Monitoring of minimal residual disease (MRD) is useful to predict prognosis of adult patients with Ph-negative ALL: results of a prospective study (ALL MRD2002 Study)

Nagafuji, Koji; Miyamoto, Toshihiro; Eto, Tetsuya; Kamimura, Tomohiko; Taniguchi, Satoshi; Okamura, Takashi; Ohtsuka, Eiichi; Yoshida, Takashi; Higuchi, Masakazu; Yoshimoto, Goichi; Fujisaki, Tomoaki; Abe, Yasunobu; Takamatsu, Yasushi; Yokota, Shouhei; Akashi, Koichi; Harada, Mine

doi:10.1186/1756-8722-6-14

Cited by 41 publications

(35 citation statements)

References 36 publications

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“…[13][14][15][16][17][18][19][20][21] They might thus be considered as a stratification tool, with the option to offer allogeneic SCT to patients with persistent molecular disease. 16,18,20,22 Conversely, novel genetic alterations originally described in children have also been reported to have an impact on the outcome of adult patients.…”

Section: Introductionmentioning

confidence: 99%

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Dhédin

Huynh

Maury

et al. 2015

Blood

239

190

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Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678

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Section: Introductionmentioning

confidence: 99%

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Dhédin

Huynh

Maury

et al. 2015

Blood

239

190

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“…164 Among the patients who achieved a CR after induction/consolidation (n = 39), those who were MRD negative (<0.1%) after induction had a significantly higher 3-year DFS (69% vs 31%; P=.004) compared with patients who were MRD positive; 3-year OS was higher among patients with MRD-negative status after induction, although the difference was not statistically significant (85% vs 59%). Based on multivariate Cox regression analysis, older age (>35 years) and MRD positivity after induction were significant independent factors predictive of decreased DFS.…”

Section: Mrd Assessment In Adult Allmentioning

confidence: 89%

“…WBC counts and MRD status after consolidation were not significant predictors of DFS outcomes. 164 Thus, MRD evaluation postinduction may provide additional risk stratification criteria among patients who would otherwise be considered standard risk according to traditional evaluation of prognostic factors.…”

Section: Mrd Assessment In Adult Allmentioning

confidence: 99%

Acute Lymphoblastic Leukemia, Version 2.2015

Alvarnas

Brown

Aoun

et al. 2015

J Natl Compr Canc Netw

139

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Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org. (J Natl Compr Canc Netw 2015;13:1240-1279 NCCN Categories of Evidence and ConsensusCategory 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. These guidelines are also available on the Internet. For the latest update, visit NCCN.org.

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“…This may highlight the molecular biology-based methods with a greater prognostic significance than conventional criteria for the detection of remission [24] [25]. Nagafuji et al [26] reported that chemotherapy should be continued as follow up therapy in ALL even with good prognosis in order to prevent leukemia relapse. However, patients with less favorable prognosis should be treated more aggressively.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Prognostic Significance of Histidine-Rich Glycoprotein in Acute Lymphoblastic Leukemia

Ahmed¹,

Almogbel²,

Khirry³

et al. 2017

OJBD

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Background: Histidine-rich glycoprotein (HRG), a multifunctional plasma protein, has a regulatory role in homeostasis, angiogenesis, and immunity; which in turn could greatly affect tumor control and metastasis. Objectives: To assess the possible role of HRG in acute lymphoblastic leukemia (ALL) tumorgenesis and follow-up. Design and Methods: HRG was quantitatively measured in serum by ELISA and its expression was assessed by real-time PCR (qPCR) in 35 patients with ALL and compared to same 25 ALL patients after induction therapy and 30 age and sex matched healthy control subjects. Results: HRG-serum protein (at cutoff value 63.55 pg/ml) and HRG-RNA (at cutoff value 0.955) were positive in all ALL patients before therapy, but in only 76% after therapy for HRG-protein and 60% for HRG-RNA and they could not be detected in the control group; P < 0.001. Additionally, the serum HRG level showed a significant positive correlation with its expression level, bone marrow blast percentage, peripheral blood blast count, P < 0.01. Also its serum and expression levels were positively related to the poor risk Philadelphia chromosome; P < 0.01. Conclusions: HRG (protein and RNA) might be considered as a novel diagnostic and prognostic marker in ALL. HRG-serum protein level, detected by simple methodology of ELISA, has more significant advantages than its expression level, motivating its application in large clinical studies as a potential marker.

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Monitoring of minimal residual disease (MRD) is useful to predict prognosis of adult patients with Ph-negative ALL: results of a prospective study (ALL MRD2002 Study)

Cited by 41 publications

References 36 publications

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Acute Lymphoblastic Leukemia, Version 2.2015

Diagnostic and Prognostic Significance of Histidine-Rich Glycoprotein in Acute Lymphoblastic Leukemia

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