Frequency of Invasive Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation Conditioned with Reduced BUCY2 and Antifungal Prophylaxis with Low Dose Amphotericin B

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5457-5457
Author(s):  
Flor Maria Armillas Canseco ◽  
Monica M Rivera Franco ◽  
Eucario Leon Rodriguez ◽  
Ricardo Antonio Terrazas Marin

Abstract Introduction: Invasive fungal infection (IFI) is a major cause of morbidity and mortality in patients with allogeneic stem cell transplantation (allo-SCT). One well-known risk factor for fungal infection includes bowel mucosal damage due to conditioning chemotherapy regimens. The use of reduced-intensity conditioning may favorably impact the epidemiology of IFI after allo-SCT. Data for IFI in this population are scarce. On the other hand, despite the low incidence of IFI with the use of the new antifungal drugs, the costs remain to be high and sometimes unaffordable for the patients. Objective: To analyze the frequency of invasive fungal infections in patients who underwent stem cell transplantation conditioned with reduced BUCY2, at INCMNSZ, from November 1998 to December 2014. Material and methods: A retrospective analysis was performed in 58 patients receiving reduced BUCY2 as part of their SCT conditioning regimen. Most of the patients received antifungal prophylaxis with low dose of amphotericin B (˂20 mg/day) during the neutropenia following transplant. Results: Fifty eight patients undergoing allo-SCT with conditioning regimen reduced BUCY2, from November 1998 to December 2014, were included. Patients (male, 57%) had a median age of 39 years (range 17-67). The median follow-up was 90 months. The patients had a following range of underlying diseases: myelodysplastic syndrome (n=14, 24.1%), chronic myeloid leukemia (CML, n=14, 24.1%), acute myeloid leukemia (AML, n=12, 21%), acute lymphoblastic leukemia (LLA, n=10, 17%), lymphomas (n=3, 5.2%), myelofibrosis (n=2, 3.4%), or others (n=3, 5.2%). All patients were conditioned with 12mg/kg of busulfan and 80mg/kg of cyclophosphamide. 22% of patients presented mucositis grade III-IV. 85% (50/59) of patients received fungal prophylaxis with low dose amphotericin B. Four patients (6.8%) presented IFI during the first 100 days post-transplant, and one (1.7%) presented late IFI. The mortality secondary to IFI was 5%. Transplant related mortality (TRM) was 17%. Conclusion: From the beginnings of our transplant program we have had a low incidence of IFI and low TRM, with the prophylactic use of low dose amphotericin B and the modified conditioning regimen reduced BUCY2, compared to the reported literature. The use of reduced BUCY2 and low dose amphotericin B can be cost-effective in medical centers in developing countries. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 441-445 ◽  
Author(s):  
Reuven Or ◽  
Michael Y. Shapira ◽  
Igor Resnick ◽  
Avraham Amar ◽  
Aliza Ackerstein ◽  
...  

Reduced-intensity or nonmyeloablative stem cell transplantation (NST) is designed to induce host-versus-graft tolerance by engraftment of donor stem cells. The rationale behind NST is to induce optimal graft-versus-leukemia (GVL) effects for elimination of all malignant cells by donor alloreactive immunocompetent cells as an alternative to standard high-dose myeloablative chemoradiotherapy. NST based on the use of fludarabine, low-dose busulfan, and anti–T-lymphocyte globulin (ATG) was employed in 24 patients aged 3 to 63 years with chronic myeloid leukemia (CML) in first chronic phase (CP). Graft-versus-host disease (GVHD) prophylaxis consisted of low-dose cyclosporine (CSP), in some cases with low-dose methotrexate. Early discontinuation of CSP was attempted in cases of mixed chimerism in an attempt to amplify GVL effects. All 24 patients showed rapid 3-lineage engraftment, mostly without complete aplasia; 6 patients did not require transfusion of any blood products. NST was associated with minimal procedure-related toxicity. The incidence of acute GVHD (grade I or higher) was 54%; however, this incidence increased following CSP withdrawal. After a follow-up of up to 70 months (median, 42 months), 21 of 24 patients remained alive and disease free. The GVL effects induced by donor immunocompetent lymphocytes eradicated all host hematopoietic cells, as evidenced by molecular testing. The Kaplan-Meier probability of survival and disease-free survival at 5 years is 85% ± 8% (95% confidence interval, 70%-100%). NST may successfully replace myeloablative stem cell transplantation, providing a safer, well-tolerated therapeutic option for all patients with CML in first CP with a matched donor. However, this conclusion must be tested in a prospective randomized clinical trial.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S75-S75
Author(s):  
Jeffrey W Jansen ◽  
Anupam Pande ◽  
Rizwan Romee ◽  
Steven J Lawrence ◽  
William Powderly

Abstract Background Invasive fungal infections (IFI) remain a serious complication in hematopoietic stem cell transplantation (HSCT) patients and are associated with increased costs, morbidity, and mortality. Posaconazole (PCZ) and voriconazole (VCZ) are frequently utilized as antifungal prophylaxis in this population. To date, no direct comparison between PCZ and VCZ exists for the prevention of IFI in adult HSCT patients. Methods A retrospective cohort analysis of HSCT patients aged ≥18 years who received ≥28 continuous days of primary (PPPx) or secondary (SPPx) antifungal prophylaxis with either VCZ or PCZ between February 26, 2003 and September 30, 2015 at Barnes-Jewish Hospital was conducted. Patients who received PPPx or SPPx with both VCZ and PCZ were analyzed following intention to treat of the initial agent received. Patients who received both PPPx and SPPx were included once for both PPPx and SPPx. The primary outcome of interest was development of possible, probable, or proven IFI as defined by EORTC/MSG guidelines. In the SPPx patients, development of IFI was confirmed as a distinct event from primary IFI based on manual chart review and radiographic evidence. Results Overall, there were 472 patients included; 402 in the VCZ group and 70 in the PCZ group. At baseline, patients in the PCZ group had more graft vs. host disease (GVHD) prior to prophylaxis (27.1% vs. 16.7%, P = 0.04) and were more likely to be on SPPx (60% vs. 41%, P < 0.01). There were 22 and 1 IFI events in the VCZ and PCZ groups, respectively, which corresponded to a crude incidence rate of 0.345 and 0.077 per 1000 person-days of prophylaxis. Figure 1 displays the Cox proportional hazard model which was completed in the backwards stepwise method accounting for gender, transplant type, GVHD prior to prophylaxis, disease remission, and PPPx or SPPX. The hazard ratio for development of IFI while on prophylaxis between VCZ and PCZ was 5.22 (95% CI: 0.69–39.4; P = 0.11) after controlling for PPPx or SPPx. Conclusion There was not a significant difference between rates of IFI in HSCT patients who received antifungal prophylaxis with VCZ compared with PCZ. Our data trends towards favoring PCZ but is limited by low rates of IFI. Larger, prospective analyses are necessary to confirm our findings. Disclosures W. Powderly, Merck: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Astellas: Grant Investigator, Research grant


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