CD19 Cell Count at Baseline Predicts B Cell Repopulation at 6 and 12 Months in Multiple Sclerosis Patients Treated with Ocrelizumab

Background: The kinetics of B cell repopulation in MS patients treated with Ocrelizumab is highly variable, suggesting that a fixed dosage and time scheduling might be not optimal. We aimed to investigate whether B cell repopulation kinetics influences clinical and radiological outcomes and whether circulating immune asset at baseline affects B cell repopulation kinetics. Methods: 218 MS patients treated with Ocrelizumab were included. Every six months we collected data on clinical and magnetic resonance imaging (MRI) activity and lymphocyte subsets at baseline. According to B cell counts at six and twelve months, we identified two groups of patients, those with fast repopulation rate (FR) and those with slow repopulation rate (SR). Results: A significant reduction in clinical and radiological activity was found. One hundred fifty-five patients had complete data and received at least three treatment cycles (twelve-month follow-up). After six months, the FR patients were 41/155 (26.45%) and 10/41 (29.27%) remained non-depleted after twelve months. FR patients showed a significantly higher percentage of active MRI scan at twelve months (17.39% vs. 2.53%; p = 0,008). Furthermore, FR patients had a higher baseline B cell count compared to patients with an SR (p = 0.02 and p = 0.002, at the six- and twelve-month follow-ups, respectively). Conclusion: A considerable proportion of MS patients did not achieve a complete CD19 cell depletion and these patients had a higher baseline CD19 cell count. These findings, together with the higher MRI activity found in FR patients, suggest that the Ocrelizumab dosage could be tailored depending on CD19 cell counts at baseline in order to achieve complete disease control in all patients.

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Treatment Free Survival of Patients with MBL and Early CLL: Follow-up of 405 Patients at Mayo Clinic.

Blood ◽

10.1182/blood.v112.11.2063.2063 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2063-2063

Author(s):

Tait Shanafelt ◽

Neil E. Kay ◽

Kari Rabe ◽

Timothy G. Call ◽

Clive S. Zent ◽

...

Keyword(s):

Flow Cytometry ◽

Natural History ◽

B Cell ◽

Cell Count ◽

Mayo Clinic ◽

Lymphocytic Leukemia ◽

Peripheral Blood Flow ◽

Time To Treatment ◽

Cell Counts

Abstract BACKGROUND: The diagnosis of monoclonal B-cell lymphocytosis (MBL) is used to characterize patients who have a circulating population of clonal B-cells, a total B-cell count of <5 x 109/L, and no other features of another B-cell lymphoproliferative disorder. In most patients the immunophenotype is similar to that of chronic lymphocytic leukemia with co-expression of CD19 and CD5. The natural history of CLL-phenotype MBL is unclear. We used the Mayo Clinic hematopathology database to identify patients with CLL-phenotype MBL and abstracted clinical information on natural history and prognostic parameters from clinical and research records. METHODS: Using hematopathology records, we identified a cohort of 1820 patients seen at Mayo Clinic between August 1998 and May 2006 who underwent investigation using peripheral blood flow cytometry and who were found to have a clonal B-cell population of CLL phenotype. After elimination of patients with advanced stage (Rai I-IV), previously treated CLL, and individuals with an established diagnosis of CLL/MBL >1 year prior to flow, 636 unique patients with isolated lymphocytosis were identified. Based on our prior analysis (Leukemia Research 32:1458) demonstrating that nearly all patients with an ALC >10x109/L have a B-cell count >5x109/L, we focused the remaining analysis on the 405/636 patients who had an ALC <10x109/L and the necessary raw data from flow cytometry analysis to determine the B-cell count. RESULTS: Among the 405 individuals with an ALC <10x109/L, 306 (76%) had a B-cell count <5x109/L at the time of flow and met the current criteria for the diagnosis of MBL (BJH 130:325). Median age at the time of MBL diagnosis was 70 years (range 34 – 93). A slight male preponderance was observed (59% male). B-cell counts ranged from 0.02 to 4.99x109/L and ALC ranged from 0.3–9.6 x109/L. CD38 status was available for 268 (88%) MBL patients of whom 20% were CD38 positive using the 30% threshold. Cytogenetic analysis by fluorescent in situ hybridization (FISH) was available in 130 (42%) MBL patients. Using the hierarchical classification system of Dohner and colleagues, 57 (44%) were 13q-, 23 (18%) were trisomy 12, 5 (4%) were 11q-, 4 (3%) were 17p-, and 39 (30%) had no defect detected. ZAP-70 status was available for 77 (25%) patients of whom 13% were ZAP-70+ positive. Patients underwent sequential monitoring with a median follow-up of 1.7 yrs (range 0–8.1 yrs). Time from diagnosis to treatment for patients meeting criteria for MBL (n=306) as compared to Rai stage 0 CLL patients with B-cell counts between 5.0 and 10.0 x109/L (n=99) was not significantly different and is shown in Figure 1 (p=0.87). For individuals with MBL, survival free of treatment was 98% (95%CI: 96–100%) at 1 year, 93% (95%CI: 89–98%) at 2 years, and 77% (95%CI: 67–89%) at 5 years. While gender (p=0.10), and B-cell count as a continuous variable (p=0.15) were not found to be associated with time to treatment (TTT) among MBL patients, age (p=0.02, HR=0.94, 95% CI: 0.89–0.99) and CD38 status (p<0.02, HR: 3.3, 95% CI: 1.2–9.2) did show a relationship with TTT. CONCLUSIONS: Although we observed a low rate of progression among individuals meeting criteria for MBL, TFS was similar to individuals meeting current criteria for Rai stage 0 CLL who had B-cell counts between 5.0 – 10.0 x109/L . Among individuals meeting criteria for MBL, younger patients and those who were CD38 positive had a shorter time to treatment. Additional studies are needed to determine what B-cell count or other characteristics should be used to distinguish between MBL and Rai stage 0 CLL. FIGURE: FIGURE:.

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Dose-dependent Pharmacological Response to Rituximab in the Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculiti

The Journal of Rheumatology ◽

10.3899/jrheum.210361 ◽

2021 ◽

pp. jrheum.210361

Author(s):

Jason M. Springer ◽

Ryan S. Funk

Keyword(s):

B Cell ◽

Antineutrophil Cytoplasmic Antibody ◽

High Dose ◽

Dosing Regimen ◽

Dosing Interval ◽

Cell Counts ◽

Pharmacological Response ◽

Trough Concentrations ◽

Cell Repopulation ◽

Trough Plasma

Objective Rituximab (RTX) is effective in induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work evaluates the relationship between variability in RTX dosing and pharmacological response in AAV. Methods A prospective cohort of AAV patients (n=28) with either GPA (n=23) or MPA (n=5) receiving maintenance RTX therapy were followed in a single tertiary care academic medical center over a 2-year period. Patient demographics, RTX dosing information, and trough plasma RTX levels were collected along with laboratory measures of pharmacologic response, including B-cell counts and ANCA titers. Results RTX dosing information from 94 infusions with 59 trough samples were collected with a mean±SD dose of 640±221 mg, dosing interval of 210±88 days, and trough plasma RTX concentration of 622±548 ng/mL. RTX trough concentrations were associated with RTX dose (ρ=0.60, p<0.0001) and dosing interval (ρ=-0.55, p<0.0001). RTX dosing intensity (mg/d) was associated with RTX trough concentrations (ρ=0.57, p<0.0001). Higher dosing intensities were associated with undetectable B-cell repopulation (p<0.0001), but not negative ANCA titers (p=0.6). Stratification of dosing intensities based on the standard dosing regimen of 500 mg every six months (2.4 to 3.3 mg/d) demonstrated that this regimen was associated with B-cell repopulation in 8 of 17 doses (47%) compared to 0 of 23 doses (0%) with the high-dose regimen (>3.3 mg/d) (p<0.0001). Conclusion RTX maintenance dosing of 500 mg every six months may be inadequate to maintain B-cell depletion in the treatment of AAV.

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Lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients

10.21203/rs.3.rs-52336/v2 ◽

2020 ◽

Author(s):

Daxian Wu ◽

Xiaoping Wu ◽

Jiansheng Huang ◽

Qunfang Rao ◽

Qi Zhang ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Count ◽

Disease Severity ◽

Lymphocyte Subsets ◽

Nk Cell ◽

Lymphocyte Subset ◽

Multivariate Logistic Regression ◽

Cell Counts ◽

Glutamyl Transpeptidase

Abstract Background: COVID-19 continuously threated public health heavily. Present study aimed to investigate the lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients.Methods: Lymphocyte subsets was classified using flow cytometry with peripheral blood collected from 106 patients.Results: Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent predictors for severe COVID-19. The T cell, CD4+ T cell and B cell counts in severe patients were significantly lower than that in mild patients (p = 0.004, 0.003 and 0.046, respectively). Only the T cell count was gradually decreased with the increase of infiltrated quadrants of lesions in computed tomography (CT) (p = 0.043). The T cell, CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increase of infiltrated area of the maximum lesion in CT (p = 0.002, 0.003, 0.028; respectively). The T cell count, as well as CD4+ T cell, CD8+ T cell, and NK cell counts were gradually decreased with the increased delayed hospitalization (p = 0.003, 0.002, 0.013, and 0.012; respectively). The proportion of T cell was gradually decreased but B cell was gradually increased with the increased delayed hospitalization (p = 0.031 and 0.003, respectively).Conclusion: T cell and CD4+ T cell counts negatively correlated with disease severity, CT manifestation and delayed hospitalization. CD4+ T cell was mainstay of immunity response in COVID-19 patients.

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Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419871187 ◽

2019 ◽

Vol 12 ◽

pp. 175628641987118 ◽

Cited By ~ 2

Author(s):

Kyomin Choi ◽

Yoon-Ho Hong ◽

So-Hyun Ahn ◽

Seol-Hee Baek ◽

Jun-Soon Kim ◽

...

Keyword(s):

B Cells ◽

Myasthenia Gravis ◽

B Cell ◽

Low Dose ◽

Therapeutic Option ◽

Treatment Protocol ◽

Induction Treatment ◽

Clinical Relapse ◽

Cell Counts ◽

Cell Repopulation

Background: The objective of this study was to evaluate the efficacy and safety of repeated low-dose rituximab treatment guided by monitoring circulating CD19+ B cells in patients with refractory myasthenia gravis (MG). Methods: Patients with refractory MG who had received rituximab treatment at two teaching hospitals between September 2013 and January 2017 were reviewed retrospectively. The treatment protocol consisted of an induction treatment with low-dose rituximab (375 mg/m2 twice with a 2-week interval), followed by retreatment (375 mg/m2 once). Retreatment was based on either circulating CD19+ B-cell repopulation or clinical relapse. Outcome measures included the MG Foundation of America (MGFA) clinical classification and postintervention status, prednisolone dose, CD19+ B-cell counts, clinical relapse, and adverse effects. Results: Of 17 patients, 11 (65%) achieved the primary endpoint, defined as the minimal manifestation or better status with prednisolone ⩽5 mg/day, after median 7.6 months (range, 2–17 months) following rituximab treatment. Over a median follow up of 24 months (range, 7–49 months), a total of 30 retreatments were undertaken due to clinical relapse without B-cell repopulation ( n = 6), on the basis of B-cell repopulation alone ( n = 16) and both ( n = 8). B-cell recovery appeared to be in parallel with clinical relapse on the group level, although the individual-level association appeared to be modest, with B-cell repopulation observed only at 57% (8/14) of clinical relapses. Conclusions: The repeated low-dose rituximab treatment based on the assessment of circulating B-cell depletion could be a cost-effective therapeutic option for refractory MG. Further studies are needed to verify the potentially better cost-effectiveness of low-dose rituximab, and to identify biomarkers that help optimize treatment in MG patients.

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Peripheral Blood CD3+CD4+ and CD3−CD56+ Cell Counts and Circulating Lymphoma Cells Are Significant Predictors of Overall Survival in Newly Diagnosed Follicular Lymphoma.

Blood ◽

10.1182/blood.v110.11.2607.2607 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2607-2607

Author(s):

Danielle Shafer ◽

Mitchell R. Smith ◽

Samuel Litwin ◽

Tianyu Li ◽

Hossein Borghaei ◽

...

Keyword(s):

Overall Survival ◽

Cell Count ◽

Peripheral Blood ◽

Lymphocyte Subsets ◽

Nk Cell ◽

Cd4 Count ◽

Newly Diagnosed ◽

Original Diagnosis ◽

Cell Counts

Abstract BACKGROUND: Interaction between the immune system and follicular lymphoma (FL) is well recognized from immunohistochemical as well as microarray studies, but is not yet fully elucidated. A recent report suggested that a higher absolute lymphocyte count (ALC) predicted a longer time to progression and improved response to rituximab in FL (Behl et al, Br J Haem2007). The GELA group reported a correlation between peripheral blood natural killer cell count and event free survival in diffuse large B cell lymphoma (Plonquet et al Ann Oncol2007). The influence of lymphocyte subsets in the peripheral blood (PB) on FL outcome has not been reported. PATIENTS AND METHODS: We retrospectively analyzed the immunophenotype from peripheral blood flow cytometry (PBFC) at Fox Chase Cancer Center in FL patients (pts). We identified 127 pts (82 newly diagnosed and 45 previously treated). We recorded the presence or absence of circulating monoclonal B cells (CLC) and survival in all as well as a complete PBFC panel in > 90% of pts. FLIPI and IPI scores were calculated from data at the time of diagnosis. Overall survival and time to treatment from date of original diagnosis and from date of PBFC were analyzed in relation to ALC, CLC, the lymphocyte subsets CD3+CD4+, CD3+CD8+, CD3−CD56+/CD16+ (NK cells) and FLIPI and IPI scores. A low CD4 count was defined as <500 cells/mm3, a low NK cell count as <150 cells/mm3 and a low ALC as <1500 cells/mm3. RESULTS: There were 63 females and 64 males; median age at presentation was 56 yrs (range 31–88). Median follow up intervals from original diagnosis and from PBFC were 46 months (range 3.5 – 207) and 24 months (range 0.7–138), respectively. This abstract deals principally with the 82 newly diagnosed pts. Median follow up in the newly diagnosed subset was 27.8 months (range 0.7 to – 138); thirty-five pts were subsequently treated, and 47 pts remained under observation. FLIPI scores at diagnosis were: low - 48 pts, intermediate - 25, high - 7 and unknown - 2. IPI scores were: low - 52 pts, low-intermediate - 24, high-intermediate/high - 4 and unknown - 2. CLC were present in 21% of pts. At last follow up, 74 pts were still alive. By univariate analysis, the most significant predictors for inferior overall survival (OS) from time of PBFC were low CD4 count (P = 0.03), low NK cell count (P = 0.02), and presence of CLC (P = 0.03). There was insufficient power for significance in multivariate analysis. At last follow up, survival for the low vs. high CD4 and NK cell groups was 85% vs. 97% and 85% vs.98%, respectively. FLIPI and IPI scores, low ALC, and low CD8 did not correlate with OS from time of diagnosis or time of PBFC. With respect to time to initial treatment, only a low ALC (P<0.001) and FLIPI (P<0.001) were significant. In multivariate analysis for OS of all 127 pts, low NK cell count remained significant (P = 0.03), while low CD4 count was marginally significant (P = 0.08). CONCLUSION: Analysis of PB lymphocytes by PBFC has prognostic value in previously untreated FL pts. Low CD4 and NK cell counts as well as the presence of CLC are the most significant predictors for OS in newly diagnosed FL. Our findings suggest the importance of an intact immune system. They merit further prospective studies to ascertain the impact of treatment on subsets of pts with specific immunophenotypes and may prove useful in FL management.

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Risk Adjusted Management of Newly Diagnosed High and Intermediate FLIPI Follicular Lymphoma Using (90)Y Ibritumomab Tiuxetan

Blood ◽

10.1182/blood.v128.22.1794.1794 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1794-1794

Author(s):

Neil L Berinstein ◽

Nancy M Pennell ◽

Rashmi Weerasinghe ◽

Matthew C. Cheung ◽

Eugenia Piliotis ◽

...

Keyword(s):

High Risk ◽

Follicular Lymphoma ◽

B Cell ◽

International Prognostic Index ◽

Prognostic Index ◽

Newly Diagnosed ◽

Ibritumomab Tiuxetan ◽

Cell Counts ◽

Post Therapy

Abstract Background: Although the natural history of follicular lymphoma is indolent with a median overall survival of about 12-15 years, the disease is heterogeneous. The 5 and 10 year overall survival (OS) of low, intermediate and high risk FLIPI is 91%, 78% and 53% and 71%, 51% and 36% using standard rituximab-based treatment. 5-year progression-free survival (PFS) is 80%, 70% and 48% respectively. Methods: Based upon this we conducted an investigator-initiated single-centre Phase II trial of intensified therapy with CHOP-R followed by (90)Y ibritumomab tiuxetan consolidation and 24 months of rituximab maintenance as treatment for patients with intermediate and high-risk newly diagnosed symptomatic follicular lymphoma. 33 patients were enrolled. Results: The addition of (90)Y ibritumomab tiuxetan was well tolerated but resulted in asymptomatic grade 3 or 4 thrombocytopenia and neutropenia in11-36% and 10-24% of patients between weeks 2-8 post (90) Y. After 9 years of follow-up (median follow-up 61 months) the 0S for intermediate and high risk FLIPI was 95% and 78%. The 5 year PFS was 79% and 64% for intermediate and high risk FLIPI, respectively. Responses at three months post consolidation were as follows: 3/33 (9%) achieved CR, 25/33(76%), achieved CRU, 1/33(3%) had PR, and 1/33(3%) had PD. Three patients did not receive (90)Y ibritumomab tiuxetan due to disease progression 2/33(6%), or death 1/33(3%). Of 19 patients who had a molecular marker for their lymphoma, 18 (95%) achieved molecular remissions in peripheral blood with CHOP-R therapy. Nine (47%) of these patients have been recently assessed for MRD and remain in molecular remission. The therapy resulted in decreased levels of IgG, IgM and IgA below the lower normal level in 33%, 40% and 23% of patients respectively post therapy. These levels did not recover in most of these patients. B cells were depleted to undetectable levels during therapy including rituximab maintenance. In 18 evaluable patients only 11 recovered normal B cell counts post maintenance rituximab. There was no correlation between normal B-cell recovery and Ig levels. Many patients with low or no B cell counts had normal IgG levels, whereas some patients who regained normal B cell counts were still unable to reach normal Ig levels. No patient developed human anti-mouse antibody. Immunity to measles, mumps, or rubella was retained post therapy. Patients did not have significant infections or opportunistic infections (although 2 developed Grade 1 shingles post (90)Y ibritumomab tiuxetan) and none required IVIG. Conclusions: We conclude that this intensified regimen is highly active in cyto-reducing lymphoma in high and intermediate risk FLIPI follicular lymphoma patients. The toxicity is tolerable although a significant percentage of patients will end up with persistent asymptomatic reductions in B cells and serum Ig. Only randomized trials will determine whether this regimen enhances outcome over standard of care in this higher risk follicular lymphoma population. References: 1.Examination of the follicular lymphoma international prognostic index (FLIPI) in the National LymphoCare study (NLCS): a prospective US patient cohort treated predominantly in community practices. Nooka AK, Nabhan C, Zhou X, Taylor MD, Byrtek M, Miller TP, Friedberg JW, Zelenetz AD, Link BK, Cerhan JR, Dillon H, Sinha R, Shenoy PJ, Levy D, Dawson K, Hirata JH, Flowers CR. Ann Oncol. 2013 Feb;24(2):441-8. doi: 10.1093/annonc/mds429. Epub 2012 Oct 5 2.Validation, revision and extension of the Follicular Lymphoma International Prognostic Index (FLIPI) in a population-based setting. van de Schans SA, Steyerberg EW, Nijziel MR, Creemers GJ, Janssen-Heijnen ML, van Spronsen DJ. Ann Oncol. 2009 Oct;20(10):1697-702. doi: 10.1093/annonc/mdp053. Epub 2009 Jun 23. PMID: 19549712 Disclosures Buckstein: Novartis: Honoraria; Celgene: Honoraria, Research Funding.

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B Cell Reconstitution after Gene Therapy in Patients with Wiskott Aldrich Syndrome and Comparison with Mismatched Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v126.23.3235.3235 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3235-3235

Author(s):

Alessandra Magnani ◽

Cécile Roudaut ◽

Aurelie Gabrion ◽

Laure Caccavelli ◽

Fabien Touzot ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Cell Count ◽

Lentiviral Vector ◽

Cell Phenotype ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Normal Ranges ◽

Ivig Replacement

Abstract Background. Wiskott Aldrich Syndrome (WAS) is a rare primary immunodeficiency associated with thrombocytopenia, eczema, severe infectious and autoimmune complications, and lymphomas. Mismatched allogeneic hematopoietic stem cell transplantation (HSCT) is an alternative for patient lacking an HLA-matched donor but is associated with an increased frequency of complications. Moreover low lymphoid and myeloid chimerism is related to a higher rate of autoimmunity and thrombocytopenia. Recent gene therapy (GT) trials showed that gene-corrected autologous CD34+ cells infusion could be an appropriate therapeutic approach for these patients. It has been recently shown that B cell homeostasis is altered in WAS. As the B cell reconstitution participates to the restoration of immunological competence, a comprehensive study of this compartment after GT and the comparison with mismatched allogeneic HSCT is crucial. Objective. To perform a longitudinal study of B cell reconstitution in WAS patients after lentiviral vector-mediated GT, compared to mismatched allogeneic HSCT. Methods. Five patients (age 0.8-15.5 years) underwent GT at our center since 2011(follow-up 1.5-4.2 years) after near-myeloablative and immunosuppressive conditioning regimen with (n=3) or without (n=2) anti-CD20 administration. Patient 2 (P2) died 7 months after GT from a pre-existing infectious complication. Eleven patients undergoing mismatched allogeneic HSCT (age 0.6-10.9 years) at the same center were studied (follow-up 5.1-14.7 years). Longitudinal B cell assessment included B cell count before and after treatment, and the following subsets: switched memory (SM, CD19+ CD27+ IgD-), marginal zone (MZ, CD19+ CD27+ IgD+), naives (CD19+ CD27- IgD+), transitional (CD19+ CD27- IgD+ CD24high CD38high), circulating plasma cells (CD19+ CD27+ IgD- CD27high CD38high) and CD21low B cells (CD19+ CD21low CD38-), a subset abnormally expanded in WAS. Quantification of the B cell replication history was assessed through k-deleting recombination excision circles (KRECs). Analyses were compared to age-matched controls. WAS protein (WASP) expression and vector copy number (VCN) were measured in sorted B cells. Results. All alive GT patients show stable engraftment of functionally corrected lymphoid cells, without adverse events. Transduced B cells number and WASP expression increased progressively after GT. Absolute B cell count attained normal values in all the patients, and correlates with WASP expression and VCN in B cells. IgM levels are below normal ranges in four patients. P3 and P4 attained a B-cell phenotype within normal ranges; P3 discontinued intravenous immunoglobulin (IvIg) replacement. No expansion of CD21low B cells was observed. P1 and P5 (follow-up 18 months) present a variable defect in SM, naives and/or MZ B cells. P1 recently developed autoimmune manifestations; no significant changes were observed concomitantly. A defect in B cell lymphopoiesis was observed before GT as measured by KRECs analysis, normalizing after GT (P1, P3 and P4). Several complications were recorded in patients undergoing mismatched allogeneic HSCT, including dysimmunity, arthritis, developmental deficit and infections. Total B cell count normalized in eight patients, IgM levels were low in three. Among patients with available information, four still remain under IvIg replacement. Four patients developed a mixed lymphoid and myeloid chimerism, variably associated with low B cell count, low IgM and IvIg replacement. A complete B cell assessment for these patients is ongoing. Conclusions. B cell transgene expression is obtained after lentiviral vector-mediated GT in WAS patients and is associated with improved B cell lymphopoiesis. A correct B cell phenotype is observed in two patients who did not receive rituximab prior GT. The question whether this is related to the treatment will need a longer follow-up to be answered. Patients undergoing mismatched allogeneic HSCT present a higher frequency of complications. Although a higher proportion of these patients discontinued IvIg replacement, B cell reconstitution is not optimal. Analysis of patients in particular with mixed chimerism will provide important information in the setting of GT. The analysis of B cell reconstitution after GT and mismatched allogeneic HSCT deserves particular attention in the assessment of immunological reconstitution. Disclosures No relevant conflicts of interest to declare.

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Preserved T-cell Response in anti-CD20 Treated Multiple Sclerosis Patients Following SARS-CoV-2 Vaccination

10.21203/rs.3.rs-1109886/v1 ◽

2021 ◽

Author(s):

Simon Faissner ◽

Neele Heitmann ◽

Ricarda Rohling ◽

Ulas Ceylan ◽

Marielena Bongert ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Response ◽

T Cell ◽

B Cell ◽

T Cell Response ◽

Th2 Cells ◽

Multiple Sclerosis Patients ◽

Cellular Immune ◽

Cell Repopulation

Abstract The SARS-CoV-2 pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20+ B cells (aCD20). We here investigated humoral and cellular immune responses, including neutralization against SARS-CoV-2 WT and delta variant and T cell responses of aCD20-treated MS patients following SARS-CoV-2 vaccination compared to healthy controls. aCD20-treated MS patients had lower anti-SARS-CoV-2-Spike titers, which correlated with B-cell repopulation. Sera of aCD20 treated patients had reduced capacity to neutralize WT and delta pseudoviruses in vitro. On the contrary, aCD20 treated patients elicited higher frequencies of CD3+ T cells, Th1 cells, Th2 cells, Tc1 cells and CD8+IFN-γ+IL-2+ cells. In summary, aCD20 treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with a shift of cellular immune response to a stronger Th1, Th2 and Tc1 phenotype, suggesting strong cellular protection against SARS-CoV-2.

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Monitoring B-cell repopulation after depletion therapy in neurologic patients

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000463 ◽

2018 ◽

Vol 5 (4) ◽

pp. e463 ◽

Cited By ~ 27

Author(s):

Erik Ellwardt ◽

Lea Ellwardt ◽

Stefan Bittner ◽

Frauke Zipp

Keyword(s):

B Cells ◽

B Cell ◽

Cell Depletion ◽

Close Monitoring ◽

B Cell Depletion ◽

Cell Recovery ◽

Cell Counts ◽

White Blood Cell Counts ◽

Anti Cd20 ◽

Cell Repopulation

ObjectiveTo determine the factors that influence B-cell repopulation after B-cell depletion therapy in neurologic patients and derive recommendations for monitoring and dosing of patients.MethodsIn this study, we determined the association of body surface area (BSA; calculated by body weight and height with the Dubois formula), sex, pretreatment therapy, age, CSF data, and white blood cell counts with the risk and timing of B-cell repopulation, defined as 1% CD19+ cells (of total lymphocytes), following 87 B cell–depleting anti-CD20 treatment cycles of 45 neurologic patients (28 women; mean age ± SD, 44.5 ± 15.0 years).ResultsPatients with a larger BSA had a higher probability to reach 1% CD19+ cells than those with a smaller BSA (p < 0.05) following B-cell depletion therapy, although those patients had received BSA-adapted doses of rituximab (375 mg/m2). Sex, pretreatment, age, CSF data, or absolute lymphocyte and leukocyte counts during treatment did not significantly influence CD19+ B-cell recovery in the fully adjusted models. Intraindividual B-cell recovery in patients with several treatment cycles did not consistently change over time.ConclusionsB-cell repopulation after depletion therapy displays both high inter- and intra-individual variance. Our data indicate that a larger BSA is associated with faster repopulation of B cells, even when treatment is adapted to the BSA. A reason is the routinely used Dubois formula, underestimating a large BSA. In these patients, there is a need for a higher therapy dose. Because B-cell count–dependent therapy regimes are considered to reduce adverse events, B-cell monitoring will stay highly relevant. Patients' BSA should thus be determined using the Mosteller formula, and close monitoring should be done to avoid resurgent B cells and disease activity.

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Immunologic Benefits of Enfuvirtide in Patients Enrolled in a Drug Assistance Program

Annals of Pharmacotherapy ◽

10.1345/aph.1k572 ◽

2008 ◽

Vol 42 (5) ◽

pp. 621-626 ◽

Cited By ~ 2

Author(s):

Parya Saberi ◽

Nikolai H Caswell ◽

Cristina I Gruta ◽

Jason N Tokumoto ◽

Betty J Dong

Keyword(s):

Cell Count ◽

Viral Suppression ◽

Cd4 Cell Count ◽

Hiv Rna ◽

Cell Counts ◽

Background Regimen ◽

Cd4 Cell Counts ◽

Cd4 Cell ◽

Cell Count Increase

Background: Randomized clinical trials have demonstrated that enfuvirtide plus an optimized background regimen can cause a significant increase in CD4+ cell counts and a reduction in HIV RNA levels. Objective: To describe and anaiyze CD4+ cell count and HIV RNA changes in HIV-infected patients receiving enfuvirtide and a prescribed background regimen (PBR) in a primarily clinical setting. Methods: A retrospective review from September 1998 through August 2005 of CD4+ cell counts and HIV RNA changes from baseline was conducted in patients receiving enfuvirtide. Data were stratified and analyzed according to baseline CD4+ cell count and HIV RNA. Results: A mean CD4+ cell count increase of approximately 102 cells/mm3 was observed, regardless of baseline CD4+ cell count, in 187 patients receiving enfuvirtide during a mean of 19.4 months of follow-up. During 3 years of follow-up, patients initiating enfuvirtide at CD4+ cell counts less than 100 cells/mm3 never achieved absolute CD4+ cell counts comparable to the counts in patients starting enfuvirtide at CD4+ cell counts of 100 cells/mm3 or more. In 38.3% of patients achieving an undetectable HIV RNA level, a mean CD4+ cell count increase of 185 cells/mm3 was observed. An unexpected finding was that a mean CD4+ cell count increase of 76 cells/mm3 occurred in 61.7% of patients not achieving complete viral suppression. Conclusions: Immunologic benefits were observed in subjects continuing enfuvirtide plus a PBR irrespective of baseline CD4+ cell count, complete viral suppression, or antiretroviral susceptibility data. Dala suggest that initiation of enfuvirtide at CD4+ cell counts greater than 100 celis/mm3 may be immunologically advantageous and independent of complete virologic response.

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