CLINICAL OUTCOMES OF PEGASPARGASE COMBINED WITH HYPER-CVAD IN ADULT ALL AND LYMPHOBLASTIC LYMPHOMA
- 1Universidade Federal do Rio de Janeiro (UFRJ), Niterói, RJ, Brazil
- 2Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
Abstract
Background: The outcomes of acute lymphoblastic leukemia (ALL) treatment in adults have historically been inferior to those achieved in children. This inequality is partially attributed to a higher prevalence of comorbidities and high-risk genetic alterations in adult leukemias. In pediatric protocols, the incorporation of pegylated Escherichia coli–derived L-asparaginase (pegasparse) has improved clinical outcomes. In contrast, its safety and efficacy are less well established in older adults. Methods: We analyzed the outcomes of adult patients with ALL treated at a single center with the Hyper-CVAD/HD MTX-Ara-C regimen in combination with pegaspargase. The intensive treatment backbone consisted of eight cycles of Hyper-CVAD alternating with high-dose methotrexate with cytarabine (HD MTX–Ara-C), with the adition of pegaspargase. The planned pegaspargase dose was 2.000u/m2 intravenous on day 15 of each Hyper-CVAD cycle (total of 8 doses). The doses were capped at 3,750 IU, corresponding to the content of a single vial of the drug. Results: A total of 16 patients were treated with pegaspargase in combination with Hyper-CVAD. Median age of patients was 28 years (range 17 – 45). The most common diagnosis was B-cell acute lymphoblastic leukemia (B-ALL), observed in 6 patients (37.5%), followed by T-cell acute lymphoblastic leukemia (T-ALL) in 4 patients (including 2 cases of early T-cell ALL), lymphoblastic lymphoma in 4 patients, and mixed-phenotype acute leukemia (MPAL) in 2 patients. Complete remission (CR) was achieved in 13 of the 16 treated patients (81.2%). Two patients (12.5%) died during induction therapy before CR could be documented, while three patients (18.75%) were refractory to treatment. After a median follow-up of 24.2 months, relapse occurred in 2 of the 13 patients (15.3%) who achieved CR. At the time of analysis, 8 patients (50%) remained alive in first complete remission (CR1). The median overall survival (OS) was 70 months. Discussion: We retrospectively evaluated the clinical characteristics and outcomes patients with acute leukemia or lymphoblastic lymphoma treated with pegaspargase in combination with Hyper-CVAD. Similar to our previous Hyper-CVAD study, the median patient age was approximately 30 years, and B-lineage acute lymphoblastic leukemia (ALL) was the most prevalent malignancy. However, in the present cohort, we observed a lower CR rate, accompanied by a lower relapse incidence and improved overall survival. The major contribution of asparaginase in the treatment of acute lymphoblastic leukemia (ALL) appears to be less related to increasing CR rates and more associated with improving the quality and durability of remission. The augmented Hyper-CVAD experience, demonstrated the feasibility of combining pegaspargase with Hyper-CVAD in a pediatric-inspired approach. Nevertheless, that regimen was specifically designed for patients with relapsed or refractory ALL. Conclusion: In this retrospective study, the addition of pegaspargase to the Hyper-CVAD regimen was feasible and was associated with favorable overall survival outcomes. As Hyper-CVAD is widely used as a backbone for the incorporation of novel agents in the treatment of acute lymphoblastic leukemia (ALL), the inclusion of pegaspargase should be considered as a potential therapeutic option for adults with ALL and lymphoblastic lymphoma.
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BibTeX
@article{cuquetto2026clinical,
title = {{CLINICAL OUTCOMES OF PEGASPARGASE COMBINED WITH HYPER-CVAD IN ADULT ALL AND LYMPHOBLASTIC LYMPHOMA}},
author = {Gustavo Monteiro CUQUETTO and Liz Gomes da Silva LUTTERBACH and Katia Petruccio Urago TURON and Rodrigo Doyle PORTUGAL},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107572},
url = {https://doi.org/10.1016/j.htct.2026.107572},
note = {CC BY},
}
RIS
TY - JOUR
TI - CLINICAL OUTCOMES OF PEGASPARGASE COMBINED WITH HYPER-CVAD IN ADULT ALL AND LYMPHOBLASTIC LYMPHOMA
AU - Gustavo Monteiro CUQUETTO
AU - Liz Gomes da Silva LUTTERBACH
AU - Katia Petruccio Urago TURON
AU - Rodrigo Doyle PORTUGAL
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107572
UR - https://doi.org/10.1016/j.htct.2026.107572
AB - Background: The outcomes of acute lymphoblastic leukemia (ALL) treatment in adults have historically been inferior to those achieved in children. This inequality is partially attributed to a higher prevalence of comorbidities and high-risk genetic alterations in adult leukemias. In pediatric protocols, the incorporation of pegylated Escherichia coli–derived L-asparaginase (pegasparse) has improved clinical outcomes. In contrast, its safety and efficacy are less well established in older adults. Methods: We analyzed the outcomes of adult patients with ALL treated at a single center with the Hyper-CVAD/HD MTX-Ara-C regimen in combination with pegaspargase. The intensive treatment backbone consisted of eight cycles of Hyper-CVAD alternating with high-dose methotrexate with cytarabine (HD MTX–Ara-C), with the adition of pegaspargase. The planned pegaspargase dose was 2.000u/m2 intravenous on day 15 of each Hyper-CVAD cycle (total of 8 doses). The doses were capped at 3,750 IU, corresponding to the content of a single vial of the drug. Results: A total of 16 patients were treated with pegaspargase in combination with Hyper-CVAD. Median age of patients was 28 years (range 17 – 45). The most common diagnosis was B-cell acute lymphoblastic leukemia (B-ALL), observed in 6 patients (37.5%), followed by T-cell acute lymphoblastic leukemia (T-ALL) in 4 patients (including 2 cases of early T-cell ALL), lymphoblastic lymphoma in 4 patients, and mixed-phenotype acute leukemia (MPAL) in 2 patients. Complete remission (CR) was achieved in 13 of the 16 treated patients (81.2%). Two patients (12.5%) died during induction therapy before CR could be documented, while three patients (18.75%) were refractory to treatment. After a median follow-up of 24.2 months, relapse occurred in 2 of the 13 patients (15.3%) who achieved CR. At the time of analysis, 8 patients (50%) remained alive in first complete remission (CR1). The median overall survival (OS) was 70 months. Discussion: We retrospectively evaluated the clinical characteristics and outcomes patients with acute leukemia or lymphoblastic lymphoma treated with pegaspargase in combination with Hyper-CVAD. Similar to our previous Hyper-CVAD study, the median patient age was approximately 30 years, and B-lineage acute lymphoblastic leukemia (ALL) was the most prevalent malignancy. However, in the present cohort, we observed a lower CR rate, accompanied by a lower relapse incidence and improved overall survival. The major contribution of asparaginase in the treatment of acute lymphoblastic leukemia (ALL) appears to be less related to increasing CR rates and more associated with improving the quality and durability of remission. The augmented Hyper-CVAD experience, demonstrated the feasibility of combining pegaspargase with Hyper-CVAD in a pediatric-inspired approach. Nevertheless, that regimen was specifically designed for patients with relapsed or refractory ALL. Conclusion: In this retrospective study, the addition of pegaspargase to the Hyper-CVAD regimen was feasible and was associated with favorable overall survival outcomes. As Hyper-CVAD is widely used as a backbone for the incorporation of novel agents in the treatment of acute lymphoblastic leukemia (ALL), the inclusion of pegaspargase should be considered as a potential therapeutic option for adults with ALL and lymphoblastic lymphoma.
SN - 2531-1379
SN - 2531-1387
ER -