OBJECTIVES
Genetic rare diseases (GRDs), including chronic granulomatous disease, familial hemophagocytic lymphohistiocytosis, and congenital neutropenia, often require hematopoietic stem cell transplantation (HSCT) as the only curative option. Conventional myeloablative regimens are associated with considerable toxicity, whereas reduced-intensity regimens carry an increased risk of graft failure. To address the narrow therapeutic window of busulfan, we developed a pharmacokinetic-guided dosing strategy and evaluated it in a prospective study.
METHODS
Children with GRDs undergoing HSCT received a conditioning regimen comprising fludarabine 40 mg/m2 (days -8 to -4), anti-thymocyte globulin 2.5 mg/kg (days -4 to -2), and once-daily busulfan (days -9 to -6), with intensive pharmacokinetic monitoring and dose adjustments to achieve target exposure.
RESULTS
Twenty patients with GRDs (median age, 3.6 years) received HSCT with a targeted busulfan-based myeloablative regimen. No engraftment failure occurred. Cumulative incidences of Grade II-IV and Grade III-IV acute graft-versus-host disease and moderate-to-severe chronic graft-versus-host disease were 25%, 5%, and 23%, respectively. Ten-year overall survival, event-free survival, and transplant-related mortality rates were 90%, 90%, and 5%, respectively.
CONCLUSIONS
Pharmacokinetic-guided busulfan-fludarabine conditioning achieved reliable engraftment with acceptable toxicity in children with GRDs, supporting its use as a safe, effective HSCT conditioning strategy in vulnerable populations.
B. Kim, K. Hong, J. Choi et al.· European Journal of Haematol...· 0 citations
Purpose
Chemoimmunotherapy has improved outcomes in extensive-stage small-cell lung cancer (ES-SCLC), but its benefit in older adults remains uncertain because this population is underrepresented in clinical trials. We evaluated the real-world efficacy of first-line atezolizumab plus etoposide-carboplatin according to age in patients with ES-SCLC.
Materials and Methods
We conducted a multicenter retrospective study across seven Korean institutions and identified patients with ES-SCLC treated between 2016 and 2022 with atezolizumab plus etoposide-carboplatin or etoposide-platinum chemotherapy alone. Patients with recurrence after prior limited-stage disease or incomplete records were excluded. End points were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), assessed using Kaplan-Meier methods and Cox regression models.
Results
Among 550 identified patients, 538 were included: 247 received atezolizumab plus chemotherapy and 291 received chemotherapy alone. Overall, 111 patients (20.2%) were aged 75-80 and 57 (10.4%) were older than 80years. In the overall population, atezolizumab was associated with improved PFS (hazard ratio [HR], 0.78; 95% CI, 0.65 to 0.93; p=0.006) and OS (HR, 0.76; 95% CI, 0.63 to 0.93; p=0.006). Age-stratified analyses showed significant PFS benefit only in patients aged 70-75 (HR, 0.67; p=0.049) and significant OS benefit only in patients aged 65-70 (HR, 0.65; p=0.044). Beyond 75 years, neither PFS nor OS was significantly improved. Patients aged ≥75years also had lower ORR and more progressive or non-evaluable disease compared with <75years.
Conclusion
The clinical benefit of adding atezolizumab appears attenuated in ES-SCLC patients age 75 years or older, supporting careful selection and age-adapted treatment strategies.
Yun-Gyoo Lee, Tae-Hwan Kim, Du-Young Kang et al.· Cancer research and treatmen...· 0 citations
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