Loan Hsieh

Thrombopoietic Agents for the Treatment of Persistent and Chronic Immune Thrombocytopenia in Children

OBJECTIVES To determine the safety, tolerability, or efficacy of 2 licensed thrombopoietic agents in children with persistent and chronic immune thrombocytopenia (ITP). STUDY DESIGN Retrospective analysis approved by the institutional review board of children with ITP not on-study who received thrombopoietin (TPO) therapy; 21 received romiplostim (11 at Childrens Hospital of Orange County, 10 at Weill Cornell Medical Center) and 12 received eltrombopag (all at Weill Cornell Medical Center). Primary response measures were platelet counts ≥ 50 × 10(9)/L or ≥ 20 × 10(9)/L above baseline for 2 consecutive weeks and 50% of platelet counts ≥ 50 × 10(9)/L. Duration of treatment and adverse events, including bone marrow myelofibrosis (MF) consensus grades, were tabulated. RESULTS Twenty-seven of 33 (82%) patients responded to TPO agents, 18 of 21 to romiplostim, and 9 of 12 to eltrombopag, after an average of 3.6 previous ITP therapies. These 27 patients had platelet counts ≥ 50 × 10(9)/L and ≥ 20 × 10(9)/L above baseline for 2 consecutive weeks; 26 had 50% of platelet counts ≥ 50 × 10(9)/L. Duration of romiplostim use ranged from 6 to 44 months (11/18 ongoing) and of eltrombopag 23 to 53 months (7/12 ongoing). One patient on eltrombopag experienced a provoked deep-vein thrombosis at site of ankle fracture. No other serious drug-related adverse events occurred. Among 24 bone marrows, 10 after greater than 2 years of therapy, 23 were normal (MF grades 0-1); 1 was MF-2. CONCLUSION Retrospective analysis of off-study use of TPO agents in children with mainly chronic ITP showed increases in platelet counts in more than 4 of 5 children. The long-term use of TPO agents, up to 53 months, without tachyphylaxis supports their efficacy. These agents appear safe, effective, and tolerable in children with chronic ITP.

Unrelated hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia and iron overload

Buchbinder D, Nugent D, Vu D, Soni A, Stites J, Hsieh L, Puthenveetil G. Unrelated hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia and iron overload.

Successful treatment of post-transplant thrombocytopenia with romiplostim in a pediatric patient with X-linked chronic granulomatous disease.

Thrombocytopenia is a frequent complication following HSCT in pediatric patients. Romiplostim is a TPO receptor agonist that has been utilized successfully in the treatment of pediatric patients with immune thrombocytopenia. We describe a three‐yr‐old male with X‐linked CGD treated with an unrelated donor bone marrow transplant. His course was complicated by the development of symptomatic thrombocytopenia. He was started on romiplostim with prompt improvement in his thrombocytopenia. We found the use of romiplostim to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of immunosuppressive agents such as corticosteroids.

Successful cord blood transplantation in a patient with malignant infantile osteopetrosis and hemophilia

Buchbinder D, Steward CG, Puthenveetil G, Nugent D, Hsieh L, Kirov I, Neudorf S, Soni A. Successful cord blood transplantation in a patient with malignant infantile osteopetrosis and hemophilia.

Rare factor deficiencies.

Purpose of reviewBy definition, rare factor deficiencies have a prevalence of less than 200 000 in the US population, or an incidence of less than one in 2000 in Europe. The very small numbers of patients with rare disorders present challenges in diagnosis, evaluation of bleeding risk and treatment. Use of new assays, full genome sequencing, and global clotting assays will significantly improve diagnosis of patients with rare bleeding disorders. Recent findingsIn addition to new assays available for monitoring patients, new therapy, both recombinant and plasma derived, is now available. Registries and clinical trials have demonstrated decreased bleeding and improved outcomes when patients are treated with these agents. Expanding international registries have been initiated to correlate genotype and bleeding phenotype in conjunction with global assays. SummaryOngoing research continues to expand our understanding of the pathophysiology of rare factor deficiencies. This work complements medical practice to incorporate early diagnosis and new treatment options for patients, resulting in safer and less sensitizing regimens and much improved clinical outcomes.

Spotlight on romiplostim in the treatment of children with chronic immune thrombocytopenia: design, development, and potential place in therapy

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia. In approximately one-third of cases, the duration of thrombocytopenia will extend beyond 12 months consistent with a diagnosis of chronic ITP. Minor bleeding manifestations are common in chronic ITP while severe or life-threatening bleeding complications are uncommon. Moreover, spontaneous resolution occurs in the majority of children with chronic ITP necessitating treatment in only those children with ongoing bleeding manifestations or impairment in health-related quality of life (HRQOL). The characterization of thrombopoietin (TPO) and remarkable advancements in our understanding of the pathophysiology of ITP has led to the development of a new class of agents, the TPO-receptor agonists that have documented efficacy in the amelioration of thrombocytopenia and bleeding manifestations in chronic ITP. Romiplostim is a second-generation TPO-receptor agonist that has undergone limited evaluation in the treatment of chronic ITP in children. Evolving data suggest that romiplostim may be a safe and effective agent in the treatment of chronic ITP in children. Additional data are needed to confirm its ability to increase platelet counts, decrease bleeding manifestation, and improve the HRQOL of children and caregivers impacted by chronic ITP.

Successful treatment of secondary graft failure following unrelated cord blood transplant with hematopoietic growth factors in a pediatric patient with Fanconi anemia

Graft failure following allogeneic HCT in Fanconi anemia is associated with significant mortality. Retransplantation may be considered; however, the limited toxicity profile of HGFs also makes them an option for the treatment of graft failure. We describe a five‐yr‐old female diagnosed with Fanconi anemia and marrow failure treated with HCT. The course was complicated by secondary graft failure treated successfully with HGFs including G‐CSF, EPO, and romiplostim. The outcome could be related to the intervention, but could also be the natural course of recovery, including recovering from a recent CMV infection treated with ganciclovir. We found the use of HGFs to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of retransplantation.

Inflammatory polyps following successful HLA‐matched cord blood transplantation in a patient with X‐linked lymphoproliferative syndrome

Buchbinder D, Younes B, Sassoon A, Soni A, Hsieh L, Puthenveetil G, Stites J, Ness‐Jorden T, Neudorf S, Nugent D. Inflammatory polyps following successful HLA‐matched cord blood transplantation in a patient with X‐linked lymphoproliferative syndrome.