Biomedical subjects

Mitchell S Cairo

Publications and source records attributed to Mitchell S Cairo.

59 records · Page 4Linked to original sources

PubMed2002

Ex vivo expansion, maturation, and activation of umbilical cord blood-derived T lymphocytes with IL-2, IL-12, anti-CD3, and IL-7. Potential for adoptive cellular immunotherapy post-umbilical cord blood transplantation.

OBJECTIVES: We investigated whether umbilical cord blood (UCB) T cells could be ex vivo expanded and activated in short-term culture for potential utilization as adoptive cellular immunotherapy post-umbilical cord blood transplantation (UCBT). METHODS: Fresh UCB mononuclear cells (MNCs) were isolated by Ficoll density centrifugation. Cryopreserved UCB mononuclear cells were thawed and washed with 2.5% human serum albumin and 5% dextrose in isotonic saline. The nonadherent MNC fraction were then plated in a serum-free cocktail of IL-2, IL-12, and anti-CD3 with and without IL-7 for 48 hours. Proliferation, cytotoxicity, TH1 (IFN-gamma), CD25, and CD45RO assays were performed. RESULTS: Proliferation studies demonstrated a significant increase in the proliferative ability of the UCB MNCs incubated in anti-CD3, IL-2, IL-12, and IL-7 (fresh--p < 0.005, and thawed--p < 0.001). The combination of all four agonists significantly induced expression of CD45 RO (fresh--p < 0.05, and thawed--p < 0.001) in both the CD4(+) and CD8(+) T cells expressing CD25 (fresh UCB--p < 0.01 [CD4] and p < 0.005 [CD8], respectively; thawed UCB--p < 0.001 [CD4] and p < 0.001 [CD8]). Intracellular cytokine profiles also revealed a significant increase in the production of IFN-gamma (TH1 cells) (fresh UCB--p < 0.005, and thawed UCB--p < 0.001). The combination also significantly increased the killing of K562-labeled target cells (fresh--p < 0.0001, and thawed--0.731 +/- 0.03 vs 0.16 +/- 0.01) (p < 0.001). CONCLUSIONS: These data suggest that the ex vivo combination of IL-2, IL-12, anti-CD3, and IL-7 significantly enhances the proliferation, activation, maturation, and cytotoxic potential of UCB T cells of both fresh and thawed UCB MNC. Further studies, however, are required to determine whether these ex vivo--expanded MNC could also potentially exacerbate acute or chronic graft-vs-host disease and/or other toxicities if utilized post-UCBT.

Antibodies↗

PubMed2002

Myeloid hematopoietic growth factors and their role in prevention and/or treatment of neonatal sepsis.

Sepsis continues to be an important cause of morbidity and mortality among both full-term and preterm infants, secondary to an immaturity in neonatal host defense. The incidence of neonatal sepsis ranges from 30% in very low birth weight infants to 0.4% in preterm neonates and 0.1% in term neonates. The dysregulation of the expression and production of hematopoietic cytokines in the neonate contributes to quantitative and qualitative deficiencies in neonatal myeloid progenitor activity and decreased availability and function of mature effector neutrophils. These abnormalities contribute in large part to the increased incidence and mortality associated with neonatal sepsis. In this review, we have summarized and analyzed the studies investigating the dysregulation, expression and production of myelopoietic growth factors in neonates, the preclinical in vivo effects of myelopoietic growth factors in neonatal animals, the preclinical in vivo effects of myelopoietic growth factors during experimental sepsis in neonatal animals, the in vitro effects of growth factors on human neonatal phagocytic immunity, and clinical results of myelopoietic growth factors in human neonates. Future studies should be focused on investigating other abnormalities of neonatal host defense and multiple and simultaneous approaches to circumvent identified defects to attempt to reduce both the incidence and severity of neonatal host defense.

Adult↗

PubMed2002

Mobilization of peripheral blood stem cells with paclitaxel and rhG-CSF in high-risk breast cancer patients.

Preclinical studies have demonstrated the rapid and efficient mobilization of hematopoietic peripheral blood stem cells (PBSC) in a mouse model using the combination of paclitaxel with recombinant human granulocyte colony-stimulating factor (rhG-CSF). On the basis of these results, a clinical trial was initiated using rhG-CSF with paclitaxel for PBSC mobilization in high-risk breast cancer patients. The mobilized PBSC were evaluated for CD34(+) cell number, mononuclear cell content, and clonogenic potential. One-hundred and seventeen breast cancer patients received paclitaxel (300 mg/m(2)) administered as a 24-h continuous intravenous infusion. Forty-eight hours after completing paclitaxel, rhG-CSF (5 microg/kg) was initiated and continued until completion of PBSC collection. Leukapheresis was initiated once the white blood cell count reached 1.0 x 10(9)/L. Each collection was evaluated for the numbers of mononuclear cells (MNC) and CD34(+) cells. Clonogenic potential was enumerated using colony-forming units-granulocyte-macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E). Patients receiving paclitaxel with rhG-CSF mobilized a large number of mononuclear cells/apheresis (mean, 3.7 x 10(8); range, 3.3-4.1) and CD34(+) cells/apheresis (mean, 7.2 x 10(6); range, 6.1-8.4). The average number of leukophereses needed was 1.8 (mean, range 1.6-2.0). Colony growth was normal with 178.9 x 10(5) and 214.8 x 10(5) colonies counted in CFU-GM and BFU-E assays, respectively. Patients engrafted platelets and neutrophils on day 10 following transplantation. In conclusion, PBSC mobilization with paclitaxel and rhG-CSF results in a large number of mononuclear cells and CD34(+) cells with normal clonogenic potential. The cells engraft normally following high-dose chemotherapy and autologous stem cell transplantation in high-risk breast cancer patients. These results demonstrate that paclitaxel with rhG-CSF is an efficient mobilizing agent in high-risk breast cancer patients.

Adult↗

PubMed2002

Treatment of severe thrombocytopenia with IL-11 in children with Wiskott-Aldrich syndrome.

This report examines the safety and efficacy of IL-11 in treating severe thrombocytopenia secondary to Wiskott-Aldrich syndrome in two pediatric patients before allogeneic stem cell transplantation (SCT). Both patients had a substantial increase in their platelet counts and a decrease in bleeding episodes and platelet transfusions. The median platelet count increased from 32,000/mm3 to 64,000/mm3. Each subsequently received allogeneic SCT; 1 year after transplantation, both are reconstituted with 100% donor hematopoietic stem cells with sustained normal platelet counts (>200 K/mm3). Larger studies are required to confirm this observation of the safety and efficacy of IL-11 in this setting.

Child, Preschool↗

PubMed2002

Prevention and treatment of hyperuricemia in hematological malignancies.

The standard prophylactic and treatment regimen for hyperuricemia in patients with hematological malignancies previously included vigorous hydration, urinary alkalinization, and a xanthine oxidase inhibitor, allopurinol, which blocks the conversion of hypoxanthine and xanthine to uric acid. However, xanthine is less soluble than uric acid, and preexisting uric acid is not affected by allopurinol. The enzyme urate oxidase, not present in mammals, converts uric acid to allantoin, which is 5-10 times more soluble than uric acid. A new recombinant form of urate oxidase, rasburicase, has recently been developed. In a phase I/II study of rasburicase in children and young adults with hematological malignancies, rasburicase was demonstrated to be well tolerated at 0.2 mg/kg/day intravenously, had a mean T1/2 of 21.2 +/- 12.0 hours, and induced a median decrease in uric acid from 9.7 mg/dL to 1.0 mg/dL (P < 0.001). We recently demonstrated, in a randomized prospective trial comparing rasburicase versus allopurinol in children with hematological malignancies at high risk of tumor lysis syndrome, that rasburicase significantly lowered the mean uric acid area under the curve 0 to 96 hours (128 +/- 70 mg/dL/hour vs. 329 +/- 129 mg/dL/hour; P < 0.001) and 4 hours post uric acid by 86% versus 12% (P < 0.001). Furthermore, in the hyperuricemic group, the baseline creatinine level decreased from 144% to 102% by 96 hours following rasburicase compared to an increase from 132% to 147% following allopurinol. Although the difference in effect on creatinine levels is not significant, the study was not designed or powered to question this effect. Lastly, in 510 patients with hematological malignancies at risk for tumor lysis syndrome who received rasburicase, only 2 (0.4%) have developed new renal complications requiring hemodialysis. In summary, in the prevention and treatment of hyperuricemia, patients with hematological malignancies at risk of tumor lysis syndrome appear to benefit significantly from the use of a recombinant urate oxidase (rasburicase).

Allopurinol↗