-
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 -
Transfusion and Apheresis Science :... Apr 2018Graft failure is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) defined as either lack of initial engraftment of donor cells... (Review)
Review
Graft failure is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Successful transplantation depends on the formation of engrafment, in which donor cells are integrated into the recipient's cell population. In this paper, we distinguish two different entities, graft failure (GF) and poor graft function (PGF), and review the current comprehensions of the interactions between the immune and hematopoietic compartments in these conditions. Factors associated with graft failure include histocompatibility locus antigen (HLA)-mismatched grafts, underlying disease, type of conditioning regimen and stem cell source employed, low stem cell dose, ex vivo T-cell depletion, major ABO incompatibility, female donor grafts for male recipients, disease status at transplantation. Although several approaches have been developed which aimed to prevent graft rejection, establish successful engraftment and treat graft failure, GF remains a major obstacle to the success of allo-HSCT. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) still remains to be the curative treatment option for various non-malignant and malignant hematopoietic diseases. The outcome of allo-HSCT primarily depends on the engraftment of the graft. Graft failure (GF), is a life-threatening complication which needs the preferential therapeutic manipulation. In this paper, we focused on the definitions of graft failure / poor graft function and also we reviewed the current understanding of the pathophysiology, risk factors and treatment approaches for these entities.
Topics: Female; Graft Rejection; Hematopoietic Stem Cell Transplantation; Humans; Male; Transplantation Conditioning; Transplantation, Homologous
PubMed: 29724627
DOI: 10.1016/j.transci.2018.04.014 -
Critical Reviews in Oncology/hematology Mar 2018Hematologic malignancies may require, at one point during their treatment, allogeneic bone marrow transplantation. Total body irradiation combined with chemotherapy or... (Review)
Review
Hematologic malignancies may require, at one point during their treatment, allogeneic bone marrow transplantation. Total body irradiation combined with chemotherapy or radiomimetic used in allogeneic bone marrow transplantation is known to be very toxic. Total body irradiation (TBI) induces immunosuppression to prevent the rejection of donor marrow. TBI is also used to eradicate malignant cells and is in sanctuary organs that are not reached by chemotherapy drugs. TBI has evolved since its introduction in the late fifties, but acute and late toxicities remain. Helical tomotherapy, which is widely used for some solid tumors, is a path for the improvement of outcomes and toxicities in TBI because of its sparing capacities. In this article, we first review the practical aspects of TBI with patient positioning, radiobiological considerations and total dose and fractionation prescriptions. Second, we review the use of intensity modulated radiation therapy in bone marrow transplantation with a focus on helical tomotherapy TBI, helical tomotherapy total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) and their dosimetric and clinical outcomes. Finally, we review the perspective of dose escalation and the extension to older patients and patients with comorbidity who do not benefit from a standard bone marrow transplantation conditioning regimen.
Topics: Age Factors; Bone Marrow; Bone Marrow Transplantation; Comorbidity; Humans; Neoplasms; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Transplantation Conditioning; Transplantation, Homologous; Whole-Body Irradiation
PubMed: 29482775
DOI: 10.1016/j.critrevonc.2018.01.011 -
Bone Marrow Transplantation Nov 2009Reduced-intensity conditioning (RIC) preparative regimens are now widely used in umbilical cord blood (UCB) transplantation. Developed to reduce the rate of... (Review)
Review
Reduced-intensity conditioning (RIC) preparative regimens are now widely used in umbilical cord blood (UCB) transplantation. Developed to reduce the rate of transplant-related morbidity and mortality as in adult stem cell donor transplantation, they are becoming more widely accepted. Results from RIC UCB series show a shortened time to engraftment, ranging from 12 to 24 days, with rates of TRM that generally do not exceed the rates seen with myeloablative UCB transplantation. There does not seem to be a convincing trend toward an increase in the rate of malignant relapse after RIC UCB transplantation, despite the lower intensity of the conditioning regimen. In this review, the results from several RIC UCB series are reviewed, comparisons with myeloablative UCB experiences are made and hypotheses regarding the engraftment potential of UCB after RIC regimens are discussed. In addition, a strategy for the optimal use of RIC regimens and UCB transplantation is presented.
Topics: Adult; Aged; Animals; Clinical Trials as Topic; Cord Blood Stem Cell Transplantation; Humans; Middle Aged; Transplantation Conditioning; Treatment Outcome; Young Adult
PubMed: 19802028
DOI: 10.1038/bmt.2009.283 -
The New England Journal of Medicine Jun 2022
Topics: Bone Marrow Transplantation; Chimerism; Hematopoietic Stem Cell Transplantation; Humans; Transplantation Chimera; Transplantation Conditioning; Transplantation Tolerance
PubMed: 35704487
DOI: 10.1056/NEJMe2204651 -
Expert Review of Hematology Jun 2014Development of reduced-intensity conditioning regimens (RIC) has enabled older or medically infirm patients with hematologic malignancies to be treated with allogeneic... (Review)
Review
Development of reduced-intensity conditioning regimens (RIC) has enabled older or medically infirm patients with hematologic malignancies to be treated with allogeneic hematopoietic cell transplantation (HCT). This broader transplant eligibility has tripled the number of RIC-HCT procedures performed each year, with over 3000 in 2012. Currently about 50% of RIC-HCTs use unrelated donors, since many patients are older and do not have matched sibling donors. Naturally, this makes graft-versus-host disease (GVHD) prevention of particular importance. The ideal GVHD prophylaxis must balance tumor control/GVL with toxicity/GVHD. In this review, we discuss challenges in developing effective GVHD prophylaxis for RIC-HCT, various GVHD prophylactic regimens that are sometimes specific to the conditioning regimen, and the evidence to support their use.
Topics: Animals; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Transplantation Conditioning; Transplantation, Homologous
PubMed: 24702163
DOI: 10.1586/17474086.2014.898561 -
Hematology/oncology and Stem Cell... 2011High-dose chemotherapy followed by autologous hematopoietic cell transplantation continues to play an integral role in the treatment strategy in patients with newly... (Review)
Review
High-dose chemotherapy followed by autologous hematopoietic cell transplantation continues to play an integral role in the treatment strategy in patients with newly diagnosed multiple myeloma. Incorporation of newer potent anti-myeloma agents has further improved outcomes. However, disease relapse or progression remains a challenge after autologous transplantation. Allogeneic hematopoietic cell transplantation remains the only potentially curative modality for some patients due in part to graft-versus-myeloma effect. High transplant-related mortality, in the range of 30% to 40%, previously seen with myeloablative conditioning regimens, including total body irradiation plus cyclophosphamide has been significantly reduced by introducing less ablative preparative regimens, so called reduced-intensity conditioning. Cumulative evidence suggests encouraging prospects for allogeneic transplantation through improved outcomes of myeloma patients (overall survival exceeding 70% at 2 years in some studies); however, which patient population would benefit most from this treatment remains to be defined. newer strategies to augment graft-versus-myeloma effect and minimize post transplant toxicities are in need of further improvement in patients with myeloma.
Topics: Clinical Trials as Topic; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Transplantation Conditioning; Transplantation, Homologous
PubMed: 21460601
DOI: 10.5144/1658-3876.2011.1 -
Gastroenterologia Y Hepatologia Mar 2019A severe shortage of suitable allografts is a long-standing and worldwide problem for patients who are waiting for organ transplantation. Hepatocyte transplantation has...
A severe shortage of suitable allografts is a long-standing and worldwide problem for patients who are waiting for organ transplantation. Hepatocyte transplantation has been proposed as an alternative therapeutic approach for liver disease patients to address this urgent and unmet medical need. The cell replacement approach does not replace orthotopic liver transplantation (OLT), but rather it complements OLT especially for patients who do not require whole liver replacement, such as those with congenital metabolic disorders. This review article summarizes the current knowledge and limitations of clinical hepatocyte transplantation and aims to advance our understanding toward the goal of developing novel cell replacement therapies for patients who are on the OLT waiting list.
Topics: Hepatocytes; Humans; Liver Diseases; Liver Transplantation; Metabolism, Inborn Errors; Transplantation Conditioning
PubMed: 30470565
DOI: 10.1016/j.gastrohep.2018.10.007 -
Acta Haematologica 2005Most patients undergoing autologous hematopoietic stem cell transplantation for malignant diseases suffer recurrences of their neoplasms and die due to the inability of... (Review)
Review
Most patients undergoing autologous hematopoietic stem cell transplantation for malignant diseases suffer recurrences of their neoplasms and die due to the inability of conventional high-dose conditioning regimens to eradicate their malignancies. As a result, intensive efforts to develop more effective conditioning regimens are currently under way at many institutions. Encouraging results have been obtained using targeted radiotherapy with radiolabeled antibodies or bone-seeking isotopes as components of novel conditioning regimens for autologous transplantation of patients with lymphomas, multiple myeloma and bone metastases. Results with radiolabeled antibodies targeting epithelial antigens on solid tumors, however, have been less encouraging. This report reviews the status of clinical studies using myeloablative doses of targeted radiotherapy in patients undergoing autologous stem cell transplantation for hematological malignancies or solid tumors.
Topics: Humans; Neoplasm Recurrence, Local; Neoplasms; Radioimmunotherapy; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Autologous
PubMed: 16269863
DOI: 10.1159/000088414 -
European Journal of Haematology Feb 2001Allogeneic bone marrow transplantation with conventional conditioning (CC-BMT) has the potential of curing various malignant and non-malignant diseases. The curative... (Review)
Review
Allogeneic bone marrow transplantation with conventional conditioning (CC-BMT) has the potential of curing various malignant and non-malignant diseases. The curative mechanisms encompass 1) stem cell support for myeloablative radio-chemotherapy, 2) the graft-versus-tumor (GVT) effect, 3) gene replacement for genetic diseases and 4) immunoablation for autoimmune diseases. CC-BMT is characterized by high intensity conditioning, the requirement of prolonged and expensive hospital treatment and a treatment related mortality (TRM) of 10-50% depending on diagnosis, disease stage, patient age and donor type. Recent preclinical and clinical progress has resulted in the emergence of new concepts and procedures that allow replacement of patient bone marrow and immune system with that of the donor by a transplant procedure with markedly reduced conditioning (RC-BMT). This type of transplant, sometimes referred to as mini-BMT, activates curative mechanisms 2-4, which for a number of diseases seems sufficient for cure. It avoids the severe organ toxicity of myeloablative radio-chemotherapy and the complications of profound neutropenia. Patients beyond the age limit of conventional BMT (50-60 yr) may therefore be candidates for this type of transplant as well as patients which because of other medical conditions or the type of disease for which the transplant is needed are poor candidates for CC-BMT. The procedure can be performed in an outpatient setting. The resulting cost reduction should contribute to making allogenic BMT more readily available. This review describes basic concepts and procedures involved in RC-BMT and summarizes preliminary results obtained with RC-BMT in different transplant centers.
Topics: Bone Marrow Transplantation; Clinical Trials as Topic; Graft Survival; Graft vs Tumor Effect; Humans; Transplantation Conditioning; Transplantation, Homologous
PubMed: 11168513
DOI: No ID Found