Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.
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ABSTRACT:
SUBMITTER: Schwabkey ZI
PROVIDER: S-EPMC8353672 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.
Schwabkey Zaker I ZI Jenq Robert R RR
Annual review of medicine 20200101
The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these ...[more]
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Project description:BackgroundMyeloablative allogeneic hematopoietic stem-cell transplantation is curative in children with sickle cell disease, but in adults the procedure is unduly toxic. Graft rejection and graft-versus-host disease (GVHD) are additional barriers to its success. We performed nonmyeloablative stem-cell transplantation in adults with sickle cell disease.MethodsTen adults (age range, 16 to 45 years) with severe sickle cell disease underwent nonmyeloablative transplantation with CD34+ peripheral-blood stem cells, mobilized by granulocyte colony-stimulating factor (G-CSF), which were obtained from HLA-matched siblings. The patients received 300 cGy of total-body irradiation plus alemtuzumab before transplantation, and sirolimus was administered afterward.ResultsAll 10 patients were alive at a median follow-up of 30 months after transplantation (range, 15 to 54). Nine patients had long-term, stable donor lymphohematopoietic engraftment at levels that sufficed to reverse the sickle cell disease phenotype. Mean (+/-SE) donor-recipient chimerism for T cells (CD3+) and myeloid cells (CD14+15+) was 53.3+/-8.6% and 83.3+/-10.3%, respectively, in the nine patients whose grafts were successful. Hemoglobin values before transplantation and at the last follow-up assessment were 9.0+/-0.3 and 12.6+/-0.5 g per deciliter, respectively. Serious adverse events included the narcotic-withdrawal syndrome and sirolimus-associated pneumonitis and arthralgia. Neither acute nor chronic GVHD developed in any patient.ConclusionsA protocol for nonmyeloablative allogeneic hematopoietic stem-cell transplantation that includes total-body irradiation and treatment with alemtuzumab and sirolimus can achieve stable, mixed donor-recipient chimerism and reverse the sickle cell phenotype. (ClinicalTrials.gov number, NCT00061568.)
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