HLA-mismatched microtransplantation for relapsed or refractory acute myeloid leukemia as a bridge to allogeneic hematopoietic stem cell transplantation (original) (raw)
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Leukemia Research Reports
Microtransplantation (MST), a type of HLA-mismatched allogeneic cellular therapy, is a promising, cellular therapy for acute myeloid leukemia (AML). MST transfuses granulocyte colony-stimulating factor (G-CSF)-mobilized, HLA-mismatched donor peripheral blood stem cells into patients undergoing conventional chemotherapy. MST, using haploidentical donors, has been shown to yield clinical benefit without any permanent marrow engraftment in AML. Consequently, graft-versus-host disease concerns are rendered irrelevant with no need for immunosuppression. We describe the first reported patient with refractory AML who underwent salvage MST from an unrelated, complete HLA-mismatched donor. The patient achieved remission without complication, warranting further study of unrelated HLA-mismatched donor MST in AML.
Bone Marrow Transplantation, 1999
CBF/MYH11 fusion characteristic of M4Eo. A second remission was obtained with chemotherapy. Full donor chimerism was demonstrated by fluorescence in situ hybridisation. However, molecular evidence of minimal residual disease still persisted, and donor lymphocyte infusion (DLI) was administered. This resulted in molecular eradication, and the patient remained in clinical and molecular remission 16 months from DLI. Our observations showed that, for AML relapse after BMT, molecular leukaemia eradication could be achieved by DLI so that, in cases where genetic markers are available, molecular monitoring should be performed to assess the efficacy of treatment.
Bone Marrow Transplantation, 2014
The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult patients with de novo AML in first CR (CR1) given PBSC from HLA-identical siblings after chemotherapy-based RIC. A total of 554 patients did not receive any form of in vivo T-cell depletion (control group), whereas antithymocyte globulin (ATG) and alemtuzumab were given in 444 and 252 patients, respectively. The incidences of grade II-IV acute GVHD were 21.4, 17.6 and 10.2% in control, ATG and alemtuzumab patients, respectively (Po0.001). In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (Po0.001 each), but a similar risk of relapse, and of nonrelapse mortality, and similar leukemia-free survival and OS. Further, among patients given BU-based RIC, the use of o6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR ¼ 1.1), whereas there was a suggestion for higher relapse risk in patients given X6 mg/kg ATG (HR ¼ 1.4, P ¼ 0.08). In summary, these data suggest that a certain amount of in vivo T-cell depletion can be safely used in the conditioning of AML patients in CR1 given PBSC after chemotherapy-based RIC.
Bone Marrow Transplantation, 1999
A case of acute myelogenous leukemia with a t(8;21) translocation relapsed 5 months after allogeneic bone marrow transplantation (allo-BMT). After chemotherapy-induced hematologic remission, the patient received donor lymphocyte infusions (DLI); 4.9 × 10 8 /kg T cells were infused. After DLI, she achieved molecular CR for the first time after allo-BMT, which lasted for 40 months. However, she suffered from grade III acute GVHD of the skin and the liver. Hepatic GVHD was sustained and resulted in fatal outcome. The case demonstrates that DLI is a double-edged sword. Further study is necessary before DLI can be considered to be a beneficial therapy for acute leukemia. Bone Marrow Transplantation (2000) 26, 809-810.
CD6Depleted Allogeneic Bone Marrow Transplantation for Acute Leukemia in First Complete Remission
in First Complete Remission CD6-Depleted Allogeneic Bone Marrow Transplantation for Acute Leukemia http://bloodjournal.hematologylibrary.org/content/89/8/3039.full.html Updated information and services can be found at: (1927 articles) Transplantation Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub\_requests
British Journal of Haematology, 2005
The relapse of underlying haematological malignancies after allogeneic haematopoietic stem-cell transplantation (allo-SCT) is a significant problem. Adults with acute leukaemia who relapsed after allo-SCT had a median survival of 3-4 months if no treatment was given . Approaches to treating patients in relapse after allo-SCT include rapid tapering of immunosuppressive agents, donor lymphocyte infusion (DLI), re-induction chemotherapy and second transplantation. Standard chemotherapy sometimes results in complete remission (CR), but long-term disease-free survival (DFS) is unlikely, because of regimen-related toxicity (RRT) and recurrence . Although a second allograft produces sustained molecular remission in a proportion of patients, transplant-related mortality (TRM) is high with 100-d mortality rates of 25-50% and a DFS of 10% . Poor prognostic factors after second allo-SCT include an interval between the procedures of <1 year, resistance to re-induction chemotherapy, older age and poor performance status . Immunotherapy, such as cessation of immunosuppressive agents and DLI, is beneficial for patients with early relapse or those with chronic myeloid leukaemia (CML). DLI can result in a high CR rate of 60% in CML; however, it is less effective in acute leukaemia with an estimated rate of CR of only 15%
HAL (Le Centre pour la Communication Scientifique Directe), 2017
Background: The impact of the use of anti-thymocyte globulin (ATG) in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. Methods: We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6%) patients who received ATG (ATG group) to 421 (74.4%) who did not (no-ATG group). The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results: Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD) (31 vs. 52%, p = 0.0002) and of its extensive form (8 vs. 26%, p < 0.0001) but similar relapse incidence (22 vs. 27%, p = 0.23) leading to improved GVHD and relapse-free survival (GRFS) (60 vs. 40%, p = 0.0001). In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001), improved leukemia-free survival (HR = 0.67, p = 0.027), overall survival (HR = 0.65, p = 0.027), and GRFS (HR = 0.51, p = 4 × 10 −5). Recipient age above 50 years was the only other factor associated with worse survivals.
Donor lymphocyte infusion for leukemia relapse after hematopoietic stem cell transplantation
Transfusion and Apheresis Science, 2010
Leukemia relapse is a serious therapeutic challenge following hematopoietic stem cell transplantation (HSCT). In this retrospective study, 23 patients [15 (65.2%) AML, 8 (34.8%) ALL] who received DLI ± reinduction chemotherapy for post-transplant relapse were reviewed. The overall response rate of DLI was 66.7% for AML and 50% for ALL. A total of 15 patients (65.2%) developed acute graft versus host disease (GVHD). Response rates were higher in patients with GVHD (80% versus 25%; p = 0.01; OR: 12.0). The probability of OS was better in patients who respond to DLI (p = 0.04). Further strategies are required to improve the anti-tumor properties of alloreactive donor lymphocytes and to obtain durable responses with DLI in patients with relapsed acute leukemia after allogeneic HSCT.