Shawnda Tench

Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilization without an increased risk of secondary myelodysplasia and leukemia

The use of etoposide (VP-16) for stem cell mobilization has been reported as a significant risk factor for the development of therapy-related myelodysplasia/therapy-related AML (tMDS/tAML) after transplantation. We compared the safety and effectiveness of VP-16+G-CSF (VP+G) to G-CSF alone for PBPC mobilization in patients with non-Hodgkins lymphoma and Hodgkins lymphoma who underwent autologous transplantation at the Cleveland Clinic and Ohio State University. In the VP+G group, median total CD34+ cells collected were 9.34 × 106 per kg (range 0.97–180.89), with 42% of all patients having adequate (2 × 106 cells per kg) CD 34+ collection after 2 days of apheresis compared with a median in the G-CSF group of 3.83 × 106 per kg (range, 0.72–50.38), with only 16% patients having adequate collection after 2 days (P<0.001). tMDS/tAML occurred in 15 patients (2.3%) in the VP+G and in 12 patients (3.8%) receiving G-CSF alone. (P=0.62). Increased number of days of apheresis was associated with the risk of tMDS/tAML (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08–1.30, P<0.001). Priming regimen was not a significant variable for relapse-free survival or OS. The addition of etoposide significantly improves the effectiveness of mobilization at the cost of an increased incidence of neutropenic fever though with no mortalities. There is no evidence of increased incidence of tMDS/tAML in patients receiving VP+G compared with those mobilized with G-CSF alone.

Treatment with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone combined with cytarabine and methotrexate results in poor mobilization of peripheral blood stem cells in patients with mantle cell lymphoma.

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone combined with cytarabine and methotrexate) is an intense chemotherapy regimen frequently used for hematologic malignancies including mantle cell lymphoma. To address whether treatment with hyper-CVAD impairs mobilization of peripheral blood stem cells, we retrospectively analyzed mobilization data from 77 consecutive adult patients with mantle cell lymphoma who underwent peripheral blood stem cell (PBSC) mobilization for planned autologous stem cell transplant (ASCT). Compared to patients treated with alternative regimens, patients treated with hyper-CVAD collected fewer CD34+ cells, required more total days of pheresis, and more frequently required a second mobilization attempt, despite being more likely to have undergone mobilization with a VP16-containing regimen. In multivariable linear regression analysis, treatment with hyper-CVAD was associated with a significant reduction in total CD34+ cells mobilized (p < 0.001). These findings suggest that alternative mobilizing strategies prior to ASCT are needed for patients with mantle cell lymphoma who have received hyper-CVAD.

The non-relapse mortality rate for patients with diffuse large B-cell lymphoma is greater than relapse mortality 8 years after autologous stem cell transplantation and is significantly higher than mortality rates of population controls

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL). To assess long‐term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non‐relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P < 0·001], as did those who were relapsed or refractory (HR 4·9, P < 0·001). We describe the longest reported follow‐up of a large cohort of DLBCL patients uniformly‐treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time.

Apheresis days required for harvesting CD34+ cells predicts hematopoietic recovery and survival following autologous transplantation

We sought to determine whether patients requiring more aphereses to obtain adequate numbers of CD34+ cells had delayed hematopoietic recovery following autologous transplantation. We identified 496 consecutive individuals with lymphoma who underwent hematopoietic stem cell mobilization using etoposide and G-CSF and first autologous transplantation. In multivariate analysis, increased apheresis days as a continuous and as a categorical variable at ⩾5/<5 days significantly predicted neutrophil recovery. Apheresis days fell just short of significance (P=0.06) as a predictor of platelet recovery in multivariate analysis. Increased apheresis days (as both continuous and categorical variables) were also predictive of treatment-related myelodysplastic syndrome/AML. Patients who underwent ⩾5 days of pheresis had significantly worse survival (P=0.001) than patients with less pheresis days owing to significantly higher relapse mortality (P=0.001).

Effect of post-remission chemotherapy preceding allogeneic hematopoietic cell transplant in patients with acute myeloid leukemia in first remission

Patients with acute myeloid leukemia (AML) with intermediate or high risk cytogenetics are often considered for allogeneic hematopoietic stem cell transplant (AHSCT) in first remission. Between attainment of remission and AHSCT, post-remission chemotherapy is frequently administered, though there is no evidence for its effectiveness. This study was performed to determine the impact of post-remission chemotherapy on outcome after AHSCT. A subset analysis was performed to determine whether the influence of post-remission chemotherapy might be different in those with intermediate compared to high risk cytogenetics. There was no significant difference in relapse mortality (RM) (p = 0.70), non-relapse mortality (NRM) (p = 0.12), or survival (OS) (p = 0.15) between post-remission chemotherapy groups. There was no difference in RM, NRM, or OS between cytogenetic groups according to whether they received post-remission chemotherapy. No differential effect between intermediate and high risk cytogenetics was detected (RM, p = 0.80; NRM, p = 0.23; OS, p = 0.26). These data do not show a benefit of post-remission chemotherapy before AHSCT.