An Innovative Approach to Bone Marrow Collection and Transplantation in a Patient with β-Thalassemia Major: Marrow Collection Using a Perfusion Method Followed by Intra-Bone Marrow Injection of Collected Bone Marrow Cells

Abstract

Using small animals (mice and rats) and monkeys, we have found that the combination of bone marrow collection using the perfusion method (PM) and intra-bone marrow-bone marrow transplantation (IBM-BMT) of the collected cells is safe and effective in treating various intractable diseases. Based on these findings, we attempted to apply this method to humans. We report here the first case of a patient (6 years old) with beta-thalassemia major who underwent allogeneic BMT using this new PM + IBM-BMT method. The white blood cell counts of the patient gradually increased to more than 1500/microL by day 47 and continued to increase, reaching the highest level (8600/microL) on day +55. Fluorescence in situ hybridization data on day +33 showed that 98% of the peripheral blood cells were from the donor. Notably, there were no symptoms of graft-versus-host disease (GvHD). However, on day +56, the patient regrettably died of asphyxia resulting from sticky sputum. There was no evidence of infection (in the lung or liver) or GvHD (in the skin) by necropsy. We hope that this case report will help make our new strategies more readily available for the treatment of patients with various intractable diseases.

A novel method of bone marrow transplantation (BMT) for intractable autoimmune diseases

“…Regrettably, however, the patient suddenly died on day þ56 of asphyxia resulting from sticky sputum. There was no evidence of infection (in the lung or liver) or GvHD (in the skin) by necropsy [57].…”

“…Based on these findings, we carried out PM þ IBM-BMT in a patient with b-thalassemia major [57]. The recipient was a 6-year-old girl, and the donor was her 37-year-old father (4/6 HLA-matched).…”

Will hematopoietic stem cell transplantation cure human autoimmune diseases?

“…Also human blood SC were shown to be capable of suppressing antibody production in lupus mice [16], perhaps the first demonstration of a curative effect by xenogeneic SCT. Further recent improvements, always in experimental animals, have been the perfusion of the marrow source in order to avoid contamination with circulating T cells [17], and the intra-bone injection of the same [18,19], which had been first utilized for the treatment of experimental ADs [20], and is now being transferred to the clinic [20,21].…”

Ex Vivo Culture of Human Cord Blood Hematopoietic Stem/Progenitor Cells Adversely Influences Their Distribution to Other Bone Marrow Compartments After Intra-Bone Marrow Transplantation

“…Intra-bone marrow transplantation (IBMT) is a novel transplantation method that delivers cells directly into the bone marrow [1,2]. During standard i.v.…”