1.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 PEÑAFIEL ; Daniela Pérez SÁMANO ; Adán Germán Gallardo RODRÍGUEZ ; Camila Terreros PALACIO ; Irma Olarte CARRILLO ; Carlos Martínez MURILLO ; Gilberto Barranco LAMPÓN ; Álvaro Cabrera GARCÍA ; Adolfo Martínez TOVAR
Blood Research 2025;60():4-
Purpose:
Despite 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.
Methods:
This 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.
Results:
Of 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.
Conclusion
The 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.
2.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 PEÑAFIEL ; Daniela Pérez SÁMANO ; Adán Germán Gallardo RODRÍGUEZ ; Camila Terreros PALACIO ; Irma Olarte CARRILLO ; Carlos Martínez MURILLO ; Gilberto Barranco LAMPÓN ; Álvaro Cabrera GARCÍA ; Adolfo Martínez TOVAR
Blood Research 2025;60():4-
Purpose:
Despite 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.
Methods:
This 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.
Results:
Of 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.
Conclusion
The 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.
3.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 PEÑAFIEL ; Daniela Pérez SÁMANO ; Adán Germán Gallardo RODRÍGUEZ ; Camila Terreros PALACIO ; Irma Olarte CARRILLO ; Carlos Martínez MURILLO ; Gilberto Barranco LAMPÓN ; Álvaro Cabrera GARCÍA ; Adolfo Martínez TOVAR
Blood Research 2025;60():4-
Purpose:
Despite 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.
Methods:
This 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.
Results:
Of 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.
Conclusion
The 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.
4.Abnormal expression of H-Ras induces S-phase arrest and mitotic catastrophe in human T-lymphocyte leukemia
Jorge Antonio ZAMORA DOMINGUEZ ; Irma Olarte CARRILLO ; Rubén Ruiz RAMOS ; Christian Omar RAMOS-PEÑAFIEL ; Luis Jiménez ZAMUDIO ; Ethel García LATORRE ; Federico Centeno CRUZ ; Adolfo Martínez TOVAR
Blood Research 2023;58(1):20-27
Background:
Leukemia is a neoplasm with high incidence and mortality rates. Mitotic death has been observed in tumor cells treated with chemotherapeutic agents. Ras family proteins participate in the transduction of signals involved in different processes, such as proliferation, differentiation, survival, and paradoxically, initiation of cell death.
Methods:
This study investigated the effect of H-Ras expression on human T-cell acute lymphoblastic leukemia MOLT-4 cells. Cells were electroporated with either wild-type (Ras wt ) or oncogenic mutant in codon 12 exon 1 (Ras mut ) versions of H-Ras gene and stained for morphological analysis. Cell viability was assessed using trypan blue staining and cell cycle analysis using flow cytometry. H-Ras gene expression was determined using quantitative real-time reverse transcription polymerase chain reaction. The t, ANOVA, and Scheffe tests were used for statistical analysis.
Results:
Human T-cell acute lymphoblastic leukemia MOLT-4 cells showed nuclear fragmentation and presence of multiple nuclei and micronuclei after transfection with either wt or mutant H-Ras genes. Cell cycle analysis revealed a statistically significant increase in cells in the S phase when transfected with either wt (83.67%, P<0.0005) or mutated (81.79%, P<0.0001) H-Ras genes. Although similar effects for both versions of H-Ras were found, cells transfected with the mutated version died at 120 h of mitotic catastrophe.
Conclusion
Transfection of human T-cell acute lymphoblastic leukemia MOLT-4 cells with either normal or mutated H-Ras genes induced alterations in morphology, arrest in the S phase, and death by mitotic catastrophe.