Childhood acute lymphoblastic leukemia: 12 years of experience, using a Berlin–Frankfurt–Münster approach, in a Greek center

Ampatzidou, Maria; Panagiotou, John P.; Paterakis, Georgios; Papadakis, Vassilios; Papadhimitriou, Stephanos I.; Parcharidou, Agapi; Papargyri, Sophia; Rigatou, Efthymia G.; Avgerinou, Georgia; Tsitsikas, Konstantinos; Vasdekis, Vassilis G. S.; Haidas, S; Polychronopoulou, Sophia

doi:10.3109/10428194.2014.916801

Cited by 7 publications

(10 citation statements)

References 13 publications

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“…Despite the excellent survival rates achieved in pediatric acute lymphoblastic leukemia [9,10], relapsed and refractory ALL represents a distinct entity with dismal prognosis and outcome [1][2][3][4][5][6][7][8][9].…”

Section: Discussionmentioning

confidence: 99%

“…In this report we present clinical data of a Greek pediatric group of relapsed and refractory Bcp ALL patients that were treated with Blinatumomab, as a salvage treatment, in a compassionate, offlabel setting and in an effort to achieve disease clearance and proceed to subsequent allo-HSCT. performed as previously described [9][10][11][12]. CD19 status (positivity/negativity) was defined as surface antigen expression detected using flow cytometry upon diagnosis and relapse.…”

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confidence: 99%

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Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients

Ampatzidou¹,

Kattamis²,

Baka³

et al. 2021

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Pediatric refractory or relapsed acute lymphoblastic leukemia (ALL) poses unique therapeutic challenges, with novel immunotherapy approaches offering potential cure opportunities. In this frame, the use of Blinatumomab may induce durable remissions, serving as a successful bridge to allergenic hematopoietic stem cell transplantation (allo-HSCT). Herein, we retrospectively summarize the Greek experience on pediatric relapsed/refractory B-cell precursor ALL patients that were treated with Blinatumomab in a compassionate, off-label setting as an effort to achieve disease clearance and proceed to allo-HSCT. In our cohort of 9 patients, 6/9 (66.7%) responded to Blinatumomab, achieving complete morphological remission (CR) after the 1st cycle, while minimal/measurable residual disease (MRD)-negativity (< 10-4) after the 1st cycle was achieved in 2/2 patients (100.0%) with prior CR. A successful bridge to HSCT was feasible in 5/9 patients (55.6%). Median relapse-free survival (RFS) was 3.0 months (range 0.5-21.4 months) and median overall survival (OS) was 8.7 months (range 1.4-47.1 months) for the whole pediatric cohort. There was a trend of prolonged survival among patients who achieved MRD response after the 1st Blinatumomab administration. MRD response (defined as the >=2-log reduction of MRD value before and after Blinatumomab administration), was associated with a median RFS/OS of 7.4/7.6 months, while lack of MRD response was associated with a median RFS/OS of 0.5/3.0 months, respectively. Novel therapeutic maneuvers, in order to overcome disease resistance, i.e. increased usage of Blinatumomab dose bination with donor lymphocyte infusions (DLIs), use of other immunotherapy salvage approaches (inotuzumabozogamicin), are herein discussed. Additionally, the optimal number of Blinatumomab cycles, the CD19-negative relapses and lineage switch, are also addressed. Our data although referred to a limited however refractory or relapsed and heavily pretreated number of patients, strongly suggest that Blinatumomab may well induce sustained remissions and serve as an effective bridge to HSCT. Whether immunotherapy combined with chemotherapy can outweigh the need for subsequent allo-HSCT, if incorporated into

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients

Ampatzidou¹,

Kattamis²,

Baka³

et al. 2021

neo

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“…For MRD detection, a minimum of 500,000 events were collected with count extrapolation up to 3,600,000 events if needed. Sensitivity of 0.1-0.01% was achieved in most cases, with a minimum of 20 events acquisition in the MRD gate [1,3,5,6].…”

Section: Flow Cytometry (Fc)mentioning

confidence: 97%

“…The survival rates in pediatric acute lymphoblastic leukemia (ALL) have improved significantly during the past decades, with more than 80% of patients achieving remission and long-term cure. This has been accomplished mainly by the refinement of risk stratification systems, the integration of MRD in current risk-adjusted therapy and the evolution of genome-wide technologies in exploring the underlying biology [1][2][3][4][5][6][7][8][9][10][11][12]. Nevertheless, the prevention of relapse and therapy-related toxicities present major challenges.…”

Section: Introductionmentioning

confidence: 99%

Copy Number Alteration Profile Provides Additional Prognostic Value for Acute Lymphoblastic Leukemia Patients Treated on BFM Protocols

Ampatzidou

Florentin

Papadakis

et al. 2021

Cancers

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We present our data of a novel proposed CNA-profile risk-index, applied on a Greek ALLIC-BFM-treated cohort, aiming at further refining genomic risk-stratification. Eighty-five of 227 consecutively treated ALL patients were analyzed for the copy-number-status of eight genes (IKZF1/CDKN2A/2B/PAR1/BTG1/EBF1/PAX5/ETV6/RB1). Using the MLPA-assay, patients were stratified as: (1) Good-risk(GR)-CNA-profile (n = 51), with no deletion of IKZF1/CDKN2A/B/PAR1/BTG1/EBF1/PAX5/ETV6/RB1 or isolated deletions of ETV6/PAX5/BTG1 or ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/B. (2) Poor-risk(PR)-CNA-profile (n = 34), with any deletion of ΙΚΖF1/PAR1/EBF1/RB1 or any other CΝΑ. With a median follow-up time of 49.9 months, EFS for GR-CNA-profile and PR-CNA-profile patients was 96.0% vs. 57.6% (p < 0.001). For IR-group and HR-group patients, EFS for the GR-CNA/PR-CNA subgroups was 100.0% vs. 60.0% (p < 0.001) and 88.2% vs. 55.6% (p = 0.047), respectively. Among FC-MRDd15 + patients (MRDd15 ≥ 10−4), EFS rates were 95.3% vs. 51.7% for GR-CNA/PR-CNA subjects (p < 0.001). Similarly, among FC-MRDd33 + patients (MRDd33 ≥ 10−4), EFS was 92.9% vs. 27.3% (p < 0.001) and for patients FC-MRDd33 − (MRDd33 < 10−4), EFS was 97.2% vs. 72.7% (p = 0.004), for GR-CNA/PR-CNA patients, respectively. In a multivariate analysis, the CNA-profile was the most important outcome predictor. In conclusion, the CNA-profile can establish a new genomic risk-index, identifying a distinct subgroup with increased relapse risk among the IR-group, as well as a subgroup of patients with superior prognosis among HR-patients. The CNA-profile is feasible in BFM-based protocols, further refining MRD-based risk-stratification.

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“…Acute lymphoblastic leukemia (ALL) is a malignancy derived from the medullary or lymphocyte precursor cells 1. ALL is the most common cancer in children, accounting for 25%–35% of pediatric cancers 2,3. With the understanding of the pathogenesis of ALL and individualized stratified therapy, the clinical efficacy of children with ALL has been significantly improved 4–8.…”

Section: Introductionmentioning

confidence: 99%

<p>Proteomic analysis of cerebrospinal fluid in pediatric acute lymphoblastic leukemia patients: a pilot study</p>

Guo¹,

Ren²,

Zeng³

et al. 2019

OTT

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Purpose Involvement of central nervous system in acute lymphoblastic leukemia (CNSL) remains one of the major causes of pediatric acute lymphoblastic leukemia (ALL) treatment failure. However, the current understanding of the pathological process of CNSL is still limited. This study aimed to better understand the protein expression in cerebrospinal fluid (CSF) of ALL and discover valuable prognostic biomarkers. Materials and methods CSF samples were obtained from ALL patients and healthy controls. Comparative proteomic profiling using label-free liquid chromatography-tandem mass spectrometry was performed to detect differentially expressed proteins. Results In the present study, 51 differentially expressed proteins were found. Among them, two core clusters including ten proteins (TIMP1, LGALS3BP, A2M, FN1, AHSG, HRG, ITIH4, CF I, C2, and C4a) might be crucial for tumorigenesis and progression of ALL and can be potentially valuable indicators of CNSL. Conclusion These differentially expressed proteins of ALL children with central nervous system involvement and normal children may work as diagnostic and prognostic factors of ALL patients.

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Childhood acute lymphoblastic leukemia: 12 years of experience, using a Berlin–Frankfurt–Münster approach, in a Greek center

Cited by 7 publications

References 13 publications

Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients

Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients

Copy Number Alteration Profile Provides Additional Prognostic Value for Acute Lymphoblastic Leukemia Patients Treated on BFM Protocols

<p>Proteomic analysis of cerebrospinal fluid in pediatric acute lymphoblastic leukemia patients: a pilot study</p>

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