Summary
Background
Outcomes of adults with acute lymphoblastic leukemia (ALL) in Latin America remain poorly characterized, particularly across public and private healthcare systems. In this study, we evaluated overall survival (OS) and relapse rates in a multinational cohort, aiming to identify key factors associated with these outcomes.
Methods
We retrospectively analyzed patients aged ≥15 years with newly diagnosed ALL treated at 45 centers in Brazil, Argentina, and Chile between 2015 and 2023. Overall survival (OS) and event-free survival (EFS) were estimated using Kaplan–Meier methods. Cox models incorporating country as a shared frailty term evaluated factors associated with mortality.
Findings
Among 1121 patients, median age was 34 years, 56.1% were male, 81.4% had B-lineage ALL, and 24.7% had Philadelphia chromosome–positive (Ph-positive) ALL. Overall, 53% were treated in public centers. Induction mortality was higher in public than private settings (10.0% vs. 1.2%; p < 0.0001), whereas hematopoietic stem cell transplantation was less frequent (18.1% vs. 46.6%; p < 0.0001). At a median follow-up of 36.2 months, 3-year OS and EFS were 49.9% and 41.1%, respectively. Three-year OS was 42.9% in public and 57.6% in private centers (p < 0.0001). Private healthcare remained independently associated with lower mortality overall (HR 0.53, 95% CI 0.42–0.68) and across major subgroups. Three-year relapse incidence was 43.9%. Among Ph-negative adolescents and young adults, male sex and leukocytosis were independently associated with increased mortality. In Ph-positive ALL, upfront dasatinib was associated with improved OS, primarily through lower non-relapse mortality rather than reduced relapse incidence.
Interpretation
Survival of adults with ALL in Latin America has improved compared with historical reports, but substantial disparities persist between public and private settings. Our findings support prioritizing investment in public-sector supportive care, diagnostic and treatment infrastructure, timely access to transplantation, and equitable availability of effective therapies as key strategies to improve survival across the region.
Funding
None.
Keywords: Acute lymphoblastic leukemia, Latin America, Healthcare disparities, Overall survival, Public and private healthcare
Research in context.
Evidence before this study
We searched PubMed/MEDLINE from December, 2025 to July 02, 2026, without language restrictions, and reviewed the reference lists of relevant original articles, systematic reviews, and regional recommendations. We used combinations of the terms “acute lymphoblastic leukemia”, “acute lymphocytic leukemia”, “adult”, “adolescent and young adult”, “Latin America”, “South America”, “Central America”, “Hispanic”, “survival”, “outcomes”, “healthcare disparities”, “healthcare access”, “socioeconomic factors”, “public hospital”, “private hospital”, “health insurance”, “treatment setting”, “pediatric-inspired regimen”, and “hematopoietic stem-cell transplantation”. We included observational studies, clinical cohorts, population-based analyses, and systematic or narrative reviews reporting treatment patterns, access to care, or survival outcomes among adults with acute lymphoblastic leukemia (ALL), particularly studies conducted in Latin America or involving Hispanic populations. Studies exclusively involving children, case reports, and reports without survival or healthcare-access information were excluded, although studies spanning adolescents and adults were considered when adult-specific findings were available.
Previous studies showed that outcomes of adult ALL in Latin America remain inferior to those reported in contemporary clinical trials and high-income settings. Regional reports also described substantial variation in access to molecular diagnostics, tyrosine kinase inhibitors, asparaginase, immunotherapies, supportive care, measurable residual disease assessment, and allogeneic haematopoietic stem-cell transplantation. Population-based studies from the USA suggested poorer survival among Hispanic patients and individuals with lower income or inadequate insurance coverage. However, the available Latin American evidence consisted predominantly of single-country or single-centre retrospective cohorts, selected disease subgroups, expert reviews, and studies focused on individual treatments. Most studies had a moderate-to-high risk of selection bias, incomplete adjustment for confounding, heterogeneous treatment definitions, and limited representation of both public and private healthcare systems. We identified no large multinational study directly evaluating healthcare setting as an independent determinant of survival across the full spectrum of adult ALL in Latin America.
Added value of this study
This study provides a large multinational assessment of adults with newly diagnosed ALL treated in Latin America during 2015–23 and directly compares outcomes between public and private healthcare settings. By including more than 1100 patients from several countries and adjusting for several baseline variables and country-level clustering, the study distinguishes the effect of healthcare setting from differences in patient and disease characteristics.
Patients treated in public institutions had inferior survival despite being younger, and treatment in a private healthcare setting remained independently associated with a substantially lower risk of death. Among younger patients with Philadelphia chromosome-negative disease, use of a paediatric-inspired regimen rather than Hyper CVAD did not overcome the survival difference between healthcare settings. In Philadelphia chromosome-positive disease, disparities in access to newer tyrosine kinase inhibitors and transplantation were also apparent, although the survival differences associated with treatment setting could not be explained solely by the choice of antileukaemic regimen. These findings indicate that the organisation and resources of the healthcare system—including timely diagnosis, continuity of treatment, supportive care, toxicity management, access to transplantation, and availability of novel therapies—might have a greater effect on survival than the selection of a conventional chemotherapy platform alone.
Implications of all the available evidence
The combined evidence indicates that improving adult ALL outcomes in Latin America requires more than adopting treatment protocols developed in well-resourced settings. Health policies should prioritise equitable and timely access to diagnostic testing, measurable residual disease assessment, essential antileukaemic drugs, tyrosine kinase inhibitors, asparaginase, immunotherapies, blood products, infection management, intensive care, and haematopoietic stem-cell transplantation. Regional cooperative groups and governments should also develop referral pathways, shared laboratory platforms, standardised supportive-care procedures, and mechanisms to prevent treatment interruptions and delays.
Introduction
Acute lymphoblastic leukemia (ALL) is a rare neoplasm that requires complex, intensive, multi-agent chemotherapy regimens, leading to profound immunosuppression and a high demand for supportive care.1 Recent advances in the treatment of this disease, particularly in adults, have been achieved through the incorporation of pediatric-inspired protocols, the emergence of targeted therapies, and the optimization of hematopoietic stem cell transplantation (HSCT) procedures.2
While these achievements are witnessed across the globe, the access to cancer treatment varies widely, and disparities often exist even within a single country. In Latin America, leukemia care is delivered through two distinct healthcare systems: a public health system, which serves approximately 70% of the population, and a private system.3 Historical outcomes for ALL reported in smaller studies have demonstrated substantially worse results, even in the pre-immunotherapy era, possibly related to social determinants of health, differences in disease biology, and increased toxicity from chemotherapy.4, 5, 6, 7, 8
Although there is no comprehensive survey from Latin America and healthcare systems and policies vary widely across countries, multi-site data from the United States suggest that in academic centers most patients are treated with institutional pediatric-inspired protocols, whereas in community settings the majority receive Hyper-CVAD.9
Currently, there is no comprehensive regional database for acute leukemia in Latin America that allows for the assessment of outcome disparities related to healthcare access or biological factors. In this study, we sought to analyze overall survival (OS), event-free survival (EFS) and relapse rates in a large, multinational cohort that includes both public and private institutions from Latin America, with the goal of identifying key factors associated with survival in adult patients with ALL in this scenario and comparing these outcomes.
Methods
Study design and data collection
This is a retrospective multi-site cohort study encompassing patients from 15 years and above with newly diagnosed ALL from 45 centers from Brazil, Argentina, and Chile (list of centers, see Appendix and Table S1). Patients diagnosed between Jan/2015 and Dec/2023 were included. Data were collected through an anonymized database in REDCap hosted at the University of Sao Paulo. Baseline patient's and disease characteristics were collected, along with frontline treatment, response, and survival endpoints. Patients were treated using chemotherapy protocols at the physician's discretion, following local recommendations and practices. All cases were diagnosed using the WHO criteria.10
Definitions and statistical analysis
Regimens were divided into pediatric-inspired regimens (PIR) (those including asparaginase into a chemotherapy backbone11,12), Hyper-CVAD-based (HCVAD) (those using the Hyper-CVAD alternating with high-dose methotrexate and cytarabine as published13), and elderly protocols (published adaptations for elderly patients, such as mini-CVD, GRAALL-Elderly, and EWALL protocols14,15). Patients who did not receive chemotherapy were categorized under the “supportive care” category. All centers had access to measurable residual disease (MRD) by flow cytometry for disease evaluation. All Philadelphia-positive cases (Ph+) received tyrosine-kinase inhibitor (TKI) along with the frontline treatment. Indications for HSCT in first complete remission (CR1), and supportive care were managed independently by each center. Central nervous system (CNS) disease was defined as any cytologic evidence of leukemic involvement in the cerebrospinal fluid, neurological symptoms attributable to CNS involvement, or the presence of CNS masses. Leukocytosis was defined as a white blood cell count ≥50 × 109/L, according to the NCI criteria.16
Quantitative variables were summarized using medians and interquartile ranges and were retained as continuous variables in regression models. Descriptive analyses were performed to characterize baseline demographic, clinical, disease-related, and treatment-related features. Survival outcomes were estimated using the Kaplan–Meier method and compared with log-rank tests, while Cox regression models were used to adjust associations with survival outcomes. Variables with preliminary association with survival or p < 0.2 in the univariate regression were included in the multivariable models. Country-level clustering was accounted for by incorporating country of origin as a shared frailty term in the multivariable Cox regression models. OS was defined as the time from diagnosis to death from any cause, and EFS as the time from diagnosis to treatment failure, relapse, death, or last follow-up, whichever occurred first. Relapse was defined as hematologic or extramedullary disease recurrence after achievement of complete remission. Cumulative relapse incidence (CIR) was calculated considering death as a competitor. Patients without an event were censored at the date of last follow-up. Early death was defined as death occurring within 30 days of diagnosis. Missing data were not imputed. For multivariable analyses, only variables with less than 10% missing data were considered for inclusion, and complete-case analysis was then performed for the covariates entered into each model. Subgroup analyses were performed according to clinically relevant disease groups, including Ph-negative adolescents and young adults (AYA), with 15–59 years at the diagnosis,17 Ph-negative older patients, with older age defined as ≥60 years, as well as Ph-positive ALL. Sensitivity analyses explored the role of healthcare setting across different analytic scenarios to assess the consistency of its association with outcomes.
Ethics statement
The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and applicable local regulations. The protocol was reviewed and approved by the institutional review board from University of Paulo (CAAE 16697119.5.1001.0065, Plataforma Brasil). Given the retrospective and observational nature of the study, informed consent was waived, and all data were anonymized or de-identified before analysis to ensure patient confidentiality.
Role of the funding source
The funders had no role in the study design, data collection, data analysis, interpretation, writing of the manuscript.
Results
A total of 1121 patients met the eligibility criteria and were analyzed in this cohort. Median age was 34 years (range, 15–87) and 56.1% (627/1121) were male. Most cases were B-lineage (81.4%, 913/1121), and 24.7% (273/1105) were Ph+. Leukocytosis (≥30 for B or ≥100 for T-lineage) was registered in 29.2% (309/1057). Positive CSF cytology was found in 17.6% (182/1037). In this cohort, 53% (594/1121) of patients were treated in public centers, while remaining cases were treated in private centers. Most cases were from Argentina (43.5%, 488/1121) and Brazil (39.5%, 447/1121). Baseline characteristics and initial treatment subgroup according to the setting are summarized in Table 1.
Table 1.
Baseline comparative features between patients from public and private settings.
| Overall (n = 1121) | Public (n = 594) | Private (n = 527) | p-value | |
|---|---|---|---|---|
| Age—median (range, IQR) | 34 (15–87, 23–50) | 31 (15–82, 22–48) | 37 (15–87, 24–52) | 0.0020 |
| Male sex—n (%) | 627 (56) | 343 (57.8) | 284 (54.0) | 0.22 |
| CNS diseasea—n (%) | 182 (17.6) | 109 (21.1) | 73 (14.0) | 0.0031 |
| Phenotype—n (%) | B: 913 (81.4) T: 208 (18.6) |
B: 455 (76.6) T: 139 (23.4) |
B: 458 (86.9) T: 69 (13.1) |
<0.0001 |
| Ph + ALLb—n (%) | 273 (24.7) | 148 (25.3) | 125 (24.1) | 0.69 |
| CD1a negativity in T-ALLc—n (%) | 94 (56.3) | 55 (49.5) | 39 (69.6) | 0.021 |
| Pro-B phenotype in B-ALL—n (%) | 75 (8.9) | 35 (8.5) | 40 (9.3) | 0.77 |
| Hemoglobin (g/dl)—mean (SD) | 8.89 (2.67) | 8.39 (2.65) | 9.27 (2.63) | <0.0001 |
| WBC (x109/L)d—n (%) | 0.75 | |||
| <30 | 703 (66.5) | 389 (67.2) | 314 (65.7) | |
| 30–49 | 86 (8.1) | 45 (7.8) | 41 (8.6) | |
| 50–99 | 116 (11.0) | 59 (10.2) | 57 (11.9) | |
| ≥100 | 152 (14.4) | 86 (14.9) | 66 (13.8) | |
| Blasts in PB (%)—mean (SD) | 52.5 (33.9) | 55.9 (32.9) | 49.7 (34.5) | 0.0090 |
| Initial regimen (Ph-negative)—n (%) | PIR: 892 (88.6) | PIR: 503 (92.1) | PIR: 389 (84.4) | 0.0001 |
| HCVAD: 93 (9.2) | HCVAD: 35 (6.4) | HCVAD: 58 (12.6) | ||
| Elderly: 22 (2.2) | Elderly: 8 (1.5) | Elderly: 14 (3.0) | ||
| Initial regimen (Ph-positive)—n (%) | PIR: 69 (34.1) | PIR: 28 (26.4) | PIR: 41 (42.7) | <0.0001 |
| Elderly: 31 (15.3) | Elderly: 9 (8.5) | Elderly: 22 (22.9) | ||
| HCVAD: 70 (34.6) | HCVAD: 37 (34.9) | HCVAD: 33 (34.4) | ||
| Others: 32 (15.8) | Others: 32 (30.2) | Others: 32 (15.8) | ||
| Frontline TKI—n (%) | Imatinib: 110 (45.1) | Imatinib: 73 (59.3) | Imatinib: 37 (30.6) | <0.0001 |
| Dasatinib: 124 (50.8) | Dasatinib: 46 (37.4) | Dasatinib: 78 (64.5) | ||
| Ponatinib: 9 (3.7) | Ponatinib: 4 (3.3) | Ponatinib: 5 (4.1) | ||
| Nilotinib: 1 (0.4) | Nilotinib: 1 (0.8) | |||
| Country—n (%) | Argentina: 488 (43.5) | Argentina: 312 (52.5) | Argentina: 135 (25.6) | <0.0001 |
| Brazil: 447 (39.9) | Brazil: 211 (35.5) | Brazil: 277 (52.6) | ||
| Chile: 186 (16.6) | Chile: 71 (12.0) | Chile: 115 (21.8) | ||
| HSCT rate—n (%) | 346 (31.7) | 103 (18.1) | 243 (46.6) | <0.0001 |
| HSCT in CR1—n (%) | 244 (85.6) | 71 (88.8) | 173 (84.4) | 0.26 |
| Myeloablative conditioning—n (%) | 148 (77.1) | 47 (75.8) | 101 (77.7) | 0.73 |
| Use of TBI—n (%) | 156 (85.7) | 49 (84.5) | 107 (86.3) | 0.92 |
CNS, central nervous system; CR1, first complete remission; HCVAD, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone; HSCT, hematopoietic stem cell transplantation; IQR, interquartile range; PB, peripheral blood; PIR, pediatric-inspired regimen; SD, standard deviation; TBI, total body irradiation; TKI, tyrosine kinase inhibitor; WBC, white blood cell count.
Missing: 7.5%.
Missing: 1.5%.
See classification for T-ALL in Habringer et al.18
Missing: 6%.
While most Ph-negative patients received a PIR as initial treatment, an increased proportion of patients in private centers were treated with HCVAD (12.6 vs. 6.4%). The rate of allo-HSCT in CR1 differed substantially between patients treated with HCVAD and those receiving PIRs (52.7% vs. 27.9%, respectively; p < 0.001). Regarding Ph + cases, more cases from private setting received dasatinib instead imatinib frontline (64.5 vs. 37.4%, p < 0.0001), while only 9/273 patients received upfront ponatinib (3.3%). Three patients/1121 (1%) from the private cohort from Chile received blinatumomab upfront for MRD positivity, only. Fifteen patients/1121 (1.3%) from the private cohort received blinatumomab in the relapsed/refractory setting, while inotuzumab ozogamicin was given as salvage for 7 patients/1121 (0.6%) (5 from the private group).
Overall, 43/1121 patients (3.8%) received supportive care only for the disease. Among those patients receiving any treatment, induction death rate was 10 and 1.2% in the public and private scenarios, respectively (p < 0.0001). Among cases with available information, bacterial infections were the leading cause of early death (45%, 9/20), with no significant difference according to healthcare setting. The rate of HSCT was greater in private centers than in public ones (46.6 vs. 18.1%, p < 0.0001), mostly in first complete remission (85.6%, 244/285). Baseline transplant characteristics did not differ between the two scenarios regarding type of donor and conditioning intensity (see Table 1). Across subgroups, HSCT was performed in 29.6% (218/736) of Ph-negative AYA patients, 16.2% (11/68) of older Ph-negative patients, and 41.9% (113/270) of Ph-positive patients. With a median follow-up of 36.2 months, 3-year OS for all cohort was 49.9% (95% confidence interval [CI] 46.6–53.3), being 42.9 and 57.6% in the public and private centers, respectively (p < 0.001). Three-year EFS was 41.1% (95% CI 38–44.5), being also statistically different for public (33.7%) and private (49.3%) settings (p < 0.001) (see Fig. 1). This difference was also significant within the T-cell subset (n = 208), with patients treated in the private setting experiencing better OS (3-year OS, 59.9% vs. 43.0%; p = 0.0043). Median time between diagnosis and HSCT in CR1 was 7.2 months, with no difference between public and private settings (p = 0.265). Outcomes of allografted patients are summarized in Table 2. OS outcomes for the three analyzed subgroups are shown in Fig. 2a.
Fig. 1.
Overall survival and event-free survival in the entire cohort of patients with newly diagnosed ALL from participating centers between 2015 and 2023 (n = 1125).
Table 2.
Summary of outcomes among transplanted ALL patients in the cohort (≤60 years).
| 3-year OS (95% CI) | 3-year EFS (95% CI) | 3-year CIR (95% CI) | |
|---|---|---|---|
| Ph-negative (n = 223) | CR1: 68.1% (60.8–76.3) | CR1: 60.6% (53.2–68.9) | CR1: 27.1% (19.9–34.3) |
| CR2+: 67.3% (49.5–91.7) | CR2+: 50.8% (34.8–74) | CR2+: 49.2% (29.5–68.9) | |
| Ph-positive (n = 114) | CR1: 62.5% (49.5–78.9) | CR1: 47% (34.8–63.4) | CR1: 37.1% (23.2–51) |
| CR2+: 62.5% (32–100) | CR2+: 43.8% (18.9–100) | CR2+: 56.5% (14.8–97.7) |
Fig. 2.
(a) OS according the three subgroups—Ph-negative AYA, Ph-negative Older, and Ph-positive patients; (b) Comparison of OS among Ph-negative AYA treated with PIR vs. HCVAD. OS = overall survival; AYA = adolescent and young adult; PIR = pediatric-inspired regimen; HCVAD = Hyper-CVAD regimen.
For Ph-negative AYA pts (n = 757), in a multivariable Cox regression model incorporating country of origin as a gamma-distributed frailty term, private vs. public healthcare setting remained independently associated with lower mortality risk (HR 0.54, 95% CI 0.42–0.69; p < 0.001). Older age (HR 1.02 per year, 95% CI 1.01–1.03; p < 0.001), male sex (HR 1.35, 95% CI 1.05–1.74; p = 0.025), and NCI-defined leukocytosis (HR 1.50, 95% CI 1.14–1.96; p = 0.0041) were independently associated with increased mortality risk. CNS involvement (HR 1.29, 95% CI 0.95–1.75; p = 0.11) and use of frontline pediatric regimen (HR 0.97, 95% CI 0.67–1.39; p = 0.85) were not significantly associated with OS (see Table S2). The estimated country-level frailty variance was negligible, indicating no meaningful residual heterogeneity by country after adjustment for the included covariates. Treatment with a PIR rather than HCVAD was not associated with OS in this subgroup (Fig. 2b). Three-year CIR and non-relapse mortality (NRM) for this subgroup were 41.4% and 14.3%, respectively. The inferior OS observed among male patients was primarily driven by a higher CIR rather than by differences in NRM (44.3% vs. 36.8%, p = 0.031; and 15.1% vs. 13.2%, p = 0.51, respectively). When modeled as a time-dependent covariate, allo-HSCT in CR1 was not independently associated with OS in this subgroup (HR 0.83, 95% CI 0.56–1.25; p = 0.37).
For Ph-negative older patients (≥60 years-old, n = 74), the multivariable Cox regression model for OS, incorporating country of origin as a gamma-distributed frailty term, private vs. public healthcare setting remained associated with lower mortality risk (HR 0.42, 95% CI 0.18–0.96; p = 0.040), while older age was associated with increased mortality risk (HR 1.08 per year, 95% CI 1.02–1.14; p = 0.012). Blast percentage, CNS involvement, and NCI-defined leukocytosis were not significantly associated with mortality (see Table S3). The estimated country-level frailty variance was also negligible. Given the limited sample size, these findings should be interpreted with caution. Three-year CIR and non-relapse mortality (NRM) for this subgroup were 44.3% and 23.3%, respectively.
Regarding Ph + ALL cases (n = 273), in the multivariable model, private vs. public healthcare setting remained independently associated with lower mortality risk (HR 0.47, 95% CI 0.28–0.79; p = 0.0045), while older age was associated with increased mortality risk (HR 1.02 per year, 95% CI 1.01–1.04; p = 0.0041). Use of dasatinib into the initial regimen was associated with lower mortality risk compared with the imatinib (HR 0.45, 95% CI 0.27–0.75; p = 0.0022). Use of pediatric-inspired protocols and elderly protocols were also associated with lower mortality risk compared with HCVAD (HR 0.34, 95% CI 0.19–0.61; p < 0.001, and HR 0.38, 95% CI 0.18–0.79; p = 0.0092, respectively). CNS involvement and NCI-defined leukocytosis were not independently associated with mortality (see Table S4). Again, the country-level frailty variance was not significant in this model. Compared with patients treated with imatinib, those who received upfront dasatinib were more frequently treated in the private setting (62.3% vs. 33.6%) and underwent HSCT in CR1 more often (52.1% vs. 37.3%). After inclusion in the Cox regression model, HSCT was not significantly associated with OS when modeled as a time-dependent exposure (HR 0.85, 95% CI 0.51–1.42; p = 0.54) (see Fig. 3). Treatment in the private setting (HR 0.57, 95% CI 0.37–0.86; p = 0.0081) and dasatinib (HR 0.60, 95% CI 0.39–0.92; p = 0.019) remained associated with lower mortality risk. Three-year CIR in Ph + ALL was 35.2%, while NRM was 29.2%. The OS benefit associated with upfront dasatinib was primarily driven by lower NRM rather than by differences in CIR (24.2% vs. 38.5%, p = 0.021; and 29.2% vs. 31.5%, p = 0.92, respectively).
Fig. 3.
Simon–Makuch plot evaluating the impact of HSCT in first complete remission on OS among patients with Ph-positive ALL in this cohort.
Summarily, in this large contemporary database of ALL patients from Latin America, treatment in a private center (HR 0.53, 95% CI 0.42–0.68, p < 0.001) was independently associated with OS globally and in all subgroups (B vs. T, Ph+, elderly), even when adjusted for age, CNS disease, and HCT in CR1 in the MVA.
Discussion
This study reports a contemporary multicenter database of adults with newly diagnosed ALL from several centers across South America. In most Latin American countries, there are no comprehensive governmental initiatives to systematically evaluate survival outcomes among patients with cancer, making multicenter collaborations essential to understanding outcomes and exploring disparities across different healthcare settings.19 Similar disparities in access to specialized care, transplantation, supportive care, and novel therapies have also been reported in other resource-constrained settings, including India and sub-Saharan Africa, suggesting that some of the challenges observed in our cohort may have broader relevance beyond Latin America.20,21
Based on studies from the United States, it has been hypothesized that patients with ALL from Latin America may present with distinct baseline features, including more aggressive disease, higher WBC counts, greater CNS involvement, and an increased prevalence of Ph-like signatures within the B-cell subset.22, 23, 24 This may be partly explained by the higher proportion of Indigenous ancestry across Latin American populations. However, when comparing the findings of this database with large cohorts from Europe and the United States, we did not identify major differences in the distribution of T-cell phenotype, Ph-positive disease, WBC counts, or CNS involvement.25,26 When comparing the two healthcare settings evaluated in this study, public vs. private, the most notable baseline difference was the higher frequency of CNS disease among patients treated in the public setting. One might wonder whether this finding could be related to delayed diagnosis in the public setting or to more aggressive disease biology among historically underserved populations in Latin America, including those with greater Black and Indigenous ancestry.
Compared with prior reports from Latin America, most of which were single-center studies, this contemporary multicenter cohort showed improved survival outcomes. Historically reported survival rates from single-center studies in the region have ranged from approximately 15%–35%, whereas survival reached nearly 50% in the present large cohort.4, 5, 6,27 These findings suggest that outcomes are gradually improving in Latin America, even in the absence of broad access to novel agents and CAR T-cell therapy. The implementation of PIRs, together with improved recognition and mitigation of treatment-related adverse events, may have contributed to these gains. As demonstrated in this cohort, fewer patients treated with PIR required allo-HSCT in CR1, which may be particularly relevant in Latin America, where access to transplantation remains a major bottleneck to improving survival outcomes in adults with ALL.28 Although not directly examined in this study, the increasing dissemination of MRD assessment by flow cytometry across centers in Latin America over the past decade should not be overlooked, given its central role in risk stratification and treatment adaptation in ALL.
Healthcare setting should not be interpreted as a direct causal determinant of survival, but rather as an indirect proxy for a broader set of structural and socioeconomic factors that may influence outcomes. Differences between public and private care may reflect variation in socioeconomic conditions, timely access to diagnostic procedures and newer therapies, supportive care resources, infection management, treatment continuity, and overall healthcare infrastructure. Although we adjusted for several relevant clinical covariates, residual confounding by unmeasured factors is likely.
Interestingly, among AYA patients with Ph-negative ALL, male sex remained an independent adverse prognostic factor for survival, mirroring findings reported by pediatric groups. Although this association remains controversial, some studies have also described inferior outcomes among boys with childhood ALL, largely driven by higher relapse rates.29,30 Although not specifically addressed in the present study, differences in treatment adherence, disease biology, and pharmacologic factors may contribute to sex-based differences in outcomes. Most adult cohorts have not reported this finding, which warrants further investigation in future studies.31
In Ph-positive ALL, upfront dasatinib use and treatment in private healthcare settings were independently associated with better OS. However, in the competing-risk analysis, the apparent benefit of dasatinib seemed to be primarily related to improved local conditions and supportive care at these centers, rather than to a direct biological effect of frontline dasatinib itself. Although dasatinib is more potent than imatinib, its widespread frontline use is not supported by phase III trial data, and its use as a second-line strategy may preserve its therapeutic benefit.1,32 From a cost-saving perspective in Latin America, upfront dasatinib for all patients may not be necessary and could be reserved for those who fail to achieve an adequate molecular response. In Latin America, the role of allogeneic SCT in Ph + ALL has evolved only recently, shifting from a strategy in which transplantation in CR1 was broadly recommended toward a more individualized, MRD-driven approach. Our findings should therefore be interpreted in the context of heterogeneous and, in some centers, limited access to molecular MRD assessment during the study period. Expanding access to standardized quantitative BCR:ABL1 testing across Latin America is an urgent priority, as it may improve transplant selection, reduce unnecessary procedures, and allow earlier identification of patients requiring TKI change.33
This study has several limitations. First, although the cohort included 40 centers from three middle-income countries, it does not capture the full diversity of healthcare systems, treatment practices, and socioeconomic conditions across Latin America, limiting the generalizability of our findings to the region as a whole. Second, important disease-response variables, including complete remission and MRD rates, were not uniformly available and therefore could not be incorporated into the analyses. Treatment was also heterogeneous across centers, including differences in chemotherapy backbones and in the availability and formulation of asparaginase, which may have influenced outcomes. In addition, the inferior outcomes observed in public hospitals cannot be attributed solely to differences in quality of care, as they may also reflect a higher burden of adverse disease biology, delayed diagnosis, socioeconomic disparities, differences in access to supportive care and HSCT, or a combination of these factors. Finally, the use of immunotherapeutic agents was very limited in this cohort, precluding any meaningful conclusions regarding their impact on outcomes or their potential to mitigate disparities between healthcare settings.
Summarily, the impact of socioeconomic factors on outcomes in adult ALL appears to be particularly significant in Latin America. Beyond financial disparities, improved infrastructure and the availability of HCT in private centers may contribute to the observed survival disparities. In contrast, public centers—despite treating many patients with pediatric-inspired protocols—continue to face limitations that substantially contribute to poorer outcomes. This study provides the largest contemporary survival dataset of adults with ALL from Latin America. Our findings suggest that, in the context of increasing availability of novel agents and HCT, pediatric-inspired regimens may not provide the same benefit for all younger patients with ALL. However, these regimens remain the current standard of care, supported by prior prospective studies, and our observational findings should be interpreted cautiously.
Contributors
W.F.S., L.F., and M.E. contributed to conceptualization. W.F.S., L.F., M.E., E.C., B.K.L.D., A.D.A., A.G.O.B., I.D., J.R., N.Q., E.Z., G.G., D.S., N.R., M.L. collected the data and contributed to database organization. W.F.S., L.F., M.E., E.C., B.K.L.D., A.D.A., and A.G.O.B. contributed to data curation. C.C., M.M., M.E.R., N.O., M.B.C., Y.S., A.N., A.R.D., J.G., M.I.P., M.M.R., A.E.M., J.M., A.G.C., E.B.B., L.R., N.C., S.P., J.F. also contributed with data collection and revision of the analysis and original draft. W.F.S. and E.M.R. accessed and verified the underlying data and performed the formal analysis. W.F.S., L.F., M.E., and A.D.A. contributed to methodology. W.F.S. was responsible for project administration, the decision to publish this manuscript, and drafted the original manuscript. I.F., F.K., P.N., N.H., A.B., V.R. and E.M.R. provided supervision. All authors read and approved the final version.
Data sharing statement
Deidentified individual participant data collected for this study, together with the corresponding data dictionary, may be made available to qualified researchers upon reasonable requests. Additional study-related documents, including the statistical analysis plan and data collection forms, may also be shared when applicable. Data will be available beginning with publication, with no predetermined end date. Requests should be submitted to the corresponding author at wellington.fernandes@hc.fm.usp.br and must include a detailed research proposal describing the objectives, planned analyses, investigators involved, and intended use of the data. Access will be considered for scientifically sound proposals that are consistent with the original ethical approvals and applicable data-protection regulations. All requests will require approval from the study steering committee and all participating coauthors or institutional representatives, as applicable. Data will be shared through a secure electronic transfer mechanism and may be provided with investigator support, depending on the scope of the approved proposal and the availability of the study team.
Declaration of interests
W.F.S. has received honoraria from Amgen, Servier, Abbvie, and Pfizer. A.B. received honoraria from Amgen and MSD. V.R. received honoraria from Kite. E.R. received honoraria from Abbvie, Astellas and Servier. Remaining authors declare no conflict of interest.
Acknowledgements
We sincerely thank the patients whose data made this study possible, as well as the physicians, nurses, data managers, and other colleagues from all participating centers for their collaboration and contribution to this multicenter effort. ChatGPT (OpenAI) was used solely for English-language editing and stylistic refinement of the manuscript. It was not used for data analysis, interpretation of results, generation of scientific content, or decision-making. All suggested edits were reviewed and approved by the authors, who take full responsibility for the final content of the manuscript.
Footnotes
Supplementary data related to this article can be found at https://doi.org/10.1016/j.lana.2026.101655.
Appendix A. Supplementary data
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