|
|
char = B;code = 66
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char = s;code = 115
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char = ;code = 32
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char = o;code = 111
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char = ;code = 32
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char = l;code = 108
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char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
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char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = n;code = 110
char = e;code = 101
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char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
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char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
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char = e;code = 101
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char = o;code = 111
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char = c;code = 99
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char = q;code = 113
char = u;code = 117
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char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = .;code = 46
result sql = Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model.
Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model.char = <;code = 60
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char = T;code = 84
char = I;code = 73
char = V;code = 86
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char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
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char = G;code = 71
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char = r;code = 114
char = a;code = 97
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char = e;code = 101
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char = e;code = 101
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char = e;code = 101
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char = ;code = 32
char = T;code = 84
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result sql = OBJECTIVE : Gene transfer to hematopoietic stem cells has recently been demonstrated to benefit a small number of patients in whom a selective advantage is conferred upon genetically modified cells; however, in disorders where no such selective advantage is conferred, conditioning appears necessary to allow adequate engraftment. To decrease the toxicity profile, we sought to develop nonmyeloablative conditioning regimens and in this work, explored the use of intravenous busulfan in a large animal model.
METHODS : Busulfan pharmacokinetics and toxicity were monitored in young rhesus macaques at two dosing levels (4 and 6 mg/kg). These doses were then employed to condition two animals at each dose level prior to autologous transplantation of genetically modified cells using our standard methods.
RESULTS : Busulfan pharmacokinetic (PK) data showed the area under the curve (AUC), drug half-life, and drug clearance were consistent within each dose group and similar to those reported in children. Single doses of busulfan were well tolerated and produced dose-dependent myelosuppression, most notably in the neutrophil and platelet counts. Although marking levels reached over 1% early in one animal, the long-term marking was low but detectable at 0.01 to 0.001%.
CONCLUSIONS : We conclude that low-dose intravenous bolus infusion of busulfan is well tolerated, has dose-dependent effects on peripheral blood counts, and allows long-term engraftment of genetically modified cells, but at levels too low for most clinical disorders.
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char = e;code = 101
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char = l;code = 108
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char = p;code = 112
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char = m;code = 109
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char = d;code = 100
char = e;code = 101
char = l;code = 108
char = .;code = 46
result sql = Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model.
char = b;code = 98
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char = B;code = 66
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char = d;code = 100
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char = p;code = 112
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char = ;code = 32
char = T;code = 84
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char = m;code = 109
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char = i;code = 105
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char = d;code = 100
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char = <;code = 60
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char = r;code = 114
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char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
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char = u;code = 117
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char = m;code = 109
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
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char = K;code = 75
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char = d;code = 100
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char = e;code = 101
char = a;code = 97
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char = d;code = 100
char = e;code = 101
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char = ;code = 32
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char = e;code = 101
char = ;code = 32
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char = r;code = 114
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char = e;code = 101
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char = ;code = 32
char = d;code = 100
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char = ;code = 32
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char = e;code = 101
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char = a;code = 97
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char = e;code = 101
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char = e;code = 101
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char = e;code = 101
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char = o;code = 111
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char = s;code = 115
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char = s;code = 115
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char = n;code = 110
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char = t;code = 116
char = h;code = 104
char = i;code = 105
char = n;code = 110
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char = e;code = 101
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char = c;code = 99
char = h;code = 104
char = ;code = 32
char = d;code = 100
char = o;code = 111
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char = e;code = 101
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
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char = m;code = 109
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = s;code = 115
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char = e;code = 101
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char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
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char = n;code = 110
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char = c;code = 99
char = h;code = 104
char = i;code = 105
char = l;code = 108
char = d;code = 100
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = l;code = 108
char = e;code = 101
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char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
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char = ;code = 32
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char = s;code = 115
char = u;code = 117
char = l;code = 108
char = f;code = 102
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
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char = e;code = 101
char = p;code = 112
char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
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char = o;code = 111
char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
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char = ;code = 32
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char = o;code = 111
char = s;code = 115
char = t;code = 116
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char = n;code = 110
char = o;code = 111
char = t;code = 116
char = a;code = 97
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char = l;code = 108
char = y;code = 121
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = e;code = 101
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char = t;code = 116
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char = p;code = 112
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char = i;code = 105
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char = ;code = 32
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char = d;code = 100
char = ;code = 32
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char = t;code = 116
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char = l;code = 108
char = e;code = 101
char = t;code = 116
char = ;code = 32
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char = o;code = 111
char = u;code = 117
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
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char = h;code = 104
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = 1;code = 49
char = %;code = 37
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
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char = n;code = 110
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
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char = n;code = 110
char = i;code = 105
char = m;code = 109
char = a;code = 97
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = -;code = 45
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 1;code = 49
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 0;code = 48
char = 1;code = 49
char = %;code = 37
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = -;code = 45
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = f;code = 102
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = o;code = 111
char = o;code = 111
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = s;code = 115
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = -;code = 45
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = f;code = 102
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = o;code = 111
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = .;code = 46
result sql = OBJECTIVE : Gene transfer to hematopoietic stem cells has recently been demonstrated to benefit a small number of patients in whom a selective advantage is conferred upon genetically modified cells; however, in disorders where no such selective advantage is conferred, conditioning appears necessary to allow adequate engraftment. To decrease the toxicity profile, we sought to develop nonmyeloablative conditioning regimens and in this work, explored the use of intravenous busulfan in a large animal model.
METHODS : Busulfan pharmacokinetics and toxicity were monitored in young rhesus macaques at two dosing levels (4 and 6 mg/kg). These doses were then employed to condition two animals at each dose level prior to autologous transplantation of genetically modified cells using our standard methods.
RESULTS : Busulfan pharmacokinetic (PK) data showed the area under the curve (AUC), drug half-life, and drug clearance were consistent within each dose group and similar to those reported in children. Single doses of busulfan were well tolerated and produced dose-dependent myelosuppression, most notably in the neutrophil and platelet counts. Although marking levels reached over 1% early in one animal, the long-term marking was low but detectable at 0.01 to 0.001%.
CONCLUSIONS : We conclude that low-dose intravenous bolus infusion of busulfan is well tolerated, has dose-dependent effects on peripheral blood counts, and allows long-term engraftment of genetically modified cells, but at levels too low for most clinical disorders.
Publication: Exp. Hematol. 2006 Feb ;34(2)::132-9.
Publication Date: 2006 Feb
Study Author(s): Kang, Elizabeth M;Hsieh, Matthew M;Metzger, Mark;Krouse, Allen;Donahue, Robert E;Sadelain, Michel;Tisdale, John F;
Institution: Laboratory of Host Defense, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
Shortcut link to this study:
Publication Date: 2006 Feb
Study Author(s): Kang, Elizabeth M;Hsieh, Matthew M;Metzger, Mark;Krouse, Allen;Donahue, Robert E;Sadelain, Michel;Tisdale, John F;
Institution: Laboratory of Host Defense, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
Shortcut link to this study:
OBJECTIVE : Gene transfer to hematopoietic stem cells has recently been demonstrated to benefit a small number of patients in whom a selective advantage is conferred upon genetically modified cells; however, in disorders where no such selective advantage is conferred, conditioning appears necessary to allow adequate engraftment. To decrease the toxicity profile, we sought to develop nonmyeloablative conditioning regimens and in this work, explored the use of intravenous busulfan in a large animal model.
METHODS : Busulfan pharmacokinetics and toxicity were monitored in young rhesus macaques at two dosing levels (4 and 6 mg/kg). These doses were then employed to condition two animals at each dose level prior to autologous transplantation of genetically modified cells using our standard methods.
RESULTS : Busulfan pharmacokinetic (PK) data showed the area under the curve (AUC), drug half-life, and drug clearance were consistent within each dose group and similar to those reported in children. Single doses of busulfan were well tolerated and produced dose-dependent myelosuppression, most notably in the neutrophil and platelet counts. Although marking levels reached over 1% early in one animal, the long-term marking was low but detectable at 0.01 to 0.001%.
CONCLUSIONS : We conclude that low-dose intravenous bolus infusion of busulfan is well tolerated, has dose-dependent effects on peripheral blood counts, and allows long-term engraftment of genetically modified cells, but at levels too low for most clinical disorders.
METHODS : Busulfan pharmacokinetics and toxicity were monitored in young rhesus macaques at two dosing levels (4 and 6 mg/kg). These doses were then employed to condition two animals at each dose level prior to autologous transplantation of genetically modified cells using our standard methods.
RESULTS : Busulfan pharmacokinetic (PK) data showed the area under the curve (AUC), drug half-life, and drug clearance were consistent within each dose group and similar to those reported in children. Single doses of busulfan were well tolerated and produced dose-dependent myelosuppression, most notably in the neutrophil and platelet counts. Although marking levels reached over 1% early in one animal, the long-term marking was low but detectable at 0.01 to 0.001%.
CONCLUSIONS : We conclude that low-dose intravenous bolus infusion of busulfan is well tolerated, has dose-dependent effects on peripheral blood counts, and allows long-term engraftment of genetically modified cells, but at levels too low for most clinical disorders.
PMID: 16459181
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