Phase 2 study of intensified chemotherapy and allogeneic hematopoietic stem cell transplantation for older patients with acute lymphoblastic leukemia.

BACKGROUND: Outcomes among older patients with acute lymphoblastic leukemia remain poor. This study sought to determine the efficacy of an intensified, multi-agent approach derived from a Dana-Farber consortium trial in younger adults for patients older than 50 years (trial identifier NCT00973752). METHODS: The primary endpoint was overall survival (OS) at 1 year. Patients received induction chemotherapy with vincristine, prednisone, doxorubicin, and pegylated asparaginase. Imatinib was incorporated for Philadelphia chromosome-positive disease. After induction, the first consolidation incorporated clofarabine. Patients in remission could proceed to allogeneic hematopoietic cell transplantation (HCT) after induction and consolidation I. Those not receiving HCT went on to receive central nervous system, consolidation II, and continuation phases of treatment. RESULTS: Thirty patients were enrolled: 19 achieved a complete remission (CR) after induction and 1 achieved CR after consolidation I for a CR rate of 67%. Sixteen patients underwent HCT. The proportion surviving at 1 year was 63%, and this met the primary endpoint. The 2-year OS rate was 52% (n = 30), and the 2-year disease-free survival rate was 52% for patients achieving CR (n = 20). There was no survival advantage among those undergoing HCT. Therapy-related hyperbilirubinemia prompted adjustments and limitations to asparaginase dosing. CONCLUSIONS: Intensified chemotherapy can result in improved outcomes in comparison with historical data. Additional studies of similarly intensive regimens are warranted in this population. Cancer 2016;122:2379-2388. © 2016 American Cancer Society.

The impact of involved field radiation therapy in the treatment of relapsed or refractory non-Hodgkin lymphoma with high-dose chemotherapy followed by hematopoietic progenitor cell transplant.

BACKGROUND: Patients with refractory/relapsed non-Hodgkin lymphoma (NHL) often receive high-dose chemotherapy (HDCT) followed by hematopoietic progenitor cell transplant (HPCT) as salvage therapy. We examined the role of involved field radiation therapy (IFRT) in this setting. METHODS: The records of 167 patients with refractory/relapsed NHL who underwent HDCT followed by HPCT between February 1990 and November 2003 were reviewed. Fifty-three patients received IFRT and 114 did not receive IFRT in the peritransplant period. RESULTS: Eighty patients were alive at the time of analysis with a median follow up for alive patients of 4.5 years in the no IFRT group and 4.2 years in the IFRT group (P = 0.53). Patients undergoing IFRT were more likely to have bulky (P = 0.02) and extranodal (P= 0.04) disease at initial diagnosis. There was no significant difference between the treatment groups regarding mortality in the first 100 days after HPCT (P = 0.31). Five-year overall survival rates were 46.7% for the no IFRT group and 40.0% for the IFRT group (P= 0.15). Disease-free survival was significantly worse for patients receiving IFRT (P = 0.02); however, when considering local control, the addition of IFRT resulted in a 5-year rate similar to that for patients who did not receive IFRT (68.6% vs. 72.0% respectively, P= 0.73). CONCLUSIONS: Although disease-free survival was inferior in patients who received IFRT, despite more adverse clinical features the use of IFRT resulted in similar rates of local control and overall survival compared with those who did not receive IFRT. The use of IFRT was not associated with an increase in the risk of acute mortality or late events.

The impact of involved field radiation therapy for patients receiving high-dose chemotherapy followed by hematopoietic progenitor cell transplant for the treatment of relapsed or refractory Hodgkin disease.

OBJECTIVES: Patients with refractory/relapsed Hodgkin disease (HD) often receive high-dose chemotherapy (HDCT) followed by hematopoietic progenitor cell transplant (HPCT) as salvage therapy. This study sought to determine if involved field radiation therapy (IFRT) in this setting improves patient outcomes. METHODS: The records of 65 patients with refractory/relapsed HD who underwent HDCT followed by HPCT between September 1988 and October 2003 were retrospectively reviewed. Forty-four patients did not receive IFRT and 21 received IFRT. RESULTS: Thirty-eight patients were alive at the time of analysis with a median follow-up of 3.4 years in the no IFRT group and 1.8 years in the IFRT group (P = 0.38). IFRT patients were more likely to have bulky disease at initial diagnosis (P = 0.05). Progression-free survival (PFS) was similar in the 2 groups (P = 0.83). Twenty-two patients in the no IFRT group and 5 in the IFRT group have died (P = 0.06). Five-year overall survival rates were 55.6% for the no IFRT group and 73.3% for the IFRT group (P = 0.16). There was no significant difference between the treatment groups regarding mortality in the first 100 days after HPCT (P = 0.41), late events (P = 0.26), or failure in sites previously involved with disease (P = 0.76). CONCLUSIONS: Although the current study did not demonstrate an improvement in PFS with the addition of IFRT to HDCT and HPCT, there was a trend toward improved overall survival. The potential benefit of IFRT may be underestimated because of the heterogeneity of the treatment groups. The use of IFRT was not associated with an increase in the risk of acute mortality or late events.