High-dose ara-C with autologous peripheral blood progenitor cell support induces a marked progenitor cell mobilization:: an indication for patients at risk for low mobilization

A high-dose (HD) chemotherapy scheme was designed for the collection of large numbers of peripheral blood progenitor cells (PBPC) in lymphoma patients who were candidates for myeloablative therapy with autograft. The scheme included the sequential administration of HD cyclophosphamide (CY) (7 g/m(2)) and HD ara-C (2 g/m(2) twice a day for 6 consecutive days), followed by final consolidation with PBPC autograft. PBPC harvests were scheduled following both HD CY and HD ara-C. To minimize hematologic toxicity, small aliquots of PBPC (less than or equal to3 X 10(6) CD34(+) cells/kg) collected following HD CY were reinfused following HD ara-C. The treatment was delivered to 112 patients (median age: 43 years) with lymphoid malignancies (107 non-Hodgkin's lymphoma, four Hodgkin's lymphoma, one amyloidosis); 75 patients were at disease onset, whereas 37 had relapsed or were refractory after first-line conventional therapy. PBPC mobilization was assessed in terms of peak values of circulating CD34(+) cells/mul, as well as total CD34(+) cells/kg collected. In a few patients CFU-GM/kg were also evaluated. At the time of maximal mobilization following HD CY, 93 'high-mobilizer' patients had >20 circulating CD34(+) cells/mul, whereas the remaining 19 'low-mobilizer' patients did not reach this cut-off value. In spite of poor mobilization after HD CY, 16 out of 19 low mobilizers provided good harvests following HD ara-C; overall, median collected CD34(+) cells X 10(6)/kg were 1.4 (0-3.1) and 10.2 (0-37) after HD CY and HD ara-C, respectively (P = 0.00007). Similar patterns were observed when PBPC were evaluated by CFU-GM/kg. Complete and durable hemopoietic reconstitution followed autograft with post HD ara-C PBPC. Within the high-mobilizer group, 88 patients received HD ara-C and 79 (90%) still showed high mobilization; overall, median collected CD34(+) cells x 10(6)/kg were 17.8 (range 3-94) and 19 (range 0-107) after HD CY and HD ara-C respectively (P = NS). Thus, the scheme allowed sufficient PBPC collections for autografting in low mobilizer patients; in addition, the scheme could be considered whenever extensive chemotherapy debulking is needed prior to PBPC collection.