Feasiblity of Autologous Stem Cell Transplantation (ASCT) in Chronic Lymphocytic Leukemia (CLL) Patients Treated with Sequential Fludarabine and Campath-1H.
Authors: Tedeschi Alessandra , Cairoli Roberto , Montillo Marco , Marenco Paola , Grillo Giovanni , Rossi Valentina , Cafro Anna Maria , Intropido Liliana , Morra Enrica 
Published: October 2019

The efficacy of ASCT in pts with CLL may be compromised by the reinfusion of neoplastic cells with the autograft leading to relapse. For this reason in our Institution pts eligible for an ASCT receive Campath-1H before peripheral blood stem cell (PBSC) mobilization to perform a purging in vivo in order to minimise the contamination of the collection. We evaluate the safety and feasibility of APBSCT in fourteen CLL patients pretreated with Fludarabine (FAMP) containing regimens and subsequent Campath-1H subcutaneusly (10 mg x 3/w for 6 weeks). A FAMP containing regimen had been administered as first line treatment in 12 cases and as second line in 2 cases; median number of FAMP cycles administered was 6 (range 4–8). In all but one pts PBSC were mobilized with Ara-C (800mg/m2/12h x 3 d) followed by G-CSF while the last pt received only G-CSF. Median age at transplant was 57.5 y (range 45–63); all pts were in CR, 9 pts showing a polyclonal rearrangement of the IgH at PCR by consensus primer. Conditioning regimen consisted of 12 Gy TBI plus cyclophosphamide 120 mg/kg in 9 pts aged < 60 y, Melphalan 180 mg/sqm in the 5 pts aged > than 60 y. Median number of CD34+ cells reinfused was 17.1 x106/kg (range3.4–30.4), the reinfused product was polyclonal for the IgH in 9 cases. The median time for PMN (> 500/μl) and PLT (> 20000/μl) recovery was 9 (range 8–10) and 11 (range 9–13) days respectively. During marrow aplasia nine pts experienced an episode of fever > 38°C with a median duration of 2 days (1–8); in three pts the cause of fever remained of unknown origin while in the remaining 6 cases a sepsis due to Staphilococcus Aureus was recorded. Intravenous antibiotics were administered in 7 cases; none of the pts required intravenous antifungal therapy. No grade 3–4 extrahematological toxicity and no treatment related deaths were observed. During the 3 months post transplant period two pts required hospitalisation for fever in one case and for acute polineuropathy in the other case; in both cases no pathogens have been isolated. In none of the pts a CMV reactivation was recorded even in the 6 cases showing a reactivation during Campath-1H treatment. An Herpes Zooster infection was observed in 2 pts after 5 and 10 months from transplant. The recovery of CD4+ and CD8+ cells is illustrated in the followig table.

CD4 and CD8 reconstitution after ASCT

pre ASCT month +3 month +6 month +12 * * 6 pts CD4/ μl 57 91 86 174 CD8/ μl 171 310 377 540

After a median follow-up of 10 months (3–30) from transplant all pts are in CR. At the three months post-transplant evaluation, performed in 13 cases, all but one pts showed polyclonal IgH rearrangement. ASCT after sequential treatment with FAMP and Campath-1H is feasible with any evidence of increased number of major infections; a substantial number of pts achieved after transplant a polyclonal IgH rearrangement.