A myeloablative conditioning regimen with fludarabine demonstrates good results in UCBT for 30 pediatric patients with hematologic malignancies, especially acute lymphoblastic leukemia

Abstract

We retrospectively analyzed the safety and efficacy of a myeloablative conditioning regimen with fludarabine (FLU) in unrelated cord blood transplantation (UCBT) of 30 pediatric patients with hematologic malignancies. The conditioning regimen consisted of FLU, busulfan (BU) and cyclophosphamide (CY). All of the patients received Cyclosporine (CSA) and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prophylaxis. We achieved high engraftment rates (96.7%) and rapid hematopoietic reconstitution. Acute GVHD occurred in 12 cases of the 29 engraftment patients (41.4%), and 6 cases (20.7%) were of grade III-IV. Chronic GVHD only occurred in 1 of 28 evaluable patients (3.6%). Twenty-three patients (76.7%) became infected, and 3 cases (10.0%) died of severe infections. Cytomegalovirus (CMV) reactivation occurred in 70.0% of the patients, but no CMV diseases were observed, nor did any patients die of CMV infection. The cumulative incidence of relapse (6.7%) was significantly reduced, and none of the acute lymphoblastic leukemia (ALL) patients relapsed. The 3-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 70.0%, respectively. The 3-year OS and EFS of the ALL patients was 75.0%. This conditioning regimen demonstrates good results and security in UCBT, especially in acute lymphoblastic leukemia. Key words: conditioning regimen, cord blood transplant, fludarabine, hematologic malignanciesUmbilical cord blood transplantation (UCBT) has increasingly been used as a therapeutic option for patients affected by many disorders of either hematologic or non-hematologic origin [1][2][3]. In comparison to bone marrow transplantation (BMT), UCBT offers the advantage of easier procurement with no risk for the donor. In addition, there are lower risks of transmitting infections and of developing both acute and chronic GVHD. Despite the lower incidence of acute and chronic GVHD in UCB transplant recipients, the risk of leukemia relapse is not increased [4,5]. UCBT allows also transplantation in the absence of full HLA compatibility in the donor/recipient pair. Moreover, UCBT from unrelated donors offers the advantage of rapid availability of cryopreserved cells, and the median time for a successful donor search is less than 1 month [6]. However, there are also some drawbacks with UCBT in comparison with BMT. The nucleated cells contained in umbilical cord blood constitute only 1/10 of the number of nucleated cells in the peripheral blood stem cells or bone marrow. Additionally, the T and B lymphocytes contained in umbilical cord blood are in their naïve state [7]. The limited number of cells and low immunogenicity of the nucleated cells could lead to the high incidence of engraftment failure and might slow hematopoietic and immune reconstitution, which could result in the high incidence of early opportunistic infections [8,9].How to increase the UCBT engraftment rate and reduce the incidence of infections is an important area of study. Researchers have attempted to solve both of these problems ...

Potential mechanisms for cell-based gene therapy to treat HIV/AIDS

“…In this regard the use of mild myeloablation methods may facilitate more efficient engraftment by making space for the gene-modified HSCs. This approach can be used in a safe manner in a gene therapy setting [152][153][154][155].…”

Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival

“…Umbilical cord blood transplantation (UCBT) is an important approach for patients with hematological diseases, and its use has made HSCT available to additional patients [ 5 ]. Starting in 2007, our transplant center began to use an intensive myeloablative conditioning regimen without antithymocyte globulin (ATG) for UCBT and cyclosporine combined with mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis [ 6 , 7 ]. After using this protocol, we increased the UCBT engraftment rate; in addition, the infection rate, transplantation-related mortality, and relapse rate were decreased, while the incidence of acute GVHD (aGVHD) and chronic GVHD (cGVHD) did not increase [ 8 ].…”