Bacterial Contamination of Autologous Bone Marrow: Reinfusion of& ;Culture-Positive Grafts Does Not Result in Clinical Sequelae during the Posttransplantation Course

Abstract

Objectives: Microbiological cultures and posttransplantation course were analyzed in order to investigate the incidence and clinical significance of bacterial contamination of autologous bone marrow (BM) grafts. Methods: Cultures were obtained from BM after collection, BM concentrate after processing, contaminated/cryopreserved BM at thawing, and from peripheral blood (PB) following autologous BM transplantation (ABMT). The posttransplantation course of patients grafted with culture-positive BM was recorded and compared with patients who underwent ABMT with noncontaminated BM grafts. Results: In 239 BM grafts processed, the incidence of microbiological contamination was 26.4% (n = 63). Fifty marrow grafts were contaminated by bacteria from the skin flora: coagulase-negative Staphylococcus (CNSC), Propionibacterium, and Corynebacterium species (79%). Thirty-eight patients underwent ABMT (day 0) with cryopreserved culture-positive BM, and 32 patients were evaluable for microbiological cultures at thawing: in 10 of 32 BM grafts CNSC was found prior to reinfusion. Following ABMT, PB cultures revealed CNSC in 5 of 38 patients between days +4 and +12. However, the late occurrence of positive PB cultures after BM reinfusion made a relationship between BM CNSC and PB CNSC unlikely. In 33 of 38 patients, no graft-contaminating bacteria were detected in PB. Comparison of the posttransplantation course of patients who received contaminated BM with that of patients grafted with noncontaminated BM showed no significant differences concerning time to engraftment, febrile days, and days on antibiotics. Conclusion: (1) Collection and/or ex vivo processing can result in microbiological contamination of BM grafts predominantly with bacteria from the skin flora, and (2) only CNSC can be cultured at thawing from previously contaminated/cryopreserved BM. Since patients undergoing ABMT usually receive oral antibiotics from beginning of the conditioning regimen which are active against CNSC, no further administration of antibiotics is recommended for the reinfusion of bacterially contaminated BM grafts.

Microbial contamination of hematopoietic progenitor cell products: clinical outcome

“…Some authors reported that they did not recover CNS from contaminated products after they were cryopreserved and subsequently thawed, while other authors stated that CNS can survive the cryopreservation and thawing procedures. 8,11,14 In our series, we found 5 products, among 13, which had positive cultures for CNS before cryopreservation and remained positive after thawing -making it important to take into account a positive culture before cryopreservation, when discussing antibiotic therapy.…”

“…All autologous transplant patients had neutrophil recovery at a median of 10 days (range, [8][9][10][11][12][13][14]. Among the allogeneic transplant patients, all but one engrafted in a median of 13 days (range, 5-21).…”

“…Commonly documented species are part of the normal flora of the skin. 7,8 Several small studies have reported favorable outcomes after infusion of contaminated products with minimal clinical consequences. [9][10][11] The US Food and Drug Administration (FDA) has recently established new rules for 'current good tissue practice for manufacturers of human cellular and tissue-based products', in which they describe a risk of 2.4% for contamination and raise concerns that there was a high rate of morbidity and mortality after receiving a contaminated product.…”

Recomendaciones para el estudio microbiológico de tejidos preservados para implantes

“…En algunos de estos estudios, se han realizado comparaciones en el curso post trasplante de pacientes que recibieran cosechas de médula ósea contaminadas y no contaminadas. Aquellos pacientes infundidos con cosechas contaminadas no mostraron diferencias importantes con pacientes que recibieron médula ósea no contaminada, en cuanto a tiempo de reconstitución hematopoyética, días febriles y/o días con antimicrobianos 40,41 .…”

Ten Years of External Quality Control for Cellular Therapy Products in France

“…This is completely different for a cell therapy product where volume available is very small, and the concentration of germs, if 85 there are, very low. At the time of implementation, based growth methods with rich medium as those for blood culture were used for the control of labile blood products (Brecher et al, 2001;McDonald et al, 2001;Dunne et al, 2005) as for bone marrow control (Schwella et al, 1998). Taking together, it was decided to evaluate an automated blood culture system for the microbiological control of cell therapy products.…”