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Editorials
patients resistant or intolerant to imatinib. Results from a real life- based Italian multicenter retrospective study on 114 patients. Am J Hematol. 2010;85(12):960-963.
15. Clark RE, Polydoros F, Apperley JF, et al. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analy- sis of a non-randomised, phase 2 trial. Lancet Haematol. 2017;4(7):e310-e316.
16. Naqvi K, Jabbour E, Skinner J, et al. Early results of lower dose dasa-
tinib (50 mg daily) as frontline therapy for newly diagnosed chronic-
phase chronic myeloid leukemia. Cancer. 2018;124(13):2740-2747. 17. Schiffer CA. The evolution of dasatinib dosage over the years and its relevance to other anticancer medications. Cancer. 2018;124(13):
2687-2689.
18. Fassoni AC, Baldow C, Roeder I, Glauche I. Reduced tyrosine kinase
inhibitor dose is predicted to be as effective as standard dose in chronic myeloid leukemia: a simulation study based on phase III trial data. Haematologica. 2018;103(11):1825-1834.
The only thing that stops a bad microbiome, is a good microbiome
Jessica R. Galloway-Peña1,2 and Robert R. Jenq1,3
1Department of Genomic Medicine; 2Department of Infectious Diseases, Infection Control and Employee Health and 3Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
E-mail: jrgalloway@mdanderson.org/rrjenq@mdanderson.org doi:10.3324/haematol.2019.222430
Multidrug resistant (MDR) bacterial colonization in the gut is frequently induced by excessive use
1
of antibiotics. Fecal microbiota transplantation
(FMT) has been shown to be quite successful in treating refractory and recurrent Clostridium difficile infection.2 Thus, current research is focusing on how FMT may also help in decolonizing MDR organisms (MDRO) and in preventing recurrent MDR infections.3 Decolonization of MDRO via FMT may be particularly useful in patients with hematologic malignancies, such as those undergo- ing hematopoietic stem cell transplantation (HSCT),4 as use of chemotherapeutic agents and frequent administra- tion of antibiotics can favor the selection of resistant pathogens.5,6
In spite of the increasing evidence that the feasibility and safety of FMT in immunocompromised cohorts is comparable to that of immunocompetent patients, administering FMT in the setting of hematologic malig- nancy remains a cause for concern due to perceived risks of translocation and sepsis.7,8 Given the growing body of literature associating a dysbiotic microbiome with adverse HSCT outcomes and treatment-related toxicities, including infection, delivering a diverse microbiome via FMT to immunocompromised patients may provide a variety of benefits, such as promoting colonization resist- ance and reducing the risk of bacterial translocation.9 Thus, attempts to better characterize the safety and effi- cacy of FMT in these patients are merited.
In this issue of the Journal, Battipaglia et al.10 describe a retrospective case series of 10 patients with hematologic malignancies undergoing FMT for MDRO colonization before or after allogeneic HSCT. In this study, the authors show both the safety and efficacy of using FMT for decolonization of carbapenem-resistant Enterobactericeae (CRE), carbapenem-resistant Pseudomonas (CRP), and vancomycin-resistant Enterococcus (VRE). Notably, the study reports FMT both pre- and post transplant. The majority of patients who received FMT prior to transplant did not have recurrent MDRO even after HSCT, indicating the prophylactic use of FMT. Interestingly, the procedure remained effective for long-
term MDRO decolonization in the majority of patients despite the use of broad-spectrum antibiotics in some of the patients after FMT. This implies that FMT can poten- tially achieve full decolonization of MDRO rather than merely reducing the levels of MDRO below the limit of detection.
While FMT was shown to be successful in decolonizing the MDRO studied, the FMT did not always prevent additional post-transplant infections from other bacteria susceptible to antibiotics. Interestingly, only 50% of patients concomitantly colonized with extended spec- trum β-lactamase (ESBL)-producing Enterobacteriaceae obtained decolonization. This is reminiscent of a case report by Stalenhoef et al. where FMT successfully eradi- cated a Pseudomonas aeruginosa urinary tract infection, while stool cultures remained positive for extended-spec- trum β-lactamase (ESBL)-producing Enterobacteriaceae three months after FMT.11 Thus, the higher frequency of failure of FMT to eradicate the ESBL-producing Enterobacteriaceae in these two studies may suggest potential limitations to this therapy.
Although the specific mechanisms underlying the suc- cess of FMT for MDRO colonization remain unclear, Figure 1 depicts an overview of the general concepts regarding the use of FMT for MDRO in patients with hematologic malignancies. Given that this study looked specifically at CRE, CRP, and VRE, it remains unclear if other MDRO may be equally responsive to FMT. Furthermore, given the seemingly discrepant results for CRE, CRP, and VRE compared to ESBL-producing organ- isms, one might consider that distinct mechanisms of action underlie how FMT mediates response for different MDRO.
Due to the retrospective nature of the study, in contrast to a controlled study, it is unclear how physicians decided to treat each patient with FMT case by case. Moreover, there was a large variation between cases in the time of FMT relative to HSCT and the MDRO colonization/infection in both pre- and post-HSCT groups. Thus, it remains to be determined what the ideal timeframe for FMT is in both scenarios. The use of relat-
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