PubMed Health⌕ Search

PubMed · 10877046

Graft engineering.

Abstract

Improvements in supportive care, antimicrobials, immunosuppressant therapy, and health care delivery have shifted the emphasis in hematopoietic stem cell transplantation toward raising cure rates and improving the quality of life in the years that follow transplantation. Many large centers have significantly reduced the morbidity of allogeneic transplantation by effecting a decrease in acute and chronic graft-versus-host disease. Extension of this modality through the use of unrelated donors, peripheral blood stem cell products, and HLA-mismatched family members has again introduced significant posttransplantation complications. Conversely, the posttransplantation morbidity of autologous transplantation is minimal, but the chances of remaining in long-term remission are still inferior to those afforded by allogeneic hematopoietic stem cell transplantation. One approach developed to reduce these long-term complications is referred to as "graft engineering." Through the use of successive clinical protocols, hematopoietic grafts and host immune properties can be manipulated in a stepwise fashion using several outcome parameters to judge efficacy. This report details one center's experiences with graft engineering over 12 consecutive years of clinical trials and speculates on future approaches that may supplant transplantation in the new millennium.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S J Noga. 2000. Graft engineering.. https://pubmed.ncbi.nlm.nih.gov/10877046/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Laparoscopic cholecystectomy: are patients with biliary pancreatitis at increased operative risk?

BACKGROUND: Previous reports of laparoscopic cholecystectomy (LC) in patients with biliary pancreatitis suggested increased operative difficulty, high rates of conversion, and greater morbidity and mortality. METHODS: Between 1990 and 1997, LC was performed for biliary pancreatitis in 63 patients (Group I) and for other causes in 829 patients (Group II). RESULTS: Patients with biliary pancreatitis were significantly older (median age 57 vs 50 years, p = 0.009), with greater co-morbidity (ASA III/IV 24% vs 11%, p = 0.008). The groups were comparable with respect to the frequency of previous abdominal operations, acute inflammation of the gallbladder, and the frequency of bile duct calculi detected by intraoperative cholangiography. Moderate to severe adhesions involving the gallbladder were significantly more frequent in patients with biliary pancreatitis (46% vs 29%, p = 0.004). No significant differences were observed between the two groups with respect to intraoperative (1.5% Group I vs 6.0% Group II, p = 0.109) or postoperative complications (10% vs 8%, p = 0.426), conversion rate (0 vs 2.7%, p = 0.181), or duration of operation (median 92 vs 85 min, p = 0.33). CONCLUSION: Despite increased age and co-morbidity and more frequent adhesions, our data showed no evidence that intraoperative or postoperative complications were more frequent in patients with biliary pancreatitis than in other patients undergoing LC.

Acute Disease↗

A white blood cell index as the main prognostic factor in t(8;21) acute myeloid leukemia (AML): a survey of 161 cases from the French AML Intergroup.

While the t(8;21) translocation is one of the most recurrent chromosomal abnormalities in acute myeloid leukemia, prognostic studies have been hampered by the relatively few number of patients reported. We thus performed a large retrospective study in 161 adults and children with t(8;21) acute myeloid leukemia, all prospectively enrolled in 6 different trials conducted in France between 1987 and 1998 (median follow-up 4.9 years). Prognostic studies were performed in the 154 patients who achieved a complete remission. Individual data were registered, including sex, age, blood and marrow counts, extramedullary disease, and cytogenetics. The value of allogeneic stem cell transplantation versus chemotherapy as postremission therapy was evaluated according to the intent-to-treat principle. Estimated 5-year disease-free survival (DFS) and overall survival were 52% and 59%, respectively. Outcome was not significantly better in patients from the stem cell transplantation group (estimated 5-year DFS and survival, 56% vs 52% and 67% vs 57%; P =.55 and.64, respectively). White blood cell count (WBC) was the only identified prognostic factor. To further take into account the spontaneous differentiation potential of the leukemic clone, a WBC index was derived as the product of WBC by the ratio of marrow blast. This WBC index was a more powerful factor than the original WBC, allowing us to distinguish 3 subgroups of patients with different outcomes (low index, < 2.5; intermediate index, 2.5-20; high index, 20 or more). In multivariate analysis, the WBC index was the only prognostic factor for DFS (P =.003), complete remission duration (P =.002), and overall survival (P =.04).

Acute Disease↗

Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia.

The cytolytic function of natural killer (NK) cells is induced by the engagement of a series of activating receptors and coreceptors some of which have recently been identified and collectively termed natural cytotoxicity receptors (NCRs). Here, we analyzed the cytolytic function of NK cells obtained from patients with acute myeloid leukemia (AML). In sharp contrast with healthy donors, in most (16 of 18) patients with AML the majority of NK cells displayed low NCR surface density (NCR(dull)). This phenotype correlated with a weak cytolytic activity against autologous leukemic cells that could not be reversed by the monoclonal antibody-mediated disruption of HLA class I/killer immunoglobulinlike receptor interaction. The remaining 2 patients were characterized by NK cells having an NCR(bright) phenotype. Surprisingly, although displaying NCR-mediated cytolytic activity, these NCR(bright) NK cells were unable to kill autologous leukemic blasts. Importantly, the leukemic blasts from these 2 patients were also resistant to lysis mediated by normal NCR(bright) allogeneic NK cells. Our study suggests that in most instances the inability of NK cells to kill autologous leukemic blasts is consequent to low NCR surface expression. In few cases, however, this failure appears to involve a mechanism of tumor escape based on down-regulation of ligands relevant for NCR-mediated target cell recognition.

Acute Disease↗