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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... May 2014Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. This article reviews the... (Review)
Review
Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation practice guideline committee.
Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. This article reviews the current published literature on the dosing of pharmacologic agents used for HCT preparative regimens with specific focus on the obese patient population. The review found that dose adjustments for obesity have, to date, been based empirically or extrapolated from published data in the nontransplantation patient population. As a result, the Committee determined that clear standards or dosing guidelines are unable to be made for the obese population because Level I and II evidence are unavailable at this time. Instead, the Committee provides a current published literature review to serve as a platform for conditioning agent dose selection in the setting of obesity. A necessary goal should be to encourage future prospective trials in this patient population because further information is needed to enhance our knowledge of the pharmacokinetics and pharmacodynamics of conditioning agents in the setting of obesity.
Topics: Humans; Antilymphocyte Serum; Bone Marrow Transplantation; Busulfan; Cyclophosphamide; Cytarabine; Drug Administration Schedule; Drug Dosage Calculations; Etoposide; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Melphalan; Myeloablative Agonists; Obesity; Transplantation Conditioning
PubMed: 24462742
DOI: 10.1016/j.bbmt.2014.01.019 -
Journal of Clinical Oncology : Official... Feb 2022Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies.
PURPOSE
Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).
METHODS
This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS).
RESULTS
Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; = .02), 76.2% (HR, 1.02; 0.60 to 1.72; = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; = .037).
CONCLUSION
CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.
Topics: Adolescent; Adult; Aged; Calcineurin Inhibitors; Chronic Disease; Cyclophosphamide; Disease-Free Survival; Drug Therapy, Combination; Female; Germany; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Myeloablative Agonists; Recurrence; Tacrolimus; Time Factors; Transplantation Conditioning; United States; Young Adult
PubMed: 34855460
DOI: 10.1200/JCO.21.02293 -
The Malaysian Journal of Pathology Dec 2017POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the...
POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the 2-day-history of inability to walk, 4-month-history of progressive worsening of muscle weakness of both lower limbs and 1-year-history of progressive worsening of bilateral numbness of lower limbs. Nerve conduction study revealed generalized sensorimotor demyelinating polyneuropathy. She was initially treated as chronic inflammatory demyelinating polyradiculoneuropathy with intravenous immunoglobulin (IVIG) and high-dose prednisolone. However, she had no significant neurological improvement despite getting standard therapy. In addition to peripheral neuropathy, the presence of hepatosplenomegaly, skin changes, polycythaemia and thrombocytosis prompted for further investigations. She was diagnosed as POEMS syndrome based on the presence of two mandatory major criteria [polyneuropathy, monoclonal plasma cell proliferative disorder (lambda)], one major criterion (sclerotic bone lesions) and three minor criteria (organomegaly, skin changes and thrombocytosis/polycythaemia). She received treatment with melphalan and prednisolone. She achieved clinical improvement and partial response (haematologic and radiological) after six cycles of therapy. We highlight the awareness of this rare syndrome, for patients presenting with peripheral neuropathy and not responding to its standard therapy, by recognizing other associated clinical manifestations and proceeding further diagnostic work-up.
Topics: Aged; Anti-Inflammatory Agents; Female; Humans; Melphalan; Myeloablative Agonists; POEMS Syndrome; Prednisolone
PubMed: 29279594
DOI: No ID Found -
Biology of Blood and Marrow... Jan 2015Allogeneic stem cell transplantation is an increasingly important treatment option in the management of adult acute myeloid leukemia (AML). The major causes of treatment... (Review)
Review
Allogeneic stem cell transplantation is an increasingly important treatment option in the management of adult acute myeloid leukemia (AML). The major causes of treatment failure remain disease relapse and treatment toxicity. In this review, Dr Vyas presents an overview of important recent data defining molecular factors associated with treatment failure in AML. He also identifies the emerging importance of leukemia stem cell biology in determining both response to therapy and relapse risk in AML. Dr Appelbaum discusses advances in the design and delivery of both myeloablative and reduced-intensity conditioning regimens, highlighting novel strategies with the potential to improve outcome. Dr Craddock discusses the development of both novel conditioning regimens and post-transplantation strategies aimed at reducing the risk of disease relapse.
Topics: Adult; Chromosome Aberrations; Disease Management; Drug Resistance, Neoplasm; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Myeloablative Agonists; Neoplastic Stem Cells; Recurrence; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Treatment Failure
PubMed: 25452033
DOI: 10.1016/j.bbmt.2014.10.026 -
F1000Research 2018Immunoglobulin (Ig) light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by misfolded Ig light chain deposition in vital organs of the body,... (Review)
Review
Immunoglobulin (Ig) light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by misfolded Ig light chain deposition in vital organs of the body, resulting in proteotoxicity and organ dysfunction. Owing to its diverse clinical presentations and a tendency to mimic common medical conditions, AL amyloidosis is often diagnosed late and results in dismal outcomes. Early referral to a specialized center with expertise in management of AL amyloidosis is always recommended. The availability of sensitive biomarkers and novel therapies is reforming our approach to how we manage AL amyloidosis. Treatment for patients with AL amyloidosis should be risk-adapted and customized on the basis of individual patient characteristics. In the future, approaches directed at amyloid fibril clearance in combination with agents that target plasma cells will be needed both to eradicate the malignant clone and to establish organ responses.
Topics: Animals; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Myeloablative Agonists
PubMed: 30228867
DOI: 10.12688/f1000research.15353.1 -
Comptes Rendus Biologies Mar 2013Hematopoietic stem cell transplantation (HSCT) is the one and only curative therapy available for patient with severe sickle cell disease (SCD). Until today, several... (Review)
Review
Hematopoietic stem cell transplantation (HSCT) is the one and only curative therapy available for patient with severe sickle cell disease (SCD). Until today, several hundreds of patients have undergone geno-identical HSCT. More than 200 patients were transplanted in France. The first indication was cerebral vasculopathy. Among both malignant and non-malignant diseases treated with HSCT, the success rate obtained in SCD patients appears as the best one. From the year 2000, more than 95% of transplanted patients survived the HSCT procedure and more than 90% are completely cured and experience a very satisfying health condition post-transplantation. However, the current standard procedure includes a myeloablative conditioning regimen for warranting engraftment. Such regime is linked to severe long-term side effects such as hypofertility. Due to the excellent obtained results, we have to think about a possible widening of indications, a decrease of conditioning intensity and toxicity, and about HSCT from alternative stem cell sources, such as mismatch family donor, unrelated volunteer donor or unrelated cord blood.
Topics: Adolescent; Anemia, Sickle Cell; Bone Marrow Transplantation; Child; Child, Preschool; Cord Blood Stem Cell Transplantation; Fertility Preservation; France; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Immunosuppressive Agents; Infant; Living Donors; Myeloablative Agonists; Quality of Life; Siblings; Transplantation Conditioning; Treatment Outcome
PubMed: 23643397
DOI: 10.1016/j.crvi.2012.09.004 -
Biology of Blood and Marrow... Mar 2013Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem cell transplantation (SCT). From its initial discovery more than 50 years... (Review)
Review
Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem cell transplantation (SCT). From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantations because of its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas, and it has been used successfully in preparative regimens of a variety of other hematological and nonhematological malignancies. The addition of newer agents to conditioning, such as bortezomib or lenalidomide for myeloma or clofarabine for myeloid malignancies, may improve antitumor effects for transplantation, whereas melphalan in combination with alemtuzumab may represent a backbone for future cellular therapy because of reliable engraftment and low toxicity profile. This review summarizes the development and the current use of this remarkable drug in hematopoietic SCT.
Topics: Adenine Nucleotides; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleosides; Boronic Acids; Bortezomib; Clofarabine; Graft Survival; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Melphalan; Multiple Myeloma; Myeloablative Agonists; Pyrazines; Thalidomide; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous
PubMed: 22922522
DOI: 10.1016/j.bbmt.2012.08.011 -
Acta Haematologica 2020AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High-dose intravenous melphalan and autologous stem cell... (Review)
Review
AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High-dose intravenous melphalan and autologous stem cell transplantation was developed for the treatment of AL amyloidosis in the early 1990s and was prompted by its success in myeloma. This application has evolved significantly over the past three decades. This review provides a comprehensive assessment of eligibility criteria, stem cell collection, and mobilization strategies and regimens, risk-adapted melphalan dosing, role for induction and consolidation therapies as well as long-term outcome with respect to survival, hematologic response and relapse as well as organ responses following stem cell transplantation. Continued efforts to refine patient selection and management, and incorporate novel anti-plasma cell agents in combination or sequentially to further improve outcomes in AL amyloidosis are also discussed.
Topics: Combined Modality Therapy; Disease Management; Hematopoietic Stem Cell Mobilization; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Myeloablative Agonists; Organ Specificity; Peripheral Blood Stem Cell Transplantation; Postoperative Care; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome
PubMed: 32248194
DOI: 10.1159/000506498 -
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