The Efficacy and Safety of VP-16 and G-CSF as a Mobilization Regimen Prior to Autologous Stem Cell Transplantation (ASCT) for Patients (Pts) with Multiple Myeloma (MM) and Lymphoma.

Although the number of ASCTs performed for myeloma and lymphoma continues to increase, there remains little consensus about the best means for mobilizing stem cells prior to transplantation and whether cytokine alone or cytokine plus chemotherapy is preferred. Cytokine alone, usually G-CSF, provides easy scheduling while the combination approaches generally provide higher cell yields and additional cytoreduction. Because of its value as a cytoreductive agent, and its lack of stem cell damaging properties or other toxicities such as hemorrhagic cystitis or significant liver toxicity, we investigated the use of mid-dose VP-16 plus G-CSF as a mobilizing regimen. Here, we report our experience with this regimen prior to ASCT for pts with various diseases.

Between May 2004 and June 2009, 296 pts with the following diseases underwent autologous stem cell transplantation following the use of VP-16 (375mg/m² on D#1 and D#2) and G-CSF (5mcg/kg twice daily from D#3 through the final day of collection) for mobilization: Multiple Myeloma (152), Non-Hodgkin Lymphoma (98), Hodgkin Disease (38), Acute Promyeloyctic Leukemia (4), Acute Myelogenous Leukemia (1), Chronic Lymphocytic Leukemia (1), Plasma Cell Leukemia (1), and testicular cancer (1). In 14 pts, one dose of Rituximab (375mg/m²) was also given on D#1. 125 pts were female, 171 were male, and median age at the time of transplant was 55 years (range 19-79). Stem cell collection was initiated when the peripheral blood CD34 cell count was more than 7 per microliter. The target total CD34 cell collection was 5 × 10⁶ cells.

Among all pts, 286 (97%) had stem cells successfully collected after one mobilization. An additional 7 (2%) pts required more than one mobilization or bone marrow harvest, with one pt experiencing progressive disease after failed mobilization. 117 (40%) pts required either treatment for infection (inpatient hospitalization and/or intravenous antibiotics; 14% of all pts) or at least one supportive transfusion with PRBCs or platelets (33% of all pts). 1 pt is known to have developed secondary myelodysplastic syndrome, and there are no known cases of secondary AML. The median number of days collecting stem cells was 1 for MM pts and 2 for lymphoma pts, and the median total number of CD34 cells collected was 12 × 10⁶ for MM pts and 6 × 10⁶ for lymphoma pts. 94% of MM pts and 43% of lymphoma pts collected in a single day. The median time to neutrophil engraftment was 11 days for both MM and lymphoma pts, and the median time to a sustained platelet count > 20,000 without transfusions was 16 days for MM pts and 15 days for lymphoma pts. “Poor mobilizers” were defined as pts who failed to collect 5 × 10⁶ cells in one or two days, and included 19% of all pts. 1% of MM pts and 40% of lymphoma pts were “poor mobilizers,” a statistically significant difference (p<0.001). 6 lymphoma pts failed to collect at least 2 × 10⁶ cells, though all MM pts achieved this minimum target. The pre-mobilization white blood count (p=0.01) and platelet count (p=0.006) were associated with poor mobilization in lymphoma pts by univariable logistic regression analysis. Pts requiring more than 14 days to engraft neutrophils or 27 days to engraft platelets (> 1 S.D. above the mean) were considered “poor engrafters,” and included 16 pts (6%). We failed to detect statistically significant associations between “poor engrafters” (n=6 for lymphoma, n=10 for MM) and the covariates of “poor mobilizers,” age, disease type, amount and type of prior chemotherapy, radiation therapy, marrow cellularity or disease involvement, or the pre-mobilization complete blood count.

VP-16 and G-CSF is an effective and safe mobilization regimen for pts undergoing ASCT with a low incidence of requiring hospitalization and/or IV antibiotics for fever, or of association with subsequent myelodysplasia or secondary AML. A diagnosis of lymphoma (HD or NHL) as opposed to MM, and low platelet or WBC count pre-mobilization predicted for poor CD34 cell yield. Further research is needed to help predict “poor mobilizers” and “poor engrafters” prior to transplant, as are the use of novel agents, such as the CXCR4 antagonist plerixafor, to improve outcomes in these populations.

Shea:Genzyme, Millenium, Otsuka: Research Funding; Board of Directors, CALGB; CIBMTR Scientific Advisors, President-elect: Membership on an entity's Board of Directors or advisory committees; Genzyme, Genentech, Novartis: Consultancy.