Intermediate Dose Ara-C Followed by G-CSF: An Effective and Predictable Mobilization Regimen in Hematological Malignancies.
Authors: Ricci Francesca , Montillo Marco , Tedeschi Alessandra , Miqueleiz Sara , Ravelli Erika , Intropido Liliana , Scarapati Barbara , Morra Enrica 
Published: October 2019

High dose (HD) chemotherapy followed by peripheral blood stem cell (PBSC) is widely used in the management of hematological malignancies and chemosensitive solid tumors. Different strategies of PBSC mobilization have been described, but currently the standard approach has not been established. Satisfactory results have been obtained by different chemotherapy schedules followed by haemopoietic growth factors: particularly HD Cyclophosphamyde or HDAra-C have a well known high mobilizing activity. With the intention to minimize hematological toxicity due to HD chemotherapy we performed this study to evaluate the mobilizing efficacy of intermediate dose Ara-C (IDAra-C).

Methods: Pts with haematological malignancies received as mobilization treatment Ara-C 800 mg/m2 every 12 h for 6 doses followed by G-CSF 300 μg/d starting day +3 from the end of treatment until completion of leukapheresys (LP). CD34+ cells count was performed from day + 9. Failure of mobilization was defined as a persistent CD34+ cells count <10/μL. All pts reaching >10/μL CD34+ underwent LP. Pts not reaching the target of 2.5 x 106/kg CD34+ were considered as low mobilizer.

Results: 98 pts, median age 56 y (range 27–70), underwent priming with IDAra-C. Disease characteristics are listed in table 1. All but 5 pts presented bone marrow involvement at diagnosis. Sixty-nine pts had previously received fludarabine, 56 anthracyclines and 30 alkilating agents. Thirty-three of the 98 pts had been considered low mobilizer or had failed a previous mobilization attempt, with HDAra-C in 20 cases A successful mobilization (threshold level >2.5 x 106/kg CD34+) was obtained in 73 pts (74,5%) (9/14 NHL, 42/43 CLL, 6/7 MM, 16/34 AML) with a median collection of 12,34 x 106/kg CD34+ (range 2,57–76,5). The peak value of CD34+ cells in the peripheral blood was achieved after a median of 13 d (range 10–19) from the end of therapy and a median of 1 LP (range 1–3) was required for a target collection. An adequate harvest was also observed among 17 of the 33 (51.5%) pts failing a previous mobilization attempt. After IDAra-C the median time to reach PMN >1000/μL and PLT >50000/μL was of 6 and 8 days respectively. There were no treatment-related deaths. During neutropenia we recorded 25 episodes of FUO, 9 infections microbiologically documented and 2 infections clinically documented. Median days temperature > 38°C was 2 (range 1–6). Extraematological toxicity consisted of: 1 gastrointestinal bleeding WHO III and 1 episode of atrial fibrillation. Overall 39 pts have been transplanted so far; median days for PMN >500/μL and PLT >50000/μL engraftment was of 9 and 12 d respectively. In conclusion IDAra-C and sequential G-CSF allowed predictable and efficient PBSC harvest in a limited number of leukapheresis session. Hematological recovery was rapid and toxicity manageable. These data confirm, in a larger series, the high mobilization activity of IDAra-C in CLL as previously reported. Moreover satisfactory efficacy has been observed in pts failing previous mobilization attempt with alternative regimen. This approach should be considered as an effective way to exploit a known mobilizing activity of Ara-C minimizing toxicity.

Table 1 Disease characteristics AML NHL CLL MM ToT CR 32 3 35 3 73 CR > 1 2 3 − − 5 PR − 2 − 2 4 nPR − − 6 − 6 SD − 1 1 2 4 PD/RELAPSE − 5 1 − 6 Tot 34 14 43 7 98 median time from last treatment (months) 2,0 2,3 4,3 2,6 3,4