Prognostic Effect of CD20 Expression in Adult B-cell Acute Lymphoblastic Leukemia

Esteban, Reibán-Espinoza; Bourlon, Christianne; Aguayo, Álvaro; Demichelis‐Gómez, Roberta

doi:10.1016/j.clml.2018.02.013

Cited by 11 publications

(7 citation statements)

References 30 publications

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“…In the prognostic analysis of the present study, CD20 expression was found to be associated with unfavorable outcomes in the pro-B-ALL cohort. Although the prognostic impact of CD20 expression on patients’ outcomes remains controversial [31–38], our data suggest that the combination of rituximab with current chemotherapy may be necessary for these patients. In addition, carrying KMT2A rearrangement and high MRD at day 78 were shown to be independent prognostic factors of pro-B-ALL in the present study.…”

Section: Discussionmentioning

confidence: 96%

Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children

et al. 2019

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BackgroundAlthough leukemic blast cells of Pro-B cell acute lymphoblastic leukemia (ALL) are arrested at the same stage of B cell differentiation, the immature B cell subtype is still biologically heterogeneous and is associated with diverse outcomes. This study aimed to explore the clinical-biological characteristics of pediatric pro-B ALL and factors associated with outcomes.MethodsThis study enrolled 121 pediatric patients aged 6 months to 14 years with newly diagnosed CD19+CD10− pro-B cell acute lymphoblastic leukemia (pro-B ALL) treated at Beijing Children’s Hospital from March 2003 to October 2018. Genetic abnormalities, immunophenotypic markers, minimal residual disease (MRD) at early treatment stage and long-term outcomes of children treated on two consecutive protocols were analyzed.ResultsKMT2A rearrangements were the most frequent abnormalities (incidence rate 33.06%), and were associated with lower frequency of CD13, CD33, CD22 and CD34 expression and higher frequency of CD7 and NG2 expression. Higher frequency of CD15 and CD133 expression was found in KMT2A-AFF1+ patients, exclusively. Presence of CD15 and absence of CD34 at diagnosis correlated with the high burden of MRD at the early stage of treatment. Outcomes were more favorable in patients older than 1 year, with absence of CD20 expression and KMT2A rearrangements, and with MRD lower than 1% at the end of induction and 0.1% before consolidation. Increased intensity of chemotherapy based on MRD analysis did not improve outcomes significantly (5-year EFS 73.9 ± 6.5% for BCH-2003 and 76.1 ± 5.3% for CCLG-2008, P = 0.975). Independent adverse prognostic factors were MRD ≥ 0.1% before consolidation and presence of KMT2A gene rearrangements (odds ratios [ORs] 9.424 [95% confidence interval (CI) 3.210, 27.662; P < 0.001]; 4.142 [1.535, 11.715, P = 0.005]; respectively).ConclusionsPediatric pro-B ALL is a heterogeneous disease. Genetic analysis and MRD evaluation can predict patients with dismal prognosis; however, intensive chemotherapy alone does not improve outcomes of these patients and targeted therapy or hematopoietic stem cell transplantation may be required.

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Section: Discussionmentioning

confidence: 96%

Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children

et al. 2019

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“…However, the definition of CD20 positivity with a cutoff of 20% was based on the traditional assessment that divided patients into 5 groups by the intensity of surface marker expression: negative, less than the 25th percentile, 25th to 50th percentiles, 50th to 75th percentiles, and more than the 75th percentile of the fluorescence intensity 31 . With the traditional cutoff of CD20 at 20%, several groups reported an association between high CD20 expression and worse outcome 1,14,15,32,33 . Although low CD20 expression (<20%) is associated with favorable outcomes, patients with CD20 expression of 1% to 19% may benefit from the addition of an anti‐CD20 monoclonal antibody to conventional therapy.…”

Section: Discussionmentioning

confidence: 99%

“…31 With the traditional cutoff of CD20 at 20%, several groups reported an association between high CD20 expression and worse outcome. 1,14,15,32,33 Although low CD20 expression (<20%) is associated with favorable outcomes, patients with CD20 expression of 1% to 19% may benefit from the addition of an anti-CD20 monoclonal antibody to conventional therapy.…”

Section: Outcome In the Cd20 < 20% Groupmentioning

confidence: 99%

Hyper‐CVAD plus ofatumumab versus hyper‐CVAD plus rituximab as frontline therapy in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia: A propensity score analysis

Sasaki

Kantarjian

Morita

et al. 2021

Cancer

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Background The outcome of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus ofatumumab hyper‐CVAD + ofatumumab (hyper‐CVAD + ofatumumab) has not been compared with the outcome of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus ofatumumab hyper‐CVAD plus rituximab (hyper‐CVAD + Rituximab) in Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL) in a randomized clinical trial. Methods The authors compared the outcomes of 69 patients treated with hyper‐CVAD + ofatumumab and 95 historical‐control patients treated with hyper‐CVAD + Rituximab. Historical‐control patients were treated with hyper‐CVAD + Rituximab if they had CD20 expression ≥ 20%. Ofatumumab (day 1 of course 1, 300 mg intravenously; subsequent doses, 2000 mg intravenously) was administered on days 1 and 11 of courses 1 and 3 and on days 1 and 8 of courses 2 and 4 for a total of 8 doses. A propensity score analysis with inverse probability of treatment weighting (IPTW) was performed to adjust for baseline covariates between groups. Results The median event‐free survival with stem cell transplantation (SCT) censoring was 33 and 65 months with hyper‐CVAD + Rituximab and hyper‐CVAD + ofatumumab, respectively (crude P = .064; IPTW P = .054). The median overall survival with SCT censoring was 52 months and not reached, respectively (crude P = .087; IPTW P = .097). Conclusions Hyper‐CVAD + ofatumumab was associated with better outcomes than hyper‐CVAD + Rituximab among patients with newly diagnosed Philadelphia chromosome–negative ALL.

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“…Of interest, CD20 is upregulated on B-cell acute lymphoblastic leukaemia blast cells by corticosteroids, suggesting that a relationship between benefit from rituximab and baseline CD20 3 cannot necessarily be anticipated. Additionally, higher levels of cell surface CD20 expression have been identified by some studies as an adverse prognostic biomarker in acute lymphoblastic leukaemia, 4 , 5 , 6 , 7 , 8 although several studies do not concur. 9 , 10 , 11 This is an important consideration, because studies that recruited patients with higher CD20 expression might have selected a subset of patients with a worse prognosis.…”

Section: Introductionmentioning

confidence: 99%

Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial

Marks¹,

Kirkwood²,

Rowntree³

et al. 2022

The Lancet Haematology

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Prognostic Effect of CD20 Expression in Adult B-cell Acute Lymphoblastic Leukemia

Cited by 11 publications

References 30 publications

Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children

Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children

Hyper‐CVAD plus ofatumumab versus hyper‐CVAD plus rituximab as frontline therapy in adults with Philadelphia chromosome–negative acute lymphoblastic leukemia: A propensity score analysis

Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial

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