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Blood Res (2025) 60:4

Published online January 14, 2025

https://doi.org/10.1007/s44313-024-00050-6

© The Korean Society of Hematology

Efficacy of bortezomib combined with Hyper-CVAD in adults with relapsed acute lymphoblastic leukemia or positive measurable residual disease; effect of bortezomib in leukemia

Christian Omar Ramos Peñafiel1,2 , Daniela Pérez Sámano1 , Adán Germán Gallardo Rodríguez3 , Camila Terreros Palacio1 , Irma Olarte Carrillo4 , Carlos Martínez Murillo1 , Gilberto Barranco Lampón1 , Álvaro Cabrera García2 and Adolfo Martínez Tovar4*

1 Hematology Department, General Hospital of Mexico “Dr. Eduardo Liceaga, Mexico City, Mexico. 2 Hematology Department, Regional Hospital of High Specialty of Ixtapaluca, State of Mexico, Mexico City, Mexico. 3 Hematology Research Department, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City, Mexico. 4 Hematology Laboratory, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City, Mexico.

Correspondence to : Adolfo Martínez Tovar
mtadolfo73@hotmail.com

Received: July 16, 2024; Accepted: December 4, 2024

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Abstract

PurposeDespite advances in the treatment of adult acute lymphoblastic leukemia (ALL), relapse remains the most significant challenge in improving prognosis. Measurable residual disease (MRD) assessment can predict bone marrow relapse based on MRD positivity. As access to innovative therapies remains limited because of the high cost, chemotherapy is the widely utilized treatment option. The efficacy of a combination of bortezomib and Hyper-CVAD has been reported in patients with multiple myeloma; however, its efficacy has not yet been confirmed in patients with ALL.
MethodsThis prospective cohort study involved patients with ALL who presented with MRD-positive results or relapse and received treatment with a combination of bortezomib and Hyper-CVAD at two reference centers in Mexico City.
ResultsOf the 20 patients with positive MRD included in this study, 60% (n = 12) exhibited MRD negative results after combination treatment, 30% (n = 6) persisted positive MRD results, and 10% (n = 2) passed away. Of the 23 patients with bone marrow relapse, 43.5% (n = 10) achieved a second complete remission (2CR), 34.8% (n = 6) exhibited refractory status, and 21.7% (n = 5) passed away. To achieve a 2CR, 20% (n = 2) patients required less than four cycles of treatment, 50% (n = 5) required four cycles (two A and B cycles each), and 30% (n = 3) required six cycles.
ConclusionThe combination of bortezomib and Hyper-CVAD treatment exhibited better results in achieving MRD negative results, indicating its potential as a promising first-line treatment strategy for ALL.

Keywords Bortezomib, Chemotherapy, Acute Lymphoblastic Leukemia, Relapse, Measurable Residual Disease

Article

RESEARCH

Blood Res 2025; 60():

Published online January 14, 2025 https://doi.org/10.1007/s44313-024-00050-6

Copyright © The Korean Society of Hematology.

Efficacy of bortezomib combined with Hyper-CVAD in adults with relapsed acute lymphoblastic leukemia or positive measurable residual disease; effect of bortezomib in leukemia

Christian Omar Ramos Peñafiel1,2 , Daniela Pérez Sámano1 , Adán Germán Gallardo Rodríguez3 , Camila Terreros Palacio1 , Irma Olarte Carrillo4 , Carlos Martínez Murillo1 , Gilberto Barranco Lampón1 , Álvaro Cabrera García2 and Adolfo Martínez Tovar4*

1 Hematology Department, General Hospital of Mexico “Dr. Eduardo Liceaga, Mexico City, Mexico. 2 Hematology Department, Regional Hospital of High Specialty of Ixtapaluca, State of Mexico, Mexico City, Mexico. 3 Hematology Research Department, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City, Mexico. 4 Hematology Laboratory, General Hospital of Mexico “Dr. Eduardo Liceaga”, Mexico City, Mexico.

Correspondence to:Adolfo Martínez Tovar
mtadolfo73@hotmail.com

Received: July 16, 2024; Accepted: December 4, 2024

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Abstract

PurposeDespite advances in the treatment of adult acute lymphoblastic leukemia (ALL), relapse remains the most significant challenge in improving prognosis. Measurable residual disease (MRD) assessment can predict bone marrow relapse based on MRD positivity. As access to innovative therapies remains limited because of the high cost, chemotherapy is the widely utilized treatment option. The efficacy of a combination of bortezomib and Hyper-CVAD has been reported in patients with multiple myeloma; however, its efficacy has not yet been confirmed in patients with ALL.
MethodsThis prospective cohort study involved patients with ALL who presented with MRD-positive results or relapse and received treatment with a combination of bortezomib and Hyper-CVAD at two reference centers in Mexico City.
ResultsOf the 20 patients with positive MRD included in this study, 60% (n = 12) exhibited MRD negative results after combination treatment, 30% (n = 6) persisted positive MRD results, and 10% (n = 2) passed away. Of the 23 patients with bone marrow relapse, 43.5% (n = 10) achieved a second complete remission (2CR), 34.8% (n = 6) exhibited refractory status, and 21.7% (n = 5) passed away. To achieve a 2CR, 20% (n = 2) patients required less than four cycles of treatment, 50% (n = 5) required four cycles (two A and B cycles each), and 30% (n = 3) required six cycles.
ConclusionThe combination of bortezomib and Hyper-CVAD treatment exhibited better results in achieving MRD negative results, indicating its potential as a promising first-line treatment strategy for ALL.

Keywords: Bortezomib, Chemotherapy, Acute Lymphoblastic Leukemia, Relapse, Measurable Residual Disease

Fig 1.

Figure 1.Survival rate among patients with MRD positivity and relapse

Fig 2.

Figure 2.Survival rate among patients according to the response to the combination treatment with Hyper-CVAD and bortezomib

Table 1 . Demographic characteristics of the patients.

MRD-positive (n = 20).

Relapse (n = 23).

Age (years).

26.35 (18–40).

27.73 (18–58).

Gender (M:F).

11:9.

10:13.

WBC count (× 103) at diagnosis.

32.00 (1.50–253.00).

27.90 (0.30–414.20).

Philadelphia chromosome.

 Absence.

18 (90.0%).

22 (95.7%).

 Presence.

2 (10.0%).

1 (4.3%).

Immunophenotype.

 B cell precursor ALL.

20 (100.0%).

21 (91.3%).

 T cell precursor ALL.

0 ( 0.0%).

2 (8.7%).

CNS infiltration at diagnosis.

 Negative.

19 (95.0%).

18 (78.3%).

 Positive.

1 (5.0%).

5 (21.7%).

Risk at diagnosis.

 Standard.

4 (20.0%).

2 (8.7%).

 High.

16 (80.0%).

21 (91.3%).

M Male, F Female, WBC White Blood-cell, CNS central nervous system. The values are expressed as means (rates) for the quantitative variables and absolute values (%) for the qualitative variables.


Table 2 . Treatment response characteristics of the patients.

MRD-positive (n = 20).

Relapse (n = 23).

Treatment response.

 Favorable.

12 (60.0%).

10 (43.5%).

 Refractory.

6 (30.0%).

8 (34.8%).

 Death.

2 (10.0%).

5 (21.7%).

Treatment response ALL-Ph + .

 Favorable.

1 (50.0%).

1 (100%).

 Refractory.

1 (50.0%).

(0.0%).

 Death.

0 (0.0%).

(0.0%).

Overall Survival.

 Alive.

16 (80.0%).

4 (17.4%).

 Death.

4 (20.0%).

19 (82.6%).

 Overall survival (days).

537.

(187–1000).

648.

(168–1000).

The values are expressed as medians (rates) for the quantitative variables and absolute values (%) for the qualitative variables.


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