Microbial Contamination of Haematopoietic Stem Cell Products: A Single Centre Experience
Authors: Avenoso Daniele , Bradshaw Anne , Innes Andrew , de la Fuente Josu , Olavarria Eduardo , Apperley Jane F. , Pavlů Jiří 
Published: November 2019

Abstract
Bacterial contamination of haematopoietic stem cell products (HSCP) during collection and processing is a potential risk and has been described as cause of serious morbidity and mortality. The rate of contamination is reported in the range of 0 to 4.5% in peripheral blood progenitor cell (PBPC) apheresis to as high as 26% in bone marrow (BM) harvests. Systematic microbiological testing is an important component of the HSCP quality assessment and identification of the bacteria involved helps in the management of early infective complications. Here we report the rate of contaminated HSCP collected in a single transplant centre, our policy of the management of this complication and the relevant clinical outcomes.
This is a retrospective study of prospectively collected results of microbiological analyses of 246 collections performed from January 2015 till December 2015. Stem cells were collected by BM harvesting under general anaesthesia (N=47) and by PBPC apheresis (N=199) using Optia separator system. BM harvest rather then PBPC was performed on donor request or with donor consent where BM was clinically preferable over PBPC transplant. (eg. red cell disorders). Samples of HSCP for bacterial cultures were taken pre processing, post processing, including post filtration and at defined intervals during complex procedures. Cryoprotectant is also tested to check that no contamination has occurred during manufacture of the freeze mix. Samples were cultured in BACTEC™ Lytic/10 Anaerobic/F culture vials (pre-reduced enriched Soybean-Casein Digest broth with CO2) and in anaerobic blood cultures; BACTEC Peds Plus™/F culture vials (enriched Soybean-Casein Digest broth with CO2) under aerobic conditions, both for 14 days. Organisms were specifically identified in all positive HSCP.
Sixteen bacterial contaminations of HSCP were recorded (6.09% of total collections). The most frequent product contaminated was BM (N=15, 31.9%); only one PBPC apheresis product was positive (0.5%). The following bacteria were isolated: propionibacterium (N=7), coagulase negative staphylococcus (N=4), micrococcus (N=2), staphylococcus capitis (N=1), Staphylococcus epidermidis (N=2). Seven HSCP were not infused: one patient died before undergoing to transplant, two products have been collected as stem cell rescue in case of graft failure from allogeneic donors, four collections were stored for future use. Nine patients received contaminated HSCPs. After being contemporaneously alerted to the contamination, the clinical team performed daily blood cultures (BC). From these 9 patients only two minor clinical events were recorded; One, a non-neutropaenic fever on day +2 (S. Capitis cultured from HSCP, BC negative) and the other a positive BC (micrococcus cultured from both HSCP and BC) in a patient without fever or signs of infection. Both were treated with IV vancomycin on microbiology advice.
These data showed a rate of bacterial contamination of HSCP comparable with reports from other groups. Moreover, at our centre no major clinical events were recorded after the infusion of contaminated HSCP. In this small study, the most frequent source of contaminated HSCP was BM and the most frequently isolated pathogens were skin commensals. No consensus exists on the requirement for antibiotics after the infusion of contaminated HSCP. Our experience supports a strategy of symptomatic management based on fevers or positive blood cultures with targeted antibiotics based on in vitro sensitivities rather than pre-emptive empirical treatment of all patients.

Disclosures
Apperley: Bristol Myers Squibb: Honoraria, Speakers Bureau; Ariad: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Novartis: Honoraria, Speakers Bureau.