Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia: A report of 1021 patients from India

Dikshat Gopal Gupta; Neelam Varma; Praveen Sharma; Mihai I. Truica; Sarki A. Abdulkadir; Parmod Singh; Man Updesh Singh Sachdeva; Shano Naseem; Mohammad Rizwan Siddiqui; Parveen Bose; Jogeshwar Binota; Pankaj Malhotra; Alka Khadwal; Amita Trehan; Subhash Varma

doi:10.1002/cncr.34957

Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia: A report of 1021 patients from India

Dikshat Gopal Gupta, Neelam Varma^*, Praveen Sharma, Mihai I. Truica, Sarki A. Abdulkadir, Parmod Singh, Man Updesh Singh Sachdeva, Shano Naseem, Mohammad Rizwan Siddiqui, Parveen Bose, Jogeshwar Binota, Pankaj Malhotra, Alka Khadwal, Amita Trehan, Subhash Varma

^*Corresponding author for this work

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2 Scopus citations

Abstract

Background: The published literature on hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low-income countries. For newer classifications such as BCR::ABL1-like ALLs, the scarcity of patient-level data is even more pronounced. Methods: The authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1-like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n = 1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1-like ALL subtype and other genetic subtypes of ALL. Results: Patients with BCR::ABL1-positive and BCR::ABL1-like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1-negative cases (p <.05). Logistic regression modeling of B-lineage-ALL (B-ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1-like ALL (p <.05). Furthermore, patients with BCR::ABL1-like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1-negative ALLs (p <.05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1-like ALLs compared to BCR::ABL1-negative ALL cases (p <.05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1-positive ALL cases were statistically significant (p <.05), and BCR::ABL1-like ALL cases had high MRD-positivity as compared to BCR::ABL1-negative ALL cases but did not show statistical significance. Conclusions: The findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B-ALLs. This is the first report characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India. Plain Language Summary: Characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n = 1021) of acute lymphoblastic leukemia (ALLs) in patients from India. We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs. Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1-like ALL cases compared to BCR::ABL1-negative ALL cases. Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1-like ALLs (p <.05). In terms of treatment outcomes, BCR::ABL1-positive ALL had statistically significant minimal residual disease (MRD) (p <.05), and BCR::ABL1-like ALL cases had high MRD-positivity but did not show statistical significance as compared to BCR::ABL1-negative ALLs.

Original language	English (US)
Pages (from-to)	3390-3404
Number of pages	15
Journal	cancer
Volume	129
Issue number	21
DOIs	https://doi.org/10.1002/cncr.34957
State	Published - Nov 1 2023

Funding

Jogeshwar Binota reports funding from the Post Graduate Institute of Medical Education and Research. Mihai Truica reports grant funding from the National Cancer Institute. Subhash Varma reports consulting fees from Fortis Healthcare. The other authors declare no conflicts of interest. We thank the Department of Hematology faculty members for providing the necessary infrastructure and facilities for this research study. We also thank the Department of Paediatrics, Internal Medicine and Clinical Hematology and Medical Oncology for providing the pediatric and adult B‐ALL samples. Our sincere appreciation to the technical staff (Mr. Yogesh and Mrs. Praveen Bose) and clerical staff (Mr. Gurpreet) of Hematology for their valuable support and contributions to this research work. We also extend sincere thanks to Dr. Khalid, Dr. Ahmad, and Dr. Ayesha Nayab for providing intellectual comments on the submitted work. This study was funded by the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India (INT/IEC/2017/191; 10.23.2017). Dikshat Gopal Gupta received financial assistance (Junior Research Fellowship and Senior Research Fellowship) from the Indian Council of Medical Education and Research, New Delhi, India. We thank the Department of Hematology faculty members for providing the necessary infrastructure and facilities for this research study. We also thank the Department of Paediatrics, Internal Medicine and Clinical Hematology and Medical Oncology for providing the pediatric and adult B-ALL samples. Our sincere appreciation to the technical staff (Mr. Yogesh and Mrs. Praveen Bose) and clerical staff (Mr. Gurpreet) of Hematology for their valuable support and contributions to this research work. We also extend sincere thanks to Dr. Khalid, Dr. Ahmad, and Dr. Ayesha Nayab for providing intellectual comments on the submitted work. This study was funded by the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India (INT/IEC/2017/191; 10.23.2017). Dikshat Gopal Gupta received financial assistance (Junior Research Fellowship and Senior Research Fellowship) from the Indian Council of Medical Education and Research, New Delhi, India.

Keywords

B-acute lymphoblastic leukemia (B-ALL)
cluster of differentiation (CD) markers
flowcytometric-immunophenotyping (FCM-IP)
high-risk ALLs
PGIMER in-house rapid and cost-effective classifier (PHi-RACE)
recurrent fusion transcripts (RGFs)

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Gupta, D. G., Varma, N., Sharma, P., Truica, M. I., Abdulkadir, S. A., Singh, P., Singh Sachdeva, M. U., Naseem, S., Siddiqui, M. R., Bose, P., Binota, J., Malhotra, P., Khadwal, A., Trehan, A., & Varma, S. (2023). Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia: A report of 1021 patients from India. cancer, 129(21), 3390-3404. https://doi.org/10.1002/cncr.34957

@article{35fbddcbec6b43f381c751aab2cb4857,

title = "Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia: A report of 1021 patients from India",

abstract = "Background: The published literature on hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low-income countries. For newer classifications such as BCR::ABL1-like ALLs, the scarcity of patient-level data is even more pronounced. Methods: The authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1-like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n = 1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1-like ALL subtype and other genetic subtypes of ALL. Results: Patients with BCR::ABL1-positive and BCR::ABL1-like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1-negative cases (p <.05). Logistic regression modeling of B-lineage-ALL (B-ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1-like ALL (p <.05). Furthermore, patients with BCR::ABL1-like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1-negative ALLs (p <.05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1-like ALLs compared to BCR::ABL1-negative ALL cases (p <.05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1-positive ALL cases were statistically significant (p <.05), and BCR::ABL1-like ALL cases had high MRD-positivity as compared to BCR::ABL1-negative ALL cases but did not show statistical significance. Conclusions: The findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B-ALLs. This is the first report characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India. Plain Language Summary: Characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n = 1021) of acute lymphoblastic leukemia (ALLs) in patients from India. We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs. Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1-like ALL cases compared to BCR::ABL1-negative ALL cases. Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1-like ALLs (p <.05). In terms of treatment outcomes, BCR::ABL1-positive ALL had statistically significant minimal residual disease (MRD) (p <.05), and BCR::ABL1-like ALL cases had high MRD-positivity but did not show statistical significance as compared to BCR::ABL1-negative ALLs.",

keywords = "B-acute lymphoblastic leukemia (B-ALL), cluster of differentiation (CD) markers, flowcytometric-immunophenotyping (FCM-IP), high-risk ALLs, PGIMER in-house rapid and cost-effective classifier (PHi-RACE), recurrent fusion transcripts (RGFs)",

author = "Gupta, {Dikshat Gopal} and Neelam Varma and Praveen Sharma and Truica, {Mihai I.} and Abdulkadir, {Sarki A.} and Parmod Singh and {Singh Sachdeva}, {Man Updesh} and Shano Naseem and Siddiqui, {Mohammad Rizwan} and Parveen Bose and Jogeshwar Binota and Pankaj Malhotra and Alka Khadwal and Amita Trehan and Subhash Varma",

note = "Publisher Copyright: {\textcopyright} 2023 American Cancer Society.",

year = "2023",

month = nov,

day = "1",

doi = "10.1002/cncr.34957",

language = "English (US)",

volume = "129",

pages = "3390--3404",

journal = "cancer",

issn = "0008-543X",

publisher = "John Wiley and Sons Inc.",

number = "21",

}

Gupta, DG, Varma, N, Sharma, P, Truica, MI, Abdulkadir, SA, Singh, P, Singh Sachdeva, MU, Naseem, S, Siddiqui, MR, Bose, P, Binota, J, Malhotra, P, Khadwal, A, Trehan, A & Varma, S 2023, 'Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia: A report of 1021 patients from India', cancer, vol. 129, no. 21, pp. 3390-3404. https://doi.org/10.1002/cncr.34957

Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia: A report of 1021 patients from India. / Gupta, Dikshat Gopal; Varma, Neelam; Sharma, Praveen et al.
In: cancer, Vol. 129, No. 21, 01.11.2023, p. 3390-3404.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia

T2 - A report of 1021 patients from India

AU - Gupta, Dikshat Gopal

AU - Varma, Neelam

AU - Sharma, Praveen

AU - Truica, Mihai I.

AU - Abdulkadir, Sarki A.

AU - Singh, Parmod

AU - Singh Sachdeva, Man Updesh

AU - Naseem, Shano

AU - Siddiqui, Mohammad Rizwan

AU - Bose, Parveen

AU - Binota, Jogeshwar

AU - Malhotra, Pankaj

AU - Khadwal, Alka

AU - Trehan, Amita

AU - Varma, Subhash

PY - 2023/11/1

Y1 - 2023/11/1

N2 - Background: The published literature on hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low-income countries. For newer classifications such as BCR::ABL1-like ALLs, the scarcity of patient-level data is even more pronounced. Methods: The authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1-like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n = 1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1-like ALL subtype and other genetic subtypes of ALL. Results: Patients with BCR::ABL1-positive and BCR::ABL1-like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1-negative cases (p <.05). Logistic regression modeling of B-lineage-ALL (B-ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1-like ALL (p <.05). Furthermore, patients with BCR::ABL1-like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1-negative ALLs (p <.05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1-like ALLs compared to BCR::ABL1-negative ALL cases (p <.05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1-positive ALL cases were statistically significant (p <.05), and BCR::ABL1-like ALL cases had high MRD-positivity as compared to BCR::ABL1-negative ALL cases but did not show statistical significance. Conclusions: The findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B-ALLs. This is the first report characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India. Plain Language Summary: Characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n = 1021) of acute lymphoblastic leukemia (ALLs) in patients from India. We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs. Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1-like ALL cases compared to BCR::ABL1-negative ALL cases. Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1-like ALLs (p <.05). In terms of treatment outcomes, BCR::ABL1-positive ALL had statistically significant minimal residual disease (MRD) (p <.05), and BCR::ABL1-like ALL cases had high MRD-positivity but did not show statistical significance as compared to BCR::ABL1-negative ALLs.

AB - Background: The published literature on hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low-income countries. For newer classifications such as BCR::ABL1-like ALLs, the scarcity of patient-level data is even more pronounced. Methods: The authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1-like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n = 1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1-like ALL subtype and other genetic subtypes of ALL. Results: Patients with BCR::ABL1-positive and BCR::ABL1-like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1-negative cases (p <.05). Logistic regression modeling of B-lineage-ALL (B-ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1-like ALL (p <.05). Furthermore, patients with BCR::ABL1-like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1-negative ALLs (p <.05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1-like ALLs compared to BCR::ABL1-negative ALL cases (p <.05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1-positive ALL cases were statistically significant (p <.05), and BCR::ABL1-like ALL cases had high MRD-positivity as compared to BCR::ABL1-negative ALL cases but did not show statistical significance. Conclusions: The findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B-ALLs. This is the first report characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India. Plain Language Summary: Characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n = 1021) of acute lymphoblastic leukemia (ALLs) in patients from India. We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs. Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1-like ALL cases compared to BCR::ABL1-negative ALL cases. Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1-like ALLs (p <.05). In terms of treatment outcomes, BCR::ABL1-positive ALL had statistically significant minimal residual disease (MRD) (p <.05), and BCR::ABL1-like ALL cases had high MRD-positivity but did not show statistical significance as compared to BCR::ABL1-negative ALLs.

KW - B-acute lymphoblastic leukemia (B-ALL)

KW - cluster of differentiation (CD) markers

KW - flowcytometric-immunophenotyping (FCM-IP)

KW - high-risk ALLs

KW - PGIMER in-house rapid and cost-effective classifier (PHi-RACE)

KW - recurrent fusion transcripts (RGFs)

UR - http://www.scopus.com/inward/record.url?scp=85173691579&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85173691579&partnerID=8YFLogxK

U2 - 10.1002/cncr.34957

DO - 10.1002/cncr.34957

M3 - Article

C2 - 37498973

AN - SCOPUS:85173691579

SN - 0008-543X

VL - 129

SP - 3390

EP - 3404

JO - cancer

JF - cancer

IS - 21

ER -

Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia: A report of 1021 patients from India

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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