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PubMedDate not supplied

Lysis of fresh leukemic blasts by interferon-activated human natural killer cells.

In a comprehensive study of 30 leukemia patients, it was found that a measurable fraction of fresh leukemic blasts from 8 of 8 adult patients with chronic myelogenous leukemia (CML) in blast crisis and 10 of 11 pediatric patients with childhood acute lymphocytic leukemia (ALL) were efficiently lysed by human peripheral blood natural killer (NK) cells as measured in 4-hour chromium release assays. The observed lysis of these fresh, noncultured, neoplastic blasts was mediated by a population of interferon-augmentable, FcR-positive, non-adherent large granular lymphoid cells from normal donors, which were also able to kill the 'standard' NK target K562. It was of further interest that all 8 of the patients with blast crisis CML exhibited myeloid type morphology. Furthermore, neoplastic lymphoblasts from 9 of 10 patients with NK-susceptible childhood ALL lacked easily detectable B or T cell markers and were of 'null' cell type. In marked contrast to the lytic susceptibility of fresh leukemic blasts from patients with ALL and CML in blast crisis, fresh neoplastic granulocytes from 5 patients with chronic phase CML (2 of which eventually progressed to myeloid type blast crisis), as well as leukemic blasts from 8 patients with acute myeloid leukemias (AML, AMMoL, and AMoL) were resistant to lysis as mediated by human NK cells from normal donors. The clinical implications of these findings are discussed.

Adolescent↗

PubMedDate not supplied

Persistence of interstitial inflammation after episodes of cardiac rejection associated with systemic infection.

BACKGROUND: To determine whether systemic infection has an effect on cardiac allografts, we compared heart transplant biopsy specimens showing acute cardiac rejection in patients with and without associated systemic infection. METHODS: Systemic infection was defined as positive bacterial, viral, or fungal cultures with systemic symptoms such as sepsis, fever, or malaise. Patients were identified by chart review to verify the presence or absence of infection and the cardiac biopsy specimens were examined for evidence of rejection. Eight patients (eight episodes of treated acute rejection) with evidence of systemic infection and 11 patients (14 episodes of treated acute rejection) without evidence of systemic infection were identified. RESULTS: Patients with rejection and infection showed persistent interstitial inflammation longer than patients with only rejection and was most often represented by International Society for Heart and Lung Transplantation rejection grade 1B. Days to resolution or last biopsy was 20 to 602 days (mean 196 days) for patients with rejection and infection versus 15 to 133 days (mean 60 days) for patients with rejection alone. Results of two-tailed, unpaired t-test comparing the number of days of persistent inflammatory infiltrates in the patients with and without infection were statistically significant (p = 0.0192). CONCLUSIONS: Heart transplant recipients with treated acute rejection and systemic infection more frequently have persistent interstitial inflammatory infiltrates than do heart cardiac transplant recipients with treated acute rejection and no associated infection. No impact of acute rejection or associated infection on the incidence of allograft coronary artery disease was apparent. Although further evaluation of these findings is necessary, we speculate that heart transplant recipients with systemic infection and acute rejection have greater immunologic activity leading to persistent interstitial inflammation and may possibly be associated with a higher incidence of chronic rejection.

Adult↗