TRANSPLANTATION AND CELLULAR ENGINEERING Nonleukemic myeloid dendritic cells obtained from autologous stem cell products elicit antileukemia responses in patients with acute myeloid leukemia Juana Serrano-López, Joaquin Sanchez-Garcia, Josefina Serrano, Miguel A. Alvarez-Rivas, Jose M. Garcia-Castellano, Jose Roman-Gomez, Olga de la Rosa, Concepcion Herrera-Arroyo, and Antonio Torres-Gomez BACKGROUND: Dendritic cell (DC)-based immuno- therapeutic protocols are being developed to treat acute myeloid leukemia (AML). So far, DCs for clinical use are obtained from leukemic blasts or from monocytes, after 6 to 10 days of ex vivo culture. However, DC pre- cursors are easily driven to DCs in short-term culture. We tested if DC precursors contained in peripheral blood stem cell (PBSC) products obtained from AML patients can be used to induce antileukemia responses. STUDY DESIGN AND METHODS: PBSCs obtained from 30 consecutive AML patients were tested. Myeloid DCs (MDCs) were purified by immunomagnetic selec- tion and screened for cytogenetic and/or molecular abnormalities by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) assays. MDCs were matured and pulsed with autologous blast lysates and tested for stimulatory capability against AML cells. RESULTS: A median of 0.62 ¥ 10 6 MDCs (range, 0.04-3.25)/mL were quantified in PBSC products. Iso- lated MDC expressed Class I and II HLA but CD86, CD54, and CCR5 partially. By FISH or PCR assay, these MDCs lacked cytogenetic or molecular abnormali- ties detected in leukemia cells at diagnosis. MDCs achieved a maturated stage (mature-MDCs) after 24-hour ex vivo culture with tumor necrosis factor-a and autologous blast lysates. These mature-MDCs were capable of stimulating autologous peripheral blood effectors to exert cytotoxicity against autologous leuke- mia cells and HL-60 cell line. CONCLUSION: We conclude that PBSCs obtained for autologous stem cell transplantation can constitute a novel source of MDCs to design feasible vaccination trials. A pproximately 75% of adult patients under 65 years old diagnosed with acute myeloid leuke- mia (AML) reach a complete remission (CR) after induction therapy with cytarabine and anthracycline-based chemotherapy (CT) but most will relapse if they do not receive further therapy. Cytotoxic and immunosuppressive therapy followed by allogeneic hematopoietic stem cell transplantation from a geneti- cally HLA-identical donor can cure approximately 50% to 60% of patients and in a less proportion when alternative donors are employed. 1 Ablative intensive CT followed by autologous stem cell transplantation (auto-SCT) is a therapeutic option in low- to intermediate-risk AML who lack suitable donors. However, leukemia relapse is the most common cause of treatment failure after auto-SCT, ABBREVIATIONS: AML = acute myeloid leukemia; APC = allophycocyanin; auto-SCT = autologous stem cell transplantation; BD = Becton-Dickinson; CR = complete remission; CT = chemotherapy; DC(s) = dendritic cell(s); E:F = effector:target; FBS = fetal bovine serum; FISH = fluorescence in situ hybridization; FLT3-ITD = Flt3 internal tandem duplication; LAA(s) = leukemia-associated antigen(s); MDC(s) = myeloid dendritic cell(s); PBSC(s) = peri- pheral blood stem cell(s); PDC(s) = plasmocytoid CD303+ blood dendritic cell(s). From the Department of Hematology and Laboratory for Cellu- lar Therapy, Instituto Maimonides Investigación Biomédica (IMIBIC), and the Immunology Department, University Hospital “Reina Sofía,” Cordoba, Spain. Address reprint requests to: Joaquin Sanchez Garcia, MD, PhD, Hematology Department, University Hospital Reina Sofía, Avda. Menendez Pidal s/n, 14004 Cordoba, Spain; e-mail: joaquin.sanchez@cheerful.com. Received for publication September 20, 2010; revision received November 15, 2010, and accepted November 22, 2010. doi: 10.1111/j.1537-2995.2010.03042.x TRANSFUSION 2011;51:1546-1555. 1546 TRANSFUSION Volume 51, July 2011