|
1
|
Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party. Bone Marrow Transplant 2021; 56:2367-2381. [PMID: 33976382 PMCID: PMC8486670 DOI: 10.1038/s41409-021-01286-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 03/09/2021] [Accepted: 03/25/2021] [Indexed: 11/25/2022]
Abstract
The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30–46%) at 2 years and 25% (17–32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24–46%); Others 9% (0–17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33–67%); Other 22% (8–36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21–40%) vs. 10% (1–20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24–0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.
Collapse
|
|
2
|
Chen EC, Li S, Eisfeld AK, Luskin MR, Mims A, Jones D, Antin JH, Cutler CS, Koreth J, Ho VT, Gooptu M, Romee R, El-Jawahri A, McAfee SL, DeFilipp Z, Soiffer RJ, Chen YB, Fathi AT. Outcomes for Patients With IDH-Mutated Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation. Transplant Cell Ther 2021; 27:479.e1-479.e7. [PMID: 33840625 DOI: 10.1016/j.jtct.2021.02.028] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 02/16/2021] [Accepted: 02/16/2021] [Indexed: 12/12/2022]
Abstract
Disease relapse after hematopoietic cell transplantation (HCT) is a major cause of treatment failure for patients with acute myeloid leukemia (AML). Maintenance therapy after HCT for patients with targetable mutations such as mutated IDH1 or IDH2 may improve outcomes, and clinical trials evaluating this strategy are ongoing. However, clinical outcomes of IDH1- and IDH2-mutated AML patients after HCT have not been well described. The primary objective of this study was to describe the clinical characteristics and post-HCT outcomes of IDH-mutated AML patients. Survival outcomes included progression-free survival (PFS), overall survival, and cumulative incidences of relapse and nonrelapse mortality. In this multicenter retrospective analysis, 112 adult patients with IDH1- or IDH2-mutated AML who underwent HCT and did not receive an IDH inhibitor as maintenance therapy after HCT were identified at Massachusetts General Hospital, Dana Farber Cancer Institute, and Ohio State University. Mutation testing was performed using next-generation sequencing panels. Patient characteristics were collected retrospectively, and their survival outcomes were analyzed. Univariate and multivariate analyses were performed. The median patient age was 64.1 years. The median follow-up was 27.5 months. Among patients, 78.5% had intermediate- or adverse-risk disease by European LeukemiaNET criteria. Fifty-eight percent of patients received intensive induction chemotherapy, 82% of patients underwent HCT during first complete remission (CR) or CR with incomplete hematologic recovery (CRi), and 34% of patients received myeloablative conditioning. Frequently detected co-mutations were DNMT3A (35.7%), NPM1 (33.1%), and FLT3-ITD (13.4%); TP53 mutations were detected in 3.6% of patients. For IDH1-mutated patients transplanted during first CR/CRi, the 1- and 2-year PFS was 75% and 58%, respectively. For IDH2-mutated patients transplanted in first CR/CRi, the 1- and 2-year PFS was 64% and 58%, respectively. The 2-year cumulative incidence of relapse was 31% and 25% for IDH1- and IDH2-mutated cohorts, respectively. Multivariable analysis suggested first CR/CRi and age ≤60 was associated with improved outcomes for IDH2-mutated patients. To date, this is the largest multicenter study of outcomes of IDH-mutated AML patients after HCT. Our analysis provides important benchmarks for analysis and interpretation of results emerging from clinical trials evaluating maintenance IDH1 and IDH2 inhibitor therapy for AML patients after HCT.
Collapse
Affiliation(s)
- Evan C Chen
- Massachusetts General Hospital Cancer Center, Boston, Massachusetts
| | - Shuli Li
- Massachusetts General Hospital Cancer Center, Boston, Massachusetts
| | | | - Marlise R Luskin
- Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Alice Mims
- Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Daniel Jones
- Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Joseph H Antin
- Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Corey S Cutler
- Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - John Koreth
- Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Vincent T Ho
- Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Mahasweta Gooptu
- Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Rizwan Romee
- Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Areej El-Jawahri
- Hematopoietic Cell Transplant and Cell Therapy Program, Massachusetts General Hospital, Boston, Massachusetts
| | - Steven L McAfee
- Hematopoietic Cell Transplant and Cell Therapy Program, Massachusetts General Hospital, Boston, Massachusetts
| | - Zachariah DeFilipp
- Hematopoietic Cell Transplant and Cell Therapy Program, Massachusetts General Hospital, Boston, Massachusetts
| | - Robert J Soiffer
- Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Yi-Bin Chen
- Hematopoietic Cell Transplant and Cell Therapy Program, Massachusetts General Hospital, Boston, Massachusetts
| | - Amir T Fathi
- Center for Leukemia, Massachusetts General Hospital, Boston, Massachusetts.
| |
Collapse
|
|
3
|
Lia G, Di Vito C, Cerrano M, Brunello L, Calcaterra F, Tapparo M, Giaccone L, Mavilio D, Bruno B. Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications. Front Immunol 2020; 11:422. [PMID: 32265915 PMCID: PMC7100658 DOI: 10.3389/fimmu.2020.00422] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 02/24/2020] [Indexed: 12/11/2022] Open
Abstract
Extracellular vesicles (EVs) play an important role in the cellular crosstalk by transferring bioactive molecules through biological barriers from a cell to another, thus influencing recipient cell functions and phenotype. Therefore, EVs are increasingly being explored as biomarkers of disease progression or response to therapy and as potential therapeutic agents in different contexts including in hematological malignancies. Recently, an EV role has emerged in allogeneic hematopoietic cell transplantation (allo-HCT) as well. Allogeneic hematopoietic cell transplantation often represents the only curative option in several hematological disorders, but it is associated with potentially life-threatening complications that can have a significant impact on clinical outcomes. The most common complications have been well-established and include graft-versus-host disease and infections. Furthermore, relapse remains an important cause of treatment failure. The aim of this review is to summarize the current knowledge, the potential applications, and clinical relevance of EVs in allo-HCT. Herein, we will mainly focus on the immune-modulating properties of EVs, in particular those derived from mesenchymal stromal cells, as potential therapeutic strategy to improve allo-HCT outcome. Moreover, we will briefly describe the main findings on EVs as biomarkers to monitor graft-versus-host disease onset and tumor relapse.
Collapse
Affiliation(s)
- Giuseppe Lia
- Stem Cell Transplant Program, Department of Oncology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.,Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
| | - Clara Di Vito
- Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy.,Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Milan, Italy
| | - Marco Cerrano
- Stem Cell Transplant Program, Department of Oncology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.,Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
| | - Lucia Brunello
- Stem Cell Transplant Program, Department of Oncology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.,Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
| | - Francesca Calcaterra
- Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy.,Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Milan, Italy
| | - Marta Tapparo
- Department of Medical Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy
| | - Luisa Giaccone
- Stem Cell Transplant Program, Department of Oncology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.,Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
| | - Domenico Mavilio
- Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy.,Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Milan, Italy
| | - Benedetto Bruno
- Stem Cell Transplant Program, Department of Oncology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.,Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy
| |
Collapse
|
|
4
|
Medinger M, Passweg J. What the internist should know about stem cell transplant in the elderly patient. Eur J Intern Med 2018; 58:43-47. [PMID: 29960832 DOI: 10.1016/j.ejim.2018.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 06/21/2018] [Indexed: 11/23/2022]
Abstract
Most hematological malignancies are increasing in frequency with age. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapeutic option for patients with malignant and non-malignant hematological diseases. The treatment of elderly patients with advanced hematological malignancies has expanded to include reduced intensity conditioning allo-HCT. Physicians increasingly refer older patients for allo-HCT due to more experience and improved supportive care in allo-HCT. This review article discusses the available data regarding the feasibility, tolerability, toxicity, and effectiveness of allo-HCT in different hematological diseases in the elderly. Over the past decade, utilization and survival after allo-HCT have increased in patients ≥70 years. Selected adults ≥70 years with hematological diseases should be evaluated for transplantation.
Collapse
Affiliation(s)
- Michael Medinger
- Division of Hematology, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
| | - Jakob Passweg
- Division of Hematology, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
| |
Collapse
|