Abstract
Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched), and provide a summary of the risks and benefits of using T-cell depletion.
Highlights
Cytogenetic risk stratification in acute myelogenous leukemia (AML) allows clinicians to determine which patients are most likely to benefit from allogeneic hematopoietic stem cell transplantation (HCT), with evidence to support a survival advantage in patients with intermediate or high-risk cytogenetics [1].In addition to more accurate patient selection based on cytogenetic risk factors, over the past decades, transplantation outcomes have improved as a result of more accurate patient selection tools, such as the HCT Sorror comorbidity index [2], improvements in HLA matching techniques and supportive care.Despite these improvements, graft-versus-host disease (GVHD) remains a leading cause of post-transplant morbidity and mortality
Contemporary studies have utilized two main approaches of T-cell depletion (TCD) by CD34+ selection described above, either the ISOLEX 300i Magnetic Cell Separator followed by sheep red blood cell (sRBC)-rosette depletion or, more recently, the Miltenyi CliniMACS CD34 Reagent System
A hundred and seven patients in the MSKCC cohort received peripheral blood stem cells (PBSCs) grafts, including 85 that were CD34-selected with the ISOLEX 300i Magnetic Cell Separator followed by sRBC-rosette depletion, and 22 with the Miltenyi CliniMACS CD34 Reagent System
Summary
Cytogenetic risk stratification in acute myelogenous leukemia (AML) allows clinicians to determine which patients are most likely to benefit from allogeneic hematopoietic stem cell transplantation (HCT), with evidence to support a survival advantage in patients with intermediate or high-risk cytogenetics [1]. In addition to more accurate patient selection based on cytogenetic risk factors, over the past decades, transplantation outcomes have improved as a result of more accurate patient selection tools, such as the HCT Sorror comorbidity index [2], improvements in HLA matching techniques and supportive care. Despite these improvements, graft-versus-host disease (GVHD) remains a leading cause of post-transplant morbidity and mortality. Other methods of T-cell depletion will be mentioned for historic context only
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