Hemopoietic Progenitor Cell Mobilization and Harvest Following an Intensive Chemotherapy Debulking in Indolent Lymphoma Patients

Abstract

An in vivo purging with intensive debulking chemotherapy prior to peripheral blood progenitor cell (PBPC) collection may reduce the risk of tumor contamination of the harvest products; however, it is usually associated with a marked reduction in PBPC mobilization. These issues have been considered while designing an adapted version of the high-dose sequential regimen for patients with lymphoid malignancies and bone marrow involvement. To reduce tumor contamination risks, PBPC collection was postponed to the end of the high-dose phase; however, in order to enhance progenitor cell mobilization, a chemotherapy-free lag period was introduced prior to the final mobilizing course. Thirty-nine patients (median age 47 years, range 26-62) with previously untreated indolent lymphoma entered this pilot study; all had advanced-stage disease, and 29 had overt marrow involvement. Sufficient numbers of PBPC to perform autograft with safety were harvested in 34 patients, with a median of 3 (range 2-5) leukaphereses. A median of 14.8 × 10 6 (range 2-51) CD34 + /kg and 32.6 × 10 4 (range 1.77-250) colony forming units-granulocyte/macrophage/kg were collected per patient. In univariate analysis, the duration of the chemotherapy-free interval prior to the final mobilizing course, i.e. > or <65 days, was the most significant variable influencing progenitor mobilization. These data suggest that extensive in vivo tumor debulking is feasible provided that a sufficient chemotherapy-free period preceding the mobilizing course is allowed in order to allow a full recovery of marrow functions.

Improving stem cell mobilization strategies: future directions

“…55 Dose-dependent decreases in potentially malignant CD19 þ cells have been noted when both CY and G-CSF are used for mobilization. 121 Although mobilization regimens that include chemotherapy have been noted to reduce the risk of tumor-contaminated cell collections in patients with MM or lymphoma, 20,30 there is considerable debate as to whether the cytoreductive effects of mobilization with CY and growth factors confer any survival benefit to the patient. Dingli et al 37 showed that the addition of CY to a G-CSF mobilization regimen did not significantly improve response rates or prolong the time to disease progression.…”

“…13,30,129 Although mobilization with chemotherapy results in successful stem cell collections in the majority of patients, obtaining adequate CD34 þ cells may be more difficult in patients with low-grade lymphoma than in most other patients who are candidates for auto-HSCT. 30,129 In addition, previous courses of chemotherapy and radiotherapy can adversely influence CD34 þ cell yields.…”

“…13,30,129 Although mobilization with chemotherapy results in successful stem cell collections in the majority of patients, obtaining adequate CD34 þ cells may be more difficult in patients with low-grade lymphoma than in most other patients who are candidates for auto-HSCT. 30,129 In addition, previous courses of chemotherapy and radiotherapy can adversely influence CD34 þ cell yields. 20,30,129 Tricot et al 13 studied 225 patients with MM; of these, 215 patients received GM-CSF 250 mg/m 2 daily plus CY for mobilization and 49 patients received G-CSF 5 mg/kg daily plus CY.…”

“…30,129 In addition, previous courses of chemotherapy and radiotherapy can adversely influence CD34 þ cell yields. 20,30,129 Tricot et al 13 studied 225 patients with MM; of these, 215 patients received GM-CSF 250 mg/m 2 daily plus CY for mobilization and 49 patients received G-CSF 5 mg/kg daily plus CY. The authors reported that the target yield of 5 Â 10 6 CD34 þ cells/kg was obtained in only 28% of patients with 424 months of previous chemotherapy, whereas 91% of patients with shorter exposures to chemotherapeutic agents achieved this target.…”

“…14,[22][23][24] Current regimens to mobilize PBSC for auto-HSCT have differing stem cell yields, safety considerations, resource utilization, and levels of contamination of the apheresis product with tumor cells. 20,[25][26][27][28][29][30] The two most common mobilization strategies today use cytokines alone or cytokines after chemotherapy (chemomobilization). Table 1 lists the agents that are approved by the United States (US) Food and Drug Administration (FDA) for stem cell mobilization and the agents that are in development or used off-label for this purpose.…”