Experimental Evidence that Leukocyte (WBC) Transfusions are Efficacious in Treatment (Rx) of Neutropenics with Aspergillosis

Ref ID: 18656

Author:

M. Martinez, BS – Senior Laboratory Technician1, V. Chen, BS – Laboratory Technician 1, A. Tong, BS – Laboratory Technician 1, K. Hamilton, BS – Student 1, K. Clemons, Ph.D – Senior Lecturer in Medicine 1,2,3, D. Stevens, MD – Professor of Medicine 1

Author address:

1Calif. Inst. Med. Res., San Jose, CA, 2Sta. Clara Vly. Med. Ctr., San Jose, CA, 3Stanford Univ., Stanford, CA.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background. Wbc transfusions as Rx for infected neutropenic patients remains controversial. Although wbc are powerfully anti-Aspergillus in vitro and in vivo, transfusion trials have given conflicting results, with uncertainties re patient populations, study design, wbc dose, frequency and timing. Experimental support of the concept has been lacking. Methods. We found several challenges in development. The fungal inoculum and immunosuppression must balance to produce a progressively lethal model, yet without excess early deaths, or severity such that any Rx problematic. A safe antibacterial regimen must protect vs. confounding sepsis, and optimal PMN separation and dosing regimens determined. Through empirical investigation, we devised a satisfactory system in 6 wk.-old BALB/c male mice housed in microisolator cages, given 150 mg/kg cyclophosphamide (CTX) + a gentamicin-vancomycin-clindamycin-imepenem regimen 4d before challenge with 5×105 Aspergillus conidia intranasally, then CTX q4d + antibiotics; producing steady leukopenia (~106/ml, 10% of normal; <10% PMN) for 10d without bacterial superinfection. Wbc donors were given 100 mcg/kg rmGCSF qd for 10d, yielding 1.36x108 wbc/ml (85% PMN), enabling 1 donor to give 2 recipients 107 or 5x106 purified wbc (>99% PMN, viability 93-99%). Results. Groups of 10 mice were made neutropenic. In 2 expts. with

Abstract Number: M-300

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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