Matched and mismatched unrelated donor transplantation: is the outcome the same as for matched sibling donor transplantation? Separate statistical analyses were performed for each end point (relapse rate, TRM, LFS, and OS) and for each subgroup (autograft and allograft, children and adults). Agha NH, Baker FL, Kunz HE, Graff R, Azadan R, Dolan C, Laughlin MS, Hosing C, Markofski MM, Bond RA, Bollard CM, Simpson RJ. Biology and outcome of childhood acute megakaryocytic leukemia: a single institution's experience.
Cytotechnology. Risk factors and their individual or composite characteristics will evolve, but the need to discuss their impact on relapse and NRM continues. Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients. Cairney AEL, McKenna R, Arthur DC, et al. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors. de Oliveira JS, Sale GE, Bryant EM, et al. Substantial progress has been made in the field of allogeneic HSCT in the last decade. Comorbidity-age index: a clinical measure of biologic age before allogeneic hematopoietic cell transplantation. CA, cytogentic abnormalities; CBF, core binding factor; CN, cytogenetically normal; CRe, early complete remission; HCT-CI, hematopoietic cell transplantation comorbidity index; ITD, internal tandem duplication; MK, monosomal karyotype; NA, not applicable; –X –Y, deleted X or Y chromosome. Furthermore, we thank the personnel and centers listed in the “Appendix” for registering patients with acute megakaryocytic leukemia in the AL registry of the EBMT. Hematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin. Epub 2019 Jul 17. We conclude that M7 AML patients in CR1 (except children with Down syndrome, who already have better outcomes) can benefit from transplantation. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: a broader range of options, improved outcomes, and more therapeutic dilemmas. Successful engraftment may be related to the reversal of bone marrow fibrosis by intensive chemotherapy or chemoradiotherapy followed by BMT.19,20. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. HSCT recipients showed significantly better OS than patients receiving chemotherapeutic postremission therapy (P = .001). Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Chronic and Advanced Phase Myelofibrosis. Clift R, Goldman JM, Gratwohl A, Horowitz M. Proposal for standardized reporting of bone marrow transplantation for leukemia. NIH © 2016 by The American Society of Hematology, Copyright ©2020 by American Society of Hematology, https://doi.org/10.1182/blood-2015-07-604546, Introduction to the review series on advances in acute myeloid leukemia (AML), Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia, An update of current treatments for adult acute myeloid leukemia, Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance, Predictive model for survival in patients with AML/MDS receiving haploidentical stem cell transplantation, allogeneic hematopoietic stem cell transplant, –CA, but non-CBF, MK-negative, no abn3q26, –CA, but non-CBF, MK-negative, no abn3q26, EVI1-negative, –Non-CBF with mutant p53, or –mutant RUNX1, or mutant ASXL1 –or biallelic FLT3-ITD with –FLT3-ITD:FLT3 WT ratio of >0.6, Ciceri, 2008, retrospective, multicentric.
Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML. Our study with a median follow-up from 13 to 63 months, depending on patient age (adult or child) and transplantation modality, seems to confirm the results of preliminary observations indicating that transplantation might improve survival for patients with de novo M7 AML in CR1. Several retrospective studies addressed that question, but an independent impact of age was often absent.45,48-51 Those studies suggested no definite age limit, but they noted that the assessment of comorbidities was an essential part of the workup for every patient for whom alloHSCT was considered.52 In addition, the use of a geriatric evaluation in patients older than age 60 to 65 years is also important. After allogeneic transplantation, all relapses in children and more than 90% of relapses in adults occurred within the first year, suggesting a graft-versus-leukemia effect. Lange BJ, Kobrisky N, Barnard DR, et al. Most transplantations (except autologous transplantation in adults) used bone marrow rather than peripheral blood as a source of stem cells. Blood 2016; 127 (1): 62–70. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen. Search for other works by this author on: Acute myeloid leukemia: 2014 update on risk-stratification and management. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia. Early allo-SCT for AML with a complex aberrant karyotype–results from a prospective pilot study. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia.
Blood 2005; 105 (1): 405–409. Mature studies addressing the value of expanded UCB in AML patients are currently lacking. Is autoHSCT a valuable alternative for alloHSCT in intermediate-risk AML? Finally, it should be noted that the number of studies specifically reporting on patients with AML is very limited (Table 2). Influence of age on outcome after allogeneic hematopoietic cell transplantation: a single center study in patients aged 60.
2012;2012:223-229. Hopefully, they will yield better prospects for older patients with AML and help us to redefine the preferred type of postremission therapy and possibly also type of immunotherapeutic maintenance after transplantation. This indicates recent improvement in the management of adult patients. The results suggested that outcome after haploidentical alloHSCT may be comparable to survival after alloHSCT using a matched sibling donor for patients with AML in CR. The study covers autologous and HLA-identical sibling allogeneic transplantation. M7 AML occurred at early ages in children (median ages, 1.7 and 2.8 years after autologous and allogeneic HSCT, respectively) and at relatively young ages in adults, (45.5 and 37 years, respectively). Currently, the choice may depend on multiple parameters, including the risk score of the underlying leukemia, the response to chemotherapy as assessed by morphology and MRD markers, and the projected risks associated with type of transplantation. Although the principle of using a risk score in intermediate-risk patients is attractive, disadvantages include the poor reproducibility of parameters such as CD34 blast count and Flt3 mutant:wild-type ratio. It represents a major change because this population is at greater risk for complications and has the poorest prognosis.3,21 That poor prognosis is mainly related to the underlying mutational profile22 and ineligibility to qualify for and benefit from intensive chemotherapy.23 Early attempts have confirmed the feasibility of RIC alloHSCT in older recipients with AML,24,25 which has resulted in a worldwide increase in alloHSCT activity.26 Although recent reviews27-29 have highlighted the development of RIC alloHSCTs and weighed their efficacy, several questions remain.
After allogeneic HLA-identical transplantation, acute GVHD of grade 2 or more developed in 32% (6 of 19) of children and in 28% (9 of 32) of adults.
Epidemiology of childhood acute myelogenous leukaemia.
The evolving molecular genetic landscape in acute myeloid leukaemia. Ruiz-Arguelles GJ, Lobato-Mendizalal E, San-Miguel JF, et al.
Acute megakaryoblastic leukemia: a prospective study of its identification and treatment. From the Acute Leukemia Working Party and the Pediatric Working Party of the European Group for Blood and Marrow Transplantation (EBMT); the Centre International de Greffes, AP-HP, Université Paris VI, Paris; and the Department of Hematology and Cell Therapy, Hôpital Saint Antoine, Paris, France. Information on the presence or absence of Down syndrome was available for 100 of the 126 patients. History and Evolution Hematopoietic stem cell transplantation (HSCT) was first explored in humans in the 1950s and was based on observational studies in mice models which showed that infusion of healthy bone marrow components into a myelosuppressed bone marrow could induce recovery of its function in the recipient. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.
Fine JP, Gray RJ. Ribeiro RC, Oliveira MS, Fairclough D, et al. Long-term treatment results for acute megakaryoblastic leukaemia patients: a multicentre study.
The subset of patients with very-poor-risk AML needs special consideration. Of note, a lower relapse rate of 36% vs 50% was counterbalanced by increased NRM in alloHSCT recipients. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Although we did collect cytogenetic data, our population was too small, and there were too many missing data to define subgroups as others have done.27. Conflict-of-interest disclosure: The authors declare no competing financial interests. These results compare well to results from a retrospective study by the CIBMTR that suggested similar outcome for younger AML patients in CR1 receiving either alloHSCT from an HLA-identical sibling or an autograft using PBSCs.103 Although recipients of alloHSCT exhibited more high-risk features, had longer follow-up, and experienced a lower risk of treatment failure, no significant difference in OS was noted. These data suggest that OS after haploidentical HSCT with PT-HDCy is comparable to MUD alloHSCT. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. The study showed a nonsignificant difference in relapse-free survival (RFS) of 29% vs 38% (P = .065). The preferred type of postremission therapy in intermediate-risk AML is not definitely settled and continues to evolve. In adults, a good option is HLA-identical allogeneic transplantation because of its 26% TRM rate and 46% LFS rate at 3 years. Mehta AB, Baughan AS, Catovsky D, et al. Prediction of non-relapse mortality in recipients of reduced intensity conditioning allogeneic stem cell transplantation with AML in first complete remission.
The remaining 10% of patients were excluded from the study. The following were analyzed for their potential prognostic value: patient and donor characteristics (age, sex, and sex match) and transplantation-related factors (time from diagnosis to CR1, time from diagnosis to transplantation, source of stem cells, conditioning regimen including total body irradiation (TBI), and year of transplantation). Leukemia-free survival (LFS) was defined as survival without evidence of relapse; the event under study was death or relapse. Patients were censored at the time of relapse or last follow-up.23 LFS and OS probabilities were estimated by the product-limit method.24 The significance of differences between curves was estimated by the log-rank test (Mantel-Cox). Barban JB, Simões BP, Moraes BDGC, Anunciação CRD, Rocha CSD, Pintor DCQ, Guerra DC, Silva DA, Brandão ECM, Kerbauy F, Pires FRO, Morais GL, Schmidt Filho J, Sicchieri JMF, Barroso KSN, Viana LV, Rocha MHMD, Guimarães MP, Lazzari NLC, Hamerschlak N, Ramos P, Gomes PN, Mendonça PDS, Oliveira RC, Scomparim RC, Chiattone R, Diez-Garcia RW, Cardenas TC, Miola TM, Costa TCM, Rocha V, Pereira AZ. Alternative donor transplantation for adults with acute leukemia. Moreover, autoHSCT may be used in patients up to age 70 years with an acceptable NRM of approximately 8%, which compares favorably to 17% as was observed after RIC alloHSCT.61 The conditioning regimen for autoHSCT was based on busulfan in 85% of patients. The relapse rate was high, especially after autologous transplantation in adults (64% at 3 years, with no plateau).
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