Background: Patients with high-risk acute leukemia have a high risk of relapse after allogeneic stem cell transplantation (allo-SCT). In an effort to reduce the relapse rate, various therapeutic methods have been implemented into clinical practice. Among them, prophylactic donor lymphocyte infusion (pro-DLI) has shown significant efficacy. However, the widespread application of pro-DLI has been restricted mostly due to concerns regarding the development of graft versus host disease (GVHD). In the present study, we tested the safety and efficacy of a novel method of prophylactic-DLI based by repetitive administration of low lymphocyte doses. Methods: DLI was administered to patients with high-risk acute leukemia at a dose of 2 × 106/kg CD3-positive cells. DLI at the same dose was repeated every two months for at least 36 months post-allo-SCT, or until relapse or any clinical or laboratory feature suggested GVHD, whichever occurred first. Forty-four patients with a median age of 53 years (range 20–67) who underwent allo-SCT between 2011 and 2020 were included in our study. Thirty-three patients with high-risk acute myeloid leukemia (AML) and 11 with high-risk acute lymphoblastic leukemia (ALL) after allo-SCT from a matched sibling (MSD, no = 38 pts) or a matched-unrelated donor (MUD, no = 6 pts) received pro-DLI. Twenty-three patients were in CR1, all with unfavorable genetic features; 12 patients were in CR2 or beyond; and 9 patients had refractory disease at the time of transplant. Ten out of 23 patients in CR1 had detectable minimal residual disease (MRD) at the time of allo-SCT. Disease risk index (DRI) was high and intermediate in 21 and 23 patients, respectively. Conditioning was myeloablative (MAC) in 36 and reduced intensity (RIC) in 8 patients, while GVHD prophylaxis consisted of cyclosporine-A in combination with low-dose alemtuzumab in 39 patients or with low-dose MTX in 5 patients, respectively. Results: Thirty-five patients completed the scheduled treatment and received a median of 8 DLI doses (range 1–35). Fifteen out of 35 patients received all planned doses, while DLI was discontinued in 20 patients. Reasons for discontinuation included GVHD development in nine, donor unavailability in seven, disease relapse in three, and secondary malignancy in one patient, respectively. Nine patients were still on treatment with DLI, and they received a median of four (range 2–12) doses. Fourteen percent of patients developed transient grade-II acute GVHD while 12% developed chronic GVHD post-DLI administration. Acute GVHD was managed successfully with short course steroids, and four out of five patients with cGVHD were disease-free and off immunosuppression. With a median follow-up of 44 months (range 8–120), relapse-free (RFS) and overall survival (OS) were 74%, (95% CI, 54–87%) and 78%, (95% CI, 58–89%) respectively, while the cumulative incidence of non-relapse mortality (NRM) was 13% (95% CI, 4–28%). The cumulative incidence of relapse in patients with intermediate and high DRI is 7% and 15%, respectively. Conclusion: Prolonged—up to three years—low-dose pro-DLI administered every two months is safe and effective in reducing relapse rate in patients with high-risk acute leukemia. The low-dose repetitive administration DLI strategy reduced the risk of DLI-mediated GVHD, while the prolonged repeated administration helped in preventing relapse, possibly by inducing a sustained and prolonged immunological pressure on residual leukemic cells. This novel strategy deserves testing in larger cohort of patients with high-risk acute leukemia.
BACKGROUND The presence of pharmaceutical residues in the aquatic environment is an emerging issue due to their uncontrolled release and accumulation in the environment that may affect living organisms, ecosystems and public health. As a result, efforts are being made to develop methods to inactivate or eliminate this class of substance in the environment. RESULTS The homogeneous photocatalytic degradation of sulfamethazine (SMT), a sulfanilamide drug, has been investigated in aqueous solutions using artificial and solar illumination. The effects of initial concentration of H2O2 (10–400 mg L‐1), Fe3+ (3.5–28 mg L‐1), SMT (10–40 mg L‐1), as well as temperature (280–323 K) on mineralization rates were evaluated in a bench‐scale Pyrex reactor for the photo‐Fenton/UV‐A and photo‐Fenton/Vis processes. SMT degradation was accompanied by the release of inorganic nitrogen and sulphate ions. Experiments under natural sunlight conditions were performed in a pilot‐scale, fountain reactor at light intensities between 0.49 and 2.83 mW cm‐2. CONCLUSIONS An increase in the level of the parameters had a positive effect, with photo‐Fenton/UV‐A (at 0.94 × 10−4 einstein L−1 min−1 light flux provided by a 9 W lamp at 366 nm maximum response) being more effective than photo‐Fenton/Vis (at 0.88 × 10−4 einstein L−1 min−1 also provided by a 9 W lamp at 440 nm maximum response). Illumination for 120 min in the case of the pilot‐scale reactor at 2 mW cm‐2 intensity led to more than 70% mineralization of 20 mg L‐1 SMT, thus showing that process scale‐up is feasible. © 2013 Society of Chemical Industry
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