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Factors affecting survival in acute leukemia with donor lymphocyte infusion in the first relapse after allogeneic stem cell transplantation
Abstract
Purpose: Relapse of leukemia relapsing after allogeneic (allo) stem cell transplantation (SCT) remains an important problem. Cytoreductive chemotherapy followed by donor leukocyte infusion (DLI) is one of the treatment modalities in relapsed patients. The current study evaluated the factors affecting overall survival (OS) in allo-SCT patients who received DLI after the first relapse. Methods: In this retrospective study 54 patients (26 with acute myeloid leukemia [AML] and 28 with acute lymphoblastic leukemia [ALL]) in their first relapse after allo-SCT who received fludarabine-based chemotherapy followed by DLI were evaluated. Results: The relative risk for mortality was significantly higher in patients with acute leukemia (AL) within the highrisk group who went through transplantation (risk ratio: 4.866; 95% CI: 2.029-11.670;p<0.001) and in transplants performed in the remission phases following the first complete remission (risk ratio: 2.371; 95% CI: 1.154 - 4.872; p=0.019). Additionally, the relative mortality risk of transplantation in patients with acute leukemia (AL) with a number of DLIs applied (risk ratio: 0.456; 95% CI: 0.29 0.717; p=0.001) and non-myeloablative regimen (risk ratio: 0.229; 95% CI: 0.053-0.992; p=0.049) was significantly lower. Conclusion: Efforts to enhance the number of DLIs, thus the number of infused cells, may result in better OS in cases with AL with relapse.
The therapeutic approach for relapsed/refractory acute lymphoblastic leukemia (ALL) remains to be a challenge. The patient was diagnosed as B-cell ALL at 6 months of age and relapsed for the second time following repeat allogeneic hematopoietic stem cell transplantation (one after first complete remission [CR1] and the other after CR2). During blinatumomab monotherapy, he developed an extramedullary relapse. Finally, the combined therapy with clofarabine, donor lymphocyte infusion, and blinatumomab induced CR of the bone marrow and extramedullary relapse. Unfortunately, the patient developed central nervous system relapse, however, this case showed a promising potential for combination therapy with clofarabine, donor lymphocyte infusion, and blinatumomab in relapsed/refractory B-cell ALL.
Background
Finding the most appropriate regression model for survival data in cancer casesin order to determine prognosis is an important issue in medical research. Here we compare Cox and parametric regression models regarding survival of children with acute leukemia in southern Iran.
Methods
In a retrospective cohort study, information for 197 children with acute leukemia over 6 years was collected through observation and interviews. In order to identify factors affecting their survival, the Cox and parametric (exponential, Weibull, log-logistic, log-normal, Gompertz and generalized gamma) models were fitted to the data. To find the best predictor model, the Akaike’s information criterion (AIC) and the Coxsnell residual were employed.
Results
Out of 197 children, 164 (83.3%) had ALL and 33 (16.7%) AML; the mean (± standard deviation) survival time was 52.1±8.10 months. According to both the AIC and the Coxsnell residual, the Cox regression model was the weakest and the log-normal and Weibull models were the best for fitting to data. Based on the log-normal model, age (HR=1.01, p=0.004), residence area (HR=1.60, p=0.038) and WBC (White Blood Cell) (HR=1.57, p=0.014) had significant effects on patient survival.
Conclusion
Parametric regression models demonstrate better performance as compared to the Cox model for identifying risk factors for prognosis with acute leukemia data. Just because the assumption of PH (Proportional Hazards) is held for the Cox regression model, we should not ignore parameter models.
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