Levofloxacin Prophylaxis for Autologous Stem Cell Transplant: A Second Look

Abstract

Background: Our group previously reported a 16% incidence of HC after hematopoietic cell transplantation (HCT) involving mostly matched unrelated donors (85%) and ATG-containing regimens (80%) (Silva, Haematologica 2010). PT-Cy is an effective GVHD prophylaxis in haplo-or matched unrelated transplants. There is a paucity of information about the risk of HC in this setting. Objective: To retrospectively assess the incidence and clinical factors associated with HC in alloHCT recipients receiving PTCy as GVHD prophylaxis. Methods: A retrospective analysis of patients (pts.) who underwent HCT with PT-Cy at our center between 2012-2018 was performed. We stratified the study cohort (N=478) into HC (N=193, 40%) and Non-HC (N=285, 60%) to compare their characteristics and outcome. Association between HC and clinical variables was assessed using logistic regression modeling. Results: Pt's age, HCT-CI, # prior therapies, disease type and status were not statistically different between the 2 groups. However, the HC group pts. were more likely to have received more intense conditioning (Busulfan/Fludarabine(BF) +/-Clofarabine, or Thio; F/Melphalan (FM) 140+/-Thio or TBI vs. FM 100+/-TBI) (p=0.018), had haplo-transplants (p=0.018), BM as graft (p=0.021), and tacrolimus+mycophenolate mofetil (MMF) (p=0.043). Delayed ANC engraftment (p=0.032) and time to achieve an absolute lymphocyte count >500 was noted in HC group (p=0.014). 54% of HC pts. had grade 2-4 cystitis and BK virus was isolated in 87% of cases. CMV viremia was higher in HC group compared to Non-HC group (p<0.001). HC pts. experienced a higher # of hospitalizations (p=0.012) and longer hospital stay (p=0.06) days compared to Non-HC pts. Additionally, HC pts. were more likely to experience grade II-IV aGVHD compared to Non-HC pts (p=0.005). In multivariable analysis, conditioning intensity remained significant [HR 2.27 (95% CI: 1.28, 4.01); p=0.005]. Conclusion: Our study showed a 40% incidence of HC after HCT recipients receiving PT-Cy. The intensity of the conditioning regimen is an independent predictive factor for developing HC. A formal comparison to ATG-containing regimens is in progress.

Incidence of Febrile Neutropenia in Autologous Hematopoietic Stem Cell Transplant (HSCT) Recipients on levofloxacin prophylaxis

“…Although this is not a prospective randomized controlled study, these results reflect the significant positive impact of levofloxacin prophylaxis at our institution and can be compared with prior reports in the autologous HSCT population (Table 7) who did not receive prophylaxis. [18][19][20][21][22][23][24] In our study, multivariate analysis confirmed that absence of levofloxacin prophylaxis was independently and significantly associated with higher rates of both FN and BSI. Levofloxacin prophylaxis furthermore did not result in a difference in C difficile infections, length of stay, or death at 30-or 100-days post-HSCT in the present study, consistent with findings in other studies.…”

“…As these findings are similar to those from prior studies of fluoroquinolone prophylaxis in autologous HSCT, a reasonable argument for broader use of this intervention has been proposed in this population. [18][19][20][21][22][23][24] Complete suppression of Gram-negative BSI was particularly dramatic in this study and is unique for a study this size.…”

“…Levofloxacin prophylaxis furthermore did not result in a difference in C difficile infections, length of stay, or death at 30-or 100-days post-HSCT in the present study, consistent with findings in other studies. [18][19][20][21][22][23][24] However, ours is the first A major goal of antibiotic prophylaxis is to prevent or reduce BSI in vulnerable patients with neutropenia. Accordingly, this goal…”

“…28 Similarly, in another center, all E Coli blood isolates in the levofloxacin prophylaxis group in hematologic and oncologic pa- Despite these reports, fluoroquinolone resistance in autologous HSCT cohorts has not been a common finding in published reports ( Table 7). [18][19][20][21][22][23][24] The paucity of resistance may be because autologous HSCT populations studied are limited in size or be- have been stable between 2014 and 2018, ranging from 68% to 74% and 72%-80%, respectively, for these Gram-negative organisms. The consistency of these rates of the two study periods does not suggest a significant degree of emerging fluoroquinolone resistance so far.…”

“…prophylaxis was associated with a dramatic decrease in levofloxacin susceptibility among Gram-negative blood isolates in high-risk patients, from 94% to 0% in one study and 34% to 0% in the other (Table 7). 23,24 Reversibility of fluoroquinolone resistance in vulner- 36 Therefore, it is important to note the rise in VGS, especially as a breakthrough pathogen with fluoroquinolone prophylaxis.…”