Characteristics Predicting Outcomes of Allogeneic Stem-Cell Transplantation in Relapsed Acute Myelogenous Leukemia

Frazer, J. Kimble; Couban, Stephen; Doucette, Steven; Shivakumar, S

doi:10.3747/co.24.3485

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…In particular, patients with AML high risk have 3.08 and 2.32 times higher risks of relapse and death, respectively, than patients with other types of leukemia. This is consistent with the clinical finding that AML high risk remains the leading cause of transplant failure in medical studies (Bejanyan et al., ; Frazer, Couban, Doucette, & Shivakumar, ). The marginal copula models can reveal a similar effect of this factor on the risk of death only, while the marginal Cox models seem to overestimate effects of the disease acute lymphoblastic leukemia on the risks of both relapse and death due to ignoring potential associations between relapse and death and between acute GVHD and death.…”

Section: Real Data Analysissupporting

confidence: 90%

Joint regression analysis for survival data in the presence of two sets of semi‐competing risks

Peng

Xiang

2019

Biometrical J

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In many clinical trials, multiple time-to-event endpoints including the primary endpoint (e.g., time to death) and secondary endpoints (e.g., progression-related endpoints) are commonly used to determine treatment efficacy. These endpoints are often biologically related. This work is motivated by a study of bone marrow transplant (BMT) for leukemia patients, who may experience the acute graft-versus-host disease (GVHD), relapse of leukemia, and death after an allogeneic BMT. The acute GVHD is associated with the relapse free survival, and both the acute GVHD and relapse of leukemia are intermediate nonterminal events subject to dependent censoring by the informative terminal event death, but not vice versa, giving rise to survival data that are subject to two sets of semi-competing risks. It is important to assess the impacts of prognostic factors on these three time-to-event endpoints. We propose a novel statistical approach that jointly models such data via a pair of copulas to account for multiple dependence structures, while the marginal distribution of each endpoint is formulated by a Cox proportional hazards model. We develop an estimation procedure based on pseudo-likelihood and carry out simulation studies to examine the performance of the proposed method in finite samples. The practical utility of the proposed method is further illustrated with data from the motivating example. K E Y W O R D Scopula, dependent censoring, proportional hazards model, pseudo-likelihood, semi-competing risks 1402

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Section: Real Data Analysissupporting

confidence: 90%

Joint regression analysis for survival data in the presence of two sets of semi‐competing risks

Peng

Xiang

2019

Biometrical J

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“…The lack of difference in transplant outcomes between subgroups defined by cytogenetic risk in the latter study was likely driven by an observed improvement in survival of high risk patients with the use of newer induction and conditioning regimens as well as introduction of novel GVHD prophylactic agents. Finally, in another recent study of 55 AML patients transplanted in CR2, no association was observed between survival, CIR or NRM and cytogenetic risk at diagnosis . Although these studies did not specifically focus on CN AML, they too support the concept that the underlying genetic risk ascertained at the time of diagnosis in patients with AML may, in contrast to its usefulness in predicting which patients may benefit from HCT, have a more limited value when it comes to predicting the outcomes of HCT.…”

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 82%

Influence of FLT3‐ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML

Pašić

Da'na

Lam

et al. 2019

European J of Haematology

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Objective In individuals with cytogenetically normal (CN) AML, disease risk is estimated using molecular features such as the status of NPM1 and FLT3‐ITD genes. However, data regarding the impact of NPM1 and FLT3‐ITD status on hematopoietic stem cell transplant (HCT) outcomes are limited. We examined the effect of NPM1 and FLT3‐ITD status on transplant outcomes in 131 CN AML patients transplanted at Princess Margaret Hospital between 2006 and 2017. Methods Overall survival (OS) was calculated using Kaplan‐Meier analysis and multivariable Cox proportional hazards regression. Cumulative incidence of relapse (CIR) and non‐relapse mortality (NRM) were calculated using competing risk regression. Results There was no difference in 3‐year OS among NPM1+/FLT3‐ITD−, NPM1−/FLT3‐ITD−, NPM1+/FLT3‐ITD+ and NPM1−/FLT3‐ITD+ patients: 56% (95% CI, 29%‐76%), 61% (95% CI, 46%‐73%), 53% (95% CI, 34%‐70%) and 52% (95% CI, 17%‐78%), respectively. CIR at 3‐years was similar among NPM1−/FLT3‐ITD−, NPM1+/FLT3‐ITD+ and NPM1−/FLT3‐ITD+ patients—14% (95% CI, 6%‐26%), 13% (95% CI, 4%‐28%) and 19% (95% CI, 4%‐41%), respectively—while there were no relapses in the NPM1+/FLT3‐ITD− group. NRM at 3 years for NPM1+/FLT3‐ITD−, NPM1−/FLT3‐ITD−, NPM1+/FLT3‐ITD+ and NPM1−/FLT3‐ITD+ patients was similar at 44% (95% CI, 19%‐67%), 38% (95% CI, 25%‐50%), 43% (95% CI, 25%‐59%) and 44% (95% CI, 14%‐71%), respectively. Conclusion NPM1 and FLT3‐ITD status may provide limited prognostic information about transplant outcomes in CN AML patients.

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“…The Hematopoietic Cell Transplantation-specific Comorbidity Index includes a variety of comorbidities that are predictive of both nonrelapse mortality and post-transplantation survival. [34][35][36][37] The modified European Group for Blood and Marrow Transplantation score takes into account age, disease stage, donor type, and gender match and is also predictive of nonrelapse mortality and survival after HCT across a variety of disease types. 38 Michelis et al 34,35 compared the two risk scores as predictors of outcome in patients with AML undergoing HCT and demonstrated both scores to be prognostic for OS and nonrelapse mortality, but not predictive of the risk of relapse.…”

Section: Comprehensive Assessment Of Riskmentioning

confidence: 99%

“…This model can be incorporated into the pretransplantation assessment to assist in formulating recommendations and counseling patients about the risks and potential benefit of pursuing transplantation. [34][35][36][37]…”

Section: Comprehensive Assessment Of Riskmentioning

confidence: 99%

Acute Myeloid Leukemia in Young Adults: Does Everyone Need a Transplant?

MMSc

Langston

Heffner

2019

JOP

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With the exception of the minority of patients with acute myelocytic leukemia who are considered potentially cured by chemotherapy, hematopoietic cell transplantation (HCT) has traditionally been the recommended approach for those patients achieving complete remission who meet the criteria for HCT and have an appropriate stem-cell donor. This decision has become more complex with the discovery of new risk factors, such as genomic abnormalities and minimal residual disease, especially in younger populations. Patients younger than age 60 years who are considered fit and who do not harbor poor prognostic features are felt still to have a high likelihood of cure without having to undergo HCT. Here, we discuss the role that these emerging risk factors play in the decision to undergo transplantation, but emphasize that this remains a decision made jointly by the patient, the treating hematologist, and the transplant physician.

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Characteristics Predicting Outcomes of Allogeneic Stem-Cell Transplantation in Relapsed Acute Myelogenous Leukemia

Abstract: Background Allogeneic hematopoietic stem-cell transplantation (ahsct) is associated with significant morbidity

Cited by 7 publications

References 37 publications

Joint regression analysis for survival data in the presence of two sets of semi‐competing risks

Joint regression analysis for survival data in the presence of two sets of semi‐competing risks

Influence of FLT3‐ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML

Acute Myeloid Leukemia in Young Adults: Does Everyone Need a Transplant?

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