Automated blast cell detection for Acute Lymphoblastic Leukemia diagnosis

Abstract Background: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed.Methods: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- CSCs were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, P<0.001], and CSCs CD84+CD38- [1 (0.03-18.6) versus 0.3 (0.01-1.1), P<0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, AUC of MMP-2 were (80.3%, 53.3% and 0.568, P=0.404), and that of MMP-9 were (53.9%, 40% and 0.660, P=0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, P<0.001), and that of CSCs CD34+ CD38- were (78.9%, 73.3% and 0.855, P<0.001). There was a significant association between MMP-2 overexpression and MRD at day-15, increased BM blast cell count at diagnosis and at day-15, (P=0.020, P=0.047 and P=0.001). Increased TIMP-1 expression associated with the high-risk disease (P<0.001), increased BM blast cell count at diagnosis and at day-15 (P=0.033 and P=0.001), as well as MRD at day 15 and day 42 (P<0.001 for both). CD34+CD38- CSCs associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (P=0.015, P=0.005 and P=0.003). TIMP-1 overexpression associated with shorter DFS and OS rates (P=0.009 and P=0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, P=0.046], and CD34+CD38- CSCs [OR: 6.873, P=0.005] are independent diagnostic factors for pediatric ALL.Conclusion: TIMP-1 and CD34+CD38- CSCs could be useful independent diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

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Prognostic factors in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Blood ◽

10.1182/blood.v75.1.166.bloodjournal751166 ◽

1990 ◽

Vol 75 (1) ◽

pp. 166-173 ◽

Cited By ~ 1

Author(s):

JJ Shuster ◽

JM Falletta ◽

DJ Pullen ◽

WM Crist ◽

GB Humphrey ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Lymphoblastic Leukemia ◽

Recursive Partitioning ◽

Blast Cell ◽

Recursive Partitioning Analysis ◽

Important Predictor ◽

Massive Splenomegaly ◽

Cell Acute Lymphoblastic Leukemia ◽

Cell Expression

Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell- associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age less than or equal to 5 or less than or equal to 7 years, WBC level less than 10, less than 25, less than 50 or less than 100 x 10(3)/microL, and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level less than 50 x 10(3)/microL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows: (1) those with a WBC count less than 50 x 10(3)/microL who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts less than 50 x 10(3)/microL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts greater than 50 x 10(3)/microL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts greater than 50 x 10(3)/microL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P less than .001). The recursive partitioning was able to classify 241 (95%) of the patients.(ABSTRACT TRUNCATED AT 400 WORDS)

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Prognostic factors in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Blood ◽

10.1182/blood.v75.1.166.166 ◽

1990 ◽

Vol 75 (1) ◽

pp. 166-173 ◽

Cited By ~ 85

Author(s):

JJ Shuster ◽

JM Falletta ◽

DJ Pullen ◽

WM Crist ◽

GB Humphrey ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Lymphoblastic Leukemia ◽

Recursive Partitioning ◽

Blast Cell ◽

Recursive Partitioning Analysis ◽

Important Predictor ◽

Massive Splenomegaly ◽

Cell Acute Lymphoblastic Leukemia ◽

Cell Expression

Abstract Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell- associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age less than or equal to 5 or less than or equal to 7 years, WBC level less than 10, less than 25, less than 50 or less than 100 x 10(3)/microL, and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level less than 50 x 10(3)/microL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows: (1) those with a WBC count less than 50 x 10(3)/microL who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts less than 50 x 10(3)/microL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts greater than 50 x 10(3)/microL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts greater than 50 x 10(3)/microL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P less than .001). The recursive partitioning was able to classify 241 (95%) of the patients.(ABSTRACT TRUNCATED AT 400 WORDS)

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New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group report of 343 cases

Blood ◽

10.1182/blood.v96.7.2543 ◽

2000 ◽

Vol 96 (7) ◽

pp. 2543-2549 ◽

Cited By ~ 76

Author(s):

Nancy R. Schneider ◽

Andrew J. Carroll ◽

Jonathan J. Shuster ◽

D. Jeanette Pullen ◽

Michael P. Link ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

T Cell ◽

Pediatric Oncology ◽

Lymphoblastic Leukemia ◽

Cell Lineage ◽

Blast Cell ◽

Derivative Chromosome ◽

Oncology Group ◽

Pediatric Oncology Group ◽

B Lineage

Abstract To further define the cytogenetic differences between B-cell lineage (B-lineage) acute lymphoblastic leukemia (ALL) and T-cell lineage ALL (T-ALL) and to determine the prognostic value of cytogenetics in childhood T-ALL, the blast cell karyotypes of 343 cases of pediatric T-ALL, the largest series reported to date, were evaluated. Cytogenetics were performed in a single central laboratory, and the children were treated using a single Pediatric Oncology Group protocol. Clear differences between the karyotypic characteristics of B-lineage ALL and T-ALL were confirmed. This study suggests that there may be survival differences associated with some T-ALL blast cell karyotypes. Better survival is associated with only normal karyotypes and with t(10;14) (translocation of chromosomes 10 and 14); worse survival is associated with the presence of any derivative chromosome. Two new recurring chromosome aberrations previously not reported in T-ALL were found: del(1)(p22) and t(8;12)(q13;p13). Ten aberrations found in this series, which were reported only once previously in T-ALL, can now be considered recurring abnormalities in T-ALL. All 12 of these new recurring aberrations are targets for discovery and characterization of new genes that are important in T-cell development and leukemogenesis.

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A method for the detection of abnormal leukocytes using cytochemical criteria.

Journal of Histochemistry & Cytochemistry ◽

10.1177/29.12.6948039 ◽

1981 ◽

Vol 29 (12) ◽

pp. 1382-1386

Author(s):

P Winkel ◽

T Olesen

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Healthy Subjects ◽

Lymphoblastic Leukemia ◽

Cell Number ◽

Reference Intervals ◽

Blast Cell ◽

The Other ◽

Alarm System ◽

Cutoff Value ◽

Blood Specimens

An alarm system for the detection of abnormal leukocytes using off-line data processing of the image of the peroxidase channel oscilloscope picture of the Hemalog-D is presented. The basic idea is that areas on the oscilloscope picture where more than a negligible number of nonpathological leukocytes may be depicted are delimited from the remaining area, which is divided into three alarm zones. The corresponding alarm quantities are the large unstained cells (LUC) or the unstained alarm (UA), the intermediate alarm (IA), and the stained alarm (SA). Reference intervals for these alarms were established using blood specimens from 15 healthy subjects. The system was tested using blood specimens from four patients with acute lymphoblastic leukemia (ALL) and 11 patients with acute myeloblastic leukemia (AML). The UA was the best alarm overall, but for seven of the AML specimens the IA or the SA alarm was superior. The high peroxidase (HPX) and the remainder alarms were inferior to the other alarms. Using the reference mean plus two standard deviations as a cutoff value, the smallest blast cell number fraction detectable by the best alarm was calculated to be smaller than 2% for each of the AML specimens, while it ranged from 7 to 2.9% for the ALL specimens.

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Case Report: Remdesivir and Convalescent Plasma in a Newly Acute B Lymphoblastic Leukemia Diagnosis With Concomitant Sars-CoV-2 Infection

Frontiers in Pediatrics ◽

10.3389/fped.2021.712603 ◽

2021 ◽

Vol 9 ◽

Author(s):

Giovanni Battista Dell'Isola ◽

Matteo Felicioni ◽

Luigi Ferraro ◽

Ilaria Capolsini ◽

Carla Cerri ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Immunosuppressive Treatment ◽

Pulmonary Involvement ◽

Severe Neutropenia ◽

Rapid Resolution ◽

Life Saving ◽

Leukemia Diagnosis ◽

The Stability ◽

Challenging Situation

Introduction: The spread of Covid-19 has worsened the prognosis of oncology patients, interrupting or delaying life-saving therapies and contextually increasing the risk of severe SARS-CoV-2 infections. Acute lymphoblastic leukemia (ALL) is the most frequent cancer in pediatric age and the management of this disease with concomitant SARS-COV-2 infection represents a challenging situation.Case presentation: We present the case of a 6-year-old female newly diagnosed with ALL during a documented SARS-CoV-2 infection. Our patient was admitted 20 days after SARS-CoV-2 detection for evening-rise fever. Laboratory testing showed severe neutropenia while chest x-ray detected moderate pulmonary involvement. Acute lymphoblastic leukemia diagnosis was made through morphological and molecular analysis on bone marrow aspirate. Given the stability of the blood count and clinical conditions, antiviral therapy with Remdesivir and Convalescent Plasma was started before antileukemic treatment, obtaining a rapid resolution of the infection.Conclusion: In our experience, the treatment with Remdesivir and Convalescent Plasma led to a rapid resolution of Sars-Cov-2 infection. Our case did not present any adverse event to the therapy. Thus, this treatment could be considered in patients with malignancies, in order to accelerate the resolution of the infection and begin immunosuppressive treatment safely. Further studies are required to confirm this hypothesis.

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Effectiveness of Dexamethasone compared with Prednisolone in Induction Therapy of Childhood Acute Lymphoblastic Leukemia

Journal of Paediatric Surgeons of Bangladesh ◽

10.3329/jpsb.v6i1.27740 ◽

2016 ◽

Vol 6 (1) ◽

pp. 3-9

Author(s):

Tofazzal Hossain ◽

MA Mannan ◽

Shamsoon Nahar ◽

AKM Amirul Morshed ◽

Shahnoor Islam ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Induction Therapy ◽

Lymphoblastic Leukemia ◽

Blast Cell ◽

Newly Diagnosed ◽

Significant Difference ◽

Group A ◽

Bone Marrow Study ◽

Group B

Background: Corticosteroids are an essential component of treatment for acute lymphoblastic leukemia (ALL). Prednisolone is the most commonly used steroid. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of central nervous system compared with prednisolone.Objectives: To determine the effect of dexamethasone and prednisolone and to compare them in induction therapy of ALL in Children.Material & Methods: A total of 60 newly diagnosed cases of ALL confirmed by bone marrow study, children of either sex with age >1 year were included in this study. Variables studied were age, sex, presenting features, neutrophil count, blast cell count, platelet count, bone marrow status at diagnosis, on D15 & D29 of induction and side effects.Results: Mean age of the patients of group A was 6.28 years & that of group B was 7.2 years. Out of all patients of group A 19 (63.3%) were male and 11 (36.7%) were female. In group B 21 (70.0%) patients were male and rests 9 (30.3%) were female. No statistically significant difference was observed in both groups in terms of age, sex & presenting features. After induction significant difference was observed in liver & spleen size at day 7 and day 15. All patients of both groups had M3 marrow status at diagnosis. Overall, in group A 93.3% patients achieved M1 marrow status (fewer than 5% blasts) and 6.7% had M2 marrow status (5-25% blasts) at day 15 of induction. On the other side 66.7% patients of group B achieved M1 status and 33.3% M2 status at day 15. Statistically significant difference was observed between groups on day 15 in term of achieved marrow status (p<0.05). No statistically significant difference was observed between groups in term of infection in difference days of induction. On day 16 of induction maximum incidence of infection was observed in both groups.Conclusion: Dexamethasone may be an effective alternative option to prednisolone for the treatment of acute lymphoblastic leukemia in children.J. Paediatr. Surg. Bangladesh 6(1): 3-9, 2015 (Jan)

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A colony assay for blast cell progenitors in non-B non-T (common) acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v57.5.823.bloodjournal575823 ◽

1981 ◽

Vol 57 (5) ◽

pp. 823-829

Author(s):

CA Izaguirre ◽

J Curtis ◽

H Messner ◽

EA McCulloch

Keyword(s):

Cell Culture ◽

T Cells ◽

Acute Lymphoblastic Leukemia ◽

Mononuclear Cells ◽

Lymphoblastic Leukemia ◽

Blast Cell ◽

Proliferative Capacity ◽

Self Renewal ◽

Colony Assay ◽

Blast Cells

A clonal method in cell culture is described that permits the quantitation of blast precursors in common (non-T, non-B) ALL; the method also yields information about progenitor properties, based on analysis of cells in colonies. The technique is identical to that used successfully for normal and malignant B-cell progenitors except that it requires culture at below O2 tension (5%-7%); mononuclear cells from blood or marrow are depleted of T cells and cultured with media conditioned by T cells in the presence of phytohemagglutinin and irradiated T cells. Cultures are incubated for 5–7 days in a moist atmosphere at 5% CO2 and 5%-7% O2. Colonies were obtained from marrow or blood of 16 of 18 ALL patients. Cells in colonies had the same characteristics (E-, slg-, cALL+ and clgM+ or clgM-) as the cells in the patient. By replating pooled colonies, self-renewal of progenitors was shown. The findings are considered in light of a model of leukemic blasts that depicts such populations as lineages maintained by progenitors that either renew themselves or give rise to blast cells with little or no proliferative capacity.

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A colony assay for blast cell progenitors in non-B non-T (common) acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v57.5.823.823 ◽

1981 ◽

Vol 57 (5) ◽

pp. 823-829 ◽

Cited By ~ 32

Author(s):

CA Izaguirre ◽

J Curtis ◽

H Messner ◽

EA McCulloch

Keyword(s):

Cell Culture ◽

T Cells ◽

Acute Lymphoblastic Leukemia ◽

Mononuclear Cells ◽

Lymphoblastic Leukemia ◽

Blast Cell ◽

Proliferative Capacity ◽

Self Renewal ◽

Colony Assay ◽

Blast Cells

Abstract A clonal method in cell culture is described that permits the quantitation of blast precursors in common (non-T, non-B) ALL; the method also yields information about progenitor properties, based on analysis of cells in colonies. The technique is identical to that used successfully for normal and malignant B-cell progenitors except that it requires culture at below O2 tension (5%-7%); mononuclear cells from blood or marrow are depleted of T cells and cultured with media conditioned by T cells in the presence of phytohemagglutinin and irradiated T cells. Cultures are incubated for 5–7 days in a moist atmosphere at 5% CO2 and 5%-7% O2. Colonies were obtained from marrow or blood of 16 of 18 ALL patients. Cells in colonies had the same characteristics (E-, slg-, cALL+ and clgM+ or clgM-) as the cells in the patient. By replating pooled colonies, self-renewal of progenitors was shown. The findings are considered in light of a model of leukemic blasts that depicts such populations as lineages maintained by progenitors that either renew themselves or give rise to blast cells with little or no proliferative capacity.

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