Giralt S, Davis M, O'Brien S, van Besien K, Champlin R, de Vos D, Kantarjian H
Department of Hematology, University of Texas, MD Anderson Cancer Center, Houston 77030, USA.
Leukemia. 1997 Mar;11 Suppl 1:S32-4.
The aim was to determine the efficacy and safety of decitabine in the settings of relapse post-allogeneic progenitor cell transplantation or as part of the conditioning regimen. Three patients (two AML, one ALL) received single agent decitabine 1000 mg/m2 total dose) for treatment of relapse post-transplant (group 1). Median age was 32 years. Median time to relapse was 7 months. In another study four patients (three CML in an accelerated phase, one AMML) received decitabine 400 mg/m2, with busulfan 12 mg/kg and cyclophosphamide 100 mg/kg as conditioning for allogeneic stem cell transplantation (group 2). Median age was 42 years; median time to transplant was 5 months. All patients received at least 4 x 10(6) CD34+ cells from their HLA compatible donors. All patients in group 1 achieved complete remissions after decitabine therapy. The median time to neutrophil and platelet recovery were 24 and 23 days, respectively. Two patients required reinfusion of donor cells because of delayed engraftment. One patient remains alive and in remission 160 days post-decitabine therapy. Two patients in group 2 engrafted on days 23 and 25. Two patients required reinfusion of stem cells because of lack of neutrophil recovery by day 21. Two patients achieved complete cytogenetic and hematologic remission. Three patients are alive at 167,129, and 109 days post-transplant. One patient died of progressive Pseudomonas cellulitis 54 days post-initial infusion. Decitabine therapy is well tolerated in the setting of allogeneic stem cell transplantation, initial results in patients relapsing after transplant are encouraging and warrant further studies. The causes of delayed engraftment after single agent or combination therapy need to be better explored. The existence of active metabolites of decitabine which may still be present in the blood at the time of stem cell infusions, and/or insufficient immunosuppression of the preparative regimen are being explored as possible explanations for this phenomenon.
目的是确定地西他滨在异基因祖细胞移植后复发情况下或作为预处理方案一部分时的疗效和安全性。三名患者（两名急性髓系白血病、一名急性淋巴细胞白血病）接受单药地西他滨（总剂量1000mg/m²）治疗移植后复发（第1组）。中位年龄为32岁。复发的中位时间为7个月。在另一项研究中，四名患者（三名加速期慢性髓系白血病、一名急性粒单核细胞白血病）接受400mg/m²地西他滨，同时接受12mg/kg白消安和100mg/kg环磷酰胺作为异基因干细胞移植的预处理（第2组）。中位年龄为42岁；移植的中位时间为5个月。所有患者均接受来自与其HLA相匹配供体的至少4×10⁶个CD34⁺细胞。第1组所有患者在地西他滨治疗后均实现完全缓解。中性粒细胞和血小板恢复的中位时间分别为24天和23天。两名患者因植入延迟需要输注供体细胞。一名患者在地西他滨治疗后160天仍存活且处于缓解状态。第2组两名患者分别在第23天和第25天植入。两名患者因到第21天时中性粒细胞未恢复需要输注干细胞。两名患者实现完全细胞遗传学和血液学缓解。三名患者在移植后167天、129天和109天存活。一名患者在初次输注后54天死于进行性铜绿假单胞菌蜂窝织炎。在异基因干细胞移植情况下，地西他滨治疗耐受性良好，移植后复发患者的初步结果令人鼓舞，值得进一步研究。单药或联合治疗后植入延迟的原因需要进一步深入探究。正在探讨地西他滨的活性代谢产物在干细胞输注时可能仍存在于血液中，和/或预处理方案免疫抑制不足是否可能是这一现象的解释。
