3. ่ชฟ็็ๆณ( ้ ๅ็ๆณ)
Conditioning Preparative
็ฎ็
เนๆไพ่ถณๅค ็ๅ ็ซๆๅถไฝ็จ๏ผ้ฟๅ ็ข็ๆๆฅ
(To provide adequate immunosuppression to prevent rejection of the
transplanted graft)
เนๆ น้ค็ ๆฃๆฌ่บซ็็ ็
(To eradicate the disease for which the transplant is being
performed
ๅธธ่ฆ็่ชฟ็็ๆณ
เน้ชจ้ซๆงๆฏๆง็ๆณ( Myeloablative regimens )
เนๆธๅผทๅบฆ็ๅ็ฝฎ็ๆณ( Reduced intensity regimens )
เน้้ชจ้ซๆงๆฏๆง็ๆณ( Nonmyeloablative regimens )
4. ่ชฟ็็ๆณๅผทๅบฆไนๆฏ่ผ
No standard choice
BU indicates busulfan; CY, cyclophosphamide; TBI, total body irradiation; Flu, fludarabine (various dosing
schedules); AraC, cytosine arabinoside; ATG, antithymocyte globulin, 131I, anti-CD45 antibody conjugated to 131I.
*โHigh-doseโ TBI (800-1320 cGy). โ โLow-doseโ TBI (200-400 cGy).
Blood. 2010; 116(23): 4762โ4770.
32. ้ ้ฒGVHD๏ผMethotrexate
Day - 7 - 6 - 5 - 4 - 3 - 2 - 1 0 + 1 + 2 + 3
Busulfan l l l l l
Endoxan l l
rATG l l l
MTX
CsA l l l l l
D+1, D+3, D+6, D+11
33. ๆฉ่ฝ๏ผ
thymidine
Leucovorin calcium, a derivative of tetrahydrofolic acid, may block the effects of
methotrexate if given shortly after the antineoplastic agent.
Tissues with high rates of cellular proliferation such as neoplasms, psoriatic epidermis,
bone marrow, the lining of the GI tract, hair matrix, and fetal cells are most sensitive
to the effects of methotrexate.
38. ้ ้ฒGVHD๏ผCyclosporine
Day - 7 - 6 - 5 - 4 - 3 - 2 - 1 0 + 1 + 2 + 3
Busulfan l l l l l
Endoxan l l
rATG l l l
MTX
CsA l l l l l
D+1, D+3, D+6, D+11
ย DNAๅ ฑๅนๅๅ็ฉ็ๅฝขๆ :ย ย ็ทๅบๅ่ฅ็ฉไธป่ฆๅDNA็้นผๅบๅฝขๆๅๅ็ฉ๏ผ้ปๆญข็ดฐ่ๅ่ฃๆ้็DNA่ค่ฃฝ้็จ๏ผDNA้ญๅฐ็ ดๅฃๆฎบๆญป็ดฐ่
Busulfan is an alkylating agent which reacts with the N-7 position of guanosine and interferes with DNA replication and transcription of RNA. Busulfan has a more marked effect on myeloid cells than on lymphoid cells and is also very toxic to hematopoietic stem cells. Busulfan exhibits little immunosuppressive activity. Interferes with the normal function of DNA by alkylation and cross-linking the strands of DNA
Drug Discovery Today Volume 00, Number 00 May 2014
Phenytoin I.V. effects: Hypotension, bradycardia, cardiac arrhythmia, cardiovascular collapse (especially with rapid I.V. use), venous irritation and pain, thrombophlebitisย
ๆฏๅฆ่ฉฒๅฎๆ็ฃๆธฌphernytoin่กไธญๆฟๅบฆ๏ผ็ก็ธ้ๆ็ป๏ผ่ฅๆphenytoin toxicityไธญๆฏ
This short duration of phenytoin administration
is unlikely to be sufficient to achieve steady-state
phenytoin concentrations, which usually takes
1โ3 weeks after starting the drug
Most cases of cyclophosphamideinduced
bladder
cancer have been reported in patients who received the
drug orally for more than 1 year. A cumulative dose of
more than 20 g is the principal risk factor, with a median
interval from treatment to diagnosis of bladder cancer
of 7 years.58 Patients treated with longterm
cyclophosphamide
should be followed indefinitely with routine
urinalysis for microscopic hematuria and cysto scopy if
red blood cells are present.
The pathophysiology of graft-vs-host disease (GVHD).[162,163] The pathophysiology of GVHD involves a three-step process: (i) the
conditioning regimen injures host tissues, which results in the release of inflammatory cytokines (i.e. โcytokine stormโ); (ii) antigen-presenting
cells (APCs) and dendritic cells (DCs) activate donor T cells, followed by donor T-cell proliferation and differentiation; (iii) numerous immune
effector cells are activated, which leads to GVHD-mediated destruction of target tissue through cytotoxic and inflammatory attacks (
ๆ่ด่ Tๆทๅทด็ ็ๅ ็ซๅฐๆ็ ไบบ็ต็นๅๆ๏ผไธ่ฌไพต็ฏ็ฎ่ ่ ธ่ ่่
n the cytoplasm, cyclosporine
(CsA) binds to its immunophilin, cyclophylin (CpN), forming a complex between cyclosporine and CpN.
The cyclosporineโCpN complex binds and blocks the function of the enzyme calcineurin (CaN), which has a
serine/threonine phosphatase activity. As a result, CaN fails to dephosphorylate the cytoplasmic component of
the nuclear factor of activated T cells (NF-ATc), and thereby the transport of NF-ATc to the nucleus
and the binding of NF-ATc to the nuclear component of the nuclear factor of activated T cells (NF-ATn). The
NF-ATcโNF-ATn complex binds to the promoter of the interleukin 2 (IL-2) gene and initiates IL-2 production.
Consequently, T cells do not produce IL-2, which is necessary for full T-cell activation. Tacrolimus (FK506)
binds to FK506-binding protein (FKBP), forming a FK506โFKBP complex, which binds to and blocks CaN. The
FK506โFKBPโCaN complex inhibits the activation of NF-ATc, thus preventing its entrance into the nucleus.
Although the pre-drugs cyclosporine and FK506 bind to different target molecules, both drugs inhibit T-cell
activation in the same fashion
(~1.5 mg/kg) (ๅ ไฝต็จvoriconazole,่ตทๅงๅ้ๆธ็ด50%) 100 mg in NS 500cc
Kidney transplantation: principles and practice, 2008, page 247
