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Bone Marrow Transplantation May 2001Allogeneic hematopoietic transplantation is an effective therapy for a range of malignancies. High doses of myelosuppressive chemotherapy or radiation have been used in... (Review)
Review
Allogeneic hematopoietic transplantation is an effective therapy for a range of malignancies. High doses of myelosuppressive chemotherapy or radiation have been used in preparative regimens with the goal of preventing graft rejection and eradicating malignancy. Much of the benefit of transplantation, however, results from graft-versus-malignancy effects, mediated by donor immunocompetent cells. An alternative approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow graft-versus-malignancy effects to develop. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly or medically infirm patients not eligible for myeloablative therapy. Nonmyeloablative preparative regimens appear promising in diagnoses sensitive to graft-versus-malignancy effects and provide a platform for further development of cellular immunotherapy. Controlled clinical trials are warranted to define the role of nonmyeloablative allogeneic transplants in a range of hematologic malignancies and selected solid tumors.
Topics: Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Myeloablative Agonists; Neoplasms; Transplantation Conditioning; Transplantation, Homologous
PubMed: 11436116
DOI: 10.1038/sj.bmt.1702864 -
Biology of Blood and Marrow... Nov 2016The Practice Guidelines Committee of the American Society of Blood or Marrow Transplantation (ASBMT) sought to develop an evidence-based review about personalizing... (Review)
Review
The Practice Guidelines Committee of the American Society of Blood or Marrow Transplantation (ASBMT) sought to develop an evidence-based review about personalizing busulfan-based conditioning. The Committee sought to grade the relevant published studies (June 1, 2008 through March 31, 2016) according to criteria set forth by the Steering Committee for Evidence Based Reviews from ASBMT. Unfortunately, the published literature was too heterogeneous and lacked adequately powered and sufficiently controlled studies for this to be feasible. Despite this observation, the continued interest in this topic led the Practice Guidelines Committee to develop a list of most frequently asked questions (FAQs) regarding personalized busulfan dosing. This "Considerations" document is a list of these FAQs and their responses, addressing topics of practical relevance to hematopoietic cell transplantation clinicians.
Topics: Busulfan; Hematopoietic Stem Cell Transplantation; Humans; Myeloablative Agonists; Precision Medicine; Transplantation Conditioning
PubMed: 27481448
DOI: 10.1016/j.bbmt.2016.07.013 -
Hematology. American Society of... 2009Acute myelogenous leukemia (AML), either de novo or arising out of antecedent myelodysplasia, increases with age and is rarely curable by standard treatments used for... (Review)
Review
Acute myelogenous leukemia (AML), either de novo or arising out of antecedent myelodysplasia, increases with age and is rarely curable by standard treatments used for younger patients. Recent clinical trials using reduced-intensity allogeneic transplantation regimens suggest that a proportion of patients with this disease can be cured, with results comparable to those achieved in younger patients undergoing fully ablative transplant. Although those patients who undergo transplant in a first remission often do well, the vast majority of older patients have not benefited because of the low successful remission achieved with standard therapy, the delay in initiating a donor search, and the lack of significant benefit from transplantation in patients who are not in remission. New approaches to induction, improvements in reduced-intensity regimens, and earlier donor identification will help expand the potential clinical benefit to a larger number of older patients with the disease.
Topics: Acute Disease; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Resistance, Neoplasm; Female; Graft vs Host Disease; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Male; Middle Aged; Myeloablative Agonists; Prognosis; Recurrence; Remission Induction; Survival Analysis; Tissue Donors; Transplantation Conditioning; Treatment Outcome
PubMed: 20008226
DOI: 10.1182/asheducation-2009.1.406 -
Annals of Hematology Apr 2021A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and... (Comparative Study)
Comparative Study
Comparison of myeloablative and reduced intensity conditioning unrelated donor allogeneic peripheral blood stem cell transplant outcomes for AML using thymoglobulin for GVHD prophylaxis.
A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens using thymoglobulin for GVHD prophylaxis is limited. We evaluated outcomes of 122 AML patients who received either busulfan (Bu)/fludarabine (Flu)/low-dose total body irradiation (TBI) as RIC (n = 64, 52%) or Bu/Flu as MAC (n = 58, 48%), and thymoglobulin 4.5 mg/kg total dose between day - 3 to - 1 for GVHD prophylaxis. Grades III-IV acute GVHD (aGVHD) was lower with Bu/Flu/TBI compared with Bu/Flu (6.2% vs 26.1%, p = 0.009). At 1 year, Bu/Flu/TBI was associated with similar chronic GVHD (41.2% vs 44.8%, p = 0.75), OS (61.9% vs 56.9%, p = 0.69), relapse rate (29.9% vs 20.7%, p = 0.24), relapse-free survival (52.8% vs 50%, p = 0.80), non-relapse mortality (17.4% vs 29.3%, p = 0.41), and GVHD-free relapse-free survival (24.2% vs 27.5%, p = 0.80) compared with Bu/Flu. Multivariable analysis did not reveal any difference in outcomes between both regimens. In summary, thymoglobulin at 4.5 mg/kg did not have any adverse impact on survival when used with RIC regimen. Both Bu/Flu/TBI and Bu/Flu conditioning regimens yielded similar survival.
Topics: Aged; Allografts; Antilymphocyte Serum; Busulfan; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Infections; Leukemia, Myeloid, Acute; Lymphocyte Depletion; Male; Middle Aged; Mycophenolic Acid; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Progression-Free Survival; Retrospective Studies; T-Lymphocytes; Tacrolimus; Transplantation Conditioning; Treatment Outcome; Unrelated Donors; Vidarabine; Whole-Body Irradiation
PubMed: 33594448
DOI: 10.1007/s00277-021-04445-8 -
Current Opinion in Critical Care Dec 2017Patients with cancer increasingly make up a significant proportion of patients receiving care in the intensive care unit (ICU). Acute kidney injury and cancer-associated... (Review)
Review
PURPOSE OF REVIEW
Patients with cancer increasingly make up a significant proportion of patients receiving care in the intensive care unit (ICU). Acute kidney injury and cancer-associated electrolyte disorders are encountered in many of these patients and can significantly impact both short-term and long-term outcomes.
RECENT FINDINGS
Advances in chemotherapeutic regimens as well as in our understanding of cancer-associated kidney disease highlight the need for specialized knowledge of the unique causes and therapies required in this subset of critically ill patients. This is especially the case as targeted cancer therapies may have off-target effects that need to be recognized in a timely manner.
SUMMARY
This review outlines key knowledge areas for critical care physicians and nephrologists caring for patients with cancer and associated kidney issues such as acute kidney injury and electrolyte disorders. Specifically, understanding kidney-specific effects of new chemotherapeutic approaches is outlined, and provides an up-to-date compendium of these effects.
Topics: Acute Kidney Injury; Antineoplastic Agents; Critical Illness; Hematopoietic Stem Cell Transplantation; Humans; Intensive Care Units; Myeloablative Agonists; Neoplasms; Practice Guidelines as Topic; Water-Electrolyte Imbalance
PubMed: 28953555
DOI: 10.1097/MCC.0000000000000450 -
Blood Aug 2011Although sickle cell disease (SCD) has a variable clinical course, many patients develop end-organ complications that are associated with significant morbidity and early... (Review)
Review
Although sickle cell disease (SCD) has a variable clinical course, many patients develop end-organ complications that are associated with significant morbidity and early mortality. Myeloablative allogeneic HSCT (allo-HSCT) is curative but has been historically performed only in children younger than 16 years of age. Modest modifications in the conditioning regimen and supportive care have improved outcome such that the majority of children with a suitable HLA-matched sibling donor can expect a cure from this approach. However, adult patients have been excluded from myeloablative allo-HSCT because of anticipated excess toxicity resulting from accumulated disease burden. Efforts to use nonmyeloablative transplantation strategies in adults logically followed but were initially met with largely disappointing results. Recent results, however, indicate that nonmyeloablative allo-HSCT in adult patients with SCD allows for stable mixed hematopoietic chimerism with associated full-donor erythroid engraftment and normalization of blood counts, and persistence in some without continued immunosuppression suggests immunologic tolerance. The attainment of tolerance should allow extension of these potentially curative approaches to alternative donor sources. Efforts to build on these experiences should increase the use of allo-HSCT in patients with SCD while minimizing morbidity and mortality.
Topics: Adolescent; Adult; Anemia, Sickle Cell; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Immunosuppression Therapy; Myeloablative Agonists; Time Factors; Transplantation Conditioning; Transplantation, Homologous
PubMed: 21628400
DOI: 10.1182/blood-2011-01-332510 -
Cold Spring Harbor Perspectives in... May 2012The globally widespread single-gene disorders β-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT).... (Review)
Review
The globally widespread single-gene disorders β-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT treatment of thalassemia has substantially improved over the last two decades, with advancements in preventive strategies, control of transplant-related complications, and preparative regimens. A risk class-based transplantation approach results in disease-free survival probabilities of 90%, 84%, and 78% for class 1, 2, and 3 thalassemia patients, respectively. Because of disease advancement, adult thalassemia patients have a higher risk for transplant-related toxicity and a 65% cure rate. Patients without matched donors could benefit from haploidentical mother-to-child transplantation. There is a high cure rate for children with SCA who receive HSCT following myeloablative conditioning protocols. Novel non-myeloablative transplantation protocols could make HSCT available to adult SCA patients who were previously excluded from allogeneic stem cell transplantation.
Topics: Adult; Anemia, Sickle Cell; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Living Donors; Myeloablative Agonists; Thalassemia
PubMed: 22553502
DOI: 10.1101/cshperspect.a011825 -
Transfusion Clinique Et Biologique :... Sep 2017Sickle cell disease is the most frequent genetic disease in France, concerning 400 newborns each year. The management of these Afro-Caribbean patients requires frequent... (Review)
Review
Sickle cell disease is the most frequent genetic disease in France, concerning 400 newborns each year. The management of these Afro-Caribbean patients requires frequent transfusions from Caucasian donors. Due to important erythroid antigenic differences between Caucasian and African, the prevalence of allo-immunization is high in this population with a risk of transfusional impasse. Allogeneic stem cell transplantation is the only curative treatment for this disease and the replacement of red cells and lymphocytes of the sickle cell patient by those of the donor can also resolve the transfusional impasse. However, a close consultation between physicians from the blood bank and transplantation unit will be required for the choice of conditioning regimen and GvH prophylaxis in order to ensure the transition from a mixed chimerism to the full donor curative graft.
Topics: Anemia, Sickle Cell; Blood Group Antigens; Blood Group Incompatibility; Blood Transfusion; Clinical Trials as Topic; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Immunization; Myeloablative Agonists; Transfusion Reaction; Transplantation Conditioning
PubMed: 28648733
DOI: 10.1016/j.tracli.2017.06.007 -
Bone Marrow Transplantation Mar 2008ALL in which the Philadelphia (Ph) chromosome is detected is one of the few diseases in which there is almost unequivocal agreement that a matched sibling allogeneic... (Review)
Review
ALL in which the Philadelphia (Ph) chromosome is detected is one of the few diseases in which there is almost unequivocal agreement that a matched sibling allogeneic haematopoietic stem cell transplant in first CR is the most appropriate therapy for patients within certain age limits. Extension of allogeneic stem cell transplant to patients without matched sibling donors or to older individuals is increasingly possible due to unrelated donors, umbilical cord blood and reduced-intensity conditioning regimens. Here, we carefully review evidence supporting current practice and examine recent evidence relating to the use of newer allogeneic transplant technologies in Ph-pos ALL. We explore the burgeoning literature on the role of tyrosine kinase inhibitors in this disease and summarize their impact on the transplant practice.
Topics: Disease-Free Survival; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Humans; Myeloablative Agonists; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors; Transplantation Conditioning; Transplantation, Homologous
PubMed: 17968326
DOI: 10.1038/sj.bmt.1705904 -
Bone Marrow Transplantation May 2015
Topics: Body Weight; Female; Humans; Lymphoma; Male; Myeloablative Agonists; Stem Cell Transplantation; Transplantation Conditioning
PubMed: 25730189
DOI: 10.1038/bmt.2015.26