Blood Res 2022; 57(3):
Published online September 30, 2022
https://doi.org/10.5045/br.2022.2022104
© The Korean Society of Hematology
Correspondence to : Karthik Bommannan, M.D., D.M.
Department of Oncopathology, Cancer Institute (W.I.A), Adyar, Chennai 600020, India
E-mail: bkkb87@gmail.com
*This study was supported by a grant from Indian Council of Medical Research (ICMR) and the Indian Childhood Collaborative Leukemia (ICiCLe) project of the National Cancer Grid (NCG).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
T-lymphoblastic leukemia (T-ALL) patients expressing myeloid/stem cell antigens are classified as early T-cell precursor lymphoblastic leukemia (ETP-ALL) or near-ETP-ALL.
Methods
Clinico-laboratory profiles, flow cytometric end-of-induction measurable residual disease (EOI-MRD), and survival of treatment naïve T-ALL patients were analyzed according to their immunophenotypic subtypes.
Results
Among 81 consecutive T-ALL patients diagnosed, 21% (N=17) were ETP-ALL and 19% (N=15) were near-ETP-ALL. EOI-MRD was detectable in 39% of the 59 samples tested (31.6% of pediatric samples and 52.4% of adult samples). The frequency of EOI-MRD positivity was significantly higher among ETP-ALL (75%, P=0.001) and near-ETP-ALL (71%, P=0.009) patients compared to that in conventional-T-ALL (con-T-ALL) patients (22.5%). CD8 (P=0.046) and CD38 (P=0.046) expressions were significantly upregulated in the EOI blasts of con-T-ALL and ETP-ALL samples, respectively. The 2-year rates of overall (OS), relapse-free (RFS), and event-free survival (EFS) among the T-ALL patients (pediatric vs. adult) was 79.5% vs. 39.8% (P<0.001), 84.3% vs. 60.4% (P=0.026), and 80.3% vs. 38% (P<0.001), respectively. Univariate analysis revealed that 2-year EFS and RFS of pediatric T-ALL patients was independent of T-ALL subtype and was influenced only by EOI-MRD status. However, 2-year OS, RFS, and EFS among adult T-ALL patients were EOI-MRD independent and influenced only by the near-ETP-ALL phenotype.
Conclusion
Two-year survival among pediatric and adult T-ALL patients is attributed to EOI-MRD status and near-ETP-ALL phenotype, respectively.
Keywords Measurable residual disease, Flow cytometry, T-lineage acute lymphoblastic leuke mia, ETP-ALL, Near-ETP-ALL
Blood Res 2022; 57(3): 175-196
Published online September 30, 2022 https://doi.org/10.5045/br.2022.2022104
Copyright © The Korean Society of Hematology.
Karthik Bommannan1, Jhansi Rani Arumugam1, Venkatraman Radhakrishnan2, Jayachandran Perumal Kalaiyarasi2, Parathan Karunakaran2, Nikita Mehra2, Tenali Gnana Sagar2, Shirley Sundersingh1
Departments of 1Oncopathology and 2Medical Oncology, Cancer Institute (W.I.A.), Adyar, India
Correspondence to:Karthik Bommannan, M.D., D.M.
Department of Oncopathology, Cancer Institute (W.I.A), Adyar, Chennai 600020, India
E-mail: bkkb87@gmail.com
*This study was supported by a grant from Indian Council of Medical Research (ICMR) and the Indian Childhood Collaborative Leukemia (ICiCLe) project of the National Cancer Grid (NCG).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
T-lymphoblastic leukemia (T-ALL) patients expressing myeloid/stem cell antigens are classified as early T-cell precursor lymphoblastic leukemia (ETP-ALL) or near-ETP-ALL.
Methods
Clinico-laboratory profiles, flow cytometric end-of-induction measurable residual disease (EOI-MRD), and survival of treatment naïve T-ALL patients were analyzed according to their immunophenotypic subtypes.
Results
Among 81 consecutive T-ALL patients diagnosed, 21% (N=17) were ETP-ALL and 19% (N=15) were near-ETP-ALL. EOI-MRD was detectable in 39% of the 59 samples tested (31.6% of pediatric samples and 52.4% of adult samples). The frequency of EOI-MRD positivity was significantly higher among ETP-ALL (75%, P=0.001) and near-ETP-ALL (71%, P=0.009) patients compared to that in conventional-T-ALL (con-T-ALL) patients (22.5%). CD8 (P=0.046) and CD38 (P=0.046) expressions were significantly upregulated in the EOI blasts of con-T-ALL and ETP-ALL samples, respectively. The 2-year rates of overall (OS), relapse-free (RFS), and event-free survival (EFS) among the T-ALL patients (pediatric vs. adult) was 79.5% vs. 39.8% (P<0.001), 84.3% vs. 60.4% (P=0.026), and 80.3% vs. 38% (P<0.001), respectively. Univariate analysis revealed that 2-year EFS and RFS of pediatric T-ALL patients was independent of T-ALL subtype and was influenced only by EOI-MRD status. However, 2-year OS, RFS, and EFS among adult T-ALL patients were EOI-MRD independent and influenced only by the near-ETP-ALL phenotype.
Conclusion
Two-year survival among pediatric and adult T-ALL patients is attributed to EOI-MRD status and near-ETP-ALL phenotype, respectively.
Keywords: Measurable residual disease, Flow cytometry, T-lineage acute lymphoblastic leuke mia, ETP-ALL, Near-ETP-ALL
Table 1 . Clinical and laboratory characteristics of T-ALL subcategories..
Parameters | Overall T-ALL (N=81) | T-ALL subcategories | ||||||
---|---|---|---|---|---|---|---|---|
Con-T-ALL (N=49) | ETP-ALL (N=17) | Near-ETP-ALL (N=15) | ETP-ALL vs. Near-ETP-ALL | ETP-ALL vs. Con-T-ALL | Near-ETP-ALL vs. Con-T-ALL | |||
Median (range) age in years | 17 (1–52) | 15 (1–50) | 17 (13–39) | 23 (5–52) | 0.882 | 0.003 | 0.016 | |
Age group | 1.000 | 0.039 | 0.040 | |||||
Pediatric (%) | 47 (58) | 34 (72%) | 7 (15%) | 6 (13%) | ||||
Adult (%) | 34 (42) | 15 (44%) | 10 (29%) | 9 (27%) | ||||
Sex (male:female) | 3.8:1 | 4.4:1 | 3.2:1 | 2.7:1 | 1.000 | 0.645 | 0.485 | |
Median (range) Hb in g/L | 90 (30–142) | 90 (30–142) | 92 (30–131) | 88 (41–133) | 0.737 | 1.000 | 0.751 | |
Median (range) WBC count, ×109/L | 64.1 (1–850) | 173 (1.1–850) | 70 (1–480) | 145 (3–590) | 0.049 | 0.005 | 0.751 | |
Median (range) platelet, ×109/L | 54 (20–380) | 73 (20–366) | 125 (30–290) | 127 (20–380) | 0.911 | 0.008 | 0.080 | |
Median (range) BM blast, % | 87 (22–99) | 87 (23–97) | 86 (22–98) | 89 (50–99) | 0.473 | 0.795 | 0.663 | |
Median (range) PB blast, % | 78 (2–99) | 80 (2–97) | 42 (2–98) | 83 (2–99) | 0.193 | 0.174 | 0.411 | |
Hyperleukocytosis | 41% | 45% | 18% | 53% | 0.034 | 0.046 | 0.567 | |
Hepatomegaly | 42% | 42% | 27% | 58% | 0.204 | 0.283 | 0.319 | |
Splenomegaly | 56% | 56% | 47% | 67% | 0.516 | 0.550 | 0.489 | |
Lymphadenopathy | 78% | 73% | 87% | 86% | 1.000 | 0.290 | 0.342 | |
Mediastinal mass | 31% | 36% | 33% | 13% | 0.388 | 0.842 | 0.095 | |
CNS involvement at diagnosis | 3.2% | 2 (5) | 0% | 0% | - | 0.417 | 0.499 | |
D8BNC | 35% | 32% | 54% | 20% | 0.223 | 0.168 | 0.440 | |
EOI-MRD positive | 39% (N=59) | 22.5% (N=40) | 75%(N=12) | 71.4% (N=7) | 0.865 | 0.001 | 0.009 | |
Relapse | 20% (N=60) | 18% (N=40) | 17% (N=12) | 38% (N=8) | 0.292 | 0.947 | 0.204 | |
OS at 24 months | 65.2% (N=66) | 70.6% (N=42) | 60.4% (N=13) | 52% (N=11) | 0.180 | 0.551 | 0.019 | |
RFS at 24 months | 76.1% (N=60) | 80% (N=40) | 79% (N=12) | 54.7% (N=8) | 0.292 | 0.956 | 0.190 | |
EFS at 24 months | 64.5% (N=66) | 70.3% (N=42) | 66.6% (N=13) | 41% (N=11) | 0.076 | 0.978 | 0.013 |
Abbreviations: BM, bone marrow; CNS, central nervous system; D8BNC, day 8 blast not cleared; EFS, event-free survival; EOI-MRD, end-of-induction-measurable residual disease; Hb, hemoglobin; N, number of patients analyzed; NA, not applicable; OS, overall survival; PB, peripheral blood; RFS, relapse-free survival; WBC, white blood cells..
Table 2 . Clinical and laboratory characteristics of immunophenotypic T-ALL subcategories among pediatric and adult age groups..
Parameters | Pediatric patients | Adult patients | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
T-ALL subtype | T-ALL subtype | ||||||||||||||
Con-T-ALL (N=34) | ETP-ALL (N=7) | Near-ETP-ALL (N=6) | ETP-ALL vs. Near- ETP-ALL | ETP-ALL vs. Con-T-ALL | Near- ETP-ALL vs. Con-T- T-ALL | Con-T-ALL (N=15) | ETP-ALL (N=10) | Near-ETP-ALL (N=9) | ETP-ALL vs. Near- ETP-ALL | ETP-ALL vs. Con- T-ALL | Near- ETP-ALL vs. Con-T-ALL | ||||
Median age (range) in years | 12 (1–18) | 16 (13–17) | 13 (5–18) | 0.295 | 0.056 | 0.343 | 25 (20–50) | 34 (19–39) | 29 (20–52) | 0.842 | 0.367 | 0.290 | |||
Sex (male:female) | 3.8:1 | 6:1 | 5:1 | 0.906 | 0.307 | 0.825 | 6.5:1 | 2.3:1 | 2:1 | 0.876 | 0.702 | 0.243 | |||
Median (range) Hb in g/L | 91 (30–141) | 97 (30–131) | 83 (41–129) | 0.181 | 0.465 | 0.517 | 89 (63–142) | 80 (61–128) | 88 (69–133) | 0.356 | 0.338 | 1.000 | |||
Median (range) WBC, ×109/L | 110 (1.9–850) | 90.4 (3.2–267) | 244 (3–590) | 0.366 | 0.198 | 0.810 | 88 (1.1–349) | 55 (1–480) | 68 (3.6–131) | 0.017 | 0.036 | 0.682 | |||
Median (range) platelet, ×109/L | 83 (22–366) | 125 (30–245) | 149 (32–380) | 0.731 | 0.175 | 0.240 | 52 (20–119) | 125 (30–290) | 100 (20–218) | 0.720 | 0.016 | 0.138 | |||
Median (range) BM blast, % | 87 (23–97) | 86 (22–98) | 95 (89–99) | 0.149 | 0.845 | 0.029 | 87 (64–96) | 85 (38–95) | 76 (50–97) | 0.863 | 0.770 | 0.446 | |||
Median (range) PB blast, % | 84 (2–96) | 86 (2–98) | 98 (2–99) | 0.268 | 0.883 | 0.074 | 61 (3–97) | 36 (5–94) | 76 (5–91) | 0.161 | 0.073 | 0.770 | |||
Hyperleukocytosis | 53% | 29% | 67% | 0.089 | 0.240 | 0.533 | 27% | 10% | 44% | 0.089 | 0.307 | 0.371 | |||
Hepatomegaly | 45% | 40% | 67% | 0.109 | 0.829 | 0.478 | 36% | 20% | 56% | 0.109 | 0.404 | 0.349 | |||
Splenomegaly | 61.3% | 40% | 67& | 0.463 | 0.370 | 0.855 | 43% | 50% | 67% | 0.463 | 0.729 | 0.265 | |||
Lymphadenopathy | 75% | 100% | 100% | 0.906 | 0.207 | 0.207 | 70% | 80% | 78% | 0.906 | 0.560 | 0.658 | |||
Mediastinal mass | 40% | 20% | 17% | 0.153 | 0.402 | 0.286 | 29% | 40% | 11% | 0.153 | 0.558 | 0.322 | |||
CNS involvement | 4% | 0% | 0% | NA | 0.638 | 0.638 | 8% | 0% | 0% | NA | 0.452 | 0.620 | |||
Induction death | 7% | 0% | 0% | 0.098 | 0.508 | 0.508 | 0% | 14% | 60% | 0.098 | 0.162 | 0.002 | |||
Induction failure | 0% | 0% | 0% | NA | NA | NA | 0% | 17% | 75% | 0.065 | 0.001 | 0.001 | |||
D8BNC | 30% | 50% | 50% | 0.105 | 0.343 | 0.422 | 40% | 57% | 0% | 0.105 | 0.486 | 0.074 | |||
EOI-MRD positive | 15% (N=27) | 83% (N=6) | 60% (N=5) | 0.346 | 0.001 | 0.025 | 38.5% (N=13) | 67% (N=6) | 100% (N=2) | 0.346 | 0.252 | 0.104 | |||
Relapse | 11% (N=27) | 17% (N=6) | 17% (N=6) | 1.000 | 0.706 | 0.706 | 31% (N=13) | 17% (N=6) | 100% (N=2) | 0.035 | 0.278 | 0.278 | |||
OS at 24 months | 79% (N=29) | 67% (N=6) | 100% (N=6) | 0.564 | 0.820 | 0.297 | 48% (N=13) | 51% (N=7) | 0% (N=5) | 0.025 | 0.588 | 0.001 | |||
RFS at 24 months | 87% (N=27) | 83% (N=6) | 75% (N=6) | 0.937 | 0.805 | 0.720 | 64% (N=13) | 75% (N=6) | 0% (N=2) | 0.012 | 0.705 | 0.014 | |||
EFS at 24 months | 81% (N=29) | 80% (N=6) | 75% (N=6) | 0.937 | 0.878 | 0.943 | 45% (N=13) | 54% (N=7) | 0% (N=5) | 0.019 | 0.767 | <0.001 |
Abbreviations: BM, bone marrow; CNS, the central nervous system; D8BNC, day 8 blast not cleared; EFS, event-free survival; EOI-MRD, end-of-induction-measurable residual disease; Hb, hemoglobin; N, number of patients analyzed; NA, not applicable; OS, overall survival; PB, peripheral blood; RFS, relapse-free survival; WBC, white blood cells..
Table 3 . Univariate analysis of covariates with event-free, relapse-free, and overall survivals..
Variables | 2 years-EFS | 2 years-RFS | 2 years-OS | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
HR | 95% CI | HR | 95% CI | HR | 95% CI | |||||||
Pediatric univariate | D8BNC | 0.656 | 0.119–3.620 | 0.629 | 0.816 | 0.135–4.924 | 0.825 | 0.311 | 0.035–2.801 | 0.298 | ||
Mediastinal mass | 1.849 | 0.358–9.549 | 0.463 | 3.109 | 0.347–27.843 | 0.311 | 1.578 | 0.285–8.721 | 0.601 | |||
Hyper-leucocytosis | 0.422 | 0.082–2.179 | 0.303 | 0.693 | 0.116–4.154 | 0.688 | 0.228 | 0.027–1.951 | 0.117 | |||
EOI-MRD positive | 10.153 | 1.132–91.096 | 0.038 | 10.081 | 1.123–90.495 | 0.039 | 7.381 | 0.757–71.952 | 0.085 | |||
Con T-ALL subtype | 1.129 | 0.219–5.821 | 0.885 | 0.701 | 0.117–4.197 | 0.698 | 2.272 | 0.265–19.490 | 0.454 | |||
ETP-ALL subtype | 0.887 | 0.103–7.132 | 0.887 | 1.227 | 0.137–10.984 | 0.855 | 0.932 | 0.108–8.014 | 0.949 | |||
Near-ETP-ALL subtype | 0.956 | 0.115–7.947 | 0.967 | 1.425 | 0.159–12.757 | 0.762 | 0.780 | 0.091–6.700 | 0.821 | |||
Adult univariate | D8BNC | 1.166 | 0.326–4.172 | 0.814 | 0.448 | 0.046–4.336 | 0.488 | 1.456 | 0.388–5.462 | 0.577 | ||
Mediastinal mass | 3.000 | 0.782–11.502 | 0.109 | 2.210 | 0.426–11.462 | 0.311 | 5.008 | 1.029–24.374 | 0.056 | |||
Hyper-leucocytosis | 1.784 | 0.615–5.178 | 0.287 | 4.084 | 0.908–18.368 | 0.067 | 1.482 | 0.483–4.547 | 0.491 | |||
EOI-MRD positive | 1.648 | 0.461–5.883 | 0.442 | 1.302 | 0.291–5.828 | 0.730 | 2.024 | 0.501–8.185 | 0.323 | |||
Con-T-ALL subtype | 0.425 | 0.144–1.253 | 0.121 | 0.607 | 0.135–2.738 | 0.516 | 0.361 | 0.117–1.117 | 0.077 | |||
ETP-ALL subtype | 0.730 | 0.203–2.623 | 0.630 | 0.461 | 0.055–3.833 | 0.473 | 0.824 | 0.226–3.002 | 0.769 | |||
Near-ETP-ALL subtype | 7.995 | 2.000–31.968 | 0.003 | 11.122 | 1.533–80.719 | 0.017 | 6.649 | 1.891–23.383 | 0.003 |
Abbreviations: CI, confidence interval; D8BNC, day 8 blast not cleared; EFS, event-free survival; EOI-MRD, end-of-induction-measurable residual disease; HR, hazard ratio; OS, overall survival; PB, peripheral blood; RFS, relapse-free survival..
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