RESUMEN
In transplant-eligible patients who undergo upfront autologous stem cell transplant (ASCT) for multiple myeloma (MM), standard practice is to treat with six to eight cycles of induction therapy followed by high-dose chemotherapy with ASCT. A gap between the end of induction and the day of ASCT exists to allow stem cell mobilization and collection. Despite attempts to limit the length of this interval, we noticed that some patients experience interval progression (IP) of disease between the end of induction therapy and the day of ASCT. We analyzed 408 MM patients who underwent ASCT between 2011 and 2016. The median length of the interval between end of induction and ASCT was 38 days. We observed that 26% of patients in the entire cohort and 23.6% of patients who received induction with bortezomib-lenalidomide-dexamethasone (VRD) experienced IP. These patients deepened their responses with ASCT, independently of induction regimen. In the entire cohort, IP was significantly associated with shorter PFS in the univariable analysis (Hazard Ratio, HR = 1.37, P = 0.022) but not in the multivariable analysis (HR = 1.14, P = 0.44). However, analyzing only patients who received VRD as induction, progression-free survival (PFS) remained inferior in both the univariable (HR = 2.02; P = 0.002) and the multivariable analyses (HR = 1.96; P = 0.01). T cells and natural killer (NK) cells are increasingly studied targets of immunomodulatory therapy, as immune dysfunction is known to occur in patients with MM. Peripheral blood from 35 MM patients were analyzed. At time of ASCT, patients with IP had significantly increased percentages of CD3+CD8+CD57+ CD28- (P = 0.05) and CD3+CD4+LAG3+ (P = 0.0022) T-cells, as well as less CD56bright and CD56dim NK cells bearing activated markers such as CD69, NKG2D, and CD226. These data suggest that IP can impact the length of response to ASCT; therefore, further studies on the management of these patients are needed.
RESUMEN
BACKGROUND/AIM: Evaluations of efficacy of treatment modality in analyses on patients with acute myeloid leukemia (AML) often combine chemotherapy and stem cell transplantation (SCT). To account for the effect of SCT and determine the impact of chemotherapy alone, the National Cancer Data Base from 1998-2011 was analyzed. PATIENTS AND METHODS: Patients with AML from 1998-2011 aged 18-64 years were included. Chi-square analysis was used to assess the association between treatment and factors investigated. The Kaplan-Meier method was used to assess overall survival. Log-rank methods were used to determine factors significant for survival. Multivariable Cox regression analysis was used to determine the effect of chemotherapy alone, and both chemotherapy and SCT on survival while adjusting for other variables. RESULTS: A total of 34,816 patients from the National Cancer Database were eligible for this study. Eighty-four percent of patients received chemotherapy alone, 8.3% no chemotherapy or SCT, and 7.5 % received both chemotherapy and SCT. Five-year survival for patients without chemotherapy without SCT was 12%, survival for the group treated with chemotherapy alone was 37.8% and for those receiving both chemotherapy and SCT was 44.1%. Treatment with chemotherapy only and chemotherapy plus SCT had a hazard ratio for death of 0.42 and 0.35 compared to no chemotherapy or SCT. Advanced age, male sex, Black race, diagnosis prior to 2004, multiple comorbidities, Medicare insurance, Medicaid insurance, no insurance, lower income and low education level, distance less than 30 miles from treatment Center, diagnosis and treatment at same facility, were independently associated with worse survival. CONCLUSION: Survival analysis of AML in the National Cancer Database showed multiple factors to be independently associated with survival. Outcomes based on treatment suggest an improved survival when utilizing chemotherapy and SCT as the primary treatment modality.
