NIH-defined graft-versus-host disease after reduced intensity or myeloablative conditioning in patients with acute myeloid leukemia

Terwey, Theis H.; Vega-Ruiz, Arturo; Hemmati, Philipp; Martus, Peter; Dietz, Ekkehart; Coutre, Philipp le; Massenkeil, Gero; Dörken, Bernd; Arnold, Renate

doi:10.1038/leu.2011.230

Cited by 39 publications

(22 citation statements)

References 9 publications

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“…Wide variation exists in prior estimates of incidence of LA GVHD. [2][3][4][18][19][20][21] Our data support an incidence of 11% at 2 years after HCT. De novo onset LA GVHD is more common in patients undergoing reduced intensity HCT.…”

Section: Discussionsupporting

confidence: 79%

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors

Holtan

Khera

Levine

et al. 2016

Blood

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• Under current treatment approaches, patients with LA GVHD have poor overall and failure-free survival.• Levels of AREG are elevated in LA GVHD, and the AREG/ EGF ratio is predictive of overall survival and nonrelapse mortality in LA GVHD.Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n 5 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n 5 55) and controls (n 5 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic

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Section: Discussionsupporting

confidence: 79%

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors

Holtan

Khera

Levine

et al. 2016

Blood

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“…Neutrophil recovery was defined as achieving absolute neutrophil count greater than—or equal to—0.5 × 109/l for three consecutive days. The diagnosis and grading of acute [28] and chronic graft-versus-host disease [29] were performed by transplant centers using the standard criteria. Cytogenetics abnormalities were classified according to the European Leukemia Net cytogenetic classification system [30].…”

Section: Methodsmentioning

confidence: 99%

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

et al. 2017

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BackgroundPrimary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML.MethodsThe current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.ResultsHSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality.ConclusionsHSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0498-8) contains supplementary material, which is available to authorized users.

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“…However, there was a statistically significant inter-study heterogeneity (Chi 2 : df = 18, P < 0.005; I 2 = 53%). We explored the clinical characteristics of each included study, and found that the heterogeneity could be explained by one study [31] having significantly older patients in the RIC-HCT group compared to MAC-HCT. Excluding this study [31] reduced the inter-study heterogeneity (I 2 = 23%) and the pooled estimates of 17 studies still showed lower grade II-IV aGvHD after RIC-HCT (Table 6 and Fig.…”

Section: Graft-versus-host Diseasementioning

confidence: 99%

“…Summary of P-Value for Transplant Outcomes Between RIC-HCT and MAC-HCT Obtained from the Individual Clinical Trials Raw data not counted for aGvHD and cGvHD analysis as the patients in Hemmati PG[5] were the same as patients included in Terwey TH[31] for acute and chronic GvHD outcomes. OS, overall survival; PFS, progression-free survival; DFS, disease-free survival; LFS, leukemia-free survival; NRM, nonrelapsed mortality; TRM, treatment-related mortality; aGvHD, acute graft-versus-host disease; cGvHD, chronic graft-versus-host disease; ns, not significant.…”

mentioning

confidence: 99%

Comparison of Reduced-Intensity and Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: A Meta-Analysis

Fadilah

Ismail

Mohd-Idris

et al. 2014

Stem Cells and Development

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Currently, the indications to perform reduced-intensity conditioning allogeneic hematopoietic stem cell transplant (RIC-HCT) are based on data derived mainly from large registry and single-centre retrospective studies. Thus, at the present time, there is limited direct evidence supporting the current practice in selecting patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) for RIC versus myeloablative conditioning (MAC) transplants. To determine the relationship between dose intensity of conditioning regimen and survival outcomes after allografting in AML/ALL patients, we performed a meta-analysis of 23 clinical trials reported between 1990 and 2013 involving 15,258 adult patients that compare survival outcomes after RIC-HCT versus MAC-HCT. RIC-HCT resulted in comparable <2-year and 2-6 year overall survival (OS) rates post-transplantation even though the RIC-HCT recipients were older and had more active disease than MAC-HCT recipients. The 2-6 year progression-free survival (PFS), nonrelapse mortality, acute graft-versus-host disease (GvHD) and chronic GvHD rates were reduced after RIC-HCT, but relapse rate was increased. Similar outcomes were observed regardless of disease type and status at transplantation. Odds ratio for all outcomes remained comparable with or without performing separate analyses for the year of HCT and for retrospective versus prospective studies. Among RIC-HCT recipients, survival rates were superior if patients were in CR at transplantation. Significant inter-study heterogeneity for aGvHD data and publication bias for PFS data were observed. This meta-analysis showed no OS benefit of MAC-HCT over RIC-HCT across the entire cohort of patients suggesting that RIC-HCT could be an effective therapeutic option for AML/ALL patients who are ineligible for MAC-HCT and CR status is preferred before RIC-HCT.

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NIH-defined graft-versus-host disease after reduced intensity or myeloablative conditioning in patients with acute myeloid leukemia

Cited by 39 publications

References 9 publications

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

Comparison of Reduced-Intensity and Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: A Meta-Analysis

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