Daratumumab成功治疗急性混合细胞白血病异基因造血干细胞移植后复发1例
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摘要
复发仍然是高危急性白血病患者造血干细胞移植失败的主要原因。过去几十年,单克隆抗体治疗复发白血病取得了一定进展。Daratumumab作为一个新研发的人源化单克隆抗体,可用于治疗难治复发多发性骨髓瘤,其靶点为骨髓瘤细胞表面CD38抗原。CD38也广泛表达于白血病细胞。本文首次报道了采用Daratumumab成功治疗1例25岁青年男性急性混合细胞白血病异基因造血干细胞移植后复发的案例,为白血病移植后复发提供了一种有效的治疗手段。
Relapse remains the primary cause of failure of hematopoietic stem cell transplantation in patients with high-risk acute leukemia. In the past several decades, some progress has been made in the treatment of relapsed leukemia with monoclonal antibodies.Daratumumab, a newly developed humanized monoclonal antibody, has been applied in the treatment of refractory and recurrent multiple myeloma, targeting CD38. Yet, CD38 is also widely expressed in leukemia cells. Therefore, the successful treatment with Daratumumab for a 25-year-old male patient with mixed phenotype acute leukemia who relapsed after allogeneic hematopoietic stem cell transplantation is reported here for the first time, to provide an effective way to treat the leukemia relapse after transplantation.
Relapse remains the primary cause of failure of hematopoietic stem cell transplantation in patients with high-risk acute leukemia. In the past several decades, some progress has been made in the treatment of relapsed leukemia with monoclonal antibodies.Daratumumab, a newly developed humanized monoclonal antibody, has been applied in the treatment of refractory and recurrent multiple myeloma, targeting CD38. Yet, CD38 is also widely expressed in leukemia cells. Therefore, the successful treatment with Daratumumab for a 25-year-old male patient with mixed phenotype acute leukemia who relapsed after allogeneic hematopoietic stem cell transplantation is reported here for the first time, to provide an effective way to treat the leukemia relapse after transplantation.
引文
[1]王静波,吴彤,达万明,等.挽救性异基因造血干细胞移植治疗45例复发难治性急性髓系白血病疗效分析[J].中华血液学杂志, 2012, 33(6):467-470. doi:10.3760/cma. j. issn.0253-2727.2012.06.009.
[2]St?lzel F, Hackmann K, Kuithan F, et al. Clonal evolution including partial loss of human leukocyte antigen genes favoring extramedullary acute myeloid leukemia relapse after matched related allogeneic hematopoietic stem cell transplantation[J]. Transplantation, 2012, 93(7):744-749. doi:10.1097/TP.0b013e3182481113.
[3]Feuchtinger T, Pfeiffer M, Pfaffle A, et al. Cytolytic activity of NK cell clones against acute childhood precursor-B-cell leukaemia is influenced by HLA class I expression on blasts and the differential KIR phenotype of NK clones[J]. Bone Marrow Transplant,2009, 43(11):875-881. doi:10.1038/bmt.2008.398.
[4]Ruvolo PP. Galectins as regulators of cell survival in the leukemia niche[J]. Adv Biol Regul, 2019, 71:41-54. doi:10.1016/j. jbior.2018.09.003.
[5]Gleason MK, Lenvik TR, McCullar V, et al. Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9[J]. Blood, 2012, 119(13):3064-3072. doi:10.1182/blood-2011-06-360321.
[6]Gon?alves Silva I, Yasinska IM, Sakhnevych SS, et al. The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells[J]. EBioMedicine, 2017, 22:44-57. doi:10.1016/j. ebiom.2017.07.018.
[7]Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma(SIRIUS):an open-label, randomised, phase 2 trial[J]. Lancet, 2016, 387(10027):1551-1560. doi:10.1016/S0140-6736(15)01120-4.
[8]Aeppli S, Driessen C, Graf L, et al. Systemic treatment of a patient with relapsed and refractory extranodal NK/T-cell lymphoma(ENKL)and meningeosis leukemica with daratumumab[J]. Hematol Oncol, 2018, 36(4):713-714. doi:10.1002/hon.2533.
[9]Buteyn NJ, Fatehchand K, Santhanam R, et al. Anti-leukemic effects of all-trans retinoic acid in combination with Daratumumab in acute myeloid leukemia[J]. Int Immunol,2018, 30(8):375-383. doi:10.1093/intimm/dxy040.
[2]St?lzel F, Hackmann K, Kuithan F, et al. Clonal evolution including partial loss of human leukocyte antigen genes favoring extramedullary acute myeloid leukemia relapse after matched related allogeneic hematopoietic stem cell transplantation[J]. Transplantation, 2012, 93(7):744-749. doi:10.1097/TP.0b013e3182481113.
[3]Feuchtinger T, Pfeiffer M, Pfaffle A, et al. Cytolytic activity of NK cell clones against acute childhood precursor-B-cell leukaemia is influenced by HLA class I expression on blasts and the differential KIR phenotype of NK clones[J]. Bone Marrow Transplant,2009, 43(11):875-881. doi:10.1038/bmt.2008.398.
[4]Ruvolo PP. Galectins as regulators of cell survival in the leukemia niche[J]. Adv Biol Regul, 2019, 71:41-54. doi:10.1016/j. jbior.2018.09.003.
[5]Gleason MK, Lenvik TR, McCullar V, et al. Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9[J]. Blood, 2012, 119(13):3064-3072. doi:10.1182/blood-2011-06-360321.
[6]Gon?alves Silva I, Yasinska IM, Sakhnevych SS, et al. The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells[J]. EBioMedicine, 2017, 22:44-57. doi:10.1016/j. ebiom.2017.07.018.
[7]Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma(SIRIUS):an open-label, randomised, phase 2 trial[J]. Lancet, 2016, 387(10027):1551-1560. doi:10.1016/S0140-6736(15)01120-4.
[8]Aeppli S, Driessen C, Graf L, et al. Systemic treatment of a patient with relapsed and refractory extranodal NK/T-cell lymphoma(ENKL)and meningeosis leukemica with daratumumab[J]. Hematol Oncol, 2018, 36(4):713-714. doi:10.1002/hon.2533.
[9]Buteyn NJ, Fatehchand K, Santhanam R, et al. Anti-leukemic effects of all-trans retinoic acid in combination with Daratumumab in acute myeloid leukemia[J]. Int Immunol,2018, 30(8):375-383. doi:10.1093/intimm/dxy040.