Immunotherapy using autologous monocyte-derived dendritic cells pulsed with leukemic cell lysates for acute myeloid leukemia relapse after autologous peripheral blood stem cell transplantation.
Although a second stem cell transplantation (SCT) can be used as salvage therapy in patients with relapsing leukemia after SCT, most of these patients have a poor outcome. We tried clinical vaccination using monocyte-derived dendritic cells (DCs) pulsed with leukemic lysates to treat relapsing acute myeloid leukemia (AML) after autologous SCT. To generate DCs, CD14+ cells isolated from peripheral blood stem cell products were cultured in AIM-V in the presence of GM-CSF and IL-4. Adding TNF-alpha on day 6 induced maturation of the DCs, which were harvested on day 8 or 9. The DCs were incubated with tumor lysate and KLH for 2 hr at 37 degrees C. After certifying the absence of microorganisms and endotoxins, the patients received four DC vaccinations at two- to three-week intervals. Two patients received four DC vaccinations with means of 7.8 x 10(6) and 9 x 10(6) DCs at two- to three-week intervals. The DC vaccinations were well tolerated with no apparent side effects. After the vaccinations, the patients showed immunological responses with positive delayed-type hypersensitivity skin reaction and increasing autologous T cells stimulatory capacity to the DCs; however, the BM blast percentage of the patients did not improve. The results suggest that DCs are a feasible cellular therapy for relapsing AML after autologous SCT.
Lee
Je-Jung
JJ
Blood & Marrow Transplant Program, Chonnam National University Medical School, Gwangju, Korea. drjejung@chonnam.ac.kr
Kook
Hoon
H
Park
Myong-Suk
MS
Nam
Jong-Hee
JH
Choi
Bo-Hwa
BH
Song
Won-Hyun
WH
Park
Kyeong-Soo
KS
Lee
Il-Kwon
IK
Chung
Ik-Joo
IJ
Hwang
Tai-Ju
TJ
Kim
Hyeoung-Joon
HJ
D000293:Adolescent; D000328:Adult; D017252:CD3 Complex / Q000096:biosynthesis; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015847:Interleukin-4 / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000473:pathology* / Q000628:therapy*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D010641:Phenotype; D012008:Recurrence; D033581:Stem Cell Transplantation; D013696:Temperature; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017252:CD3 Complex; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4