A Prospective Randomized Multi-Center Study of High-Dose vs Low-Dose Cyclophosphamide in Combination with Lenograstim for Peripheral Blood Progenitor Cell Mobilization

초록

Although few randomized trials comparing mobilizing approaches have been reported and the best is not known, high-dose cyclophosphamide (CTX; 3-7 g/m2 ) is most commonly reported protocol. But the main limitations at this dosage are neutropenic sepsis and bleeding associated with myelosuppression. Another emerging impression is that adequate mobilization may occur with low-dose CTX (1-2 g/m2 ) with less morbidity. To compare the mobilizing effects and toxicities of two different doses of CTX plus lenograstim (glycosylated G-CSF), we performed a prospective randomized study in patients with hig-risk NHL and breast cancer requiring ablative chemotherapy. NHL patients received 4 cycles of CHOP chemotherapy and breast cancer patients 2-3 cycles of FAC (or FEC) adjuvant chemotherapy before mobilization. Then, patients were randomly allocated to receive 4 g/m2 CTX (Arm A) or 1.5 g/m2 (Arm B) in combination with lenograstim (250 mg/d). CD34+ cell and CFU-GM in peripheral blood and apheresis products were measured. Large volume leukapheresis was done and continued daily until the target cell dose of 2 x 106 CD34+ cell/kg was reached. After high dose chemotherapy, peripheral blood progenitor cells were reinfused and hematological recovery was evaluated. Twenty-two patients were enrolled until Jyly 2001. Grade III-IV hematological toxicities were 100% in arm A and 10% in arm B during mobilization period. Alothough the median number of leukapheresis actually performed was 2.5 in arm A and 3 in arm B, the target cell dose was obtained with the median number of one leukapheresis in both arms. The number of CD34+ cells and CFU-GM in the first 2 leukaphereses was higher in arm A (18.7 vs 12.3 x 106 /kg; n=7 vs 7; p=0.097 and 6.6 vs 5.8 x 105 /kg; n=8 vs 10; p= 0.99, additional data will be included). The hematological recovery of leukocytes and platelets after transplantation was not statistically different between two arms. In conclusion, low-dose CTX, in comparison with high-dos