Prognostic significance of myeloid-associated antigen expression on blast cells in children with acute lymphoblastic leukemia

Abstract Blast cells from 6 of 50 patients with acute lymphoblastic leukemia (ALL) displayed intracytoplasmic mu chains in the absence of detectable light chains and surface immunoglobulins. These cells also expressed lalike and common ALL antigens. Terminal deoxynucleotidyltransferase was detectable in 2 of 5 cases tested. These blast cells are probably related to early B-cell precursors (pre-B cells). In 4 of 6 cases the disease had a tumoral presentation; the prognostic significance of this new subgroup, which accounts for 20% of patients with non-T non-B ALL, remains to be established.

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Acute lymphoblastic leukemia with pre-B-cell characteristics

Blood ◽

10.1182/blood.v54.1.269.bloodjournal541269 ◽

1979 ◽

Vol 54 (1) ◽

pp. 269-273

Author(s):

JC Brouet ◽

JL Preud'homme ◽

C Penit ◽

F Valensi ◽

P Rouget ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

B Cells ◽

B Cell ◽

Lymphoblastic Leukemia ◽

Prognostic Significance ◽

Light Chains ◽

Surface Immunoglobulins ◽

Blast Cells ◽

B Cell Precursors

Blast cells from 6 of 50 patients with acute lymphoblastic leukemia (ALL) displayed intracytoplasmic mu chains in the absence of detectable light chains and surface immunoglobulins. These cells also expressed lalike and common ALL antigens. Terminal deoxynucleotidyltransferase was detectable in 2 of 5 cases tested. These blast cells are probably related to early B-cell precursors (pre-B cells). In 4 of 6 cases the disease had a tumoral presentation; the prognostic significance of this new subgroup, which accounts for 20% of patients with non-T non-B ALL, remains to be established.

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Novel Antibody-Based Therapies For Acute Lymphoblastic Leukemia

Hematology ◽

10.1182/asheducation-2011.1.243 ◽

2011 ◽

Vol 2011 (1) ◽

pp. 243-249 ◽

Cited By ~ 32

Author(s):

Dieter Hoelzer

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Kinase Inhibitors ◽

Treatment Approach ◽

Case Reports ◽

Lymphoblastic Leukemia ◽

Antigen Expression ◽

High Rate ◽

Blast Cells ◽

Specific Antigens ◽

Anti Cd20

AbstractA major breakthrough in the treatment of acute lymphoblastic leukemia (ALL) was the availability of targeted therapies targeting either specific transcripts, such as bcr-abl fusion protein by tyrosine kinase inhibitors (TKIs), or specific antigens by mAbs. ALL blast cells express a variety of specific antigens (eg, CD19, CD20, CD22, CD33, and CD52) that serve as targets for mAbs. To date, the most data are available for anti-CD20 (rituximab), which has been combined with chemotherapy for the treatment of mature B-ALL/Burkitt lymphoma. Studies with rituximab have also been completed in B-precursor ALL. Another antigen, CD19, is of great interest due to a very high rate of expression in ALL. It can be targeted by a bispecific mAb, blinatumomab, directed against CD19 and CD3. Smaller studies or case reports are also available for the anti-CD52 (alemtuzumab), anti-CD22 (epratuzumab), and anti-CD33 (gemtuzumab) mAbs. Available data demonstrate that mAb therapy in ALL is a highly promising treatment approach. However, several details for an optimal treatment approach, such as the required level of antigen expression, timing, schedule, dosage, and stage of disease, still need to be defined.

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Prognostic Significance of Fluorescence Intensity of Surface Marker Expression in Childhood B-Precursor Acute Lymphoblastic Leukemia. A Pediatric Oncology Group Study

Blood ◽

10.1182/blood.v89.11.3960 ◽

1997 ◽

Vol 89 (11) ◽

pp. 3960-3966 ◽

Cited By ~ 77

Author(s):

Michael J. Borowitz ◽

Jonathan Shuster ◽

Andrew J. Carroll ◽

Michael Nash ◽

A. Thomas Look ◽

...

Keyword(s):

Risk Factors ◽

Acute Lymphoblastic Leukemia ◽

Pediatric Oncology ◽

Fluorescence Intensity ◽

Lymphoblastic Leukemia ◽

Prognostic Significance ◽

Antigen Expression ◽

Oncology Group ◽

Color Flow ◽

Pediatric Oncology Group

Abstract This report describes the prognostic significance of the intensity of surface membrane antigen expression in a series of 1,231 children older than 1 year with newly diagnosed B-precursor acute lymphoblastic leukemia (ALL) treated on Pediatric Oncology Group (POG) treatment protocols. All patients had dual-color flow cytometric immunophenotyping performed at a central reference laboratory with a standard panel of monoclonal antibodies. The flow cytometers used in the study were calibrated with a standard fluorescence microparticle that permitted conversion of relative fluorescence channels to standard units of mean equivalents of soluble fluorochrome (MESF). In univariate analysis, fluorescence intensity of CD45 and CD20 was significantly associated with event-free survival (EFS), whereas other markers showed no significant correlation with outcome. Patients whose blasts were greater than the 75th percentile of intensity for CD45 (corresponding to 18,000 MESF units with CD45-FITC, or about 8% of the intensity of normal lymphocytes) fared significantly worse than those with lower-density CD45, and those whose blasts were greater than the 25th percentile of intensity for CD20 (corresponding to 17,900 MESF units with CD20-PE) had a poorer EFS. The intensity of both CD45 and CD20 was independently correlated with outcome. There was no significant correlation between intensity of expression of either antigen and traditional clinical risk factors, ploidy, or t(9; 22) or t(1; 19). All patients with t(4; 11) had CD45 intensity greater than the 75th percentile, but CD45 intensity retained its prognostic significance after adjusting for t(4; 11). In multivariate analysis, both CD45 intensity greater than the 75th percentile and CD20 intensity greater than the 25th percentile were significantly correlated with poor outcome independently of previously reported poor prognostic factors including National Cancer Institute (NCI) risk group, ploidy, trisomies of 4 and 10, and adverse translocations including t(1; 19), t(9; 22), and t(4; 11). We conclude that in childhood B-precursor ALL, the intensity of expression of CD20 and CD45 provides prognostic information not available from simple consideration of antigen expression as positive or negative, and adds to that obtained from traditional clinical and biologic risk factors.

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Prognostic significance of CD45 antigen expression in pediatric acute lymphoblastic leukemia

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2021.102562 ◽

2021 ◽

Vol 89 ◽

pp. 102562

Author(s):

Priyavadhana Balasubramanian ◽

Jay Singh ◽

Deepak Verma ◽

Rajive Kumar ◽

Sameer Bakhshi ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Prognostic Significance ◽

Antigen Expression ◽

Pediatric Acute Lymphoblastic Leukemia

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11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.5.909 ◽

1994 ◽

Vol 12 (5) ◽

pp. 909-915 ◽

Cited By ~ 146

Author(s):

C H Pui ◽

F G Behm ◽

J R Downing ◽

M L Hancock ◽

S A Shurtleff ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Poor Prognosis ◽

Leukocyte Count ◽

Lymphoblastic Leukemia ◽

Leukemic Cell ◽

Antigen Expression ◽

Prognostic Indicator ◽

Genetic Abnormality ◽

Increased Risk ◽

Blast Cells

PURPOSE Leukemic cell characteristics were analyzed in infants less than 1 year of age with acute lymphoblastic leukemia (ALL) to determine adverse prognostic factors that might explain the poor prognosis of this group. PATIENTS AND METHODS Treatment outcomes were analyzed according to the presenting clinical and laboratory features of 30 infants treated between May 1979 and April 1993. A stepwise multivariate regression model was used to identify the most important prognostic indicator with respect to event-free survival. RESULTS Infant ALL cases were characterized by high presenting leukocyte count (median, 87 x 10(9)/L), increased frequency of CNS leukemia (50%), and blast cells with a CD10- phenotype (67%), myeloid-associated antigen expression (48%), and 11q23/MLL rearrangement (68%). The 11q23/MLL involvement was correlated with age less than 6 months, CD10- phenotype, myeloid-associated antigen expression, and high leukocyte count. Although 11q23/MLL involvement, age less than 6 months, myeloid-associated antigen expression, and female sex were each significantly associated with an inferior treatment outcome, only rearranged 11q23/MLL emerged as an independent predictor of prognosis in multivariate analysis (P = .01). Infants with this genetic abnormality had a 4.7-fold (95% confidence interval, 1.3- to 17.0-fold) increased risk in adverse events compared to other infants. CONCLUSION The 11q23/MLL involvement of blast cells identifies a major subgroup of infant ALL cases that require an innovative treatment approach. Infants who lack this genetic abnormality have an intermediate prognosis and could be treated accordingly on risk-directed protocols.

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Myeloid-associated antigen expression lacks prognostic value in childhood acute lymphoblastic leukemia treated with intensive multiagent chemotherapy

Blood ◽

10.1182/blood.v75.1.198.bloodjournal751198 ◽

1990 ◽

Vol 75 (1) ◽

pp. 198-202 ◽

Cited By ~ 1

Author(s):

CH Pui ◽

FG Behm ◽

B Singh ◽

GK Rivera ◽

MJ Schell ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Prognostic Value ◽

Lymphoblastic Leukemia ◽

Antigen Expression ◽

Chemotherapeutic Agents ◽

Remission Induction ◽

Childhood All ◽

Prognostic Features ◽

Blast Cells ◽

Multiagent Chemotherapy

Frequency and clinical significance of myeloid-associated antigen expression in blast cells were assessed in 372 consecutive children with acute lymphoblastic leukemia (ALL). A comprehensive panel of myeloid monoclonal antibodies representing seven cluster groups showed myeloid-associated antigen expression in 61 cases (16.4%), 18 of which expressed two or more antigens. The antigens expressed comprised CD11b (8.9% of the total series), CD13 (6.5%), CD33 (3.2%), CD36 (1.9%), CD15 (1.6%), CD14 (1.3%), and CDw12 (1.1%). No significant associations were found between myeloid-associated antigen expression and the presence of known adverse prognostic features (eg, higher leukocyte count, nonwhite race, older age). Myeloid-associated antigen expression had no effect on remission induction or event-free survival for the 267 children who had been treated with the same combination of chemotherapeutic agents (P = .34). Thus, blast cell expression of myeloid-associated antigens in childhood ALL appears to lack prognostic value in the context of contemporary intensive chemotherapy.

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Prognostic significance of myeloid associated antigen expression in childhood acute lymphoblastic leukemia in Peru

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.9030 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 9030-9030

Author(s):

J. L. García ◽

A. E. Wachtel ◽

C. Pérez ◽

J. Marcial ◽

R. Dyer ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Developing Country ◽

Lymphoblastic Leukemia ◽

Statistical Significance ◽

Prognostic Significance ◽

Antigen Expression ◽

Developed Countries ◽

Childhood All ◽

Myeloid Antigens

9030 Background: The prognostic significance of coexpression of myeloid antigens in pediatric patients with acute lymphoblastic leukemia (ALL) has been reported by several authors, with a frequency that has ranged widely. All of these authors are from developed countries, the aim of this study is to evaluate the prognostic significance of these antigens in childhood ALL in a developing country. Methods: We retrospectively reviewed 729 newly diagnosed patients with ALL under 14 years of age, who had a bone marrow flow cytometry performed at our institution, between 1996–2002. Clinical data and treatment outcomes were reviewed and compared between patients with ALL who expressed myeloid antigens and those who did not using chi-square test. Results: 729 medical charts were studied, 81.6% of them were B-common, 8.2% were pro-B, 8.2% were T-cell and 2.1% were pre-B ALL patients. Overall frequency of myeloid antigen expression was 36.6%. The most frequent specific antigens found were: CD13, 15.5%; CD15, 6.0% and CD33, 4.5%. Evaluating the B-common ALL patients the presence of myeloid antigens rises to 43%. Patients who had coexpression of myeloid antigens had a relapse rate (any site) of 49.2% while 36.3% who had no coexpression had a relapse (p=0.001). There has also been statistical significance in bone marrow response on day 14 of induction with 64.9% having less than 5% blasts in the group without coexpression and 46.4% in the group with coexpression (p<0.0001). Conclusions: The present retrospective review shows the presence of associated myeloid antigens in our ALL patients in 36.6%. We have shown that it is an adverse prognostic factor for childhood ALL in a developing country, unlike reports from other centers in developed countries. No significant financial relationships to disclose.

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Myeloid-associated antigen expression lacks prognostic value in childhood acute lymphoblastic leukemia treated with intensive multiagent chemotherapy

Blood ◽

10.1182/blood.v75.1.198.198 ◽

1990 ◽

Vol 75 (1) ◽

pp. 198-202 ◽

Cited By ~ 81

Author(s):

CH Pui ◽

FG Behm ◽

B Singh ◽

GK Rivera ◽

MJ Schell ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Prognostic Value ◽

Lymphoblastic Leukemia ◽

Antigen Expression ◽

Chemotherapeutic Agents ◽

Remission Induction ◽

Childhood All ◽

Prognostic Features ◽

Blast Cells ◽

Multiagent Chemotherapy

Abstract Frequency and clinical significance of myeloid-associated antigen expression in blast cells were assessed in 372 consecutive children with acute lymphoblastic leukemia (ALL). A comprehensive panel of myeloid monoclonal antibodies representing seven cluster groups showed myeloid-associated antigen expression in 61 cases (16.4%), 18 of which expressed two or more antigens. The antigens expressed comprised CD11b (8.9% of the total series), CD13 (6.5%), CD33 (3.2%), CD36 (1.9%), CD15 (1.6%), CD14 (1.3%), and CDw12 (1.1%). No significant associations were found between myeloid-associated antigen expression and the presence of known adverse prognostic features (eg, higher leukocyte count, nonwhite race, older age). Myeloid-associated antigen expression had no effect on remission induction or event-free survival for the 267 children who had been treated with the same combination of chemotherapeutic agents (P = .34). Thus, blast cell expression of myeloid-associated antigens in childhood ALL appears to lack prognostic value in the context of contemporary intensive chemotherapy.

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Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.12.3768 ◽

1998 ◽

Vol 16 (12) ◽

pp. 3768-3773 ◽

Cited By ~ 60

Author(s):

C H Pui ◽

J E Rubnitz ◽

M L Hancock ◽

J R Downing ◽

S C Raimondi ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

B Cell ◽

Lymphoblastic Leukemia ◽

Antigen Expression ◽

Childhood Acute Lymphoblastic Leukemia ◽

Cell Precursor ◽

Childhood All ◽

Mll Gene ◽

Blast Cells

PURPOSE To reassess the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS We prospectively studied 334 newly diagnosed cases of this disease, using a comprehensive panel of antibodies that represented five myeloid cluster groups (CD13, CD14, CD15, CD33, and CD65). Blast cells were tested for ETV6 and MLL rearrangement using Southern blot analysis. RESULTS CD13 was expressed in 13.7% of cases, CD14 in 1%, CD15 in 6.6%, CD33 in 16%, and CD65 in 9.7%. Approximately one third of cases (31.4%) expressed one or more of these antigens (B-cell precursor, 31.9%; T-cell, 28.8%), while 10.5% expressed two or more (B-cell precursor, 11.3%; T-cell, 6.1%). Among the B-cell precursor leukemias, myeloid-associated antigen expression was significantly associated with a lack of hyperdiploidy and rearrangements of ETV6 or MLL gene. Most of the cases with MLL rearrangements (82%) expressed CD65, CD15, and CD33, either alone or in combination, whereas 48% of those with a rearranged ETV6 gene expressed CD13, CD33, or both. Myeloid-associated antigen expression did not correlate with event-free survival, whether the analysis was based on any of the five antigens in our panel or on the three more commonly tested antigens (CD13, CD33, and CD65). Importantly, this finding was not affected by exclusion of patients with ETV6 or MLL gene rearrangements. CONCLUSION Even though blast cell expression of myeloid-associated antigen expression shows significant associations with specific genetic abnormalities, it lacks prognostic value in childhood ALL.

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