Abstract
An 8-year-old boy with a bone marrow relapse of T cell acute lymphoblastic leukemia underwent stem-cell transplantation from a human leukocyte antigen (HLA)-haploidentical mother. Five months later, he relapsed with central nervous system (CNS) involvement. Systemic chemotherapy and repeated intrathecal chemotherapy induced consciousness disturbances and frequent arrhythmia, prompting us to discontinue the chemotherapy. He had already received an 18-Gy prophylactic cranial irradiation, an 8-Gy total body irradiation, and a 15-Gy local irradiation for pituitary gland involvement. We therefore performed five intrathecal donor lymphocyte infusions (IDLIs) in escalating doses from 1 × 104 up to 1 × 106 cells/kg. All IDLIs were safe without infusion reactions or graft-versus-host disease. After the second and later IDLIs, donor mononuclear cells were continuously detected in cerebrospinal fluid; however, he did not achieve donor-dominant chimerism. Based on our case and four cases reported in the literature, the efficacy of IDLI therapy is limited for CNS relapse of hematological malignancies. However, we suggest that IDLI remains a feasible and safe option, as no GVHD or other adverse effects occurred, even in the HLA-haploidentical setting. We will make further efforts to increase the efficacy.
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References
Rubin J, Frost BM, Arvidson J, Wide K, Gustafsson-Jernberg A, Gustafsson B. Intrathecal chemoprophylaxis after HSCT in children. Pediatr Transpl. 2008;12:889–95.
Oshima K, Kanda Y, Yamashita T, Takahashi S, Mori T, Nakaseko C, et al. Central nervous system relapse of leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2008;14:1100–7.
Shi JM, Meng XJ, Luo Y, Tan YM, Zhu XL, Zheng GF, et al. Clinical characteristics and outcome of isolated extramedullary relapse in acute leukemia after allogeneic stem cell transplantation: a single-center analysis. Leuk Res. 2013;37:372–7.
Yanagisawa R, Nakazawa Y, Sakashita K, Tanaka M, Shikama N, Kamijo T, et al. Low toxicity of a conditioning with 8-Gy total body irradiation, fludarabine and cyclophosphamide as preparative regimen for allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies. Pediatr Transpl. 2009;13:737–45.
Hirabayashi K, Nakazawa Y, Sakashita K, Kurata T, Saito S, Yoshikawa K, et al. Reduced-toxicity myeloablative conditioning consisting of 8-Gy total body irradiation, cyclophosphamide and fludarabine for pediatric hematological malignancies. Sci Rep. 2014;4:6942.
Neumann M, Blau IW, Burmeister T, Tietze-Buerger C, Blau O, Gerbitz A, et al. Intrathecal application of donor lymphocytes in leukemic meningeosis after allogeneic stem cell transplantation. Ann Hematol. 2011;90:911–6.
Meuleman N, Ahmad I, Duvillier H, Lemort M, Bennani J, Martiat M, Lagneaux L, et al. Intrathecal donor lymphocyte infusion for the treatment of suspected refractory lymphomatous meningitis: a case report. Eur J Haematol. 2006;77:523–6.
Bonadio WA. The cerebrospinal fluid: physiologic aspects and alterations associated with bacterial meningitis. Pediatr Infect Dis J. 1992;11:423–31.
Pui CH. Central nervous system disease in acute lymphoblastic leukemia: prophylaxis and treatment. Hematol Am Soc Hematol Educ Program. 2006;1:142–6.
Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Chen YH, et al. Haploidentical/mismatched hematopoietic stem cell transplantation without in vitro T cell depletion for T cell acute lymphoblastic leukemia. Biol Blood Marrow Transpl. 2012;18:716–21.
Goldberg SL, Mangan KF, Klumpp TR, Cropper TM, Schnall SF, Macdonald JS. Lack of a graft-versus-leukemia effect in an immunologically privileged sanctuary site. Bone Marrow Transpl. 1994;14:180–1.
Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W. Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. Haematologica. 2007;92:414–7.
Oehmichen M, Domasch D, Wiethölter H. Origin, proliferation, and fate of cerebrospinal fluid cells. A review on cerebrospinal fluid cell kinetics. J Neurol. 1982;227:145–50.
Ho VT, Kim HT, Kao G, Cutler C, Levine J, Rosenblatt J, Joyce R, Antin JH, Soiffer RJ, Ritz J, Avigan D, Alyea EP 3rd. Sequential infusion of donor-derived dendritic cells with donor lymphocyte infusion for relapsed hematologic cancers after allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2014;89:1092–6.
Davila ML, Bouhassira DC, Park JH, Curran KJ, Smith EL, Pegram HJ, et al. Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies. Int J Hematol. 2014;99:361–71.
Gill S, June CH. Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Immunol Rev. 2015;263:68–89.
Mamonkin M, Rouce RH, Tashiro H, Brenner MK. A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood. 2015;20(126):983–92.
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Yanagisawa, R., Nakazawa, Y., Sakashita, K. et al. Intrathecal donor lymphocyte infusion for isolated leukemia relapse in the central nervous system following allogeneic stem cell transplantation: a case report and literature review. Int J Hematol 103, 107–111 (2016). https://doi.org/10.1007/s12185-015-1902-1
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DOI: https://doi.org/10.1007/s12185-015-1902-1