Desferrioxamine Administration Post Allogeneic Stem Cell Transplantation Reduces the Relapse Risk and Improves the Disease Free Survival.
Authors: Kaloyannidis Panayotis , Yannaki Evangelia , Mpitzioni Aikaterini , Batsis Ioannis , Mallouri Despina , Bartzoudis Dimitrios , Sakellari Ioanna , Anagnostopoulos Achilles 
Published: October 2019

Abstract
Relapsed disease following allogeneic stem cell transplantation (alloTx) still remains an unresolved problem, highlighting the necessity to investigate innovative strategies that are more effective and less toxic in order to reduce relapse incidence (RI). Desferrioxamine (DFO) is the most well known chelator that has been shown to exhibit antiproliferative activities against aggressive tumors by affecting fundamental pathways in DNA synthesis, cell differentiation and cell apoptosis. Although previous clinical observations demonstrated that DFO has exhibits antileukemic activity there are no data so far with respect to its role in relapse prevention. Since 2000, according to our policy, we administer DFO in all patients (pts) with stable engraftment, serum ferritin levels >2000ng/ml plus elevated liver enzymes and in the absence of infection. This approach was based on our previous study demonstrating that treatment with DFO resulted in better liver function in allografted pts with elevated serum ferritin and liver haemosiderosis. In this retrospective study we evaluated the effect of DFO administration as well as of iron excess on RI and disease free survival (DFS) in 143 pts allografted during 2002– 07 for myeloid (n=88) or lymphoid (n=55) diseases. Patients transplanted for multiple myeloma, chronic lymphocytic leukaemia, low grade lymphomas and Hodgkin’s disease were excluded from the study as the above entities do not represent rapidly proliferating malignancies. We also excluded pts who did not achieve complete remission (CR) post alloTx or relapsed before DFO administration and pts who received DFO beyond 12 months post alloTx if they remained in continuous CR as they were in lower risk for relapse. Thirty nine pts transplanted for advanced disease while 144 in earlier disease phase. Eighteen were conditioned with a non-myeloablative and 125 with a myeloablative regimen. The graft either blood (n=135) or marrow (n=8) originated from 106 siblings, 30 from matched unrelated and 7 from haploidendical donors. As GvHD prophylaxis calcineurin inhibitors plus methotrexate were used. Thirty-seven pts were treated with DFO (SC or IV at 0,5 g/kg for 3–5 days per week) after a median of 4,4 months following alloTx; 20 for >2 months and 17 discontinued DFO treatment within 2 months due to: 9 infection, 5 fallen ferritin values <1000ng/ml, 1 TTP/HUS, 1 relapsed disease and 1 for other reason. The 5-year RI was 5% for >2 months DFO-treated pts as opposed to 41% for those <2 months DFO-treated and 47% for non-treated pts (p=0,02). Not a single relapse event was detected in DFO-treated pts transplanted in 1stCR and RI was also lower in DFO-treated pts with advanced disease (31% vs.75%, p=0,01). Patients with chronic GvHD who received DFO had lower RI than those who did not received DFO (17% vs.39%, p=0,03). Treatment mortality was similar between DFO-treated and non-treated pts. Patients treated with DFO for >2 months achieved a 5-year DFS of 76% compared to 41% for non-treated (p=0,02). In a multivariate analysis, DFO administration >2 months retained its favorable significance while GvHD existence and early disease phase were additional favorable factors for lower RI and higher DFS rates (p<0,04). To evaluate the impact of iron excess we investigated the RI in the separate group of the 106 non-treated with DFO pts. Serum ferritin values >3000 ng/ml were associated with higher RI (55% vs. 41%, p=0,04) but in multivariate analysis this finding did not retain its significance. Although retrospective, to our knowledge, this is the first clinical study investigating the role of DFO in relapse incidence. Prospective trials are needed to clarify if DFO administration would clearly have a role in relapse prevention.