Evaluation of Safety and Efficacy of Different Stem Cell Mobilization Regimens in 110 Patients with Light Chain Amyloidosis

Abstract

Introduction: High-dose melphalan (HDM) with autologous hematopoietic stem cell transplantation (SCT) is an effective treatment for patients (pts) with systemic light chain (AL) amyloidosis. Most centers use granulocyte colony-stimulating factor (G-CSF) alone for mobilization of peripheral blood stem cells. The application of mobilization chemotherapy (MC) together with G-CSF might have some advantages, e.g. a higher amount of collected SC and the reduction of the plasma cell load prior to HDM therapy. We have retrospectively analyzed all pts with AL amyloidosis admitted to our centre who received SC mobilization until 2007.Patients and methods: 110 pts received mobilization therapy. Median age was 56 years (range, 35–69 years). Major eligibility criteria were cardiac disease < NYHA stage III and performance status (PS) < 3. Prior to mobilization, 55 pts (50%) had been pre-treated with induction chemotherapy, including 19 pts who had received melphalan. MC was performed with a combination of cyclophosphamide (1g/m2)/adriamycin (60 mg/m2)/dexamethasone (160 mg) (CAD) in 82 pts. The remaining pts received ifosfamide (12 g/m2, Ifo, n=14) or other chemotherapies (n=7). G-CSF (5 ug/kg/day) was started on day 8 after start of MC. Mobilization with G-CSF alone (10 ug/kg/day) was performed in 11 pts (patientxs choice, pts after cardiac transplant). Patients were retrospectively analyzed regarding toxicity and efficacy of SC mobilization as well as hematological reconstitution after HDM.Results: No patient died during mobilization therapy and leukapheresis (LP). Median NCI grade of non-hematological toxicity was 2 and significantly depended of advanced age, lower Karnofsky performance scale and application of Ifo (p<0.05, Table 1). After CAD cardiac toxicity > NCI grade 3 was observed in 3 pts. Main problems of HD-ifo were worsening of kidney function in 8 pts and occurrence of encephalopathy in 7 pts. Due to AL amyloidosis progression 3 pts could not proceed to SC collection and further 5 pts with successful SC collection were not transplanted, respectively.SC mobilization was successful (> 2 × 106 CD34+/kg body weight (BW)) in 105 pts (95%), 4 pts had to be mobilized twice. The median number of collected SC was 8 × 106 CD34+/kg BW (range, 0–46) with a median LP of 1. Previous melphalan treatment and G-SCF mobilization alone were significantly associated with a reduced number of collected SC (p<0.01, Table 1).HDM with SCT was performed in 100 pts with a transplant-related mortality of 3%. Hematological reconstitution was regular: median time to ANC > 1.0/nl 13 days (range, 9–27 days), median time to platelets > 20/nl 11 days (range, 8–102 days). Of note, only one patient received G-CSF post SCT. There was a trend for faster leukocyte recovery for pts receiving more than 6,5 × 106 CD34+ cells/kg BW compared to < 3 × 106 CD34+ cells/kg BW (12 vs. 14 days, p=0.1). One year after SCT 13 pts (16% of evaluable pts) had a reduced platelet count (<150/nl) with a minimum value of 54/nl. This was associated with a lower amount of transplanted SC (p<0.05).Our results differ from those published by Gertz et al., Am J Med, 2002 regarding number of LP (median 2.5) and time to platelet engraftment (14 days).Conclusion: Our analysis shows that MC with CAD is safe and very effective in pts with AL amyloidosis. More than 95% of the CAD pts could proceed to HDM and had a fast and sustained hematological reconstitution after SCT. Due to the non-hematological toxicity Ifo administration can not be recommended. Mobilization with G-CSF alone is also effective and safe but results in lower amount of collected SC. MC with CAD as part of an intensive therapy approach including IC with new agents should be further evaluated in clinical trials. Mobilization therapy (number of pts) Median number of LP Median number of CD34+ cells/kg BW collected Median NCI grade of nonhematological toxicity G-CSF (n=11) 1 (1–2) 5 (0–11) 0 (0–3) CAD (n=82) 1 (1–5) 9 (0–37) 2 (0–4) Ifo (n=14) 1 (1–4) 19 (5–46) 3 (0–3)Mobilization therapy (number of pts)Median number of LPMedian number of CD34+ cells/kg BW collectedMedian NCI grade of non- hematological toxicityG-CSF (n=11)1 (1–2)5 (0–11)0 (0–3)CAD (n=82)1 (1–5)9 (0–37)2 (0–4)Ifo (n=14)1 (1–4)19 (5–46)3 (0–3)