Absolute count of leukemic blasts in cerebrospinal fluid as detected by flow cytometry is a relevant prognostic factor in children with acute lymphoblastic leukemia

Popov, Alexander; Henze, Guenter; Verzhbitskaya, Tatiana; Roumiantseva, Julia; Lagoyko, Svetlana; Khlebnikova, Olga; Streneva, Olga; Bidanov, Oleg; Tsaur, Grigory; Inaba, Hiroto; Karachunskiy, Alexander; Fechina, Larisa

doi:10.1007/s00432-019-02886-3

Cited by 28 publications

(30 citation statements)

References 23 publications

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“…For the detection of CNS involvement, MFC depends on the analysis of aberrant antigen expression and/or light chain restriction. Popov et al (2019) used a 4–6 color antibody combination based on immunophenotype of leukemic cells as determined at initial blast cells characterization including CD19/CD10/CD34/CD45 for the majority of BCP‐ALL and CD7/CD3/CD5/CD2/CD99/CD45 for T‐ALL. In B‐ALL, a similar combination was used by Cancela et al (2017).…”

Section: Points Of Discussionmentioning

confidence: 99%

“…Therefore, MFC appears an excellent candidate, better than CC, to handle specimens such as CSF characterized by a "scarce event" situation (Bento et al, 2018;Craig et al, 2011;Nückel et al, 2006). This peculiarity was confirmed in pediatric ALL patients in whom MFC was able to ameliorate significantly the demonstration of occult CSF involvement (Popov et al, 2019;Swinburne et al, 2019). Mitri et al (2014) increased detection rate of CNS involvement, as compared with CC.…”

Section: Interpretation Of Mfc Findingsmentioning

confidence: 92%

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ESCCA/ISCCA protocol for the analysis of cerebrospinal fluid by multiparametric flow‐cytometry in hematological malignancies

Principe

Gatti

Johansson

et al. 2020

Cytometry Part B Clinical

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Central nervous system (CNS) involvement is a serious but often underdiagnosed complication of hematological malignancies. Currently, the gold standard to detect CNS involvement is conventional cytology (CC) whose sensitivity though is lower than 50%. Multiparametric flow cytometry (MFC) demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies are few, a positive finding by MFC appears to anticipate an adverse outcome even if CC shows no infiltration. However, the use of MFC to diagnose CNS involvement presents some pitfalls, due to the typical hypocellularity of cerebrospinal fluids (CSF), and low cell vitality. Furthermore, the threshold to be used for defining the MFC positivity is not universally defined. In this paper, a working group of the European Society for Clinical Cell Analysis-ESCCA-and the Italian Society for Clinical Cell Analysis-ISCCA-will discuss the critical aspects of CSF processing, highlighting difficulties in storage and processing of samples, interpretation and reporting of data.

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Section: Points Of Discussionmentioning

confidence: 99%

Section: Interpretation Of Mfc Findingsmentioning

confidence: 92%

ESCCA/ISCCA protocol for the analysis of cerebrospinal fluid by multiparametric flow‐cytometry in hematological malignancies

Principe

Gatti

Johansson

et al. 2020

Cytometry Part B Clinical

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“…In subgroups 2 and 3, BM samples were collected on days 14 and 28 and then after 2, 3, 4, 6, 8, 10, 12, 24 months from the beginning of CAR-T treatment. BM samples from healthy donors (n = 12) and children with B-lineage ALL treated by conventional chemotherapy 24,25 (24 samples obtained at the end of induction and 20 at the end of consolidation) or allo-HSCT, (n = 23) without CD19 targeting were studied to compare the incidence of CD19(À) BCPs.…”

Section: Patients and Samplesmentioning

confidence: 99%

Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease

et al. 2021

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CD19-directed treatment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) frequently leads to the downmodulation of targeted antigens. As multicolour flow cytometry (MFC) application for minimal/measurable residual disease (MRD) assessment in BCP-ALL is based on B-cell compartment study, CD19 loss could hamper MFC-MRD monitoring after blinatumomab or chimeric antigen receptor T-cell (CAR-T) therapy. The use of other antigens (CD22, CD10, CD79a, etc.) as B-lineage gating markers allows the identification of CD19-negative leukaemia, but it could also lead to misidentification of normal very-early CD19-negative BCPs as tumour blasts. In the current study, we summarized the results of the investigation of CD19-negative normal BCPs in 106 children with BCP-ALL who underwent CD19 targeting (blinatumomab, n = 64; CAR-T, n = 25; or both, n = 17). It was found that normal CD19-negative BCPs could be found in bone marrow after CD19-directed treatment more frequently than in healthy donors and children with BCP-ALL during chemotherapy or after stem cell transplantation. Analysis of the antigen expression profile revealed that normal CD19-negative BCPs could be mixed up with residual leukaemic blasts, even in bioinformatic analyses of MFC data. The results of our study should help to investigate MFC-MRD more accurately in patients who have undergone CD19-targeted therapy, even in cases with normal CD19-negative BCP expansion.

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“…To determine the spread of cancer to the brain or spinal cord, current methodologies rely on neuro-imaging, clinical findings such mental status changes, new onset headaches, presence of cauda equina syndrome, changes in sensory status and microscopic evaluation (cytology) or flow cytometry of CSF. For some cancers, particularly acute lymphoblastic leukemias, effective, early detection of infiltrating tumors cells in the CSF maximizes the ability to provide early and effective therapeutic intervention (12).…”

Section: Improved Yields From Ctdna-csf Compared To Pelleted Cells Frmentioning

confidence: 99%

Genomic Profiling of Circulating Tumor DNA From Cerebrospinal Fluid to Guide Clinical Decision Making for Patients With Primary and Metastatic Brain Tumors

Ramkissoon

Pegram²,

Haberberger³

et al. 2020

Front. Neurol.

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Absolute count of leukemic blasts in cerebrospinal fluid as detected by flow cytometry is a relevant prognostic factor in children with acute lymphoblastic leukemia

Cited by 28 publications

References 23 publications

ESCCA/ISCCA protocol for the analysis of cerebrospinal fluid by multiparametric flow‐cytometry in hematological malignancies

ESCCA/ISCCA protocol for the analysis of cerebrospinal fluid by multiparametric flow‐cytometry in hematological malignancies

Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease

Genomic Profiling of Circulating Tumor DNA From Cerebrospinal Fluid to Guide Clinical Decision Making for Patients With Primary and Metastatic Brain Tumors

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