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Purpose@#A three-drug combination of cyclophosphamide, bortezomib, and dexamethasone (CVD) shows significant efficacy and manageable toxicity as induction therapy in patients with multiple myeloma. @*Materials and Methods@#In this phase II study, we enrolled 45 patients who achieved a very good partial response (VGPR) or partial response (PR) after autologous stem cell transplantation (ASCT) and evaluated the efficacy and toxicity of CVD consolidation. CVD consolidation comprised three cycles of cyclophosphamide 300 mg/m2 orally on days 1, 8, and 15, and bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, and 22, along with dexamethasone 20 mg orally or intravenously on days 1 and 2, 8 and 9, 15 and 16, and 22 and 23. @*Results@#At enrollment, 39 patients (86.7%) showed VGPR, and nine (13.3%) presented with PR. Nineteen patients (45.2%) achieved a complete response or better as their best response after the end of consolidation. Overall, 22 of 42 patients (52.4%) experienced an improved response status with CVD consolidation. Three-year overall survival and progression-free survival rates were 89.0% and 42.7%, respectively. The most common non-hematologic toxicities were peripheral neuropathy and infection (20.5%), with no grade ≥ 3 neuropathy observed. @*Conclusion@#These results showed that CVD consolidation therapy improved the response with reasonable toxicity in patients with residual disease after ASCT. This trial was registered with the Clinical Research Information Service, Republic of Korea (KCT0001327).
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Purpose@#Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis. @*Materials and Methods@#In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated. @*Results@#Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031). @*Conclusion@#Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.
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Total body irradiation (TBI) is included in the conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT), with unique advantages such as uniform distribution over the whole body and decreased exposure to cytotoxic chemotherapeutic agents. For individuals who lack matched sibling or matched unrelated donors, the use of haploidentical donors has been increasing despite challenges such as graft rejection and graft-versus-host disease (GVHD). Although a limited number of studies have been performed to assess the clinical role of TBI in haploidentical HSCT, TBI-based conditioning showed comparable results in terms of survival outcomes, rate of relapse, and GVHD in diverse hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. Advances in supportive care, along with recent technical improvements such as restriction of maximum tolerated dose, appropriate fractionation, and organ shielding, help to overcome diverse adverse events related to TBI. Post-transplantation cyclophosphamide was used in most studies to reduce the risk of GVHD. Additionally, it was found that post-transplantation rituximab may improve outcomes in TBI-based haploidentical HSCT, especially in patients with B-cell lymphoma. Along with the advances of techniques and strategies, the expansion of age restriction would be another important issue for TBI-based haploidentical HSCT considering the current tendency toward increasing age limitation and lack of matched donors. This review article summarizes the current use and future perspectives of TBI in haploidentical HSCT.
RESUMEN
Total body irradiation (TBI) is included in the conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT), with unique advantages such as uniform distribution over the whole body and decreased exposure to cytotoxic chemotherapeutic agents. For individuals who lack matched sibling or matched unrelated donors, the use of haploidentical donors has been increasing despite challenges such as graft rejection and graft-versus-host disease (GVHD). Although a limited number of studies have been performed to assess the clinical role of TBI in haploidentical HSCT, TBI-based conditioning showed comparable results in terms of survival outcomes, rate of relapse, and GVHD in diverse hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. Advances in supportive care, along with recent technical improvements such as restriction of maximum tolerated dose, appropriate fractionation, and organ shielding, help to overcome diverse adverse events related to TBI. Post-transplantation cyclophosphamide was used in most studies to reduce the risk of GVHD. Additionally, it was found that post-transplantation rituximab may improve outcomes in TBI-based haploidentical HSCT, especially in patients with B-cell lymphoma. Along with the advances of techniques and strategies, the expansion of age restriction would be another important issue for TBI-based haploidentical HSCT considering the current tendency toward increasing age limitation and lack of matched donors. This review article summarizes the current use and future perspectives of TBI in haploidentical HSCT.