence of increased thrombosis risk with thrombopoietic agents. Conclusion Our analyses generate the hypothesis that thrombopoietic agents may benefit patients with CIT. Further studies with well-characterized bleeding and platelet thresholds are warranted to explore the possible benefits of thrombopoietic agents for CIT.

Purpose To observe the efficacy and adverse reactions of eltrombopag combined with rhTPO in the treatment of lymphoma patients with chemotherapy - induced thrombocytopenia (CIT). Methods A retrospective study was performed on the clinical data of 61 patients using eltrombopag (75 mg once a day), 99 patients using rhTPO (15,000 U once daily), and 50 patients using eltrombopag (75 mg once a day) combined with rhTPO (15,000 U once daily) in the treatment of lymphoma with CIT at the First Affiliated Hospital of Guangdong Pharmaceutical University from April 2017 to May 2022.66 patients with lymphoma after chemotherapy without any platelet‐stimulating therapy were selected as observation controls. Administration of rhTPO and/or eltrombopag was initiated concurrently when the platelet count dropped below 50 × 109/L. The primary outcome measures encompassed platelet recovery, treatment duration, bleeding events, platelet transfusion requirements, and adverse events. Eltrombopag and rhTPO were discontinued when platelet count was more than 100 × 109/L. Results Pre-chemotherapy platelet count did not differ significantly among the three groups (eltrombopag, rhTPO, and combination), as indicated by P > 0.05. At day 5, mean platelet counts were (54.18 ± 20.63)×109/L (eltrombopag) (56.01 ± 28.51)×109/L (rhTPO) (68.90 ± 24.73)×109/L (combination), and (32.70 ± 15.86)×109/L (control). The combination therapy achieved significantly higher values than control (P < 0.001), rhTPO (P = 0.025), and eltrombopag (P = 0.042), while both monotherapies also showed significant elevations relative to control (both P < 0.001). At day 10, the combination group (166.30 ± 62.37 ×109/L) exhibited a significantly higher platelet count than the control (71.91 ± 42.12, P < 0.001), the rhTPO group (143.31 ± 112.45, P = 0.015), and the eltrombopag group (123.75 ± 47.90, P = 0.036). All three treatment groups demonstrated a significantly lower bleeding incidence versus the control group. The combination group had the lowest proportion of platelet transfusion units per patient (32.0%), whereas the control group had the highest (72.7%), with the eltrombopag and rhTPO groups showing intermediate rates (54.1% and 50.5%, respectively). All three treatment regimens exhibited adverse events that were mild in severity and clinically acceptable. Conclusion Eltrombopag combined with rhTPO is a effective and safe treatment for lymphoma with CIT, and the effect of the combination is better than that of eltrombopag or rhTPO alone.

… rhTPO revealed that romiplostim binds to c-Mpl on human, cynomolgus monkey, and rat platelets at sites similar to those that bind rhTPO… in vitro comparable to that of rhTPO. VB22B sc(…

… of romiplostim may have been successful in hastening platelet … rhTPO should encourage further evaluation of romiplostim to … , direct comparison of the efficacy of rhTPO and romiplostim …

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy treatment delays, dose reductions, and discontinuation. There is no US Food and Drug Administration (FDA)-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at four US centers. The primary outcome was achievement of a romiplostim response (median on-romiplostim platelet count ≥75x109/L and ≥30x109/L above baseline). Secondary outcomes included time to platelet count ≥100x109/L and rates of the following: platelet count <100×109/L, platelet count <75x109/L, platelet count <50x109/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. A total of 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of four (range: 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays, and 89% avoided platelet transfusions. Median per-patient platelet count on romiplostim was significantly higher than baseline (116x109/L vs. 60x109/L; P<0.001). Bone marrow (BM) tumor invasion, prior pelvic irradiation, and prior temozolomide exposure predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays/bleeding; intracycle dosing had an incidence rate ratio (IRR) for dose reduction/treatment delay of 3.00 (95%CI: 1.30-6.91; P=0.010) and an IRR for bleeding of 4.84 (95%CI: 1.18-19.89, P=0.029) compared with weekly dosing. Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with BM involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.

Cancer therapy-induced thrombocytopenia (CTIT) is a common complication in patients with solid tumors during their cancer treatment. The sole therapeutic agents approved for this indication are recombinant human interleukin-11 (rhIL-11) or recombinant human thrombopoietin (rhTPO). Romiplostim-N01 is a novel thrombopoietic agent launched in China in 2024, which has demonstrated preliminary therapeutic efficacy in the management of CTIT. This retrospective study compared romiplostim-N01 with rhIL-11 or rhTPO for CTIT management. Ninety-two matched consecutive patients with grade ≥2 CTIT (platelet [PLT] count < 75 × 109/L) were grouped into either the romiplostim-N01 group or the rhIL-11/rhTPO group. The primary endpoint was the proportion of treatment-marked responders, defined as patients who reached a PLT count of ≥100 × 109/L and at least 30 × 109/L higher than the pretreatment baseline within 7 days of treatment. Propensity score matching and a multivariate logistic regression model were used to estimate the treatment effects of the 2 drugs on CTIT. The 7-day marked response rate was significantly higher in the romiplostim-N01 group compared with the control group (58.7% vs 28.3%, P < .05), whereas the 14-day overall response rate was comparable between the 2 groups (89.1% vs 89.1%, P > .05). The median duration of chemotherapy delay was significantly shorter in the romiplostim-N01 group compared with the rhIL-11/rhTPO group (5.5 vs 9.5 days, P < .001). Multivariate regression analysis confirmed that romiplostim-N01 was independently associated with an elevation in PLT count. These findings position romiplostim-N01 as a favorable alternative to rhIL-11 or rhTPO in CTIT, given its enhanced early PLT response and reduced risk of chemotherapy disruption.

Thrombopoietin receptor agonists (TPO-RAs) have become an important component of pediatric immune thrombocytopenia (ITP) management, with growing evidence supporting their use in other hematologic disorders. We conducted a retrospective single-center study evaluating TPO-RA use at a pediatric oncohematology center in Poland between 1 January 2016, and 31 March 2026. Clinical indications, treatment patterns, efficacy, and safety outcomes were analyzed. Treatment response was defined as initial response (IR, platelet count [PLT] > 50 × 109/L), complete response (CR, PLT > 100 × 109/L), and sustained response (SR, PLT > 50 × 109/L maintained in ≥75% of visits over 6 months). Thirty-five patients were included in the analysis. The most common indication was ITP (27/35, 77%), followed by severe aplastic anemia (5/35, 14%), poor graft function (2/35, 6%), and inherited platelet disorders (1/35, 3%). TPO-RA use increased over time, with more than half of patients (20/35, 57%) initiating therapy between 2024 and 2026. Overall IR, CR, and SR rates were 77%, 63%, and 61%, respectively, with a median time to response of 7 days (interquartile range [IQR], 7–12.5). TPO-RAs were increasingly used earlier in the disease course, including in rescue and off-label settings. Treatment was well tolerated, with only grade 1–2 adverse events reported. Our real-world data confirm the high efficacy and favorable safety profile of TPO-RAs in pediatric patients and support their expanding role in pediatric hematology beyond disease-specific indications.