Understanding the reconstitution of the B‐cell compartment in bone marrow and blood after treatment for B‐cell precursor acute lymphoblastic leukaemia

Theunissen, Prisca; Branden, Anouk van den; Sluijs-Gelling, Alita van der; Haas, Valérie de; Beishuizen, Auke; Dongen, Jacques J. M. van; Velden, Vincent H.J. van der

doi:10.1111/bjh.14685

Cited by 8 publications

(7 citation statements)

References 45 publications

(80 reference statements)

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“…B cell repopulation pattern, including more frequent naïve and transitional subsets, and less frequent memory B cells, is consistent with recently reported results in MS [ 27 ] and is also similar to observations made in other pathologies such as rheumatoid arthritis and systemic lupus erythematosus (SLE) [ 4 , 9 , 12 ]. In contrast with the situation in NMOSD, we found no association between the frequency of memory B cells at the time of reconstitution and the occurrence of relapses [ 15 , 28 , 29 ].…”

Section: Discussionsupporting

confidence: 92%

“…Those works led to the use of B cell-depleting treatments in MS [ 3 ]. Anti-CD20 biotherapies such as rituximab and, more recently, ocrelizumab and ofatumumab, were successfully tested in MS. Rituximab is a chimeric monoclonal antibody targeting the CD20 molecule expressed by B cells from the pre-B to the plasmablast stage [ 4 ]. It induces B cell death by apoptosis induction, antibody-dependent cell cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Early B cells repopulation in multiple sclerosis patients treated with rituximab is not predictive of a risk of relapse or clinical progression

Dorcet

Migné²,

Biotti³

et al. 2022

J Neurol

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Background It is currently unknown whether early B cell reconstitution (EBR) in MS patients under rituximab is associated with a risk of relapse or progression. Objectives Analyzing EBR in rituximab-treated patients and its putative association with clinical findings. Methods Prospective lymphocytes immunophenotyping was performed in a monocentric cohort of MS patients treated by rituximab for 2 years. EBR was defined when B cells concentration was > 5 cells/mm3. B cell subsets were retrospectively associated with clinical data. Clinical and radiological monitoring included relapses, EDSS (Expanded Disability Status Scale), SDMT (Symbol Digit Modalities Test), and MRI. Results 182 patients were analyzed (61 remitting-relapsing and 121 progressive-active). 38.5% experienced EBR at least once, but very few (7/182) showed systematic reconstitution. Most patients remained stable upon treatment, regardless of the occurrence of EBR. Dynamics of B cell reconstitution featured increased naïve/transitional B cells, and decreased memory subsets. Homeostasis of the B cell compartment differed at baseline between patients experiencing or not EBR upon treatment. In patients with EBR, reciprocal dynamics of transitional and pro-inflammatory double-negative B cell subsets was associated with better response to rituximab treatment. Conclusion EBR is common in rituximab-treated MS patients and is not associated with clinical disease activity. EBR in the peripheral blood may reflect regulatory immunological phenomena in subgroup of patients.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Early B cells repopulation in multiple sclerosis patients treated with rituximab is not predictive of a risk of relapse or clinical progression

Dorcet

Migné²,

Biotti³

et al. 2022

J Neurol

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“…These results together with those previously reported for MM patients who achieve long-term disease control [22,25] suggest that full recovery of memory B-cells and end-stage nPC in BM of MM might require longer periods of time (e.g., ≥1year) during which the levels of antigen-experienced B-cells (e.g., memory B-cells and end-stage nPC) in BM return to normal [44,49] and serum immunoglobulin (Ig) levels recover in the absence of disease progression [17,50]. Altogether, these results support the notion that full B-cell reconstitution is a late and progressive process that starts early after the onset of therapy, which would lead to a full recovery of normal B-cell counts at between 6 to 12 months, when maximum B-lymphocyte levels are detected in BM [30,49]. In line with these findings, the percentage of nPC in BM as assessed by flow cytometry has also been associated with parallel recovery of Ig levels from day+100 after ASCT onward [17].…”

Section: Discussionsupporting

confidence: 78%

B-Cell Regeneration Profile and Minimal Residual Disease Status in Bone Marrow of Treated Multiple Myeloma Patients

Pontes

Flores‐Montero

Sanoja-Flores

et al. 2021

Cancers

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B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (≥50y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations. BM hemodilution was detected in 41 out of 177 (23%) patient samples, leading to lower total B-cell, B-cell precursor (BCP) and normal plasma cell (nPC) counts. Among MM BM, decreased percentages (vs. HD) of BCP, transitional/naïve B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP increased after induction therapy, whereas TBC/NBC counts remained abnormally low. At day+100 postautologous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC cell numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19− nPC counts vs. non-CR specimens. MRD positivity was associated with higher BCP and nPC percentages. Hemodilution showed a negative impact on BM B-cell distribution. Different BM B-cell regeneration profiles are present in MM at diagnosis and after therapy with no significant association with patient outcome.

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“…Moreover, we noted that the early (CD34+) stage BCPs (BCP1) compartment was relatively higher in EOI-MRD samples compared to EOC and SFU samples. It is in line with the fact that immediately after the intensivephase, BCP starts regenerating, and hence, they were rich in the early-stage compartment of BCPs (Theunissen, van den Branden et al, 2017). As these cells mature, the late-BCP compartment (BCP2) expanded at later time points.…”

Section: The Relation Between Immunophenotypic Shift and Other Risk Factorssupporting

confidence: 72%

Immunophenotypic shift in the B‐cell precursors from regenerating bone marrow samples: A critical consideration for measurable residual disease assessment in B‐lymphoblastic leukemia

Chatterjee

Sriram

Ghogale

et al. 2020

Cytometry Part B Clinical

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Accurate knowledge of expression patterns/levels of commonly used MRD markers in regenerative normal-B-cell-precursors (BCP) is highly desirable to distinguish leukemicblasts from regenerative-BCP for multicolor flow cytometry (MFC)-based measurable residual disease (MRD) assessment in B-lymphoblastic leukemia (B-ALL). However, the data highlighting therapy-related immunophenotypic-shift in regenerative-BCPs is scarce and limited to small cohort. Herein, we report the in-depth evaluation of immunophenotypic shift in regenerative-BCPs from a large cohort of BALL-MRD samples. Ten-color MFC-MRD analysis was performed in pediatric-BALL at the end-of-induction (EOI), end-of-consolidation (EOC), and subsequent-follow-up (SFU) time-points. We studied normalized-mean fluorescent intensity (nMFI) and coefficientof-variation of immunofluorescence (CVIF) of CD10, CD19, CD20, CD34, CD38, and CD45 expression in regenerative-BCP (early, BCP1 and late, BCP2) from 200 BALL-MRD samples, and compared them with BCP from 15 regenerating control (RC) TALL-MRD samples and 20 treatment-naïve bone-marrow control (TNSC) samples.Regenerative-BCP1 showed downregulation in CD10 and CD34 expression with increased CVIF and reduced nMFI (p < 0.001), upregulation of CD20 with increased nMFI (p = 0.014) and heterogeneous CD45 expression with increased CVIF (p < 0.001). Immunophenotypic shift was less pronounced in the BCP2 compared to BCP1 compartment with increased CVIF in all but CD45 (p < 0.05) and reduced nMFI only in CD45 expression (p = 0.005). Downregulation of CD10/CD34 and upregulation of CD20 was higher at EOI than EOC and SFU time-points (p < 0.001). Regenerative-BCPs are characterized by the significant immunophenotypic shift in commonly used B-ALL-MRD markers, especially CD10 and CD34 expression, as compared to treatment-naïve BCPs. Therefore, the templates/database for BMRD analysis must be developed using regenerative-BCP.

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Understanding the reconstitution of the B‐cell compartment in bone marrow and blood after treatment for B‐cell precursor acute lymphoblastic leukaemia

Cited by 8 publications

References 45 publications

Early B cells repopulation in multiple sclerosis patients treated with rituximab is not predictive of a risk of relapse or clinical progression

Early B cells repopulation in multiple sclerosis patients treated with rituximab is not predictive of a risk of relapse or clinical progression

B-Cell Regeneration Profile and Minimal Residual Disease Status in Bone Marrow of Treated Multiple Myeloma Patients

Immunophenotypic shift in the B‐cell precursors from regenerating bone marrow samples: A critical consideration for measurable residual disease assessment in B‐lymphoblastic leukemia

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