Retrospective analysis of children with high‐risk acute myeloid leukemia who underwent allogeneic hematopoietic stem cell transplantation following complete remission with initial induction chemotherapy in the AML‐05 clinical trial

Hyakuna, Nobuyuki; Hashii, Yoshiko; Ishida, Hiroyuki; Umeda, Katsutsugu; Takahashi, Yoshiyuki; Nagasawa, Mitsuru; Yabe, Hiromasa; Nakazawa, Yozo; Koh, Katsuyoshi; Goto, Hiroaki; Fujisaki, Hiroyuki; Matsumoto, Kimikazu; Kakuda, Harumi; Yano, Michihiro; Tawa, Akio; Tomizawa, Daisuke; Taga, Takashi; Adachi, Souichi; Kato, Koji

doi:10.1002/pbc.27875

Cited by 11 publications

(12 citation statements)

References 27 publications

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“…In addition, a previous study showed that the 3-year OS rates among patients who underwent transplants at CR1 and CR2 were 73% and 25%, respectively. This study supported the notion that allo-HSCT maybe a suitable treatment for high-risk AML at CR1 [19].…”

Section: Discussionsupporting

confidence: 86%

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Alternative donor peripheral blood stem cell transplantation for the treatment of high-risk refractory and/or relapsed childhood acute leukemia: a randomized trial

Zhang

Zhou

et al. 2020

Exp Hematol Oncol

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Background: The high-risk refractory and/or relapsed (R/R) childhood acute leukemia prognosis is poor, and allogeneic stem cell transplantation (allo-HSCT) is the most prudent treatment modality. However, there are limited matched sibling donors (MSDs), and alternative donors (ADs) are the main source for allo-HSCT. Thus, we evaluated the clinical efficacy of AD peripheral allo-HSCT for treating high-risk R/R childhood acute leukemia. Methods: We assessed 111 children who underwent allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University between October 2006 and July 2019. The patients were divided in the MSD and AD groups, and their clinical characteristics, complications, and survival rates were compared. Results: The cumulative incidences of Epstein-Barr virus and cytomegalovirus infections were significantly higher in the AD than in the MSD group (P < 0.001); however, the recurrence and mortality rates were significantly higher in the MSD than in the AD group (P < 0.05). Furthermore, the 5-year disease-free (DFS) (65.2% vs. 43.3%, P = 0.033) and overall survival (OS) rates (71.6% vs. 53.8%, P = 0.053) were significantly higher in the AD than in the MSD group. In the AD group, the grade II-IV acute graft-versus-host disease (aGVHD), donor-recipient ABO compatibility, conditioning regimen, and CMV infection affected the 5-year OS. The grade II-IV aGVHD also affected the 5-year DFS; however, only the donor-recipient ABO compatibility affected the 5-year DFS. The donor MSD (HR: 2.035, 95% confidence interval [CI] 1.057-3.920, P = 0.034) and the grade II-IV aGVHD (HR: 2.914, 95% CI 1.261-6.736, P = 0.012) affected the 5-year DFS of childhood acute leukemia after allo-HSCT, and the grade II-IV aGVHD (HR: 3.016, 95% CI 1.217-7.473, P = 0.017) affected the 5-year OS. Moreover, the donor source (HR: 2.836, 95% CI 1.179-6.823, P = 0.020) and grade II-IV aGVHD (HR: 3.731, 95% CI 1.332-10.454, P = 0.012) were independent predictors of the 5-year DFS, while the latter (HR: 3.524, 95% CI 1.310-10.988, P = 0.030) was an independent predictor of the 5-year OS. Conclusions: AD-PBSCT was effective for high-risk R/R childhood leukemia and may have better clinical outcomes than MSD-PBSCT; thus, it can be used as first-line treatment for high-risk R/R childhood leukemia.

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Section: Discussionsupporting

confidence: 86%

“…High-risk R/R childhood acute leukemia has a poor prognosis; allo-HSCT may provide effective treatment for afflicted patients [19][20][21]. In recent years, AD transplantation has made great progress in the treatment of childhood hematologic diseases [22][23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Alternative donor peripheral blood stem cell transplantation for the treatment of high-risk refractory and/or relapsed childhood acute leukemia: a randomized trial

Zhang

Zhou

et al. 2020

Exp Hematol Oncol

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“…This strategy misses a substantial fraction of patients who need more intensive therapy, because 20–30% of “low-risk” patients relapse [ 1 , 4 ]. At the other end of the spectrum, 25–30% of high-risk patients who are transplanted in first remission die of relapse or toxicity [ 5 , 6 ]. Our goal is to define AML-microenvironment interactions that contribute to relapse and can be targeted pharmacologically.…”

Section: Introductionmentioning

confidence: 99%

Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia

et al. 2021

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The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions.

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“…Patients with FLT3/ITD mutations accounted for 10.0% of overall FAB-M4/M5 cases and these were identi ed as an independent risk factor for relapse and survival. [29] reported the excellent effect of allogeneic HSCT for children with high-risk AML, and their results showed that the high-risk group could bene t from HSCT. In addition, haplo-HSCT was also found to have great promise for the treatment of children with FAB-M4/M5 in the current study.…”

Section: Discussionmentioning

confidence: 99%

Impact of allogeneic hematopoietic stem cell transplantation on pediatric acute myeloid leukemia of FAB subtypes M4 and M5

Xue

Suo

Cheng

et al. 2020

Preprint

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Background: FAB-M4 and M5 are unique subgroups of pediatric acute myeloid leukemia. However, for these patients, few studies have demonstrated the clinical and biological characteristics and efficacy of hematopoietic stem cell transplantation (HSCT), and especially haplo-HSCT. Procedure: We retrospectively evaluated the outcomes of 70 children with FAB-M4/M5 enrolled in our center from January 2013 to December 2017. Results: Of the patients, 32, 23, and 15 were in low-risk, intermediate-risk, and high-risk groups, respectively. T(16;16), inv16/CBFB-MYH11 was the most frequent cytogenetic abnormality. Among detected genetic alterations, WT1 was mutated at the highest frequency, followed by FLT3-ITD, NPM1, and CEBPA. Thirty-three patients received HSCT (haplo-HSCT = 30), of which four, 18, and 11 were in low-risk, intermediate-risk, and high-risk groups, respectively. For all patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 85.3 ± 4.3%, 69.0 ± 5.7%, and 27.9 ± 5.2%, respectively. By multivariate analysis, low-risk stratification predicted superior OS, EFS, and PLT ≤ 50 × 109/L at diagnosis, with FLT3-ITD mutations predicting higher CIR and poorer EFS. In intermediate- and high-risk groups, HSCT was independently associated with higher EFS and lower CIR. With a median post-transplant observation time of 30.0 months, the 3-year OS, EFS, CIR, and non-relapse mortality in the haplo-HSCT group were 74.2 ± 8.6%, 68.3 ± 8.9, 24.6 ± 7.6%, and 6.6 ± 4.1%, respectively. Conclusions: Risk-oriented treatment is important for pediatric FAB-M4/M5. For intermediate- and high-risk groups, HSCT significantly improved survival and haplo-HSCT might be a viable alternative approach.

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Retrospective analysis of children with high‐risk acute myeloid leukemia who underwent allogeneic hematopoietic stem cell transplantation following complete remission with initial induction chemotherapy in the AML‐05 clinical trial

Cited by 11 publications

References 27 publications

Alternative donor peripheral blood stem cell transplantation for the treatment of high-risk refractory and/or relapsed childhood acute leukemia: a randomized trial

Alternative donor peripheral blood stem cell transplantation for the treatment of high-risk refractory and/or relapsed childhood acute leukemia: a randomized trial

Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia

Impact of allogeneic hematopoietic stem cell transplantation on pediatric acute myeloid leukemia of FAB subtypes M4 and M5

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