Strategies to Reduce Relapse after Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia

Mawad, Raya; Lionberger, Jack M.; Pagel, John M.

doi:10.1007/s11899-013-0153-6

Cited by 13 publications

(6 citation statements)

References 57 publications

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“…This may be due to a reduction of the graft versus leukemia effect in those patients administered PTCy/ATG. However, the relapse rate in PTCy/ATG group was comparable to the reported studies 21 . In addition, the lower relapse rate in MTX/CSA group might be obscured by other causes of death in this arm.…”

Section: Discussionsupporting

confidence: 86%

Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

et al. 2020

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Post-transplant cyclophosphamide (PTCy) has been explored in several types of stem cell transplantations (SCTs) and it proved highly effective in controlling graft-versus-host disease (GvHD) without aggravating relapsed disease. However, PTCy alone has resulted in inferior outcomes in matched sibling donor (MSD) employing peripheral blood (PB) SCTs. We hypothesized that adding thymoglobulin to PTCy would be able to control GvHD effectively. We retrospectively compared the use of standard GvHD prophylaxis encompassing a combination of PTCy and thymoglobulin (ATG) in patients with myeloid malignancies in a myeloablative conditioning MSD PBSCT. Forty-two patients underwent PBSCT using either methotrexate and cyclosporine (MTX/CSA, 21 patients) or PTCy and ATG (21 patients) as a GvHD prophylaxis. With median follow-ups of 71 months, the 1-year GvHD-free, relapse-free survival rates and chronic GvHD-free survival rate of the standard and PTCy/ATG groups were similar: 24% versus 37% ( P = 0.251) and 29% versus 43% ( P = 0.095), respectively. When focusing on chronic GvHD we observed that 17/35 patients (48.6%) suffered from this, 5/18 (27.8%) treated with MTX/CSA had extensive chronic GvHD, but 0/17 PTCy/ATG did. Twenty-one patients required additional GvHD treatment; 7/21 in the PTCy/ATG received only corticosteroid, while 8/14 MTX/CSA required at least 2 drugs. The 5-year overall survival rates were 52% and 52% ( P = 0.859), and the 5-year disease-free survival rates were 52% and 52% ( P = 0.862) for the MTX/CSA and PTCy/ATG groups, respectively. We conclude that PTCy in combination with ATG without immunosuppression of a calcineurin inhibitor can effectively control GvHD.

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Section: Discussionsupporting

confidence: 86%

Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

et al. 2020

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“…Complications due to infection also occur frequently, mostly in the first year after transplantation, with bacterial and viral infection occurring in 52 and 57.9% of patients, respectively ( 7 , 8 ). In addition, up to 50% of patients treated for malignant hematologic diseases suffer cancer relapse ( 9 , 10 ). Last, graft failure is a major complication of HCT ( 11 – 14 ).…”

mentioning

confidence: 99%

Cell-free DNA profiling informs all major complications of hematopoietic cell transplantation

Cheng

Loy

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Allogeneic hematopoietic cell transplantation (HCT) provides effective treatment for hematologic malignancies and immune disorders. Monitoring of posttransplant complications is critical, yet current diagnostic options are limited. Here, we show that cell-free DNA (cfDNA) in blood is a versatile analyte for monitoring of the most important complications that occur after HCT: graft-versus-host disease (GVHD), a frequent immune complication of HCT, infection, relapse of underlying disease, and graft failure. We demonstrate that these therapeutic complications are informed from a single assay, low-coverage bisulfite sequencing of cfDNA, followed by disease-specific bioinformatic analyses. To inform GVHD, we profile cfDNA methylation marks to trace the cfDNA tissues-of-origin and to quantify tissue-specific injury. To inform infection, we implement metagenomic cfDNA profiling. To inform cancer relapse, we implement analyses of tumor-specific genomic aberrations. Finally, to detect graft failure, we quantify the proportion of donor- and recipient-specific cfDNA. We applied this assay to 170 plasma samples collected from 27 HCT recipients at predetermined timepoints before and after allogeneic HCT. We found that the abundance of solid-organ–derived cfDNA in the blood at 1 mo after HCT is predictive of acute GVHD (area under the curve, 0.88). Metagenomic profiling of cfDNA revealed the frequent occurrence of viral reactivation in this patient population. The fraction of donor-specific cfDNA was indicative of relapse and remission, and the fraction of tumor-specific cfDNA was informative of cancer relapse. This proof-of-principle study shows that cfDNA has the potential to improve the care of allogeneic HCT recipients by enabling earlier detection and better prediction of the complex array of complications that occur after HCT.

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“…Therapy with hypomethylating drugs during the post-transplant period is used to prevent and treat relapses in the patients with high risk AML [24]. Our study has shown promising results of such strategy in cases of secondary MDS/ AML as well.…”

Section: Clinical Studiesmentioning

confidence: 64%

Myelodysplastic syndrome/acute myeloid leukemia evolving from aplastic anemia: Efficacy of hematopoietic stem cell transplantation

Golubovskaya¹,

Rudnitskaya²,

Morozova³

et al. 2018

CTT

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Aplastic anemia (АА) is the most common clinical form of bone marrow failure which is still considered as a non-malignant disorder. However, development secondary myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) in long-term AA survivors is confirmed by numerous studies. Treatment of the patients with secondary MDS/AML remains unresolved problem. The aim of present study was to evaluate efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in secondary MDS/AML evolving from AA, and to determine the factors influencing clinical outcomes. The study included 26 patients with MDS/AML, previously treated with immunosuppressive treatment due to acquired AA. Median age was 25 (range, 9-45) years at the moment of MDS/AML diagnosis. Eight patients who had no available compatible donors, received chemotherapy alone, 18 patients received allo-HSCT (from matched related donor (n=6), matched unrelated donor (n=9), haploidentical donor (n=3)). Groups were comparable in pre-transplant characteristics of patients.The 2-year overall survival (OS) in the chemotherapy alone group was 0%, being 53.1% in HSCT group [(95% CI 41-65.2), p=0.024]. For the patients being in remission state at the time of allo-HSCT, the 4-year OS comprised 80% [(95% CI, 65-95), p=0.021] vs 27 % in non-remission group. The use of peripheral blood as a source of graft was associated with higher OS (p=0.014). Allo-HSCT remains the only potentially curative method for treatment of secondary MDS/AML from AA and should be performed as soon as possible in the case of registered evolution of AA to MDS/AML. Remission state at the time of allo-HSCT is the main predictor for a successful transplantation.

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Strategies to Reduce Relapse after Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia

Cited by 13 publications

References 57 publications

Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

Cell-free DNA profiling informs all major complications of hematopoietic cell transplantation

Myelodysplastic syndrome/acute myeloid leukemia evolving from aplastic anemia: Efficacy of hematopoietic stem cell transplantation

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