A Pilot Study to Evaluate the Safety and Feasibility of Induction of Mixed Chimerism in Severe Aplastic Anemia Patients With COH-MC-17: A Non-Myeloablative/ Reduced-Intensity, Conditioning Regimen and CD4+ T-Cell-Depleted Haploidentical Hematopoietic Transplant

This phase I trial evaluates the safety and feasibility of using a reduced-intensity regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin prior to a CD4+ T-cell depleted haploidentical hematopoietic cell transplant (haploHCT) for the treatment of patients with severe aplastic anemia that does not respond to treatment (refractory) or that has come back (recurrent). Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid. It may also lower the body's immune response. Pentostatin blocks a protein needed for cell growth. Anti-thymocyte globulin is an immunosuppressive drug can destroy immune cells known as T-cells. HaploHCT transfers blood-forming stem cells from a healthy partially-matched donor to a patient. Administering a regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin before haploHCT may help make room for the new, healthy cells and may reduce the risk of graft versus host disease.

开始日期2024-10-01

申办/合作机构

City of Hope National Medical Center

[+1]

NCT06517641 / Not yet recruiting临床2期IIT

A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Haploidentical Related, Partially HLA-Mismatched, or Matched Unrelated Bone Marrow for Newly Diagnosed Patients With Severe Aplastic Anemia

BMT CTN 2207 will investigate the use of marrow transplantation for treatment of severe aplastic anemia that has not previously been treated.

开始日期2024-09-01

申办/合作机构

Medical College of Wisconsin

[+3]

NCT06516484 / Not yet recruiting临床4期IIT

Ropustin for Refractory Aplastic Anaemia After Radiotherapy - a Single-centre, Prospective, Open-label, Single-arm Study

To investigate the efficacy and safety of roprostin in the treatment of refractory AA after radiotherapy.

开始日期2024-07-30

申办/合作机构

北京协和医院

100 项与难治性重度再生障碍性贫血相关的临床结果

登录后查看更多信息

100 项与难治性重度再生障碍性贫血相关的转化医学

登录后查看更多信息

0 项与难治性重度再生障碍性贫血相关的专利（医药）

登录后查看更多信息

403

项与难治性重度再生障碍性贫血相关的文献（医药）

2024-11-01·International Journal of Hematology

Expansion effect of romiplostim on hematopoietic stem and progenitor cells versus thrombopoietin and eltrombopag

Article

作者: Sumitomo, Yoshiki ; Nishii, Keigo ; Morishima, Tatsuya ; Onoda, Naoki ; Takizawa, Hitoshi ; Kai, Masayuki ; Tezuka, Yuta

AbstractRomiplostim, 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.

2024-09-01·Blood Cells, Molecules, and Diseases

Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP)

Review

作者: Pillon, M ; Verzegnassi, F ; Giagnuolo, G ; Bonanomi, S ; Lupia, M ; Palazzi, G ; Mariani, E ; Timeus, F ; Ramenghi, U ; Dell'Orso, G ; Martire, B ; Mastrodicasa, E ; Pestarino, S ; Saracco, P ; Zecca, M ; Angarano, R ; Corti, P ; Russo, G ; Barone, A ; Lucarelli, A ; Menna, G ; Massaccesi, E ; De Matteo, A ; Fioredda, F ; Saettini, F ; Iori, A P ; Arcuri, L ; Palmisani, E ; Miano, M ; Ladogana, S ; Onofrillo, D ; Notarangelo, L D ; Farruggia, P ; Crescenzi, B ; Barberi, W ; Pierri, F ; Dufour, C ; Guarina, A ; Giarratana, M C ; Cesaro, S

Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.

2024-08-13·Blood Advances

Modified Delphi panel consensus recommendations for management of severe aplastic anemia

Article

作者: Wlodarski, Marcin W ; Scott, Bart L ; Rogers, Zora R ; Broder, Michael S ; Patel, Bhumika J ; Maciejewski, Jaroslaw P ; DeZern, Amy E ; Gibbs, Sarah N ; Beenhouwer, David ; Tantravahi, Srinivas K ; de Castro, Carlos M ; Yermilov, Irina ; Babushok, Daria V ; Fanning, Suzanne R ; Hanna, Rabi

AbstractSevere aplastic anemia (SAA) is a rare hematologic condition for which there is no clear management algorithm. A panel of 11 experts on adult and pediatric aplastic anemia was assembled and, using the RAND/University of California, Los Angeles modified Delphi panel method, evaluated >600 varying patient care scenarios to develop clinical recommendations for the initial and subsequent management of patients of all ages with SAA. Here, we present the panel’s recommendations to rule out inherited bone marrow failure syndromes, on supportive care before and during first-line therapy, and on first-line (initial management) and second-line (subsequent management) therapy of acquired SAA, focusing on when transplant vs medical therapy is most appropriate. These recommendations represent the consensus of 11 experts informed by published literature and experience. They are intended only as general guidance for experienced clinicians who treat patients with SAA and are in no way intended to supersede individual physician and patient decision making. Current and future research should validate this consensus using clinical data. Once validated, we hope these expert panel recommendations will improve outcomes for patients with SAA.