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Hiroya Tamaki,
Tatsuya Fujioka,
Kazuhiro Ikegame,
Satoshi Yoshihara,
Katsuji Kaida,
Kyoko Taniguchi,
Ruri Kato,
Taduko Tokugawa, Jun Nakata,
Takayuki Inoue,
Aya Yano,
Ryoji Eguchi,
Masaya Okada,
Etsuko Maruya,
Hiroh Saji,
Hiroyasu Ogawa
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ABSTRACT: Mismatched human leukocyte antigens (HLAs) on leukemic cells can be targeted by donor T cells in HLA-mismatched/haploidentical stem cell transplantation. In two cases of acute myeloid leukemia with t(6;11)(q27;q23) abnormality presented here, flow cytometry analysis showed a lack of HLA-A unshared between recipients and donors in relapsing leukemic cells after HLA-haploidentical transplantation. However, high-resolution HLA genotyping showed that one case lacked a corresponding HLA haplotype, whereas the other preserved it. These cases suggest that leukemic cells, which lacked mismatched HLA expression, might have an advantage in selective expansion under donor T-cell immune surveillance after HLA-haploidentical transplantation. Most importantly, down-regulation of unshared HLA expression potentially occurs by genetic alterations other than loss of HLA alleles. © 2012 John Wiley & Sons A/S.
European Journal Of Haematology 10/2012; · 2.61 Impact Factor
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Kyoko Taniguchi,
Satoshi Yoshihara,
Hiroya Tamaki,
Tsuguto Fujimoto,
Kazuhiro Ikegame,
Katsuji Kaida, Jun Nakata,
Takayuki Inoue,
Ruri Kato,
Tatsuya Fujioka,
Masaya Okada,
Toshihiro Soma,
Hiroyasu Ogawa
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ABSTRACT: Adenovirus (AdV) infection is an emerging complication in patients undergoing allogeneic stem cell transplantation (SCT) and is closely associated with delayed immune reconstitution. In particular, disseminated AdV disease accompanies a high mortality. We retrospectively examined the incidence of AdV infection in patients undergoing unmanipulated haploidentical SCT. Following 121 transplantations in 110 patients, three had asymptomatic AdV viremia, three had localized AdV disease (hemorrhagic cystitis, HC), and seven had disseminated AdV disease (HC + viremia). The median time from transplantation to the onset of AdV-associated HC was 15 days (range 4-39), and the median time to the onset of disseminated AdV disease was 23 days (range 7-38). The cumulative incidence of AdV-associated HC was 8.3 %, and that of disseminated AdV disease was 5.8 %. AdV group B (type 11, type 34, or type 35) was detected in plasma samples from all the patients with disseminated AdV disease. Among them, three patients who received either cidofovir or donor lymphocyte infusion (DLI) alone progressed to pneumonia and died. The remaining four patients were treated with the combination of cidofovir and low-dose unmanipulated DLI, and all survived. We showed that disseminated AdV disease is a significant complication after haplo-SCT and that the combination of cidofovir and DLI is a promising treatment option.
Annals of Hematology 04/2012; 91(8):1305-12. · 2.62 Impact Factor
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Soyoko Morimoto,
Yoshihiro Oka,
Akihiro Tsuboi,
Yukie Tanaka,
Fumihiro Fujiki,
Hiroko Nakajima,
Naoki Hosen,
Sumiyuki Nishida, Jun Nakata,
Yoshiki Nakae, [......],
Akira Myoui,
Takayuki Enomoto,
Shuichi Izumoto,
Mitsugu Sekimoto,
Naoki Kagawa,
Naoya Hashimoto,
Toshiki Yoshimine,
Yusuke Oji,
Atsushi Kumanogoh,
Haruo Sugiyama
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ABSTRACT: Wilms' tumor gene 1 (WT1) protein is a promising tumor-associated antigen. In patients with WT1-expressing malignancies, WT1-specific CTLs are spontaneously induced as a result of an immune response to the WT1 protein. In the present study, we performed single cell-level comparative analysis of T cell receptor β-chain variable region (TCR-BV) gene families of a total of 750 spontaneously induced WT1(126) peptide (amino acids 126-134, WT1(126))-specific CTLs in both HLA-A*0201(+) patients with solid tumors and healthy donors (HDs). This is the first report of direct usage analysis of 24 kinds of TCR-BV gene families of WT1(126)-specific CTLs at the single cell level. Usage analysis with single-cell RT-PCR of TCR-BV gene families of individual FACS-sorted WT1(126) tetramer(+) CD8(+) T cells showed, for the first time, that: (i) BVs 3, 6, 7, 20, 27, and 28 were commonly biased in patients and HDs; (ii) BVs 2, 11, and 15 were biased only in patients; and (iii) BVs 4, 5, 9, and 19 were biased only in HDs. However, statistical analysis of similarity of individual usage frequencies of 24 kinds of TCR-BV gene families between patients and HDs indicated that the usage frequencies of TCR-BV gene families in patients reflected those in HDs. These results should provide us with a novel insight for a better understanding of WT1-specific immune responses.
Cancer Science 11/2011; 103(3):408-14. · 3.33 Impact Factor
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Leukemia research 07/2011; 35(12):1658-9. · 2.36 Impact Factor
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[Rinshō ketsueki] The Japanese journal of clinical hematology 05/2011; 52(5):235-42.
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International journal of hematology 04/2011; 93(4):558-60. · 1.17 Impact Factor
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ABSTRACT: Donor leukocyte infusion (DLI) has been successfully used for some life-threatening viral infections after stem cell transplantation (SCT). We describe here the first case of DLI treatment for cytomegalovirus (CMV) retinitis. A 49-year-old female patient with AML, M1 underwent SCT with a reduced-intensity conditioning regimen from HLA-haploidentical son. On day +140, the patient developed CMV retinitis of her left eye despite the continuing antiviral therapy. DLI at a dose of 1 x 10(5) CD3+ cells/kg was added to ganciclovir and foscarnet therapy. Eighteen days after the DLI, the funduscopic findings revealed improvement of the retinitis and the development of vitreous inflammation. Simultaneously, the number of CD4+ cells in the peripheral blood rapidly increased. Thus, we consider it likely that DLI induced a local immune response against CMV antigens, which resulted in the immune recovery vitritis. This case suggested the potentiality of DLI for the treatment of CMV retinitis.
European Journal Of Haematology 11/2005; 75(4):352-4. · 2.61 Impact Factor
