Original Article

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Blood Res 2022; 57(1):

Published online March 31, 2022

https://doi.org/10.5045/br.2021.2021058

© The Korean Society of Hematology

Induction-related mortality in adolescents and young adults with acute lymphoblastic leukemia in a resource-limited setting: do treatment-related complications create more impact than disease biology?

Sergio I. Inclan-Alarcon1, Santiago Riviello-Goya1, Kevin Teran-De-la-Sancha1, Oscar M. Fierro-Angulo2, Aldo A. Acosta-Medina1, Roberta Demichelis-Gomez1, Christianne Bourlon1

1Department of Hematology and Oncology, 2Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Correspondence to : Christianne Bourlon, M.D.
Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Sección XVI, Tlalpan, Mexico City 14080, Mexico
E-mail: chrisbourlon@hotmail.com

Received: March 16, 2021; Revised: December 23, 2021; Accepted: December 24, 2021

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.

Abstract

Background
Acute lymphoblastic leukemia (ALL) is a malignant clonal bone marrow disorder with a high mortality rate during the initial therapy. This retrospective study aimed to describe and analyze the risk factors and causes of induction-related mortality (IRM) in an adolescent and adult ALL population treated in a low- and middle-income country.
Methods
From 2009 to 2016, a total of 167 patients were included, of which 50.9% were male with a median age of 28 years. B-immunophenotype represented 97.6%, and high-risk cytogenetics were present in 23.3%. During induction therapy, 91% had at least 1 complication, most of which were infectious, with an IRM of 12%.
Results
Factors associated with increased mortality rate were central nervous system (CNS) status [CNS-3: hazard ratio (HR) 3.029; 95% confidence interval (CI), 0.79‒11.49; P =0.103 and CNS-2: HR, 9.98; 95% CI, 2.65‒37.65; P =0.001] and dialysis requirement (HR, 9.15; 95% CI, 2.44‒34.34; P =0.001).
Conclusion
Our study confirms that ALL patients treated in resource-constrained settings have high rates of IRM, mainly attributed to advanced disease and high tumor burden at diagnosis.

Keywords Risk factors, Treatment outcome, Chemotherapy induced mortality, Precursor cell lymphoblastic leukemia-lymphoma, Developing countries

Article

Original Article

Blood Res 2022; 57(1): 29-33

Published online March 31, 2022 https://doi.org/10.5045/br.2021.2021058

Copyright © The Korean Society of Hematology.

Induction-related mortality in adolescents and young adults with acute lymphoblastic leukemia in a resource-limited setting: do treatment-related complications create more impact than disease biology?

Sergio I. Inclan-Alarcon1, Santiago Riviello-Goya1, Kevin Teran-De-la-Sancha1, Oscar M. Fierro-Angulo2, Aldo A. Acosta-Medina1, Roberta Demichelis-Gomez1, Christianne Bourlon1

1Department of Hematology and Oncology, 2Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

Correspondence to:Christianne Bourlon, M.D.
Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Sección XVI, Tlalpan, Mexico City 14080, Mexico
E-mail: chrisbourlon@hotmail.com

Received: March 16, 2021; Revised: December 23, 2021; Accepted: December 24, 2021

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.

Abstract

Background
Acute lymphoblastic leukemia (ALL) is a malignant clonal bone marrow disorder with a high mortality rate during the initial therapy. This retrospective study aimed to describe and analyze the risk factors and causes of induction-related mortality (IRM) in an adolescent and adult ALL population treated in a low- and middle-income country.
Methods
From 2009 to 2016, a total of 167 patients were included, of which 50.9% were male with a median age of 28 years. B-immunophenotype represented 97.6%, and high-risk cytogenetics were present in 23.3%. During induction therapy, 91% had at least 1 complication, most of which were infectious, with an IRM of 12%.
Results
Factors associated with increased mortality rate were central nervous system (CNS) status [CNS-3: hazard ratio (HR) 3.029; 95% confidence interval (CI), 0.79‒11.49; P =0.103 and CNS-2: HR, 9.98; 95% CI, 2.65‒37.65; P =0.001] and dialysis requirement (HR, 9.15; 95% CI, 2.44‒34.34; P =0.001).
Conclusion
Our study confirms that ALL patients treated in resource-constrained settings have high rates of IRM, mainly attributed to advanced disease and high tumor burden at diagnosis.

Keywords: Risk factors, Treatment outcome, Chemotherapy induced mortality, Precursor cell lymphoblastic leukemia-lymphoma, Developing countries

Fig 1.

Figure 1.Cumulative mortality risk related to (A) central nervous system status and (B) dialysis requirement.
Blood Research 2022; 57: 29-33https://doi.org/10.5045/br.2021.2021058

Table 1 . Patients baseline characteristics grouped by AYA and non-AYA..

CharacteristicsAYA (N=112)Non-AYA (N=55)
Male sex, N (%)59 (52.7)26 (47.3)
Age, median (range)22 (16–39)51 (40–70)
Socioeconomic status, N (%)
Low-income111 (99.1)47 (85.5)
Middle-income0 (0)3 (5.4)
High-income1 (0.9)5 (9.1)
ECOG ≤2, N (%)109 (97.3)52 (94.5)
Comorbidities, N (%)45 (40.2)36 (65.5)
DM2 (1.8)15 (27.3)
HTN4 (3.6)9 (16.4)
Obesity21 (18.8)15 (27.3)
ALL phenotype, N (%)
B-cell leukemia109 (97.3)54 (98.2)
Pre-B102 (93.6)54 (100)
Mature B6 (5.5)0 (0)
Pro-B1 (0.9)0 (0)
T-cell leukemia3 (2.7)1 (1.8)
Cytogenetic abnormalitiesa), N (%)28 (25.5)20 (38.5)
Philadelphia chromosome17 (15.5)12 (23.1)
MLL rearrangements1 (0.9)1 (1.9)c)
Hypodiploidy0 (0)2 (3.9)
Complex karyotype5 (4.6)b)1 (1.9)
Others8 (7.3)5 (9.6)
CNS involvement, N (%)13 (11.6)6 (10.9)

a)Cases with available cytogenetics: AYA (N=110) and Non-AYA (N=52). b)Two patients Ph+ and one with MLL rearrangement in addition to complex karyotype. c)Patient Ph+ in addition to MLL rearrangement..

Abbreviations: ALL, acute lymphoblastic leukemia; AYA, adolescent and young adult; CNS, central nervous system; DM, diabetes mellitus; ECOG, Eastern Cooperative Oncology Group; HTN, hypertension; MLL, mixed-lineage leukemia; Ph+, Philadelphia positive..


Table 2 . Induction-related complications..

Complications N=152
Infectious, N (%)146 (87.4)
Bloodstream infection45 (30.8)
UTI23 (15.8)
Pneumonia55 (37.7)
Skin and soft tissue33 (22.6)
C. difficile colitis10 (6.9)
IFI29 (19.9)
Metabolic, N (%)70 (46.1)
Hipertransaminasemia22 (31.4)
Dialysis requirement7 (10.0)
TLS41 (58.6)
Hematologic, N (%)18 (11.8)
Hemorrhage5 (27.8)
Thrombosis7 (38.9)
DIC6 (33.3)

Abbreviations: DIC, disseminated intravascular coagulation; IFI, invasive fungal infections; TLS, tumor lysis syndrome; UTI, urinary tract infection..


Table 3 . Factors related to a decreased overall survival after induction..

Univariate analysis
OS day+60 (%)
PMultivariate analysis
HR (95% CI)
P
Central nervous system involvementCNS-3: 3.078 (0.81–11.67)0.09
CNS-3 vs. CNS-2 vs. CNS-173.7% vs. 37.5% vs. 92.7%<0.001CNS-2: 10.10 (2.67–38.18)0.001
TLS75.3% vs. 85.12%0.005--
DIC66.7% vs. 89.4%0.037--
Shock63.2% vs. 93.8%<0.001--
Bloodstream infection83.1% vs. 95.3%0.020--
Dialysis requirement28.6% vs. 91.0%<0.0019.224 (2.45P33.72)0.001

Abbreviations: CNS, central nervous system; DIC, disseminated intravascular coagulation; OS, overall survival; TLS, tumor lysis syndrome..


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