A Double-blind, Randomized Trial to Evaluate Miltefosine and Topical Granulocyte Macrophage Colony-stimulating Factor in the Treatment of Cutaneous Leishmaniasis Caused by Leishmania braziliensis in Brazil
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021;73(7):e2465-e2469
BACKGROUND The treatment of cutaneous leishmaniasis (CL) in Brazil using pentavalent antimony (Sbv) is associated with a high rate of failure. Miltefosine has proven efficacy for CL caused by L. braziliensis, with a cure rate (CR) of 75%. A combined treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) and miltefosine could increase CR and decrease healing time. METHODS A randomized, double-blind clinical trial to evaluate the efficacy of miltefosine combined with topical GM-CSF (M + GM) vs miltefosine and placebo (M + P) vs Sbv in 133 patients with CL caused by L. braziliensis in Bahia, Brazil. RESULTS The final CR at 180 days after the initiation of treatment was 44.4% in the Sbv group, 76.6% in the M + P group (P = .003 vs Sbv), and 75.6% in the M + GM group (P = .004 vs Sbv). The median healing time for cure was 102 days for the Sbv group and 60 days for both miltefosine groups (P = .0009). During the 6-month follow-up period, 4 relapses were documented: 1 in the Sbv group, 1 in the M + P group, and 2 in the M + GM group. Mild adverse events occurred in 65% of patients from the Sbv group, 76% and 79% from the M + P and M + GM groups respectively. CONCLUSIONS Miltefosine is more effective than Sbv for the treatment of CL caused by L. braziliensis in Brazil and accelerates the healing time. Association with GM-CSF does not improve therapeutic outcome. CLINICAL TRIALS REGISTRATION NCT03023111.
Association of Miltefosine with Granulocyte and Macrophage Colony Stimulating Factor (GM-CSF) in the Treatment of Cutaneous Leishmaniasis in the Amazon Region: a randomized and controlled trial
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2020
OBJECTIVES To compare topical GM-CSF and miltefosine (G + M) versus placebo and miltefosine (P + M) or parenteral meglumine antimoniate (MA) in the treatment of 150 patients with cutaneous leishmaniasis (CL) caused by Leishmania guyanensis in the Amazon. DESIGN A randomized and double-blinded clinical trial. RESULTS At 90 days after initiation of therapy the cure rates were 66%, 58% and 52% for the groups P + M, G + M, and MA respectively (p > 0.05). Cure rates at 180 days did not differ. Healing time was similar in the 3 groups, but faster in the MA group compared to the G + M group (p = 0.04). Mild and transitory systemic adverse events were frequent in all groups (above 85%). Nausea (85%) and vomiting (39%) predominated in the miltefosine groups; arthralgia (51%) and myalgia (48%) in the MA group. One patient (group MA) stopped treatment after presenting fever, exanthema, and severe arthralgia. CONCLUSIONS Miltefosine did not present a higher cure rate than MA, and the association of GM-CSF did not improve the therapeutic response. Nevertheless, due to its less toxicity, easier administration, and a similar cure rate when compared with MA, miltefosine should remain as one of the main drugs for treating CL due to L. guyanensis. (Clinicaltrials.gov Identifier NCT03023111).
WBC alloimmunization: effects on the laboratory and clinical endpoints of therapeutic granulocyte transfusions
BACKGROUND Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in granulocyte transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily granulocyte transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously. STUDY DESIGN AND METHODS One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for granulocyte-specific antibodies using granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory. RESULTS Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the granulocyte transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of transfusion reactions (either overall or pulmonary), or posttransfusion neutrophil increments. CONCLUSION The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of granulocyte transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing granulocyte transfusions.