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Abstract
Acute myeloid leukemia is a malignant clonal disorder of immature cells in the hematopoietic hierachial system. On the other hand chronic myeloid leukemia is a clonal disease that results from an acquired genetic change in pluripotential hematopoietic stem cell. This altered stem cell proliferates and generates a population of differentiated cells that gradually displace normal hematopoiesis and leads to a greatly expanded total myeloid mass.
Allogeneic stem cell transplantation has been established as an effective consolidation therapy in myeloid leukemias. Allogeneic BMT in first complete remission (CR), in patients under 65 years without major organ dysfunction (eg, renal pulmonary cardiac,or hepatic damage) who have an HLA-compatible related bone marrow donor or in those under age 55 years with on HLA compatible unrelated donor, results in cure in 40 to 60 percent of patients. However, toxicity is relatively high with treatment-related complications, including veno-occlusive disease, graft-versus-host disease (GVHD), interstitial pneumonitis and infections.
Dendritic cells (DC) as key intiator and directors of the immune response are central to allogeneic transplantation interactions. Preparative conventional conditioning (CC) regimens aim to control disease and ablates the host immune response to facilitate normal donor hematopoietic reconstitution.
The conditioning also unleashes a cytokine storm that activates the residual host immune system, driving host dendritic cells and donor T cell interaction that results in graft versus host disease. This led to a trend to reduce the intensity of the conditioning regimens (RIC). The reduced intensity conditioning regimens are used as alternatives in patients with co-morbid conditions. They maintain immune antileukemic activity of the T –replete hematopoietic stem cell transplantation (HSCT), which may lead to reduction of transplant-related mortality (TRM) and may delay the onset of GVHD, but the overall incidence of GVHD is unchanged.
It was demonstrated that the circulating dendritic cell pool is rapidly reconstituted from both donor and recipient origins. Around day 28, donor engraftment of DC becomes predominant. On the other hand, the circulating dendritic cells are known to have an immunoregulatory role after allogeneic hematopoietic stem cell transplantation, and recipient DCs have been shown to be important in the development of GVHD in animal models. The successful application of DC depletion to control GVHD was suggested to improve the safety of HSCT for patients with leukemia.
However, despite the importance of dendritic cells in immune reconstitution and GVHD, limited information is available about dendritic cells reconstitution after transplantation in patients receiving reduced intensity stem cell transplantation and its relation to outcome, which may influence the management decisions of transplantation -related complications.
The study was include 45 subjects classified as follows:
Group (1): 30 patients with myeloid leukemia treated with reduced- intensity conditioning allogeneic hematopoietic stem cell transplantation.
Group (2): 15 healthy volunteers as control matching the same sex and age as patient group.
Patients with AML and CML subjected to reduced - intensity conditioning allogeneic hematopoietic stem cell transplantation at least 28 days after transplantation.
Patients with previously known chronic inflammatory condition was excluded.
Patients was subjected to the following:
(1) Full history and clinical examination .
(2) Complete blood picture,ESR,LDH,PT,PTT,serum uric acid.
(3) Renal function tests.
(4) Liver function tests.
(5) Abdominal ultrasound, chest X ray, CT scan as indicated.
(6) Bone marrow aspirate for morphology and immunophenotyping and cytogenetic study and other previous diagnostic results as indicated for each disease.
(7) Necessary investigation for detection post transplantation complications.
Healthy subjects was subjected to clinical examination and basic investigations to exclude any chronic inflammatory condition.
Assessment of circulating mature-CD83-positive dendritic cells in peripheral blood using flowcytometry was done to all patients and control group.
And it was found that patients with myeloid leukemia after reduced intensity conditioning HSCT with low Cd 83 +ve cells were subjected to relapse , and subjected to GVHD more than patients with high level of CD 83 +ve cells.