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Blood Jul 2014An essential component of allogeneic and autologous hematopoietic cell transplantation (HCT) is the conditioning regimen administered before the hematopoietic cell... (Review)
Review
An essential component of allogeneic and autologous hematopoietic cell transplantation (HCT) is the conditioning regimen administered before the hematopoietic cell infusion. Early regimens relied on dose intensity, assuming that high-dose chemoradiotherapy would eliminate malignant disease and reinfusion of the graft would then restore hematopoiesis. However, as the contribution of graft-versus-tumor effects to the success of allogeneic HCT was recognized over time, in an effort to exploit these, many investigators lowered the dose of radiation and chemotherapeutic agents in the preparative regimen. This resulted in a major paradigm shift, and consequently, the pool of eligible patients underwent a remarkable expansion. In this article, we provide a review of the definition of high-dose, reduced-intensity, and nonmyeloablative conditioning regimens, the most commonly used agents and combinations, and the evolution of some early regimens. We also provide a brief review of the toxicities associated with these regimens.
Topics: Allografts; Antilymphocyte Serum; Antineoplastic Combined Chemotherapy Protocols; Autografts; Clinical Trials as Topic; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Myeloablative Agonists; Radioimmunotherapy; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 24914142
DOI: 10.1182/blood-2014-02-514778 -
Biology of Blood and Marrow... Dec 2009Defining conditioning regimen intensity has become a critical issue for the hemopoietic stem cell transplant (HSCT) community. In the present report we propose to define...
Defining conditioning regimen intensity has become a critical issue for the hemopoietic stem cell transplant (HSCT) community. In the present report we propose to define conditioning regimens in 3 categories: (1) myeloablative (MA) conditioning, (2) reduced-intensity conditioning (RIC), and (3) nonmyeloablative (NMA) conditioning. Assignment to these categories is based on the duration of cytopenia and on the requirement for stem cell (SC) support: MA regimens cause irreversible cytopenia and SC support is mandatory. NMA regimens cause minimal cytopenia, and can be given also without SC support. RIC regimens do not fit criteria for MA or NMA regimens: they cause cytopenia of variable duration, and should be given with stem cell support, although cytopenia may not be irreversible. This report also assigns commonly used regimens to one of these categories, based upon the agents, dose, or combinations. Standardized classification of conditioning regimen intensities will allow comparison across studies and interpretation of study results.
Topics: Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Transplantation Conditioning
PubMed: 19896087
DOI: 10.1016/j.bbmt.2009.07.004 -
Blood Reviews Jan 2020Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at increased risk for developing infections due to underlying... (Review)
Review
Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at increased risk for developing infections due to underlying immunosuppression. Antibiotic use, and in HSCT recipients, the use of preparative regimens prior to transplantation can deplete gut commensal bacteria, resulting in intestinal dysbiosis. Emerging evidence in transplant patients, particularly HSCT, suggest that disturbances in gut microbiota populations are associated with a number of adverse outcomes. Here, we review the outcomes of HSCT and SOT recipients with gut microbiota imbalance or dysbiosis, explore the nascent field of gut microbiome therapeutic approaches including fecal microbiota transplantation and the use of precision probiotics in HSCT and SOT recipients.
Topics: Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Hematopoietic Stem Cell Transplantation; Humans; Organ Transplantation; Transplantation Conditioning
PubMed: 31492463
DOI: 10.1016/j.blre.2019.100614 -
Current Opinion in Hematology Jul 2017Hematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including... (Review)
Review
PURPOSE OF REVIEW
Hematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including infection, inflammation, and exsanguination. HSCs possess the remarkable ability to reconstitute the entire hematopoietic system of an organism whose own hematopoietic system has been ablated. This ability is exploited routinely in the clinic via HSC transplantation (HSCT). Here, we focus on the physiological and molecular bottlenecks overcome by HSCs during transplantation.
RECENT FINDINGS
During transplantation, HSCs encounter a damaged bone marrow niche, characterized molecularly by increases in oxygen concentrations and an altered cytokine milieu. New mechanisms and pathways have been recently implicated during HSCT, including transplanted HSC-dependent secretion of conditioning molecules that facilitate engraftment and pathways that protect HSCs from perturbed organelle homeostasis.
SUMMARY
Better understanding the molecular processes HSCs employ to withstand the stress of transplant will illuminate novel targets for further improving conditioning regimens and engraftment during HSCT.
Topics: Animals; Cell Movement; Epigenesis, Genetic; Gene Expression Regulation; Graft Survival; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Homeostasis; Humans; Organelles; Oxidative Stress; Reactive Oxygen Species; Stem Cell Niche; Stress, Physiological; Transplantation Conditioning
PubMed: 28375987
DOI: 10.1097/MOH.0000000000000347 -
Blood Mar 2022
Topics: Transplantation Conditioning; Transplantation, Haploidentical
PubMed: 35267004
DOI: 10.1182/blood.2021014532 -
Hematology/oncology and Stem Cell... Dec 2017Allotransplantation cures patients by cytoreduction and the graft-versus-tumor (leukemia; graft-versus-leukemia [GVL]) alloresponse; both eliminate residual disease. The... (Review)
Review
Allotransplantation cures patients by cytoreduction and the graft-versus-tumor (leukemia; graft-versus-leukemia [GVL]) alloresponse; both eliminate residual disease. The spectrum of conditioning intensity influences toxicities and non-relapse mortality. The spectrum of tumor sensitivity to the GVL response influences relapse. Balancing tolerable toxicities (influenced by patients' performance status and comorbidities) is also influenced by the graft. Intense immunosuppression (for engraftment and graft-versus-host disease prevention) may constrain the immunologic potency of the graft and limit the antineoplastic capacity of the transplant, thus requiring more intense or more effective conditioning regimens to limit the risks of relapse and permit satisfactory disease-free survival.
Topics: Allografts; Graft Survival; Graft vs Host Disease; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Neoplasms; Transplantation Conditioning
PubMed: 28641099
DOI: 10.1016/j.hemonc.2017.05.002 -
Hematology. American Society of... Nov 2018The remarkable clinical activity of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has transformed patient outcome. Consequently, allogeneic stem... (Review)
Review
The remarkable clinical activity of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has transformed patient outcome. Consequently, allogeneic stem cell transplantation (allo-SCT) is no longer the only treatment modality with the ability to deliver long-term survival. In contrast to the central position it held in the treatment algorithm 20 years ago, allografting is now largely reserved for patients with either chronic-phase disease resistant to TKI therapy or advanced-phase disease. Over the same period, progress in transplant technology, principally the introduction of reduced intensity conditioning regimens coupled with increased donor availability, has extended transplant options in patients with CML whose outcome can be predicted to be poor if they are treated with TKIs alone. Consequently, transplantation is still a vitally important, potentially curative therapeutic modality in selected patients with either chronic- or advanced-phase CML. The major causes of transplant failure in patients allografted for CML are transplant toxicity and disease relapse. A greater understanding of the distinct contributions made by various factors such as patient fitness, patient-donor HLA disparity, conditioning regimen intensity, and transplant toxicity increasingly permits personalized transplant decision making. At the same time, advances in the design of conditioning regimens coupled with the use of adjunctive posttransplant cellular and pharmacologic therapies provide opportunities for reducing the risk of disease relapse. The role of SCT in the management of CML will grow in the future because of an increase in disease prevalence and because of continued improvements in transplant outcome.
Topics: Algorithms; Allografts; Drug Resistance, Neoplasm; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Stem Cell Transplantation; Transplantation Conditioning
PubMed: 30504307
DOI: 10.1182/asheducation-2018.1.177 -
Haematologica May 2016Most hematological malignancies occur in older patients. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic... (Review)
Review
Most hematological malignancies occur in older patients. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic hematopoietic transplantation because they were unable to tolerate the heretofore used high-dose conditioning regimens. The finding that many of the cures achieved with allogeneic hematopoietic transplantation were due to graft-versus-tumor effects led to the development of less toxic and well-tolerated reduced intensity and nonmyeloablative regimens. These regimens enabled allogeneic engraftment, thereby setting the stage for graft-versus-tumor effects. This review summarizes the encouraging early results seen with the new regimens and discusses the two hurdles that need to be overcome for achieving even greater success, disease relapse and graft-versus-host disease.
Topics: Animals; Comorbidity; Disease Models, Animal; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Mortality; Recurrence; Tissue Donors; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome
PubMed: 27132278
DOI: 10.3324/haematol.2015.132860 -
Transplantation and Cellular Therapy Oct 2022Shwachman-Diamond syndrome is a rare disorder that can develop malignant and nonmalignant hematological complications. Overall, 10% to 20% of Shwachman-Diamond patients...
Shwachman-Diamond syndrome is a rare disorder that can develop malignant and nonmalignant hematological complications. Overall, 10% to 20% of Shwachman-Diamond patients need hematopoietic stem cell transplantation (HSCT), but most centers have a limited experience and different approaches. The European Society for Blood and Marrow Transplantation-Severe Aplastic Anaemia Working Party promoted an expert consensus to propose recommendations regarding key issues in the management of Shwachman-Diamond patients with hematological complications. The main items identified as relevant for improving survival were: the importance of regular and structured hematologic follow-up, the potential reduction of transplant-related mortality by using reduced-intensity conditioning regimens, the limitation of total body irradiation, particularly for non-malignant severe cytopenia/bone marrow failure, the early diagnosis of clonal malignant evolution and early recognition of an indication for HSCT. Finally, the poor results of HSCT in patients with acute myeloid leukemia, irrespective of cytoreductive chemotherapy treatment received prior to transplantation, highlights the need for innovative approaches. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Topics: Anemia, Aplastic; Consensus; Hematopoietic Stem Cell Transplantation; Humans; Shwachman-Diamond Syndrome; Transplantation Conditioning
PubMed: 35870777
DOI: 10.1016/j.jtct.2022.07.010 -
Hematology. American Society of... Dec 2016Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Broad application is hindered by high risks of... (Review)
Review
Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Broad application is hindered by high risks of transplant-related morbidity and mortality, especially in the older age range represented by the MDS population. However, recent advances in strategies to minimize regimen-related toxicity make HCT a viable option for many more patients. Appropriate selection of patients involves consideration of patient factors, including use of geriatric assessment tools and comorbidity scales, that predict risks of regimen-related toxicity as well as disease factors, including genetic markers, which predict survival with both non-HCT and HCT therapy. Optimal timing of HCT for fit patients must consider MDS risk scores and life-years to be gained, with earlier transplantation indicated for patients with intermediate-2 and high-risk disease but judicious delay for lower risk patients. Selection of suitable conditioning regimens must balance risks of toxicity with opportunity for maximum disease control.
Topics: Allografts; Hematopoietic Stem Cell Transplantation; Humans; Myelodysplastic Syndromes; Risk Factors; Transplantation Conditioning
PubMed: 27913519
DOI: 10.1182/asheducation-2016.1.478