We present the results of a multicenter clinical trial using Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) generated from EBV-seropositive blood donors to treat patients with EBVpositive posttransplantation lymphoproliferative disease (PTLD) on the basis of the best HLA match and specific in vitro cytotoxicity. Thirty-three PTLD patients who had failed on conventional therapy were enrolled. No adverse effects of CTL infusions were observed and the response rate (complete or partial) in 33 patients was 64% at 5 weeks and 52% at 6 months. Fourteen patients achieved a complete remission, 3 showed a partial response, and 16 had no response at 6 months (5 died before completing treatment). At 5 weeks, there was a significant trend toward better responses with higher numbers of CD4 ؉ cells in infused CTL lines (P ‫؍‬ .001) that were maintained at 6 months (P ‫؍‬ .001). Patients receiving CTLs with closer HLA matching responded better at 6 months (P ‫؍‬ .048). Female patients responded better than male patients, but the differences were not statistically significant. Our results show that allogeneic CTLs are a safe and rapid therapy for PTLD, bypassing the need to grow CTLs for individual patients. The response rate in this poor prognosis patient group is encouraging. (Blood.

In a recent phase II clinical trial using banked allogeneic CTL lines to treat EBV-associated posttransplant lymphoproliferative disease, a response rate of 52% was recorded 6 mo posttreatment. Tumor response was associated with an increase in both CTL/recipient HLA matches and CD4 ؉ T cells within the infused CTL lines. The present study was undertaken to correlate tumor response with CTL specificity. The majority of CTL lines infused recognized EBV-encoded nuclear Ag-3 proteins, but CTL protein specificity itself did not correlate with tumor response. Specificity in conjunction with donor/recipient functional HLA matching as opposed to HLA matching alone, however, was important for tumor response. CTL receptor TCR ␤-chain variable gene subfamilies were polyclonal, with no preferential use of a particular family. However, tumor response was improved in those receiving CTL lines with polyclonal vs clonal distribution for subfamilies 2, 3, and 9. Interestingly, in five of six tumors (five Hodgkin's-like and one Burkitt's-like posttransplant lymphoproliferative disease) with restricted viral gene expression a complete response was recorded, although in some cases the tumor cells did not express the proteins recognized by the infused CTL. Thus CTL were advantageous when functionally HLA matched but for certain tumor types complete responses occurred in the absence of detectable specific CTL/tumor recognition. We suggest that either the allogenic CTL contained small, undetectable, EBV-specific, HLA-matched T cell populations or perhaps they stimulated nonspecific inflammatory responses in vivo, which were beneficial for tumor regression. These observations should be considered when designing and implementing CTL therapies.

SYNOPSIS Virus isolation tests on 72 sudden unexplained infant deaths and 34 cases of explained death showed that 42 and 29% respectively had virus infections. A wide range of viruses was encountered, mainly enteroviruses and adenoviruses, mostly from bowel specimens. The findings did not suggest that overwhelming virus infection was a common feature of sudden death in infancy.

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The reluctance to carry out diagnostic catherization of the bladder because of the danger of introducing infection has increased reliance on mid-stream and 'clean catch' specimens. It must be accepted that such specimens are contaminated to a greater or lesser degree and the problem resolves itself into distinguishing between mere contamination and bacteruria significant of infection. Several investigators have examined urine quantitatively and found that contamination rarely exceeds 105/ml. so that bacterial counts in excess of this are more likely to be significant (Kass, 1955 and1956;Sanford, Favour, Mao, and Harrison, 1956;Macdonald, Levitin, Mallory, and Kass, 1957;Jackson, Grieble, and Knudsen, 1958;and Monzon, Ory, Dobson, Carter, and Yow, 1958).A disadvantage of conventional quantitative techniques is that they are too time consuming for use in the routine diagnostic laboratory. Thus to be useful in a busy laboratory methods of quantitative culture must be simple, quick, and of a degree of accuracy sufficient to enable 10-fold differences in viable count, particularly over the range 103/ml. to 106/ml., to be detected.The aim of the present paper is to compare a modification of the Miles and Misra method with a standard loop technique which fulfils the above criteria. METHODSThe Miles and Misra modified technique was carried out