Intrabone Transplantation of a Single Unwashed Umbilical Cord Blood Unit with Antithymocyte Globulin-Free and Sirolimus-Based Graft-versus-Host Disease Prophylaxis: Fast Immune Reconstitution and Long-Term Disease Control in Patients with High-Risk Diseases

Giglio, Fabio; Xue, Ensheng; Barone, Angelica; Lorentino, Francesca; Greco, Raffaella; Ruggeri, Annalisa; Zambelli, Matilde; Parisi, Cristina; Milani, Raffaella; Clerici, Daniela; Piemontese, Simona; Marktel, Sarah; Lazzari, Lorenzo; Marcatti, Magda; Bernardi, Massimo; Corti, Consuelo; Lupo-Stanghellini, Maria Teresa; Ciceri, Fabio; Peccatori, Jacopo

doi:10.1016/j.jtct.2023.05.015

Cited by 1 publication

(1 citation statement)

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“…Sirolimus (rapamycin) is approved by Food and Drug Administration and other regulatory authorities to prevent organ rejection in patients receiving renal transplantation [ 44 , 45 , 46 ]. Moreover, a high number of clinical studies have been published using sirolimus as bioactive molecules in the treatment of patients who underwent transplantation of the lung [ 47 ], heart [ 48 ], pancreas [ 49 ], liver [ 50 ], intestine [ 51 ], cornea [ 52 ], and bone marrow [ 53 ]. Consequently, sirolimus (rapamycin) is of great interest for several pathologies in which transplantation is a clinical option, including (but not restricted to) solid cancers (for instance liver transplantation in hepatocellular carcinoma, or kidney transplantation in renal cancers) [ 54 , 55 ], leukemia, lymphoma and other blood cancers (for instance bone marrow transplantation in leukemia) [ 56 ], cystic fibrosis (lung transplantation) [ 57 ], serine/threonine kinase 4 (STK4) deficiency, characterized by recurrent bacterial, viral, and fungal infections (allogeneic hematopoietic stem cell transplantation, HSCT) [ 58 ], and hematological diseases (bone marrow transplantation) [ 59 ].…”

Section: Rapamycin In Organ and Tissue Transplantationmentioning

confidence: 99%

The Long Scientific Journey of Sirolimus (Rapamycin): From the Soil of Easter Island (Rapa Nui) to Applied Research and Clinical Trials on β-Thalassemia and Other Hemoglobinopathies

Gambari,

Zuccato,

Cosenza

et al. 2023

Biology

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In this review article, we present the fascinating story of rapamycin (sirolimus), a drug able to induce γ-globin gene expression and increased production of fetal hemoglobin (HbF) in erythroid cells, including primary erythroid precursor cells (ErPCs) isolated from β-thalassemia patients. For this reason, rapamycin is considered of great interest for the treatment of β-thalassemia. In fact, high levels of HbF are known to be highly beneficial for β-thalassemia patients. The story of rapamycin discovery began in 1964, with METEI, the Medical Expedition to Easter Island (Rapa Nui). During this expedition, samples of the soil from different parts of the island were collected and, from this material, an antibiotic-producing microorganism (Streptomyces hygroscopicus) was identified. Rapamycin was extracted from the mycelium with organic solvents, isolated, and demonstrated to be very active as an anti-bacterial and anti-fungal agent. Later, rapamycin was demonstrated to inhibit the in vitro cell growth of tumor cell lines. More importantly, rapamycin was found to be an immunosuppressive agent applicable to prevent kidney rejection after transplantation. More recently, rapamycin was found to be a potent inducer of HbF both in vitro using ErPCs isolated from β-thalassemia patients, in vivo using experimental mice, and in patients treated with this compound. These studies were the basis for proposing clinical trials on β-thalassemia patients.

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