Zimmer B M, Berdel W E, Ludwig W D, Notter M, Reufi B, Thiel E
Department of Hematology and Oncology, Universitätsklinikum Steglitz, Freie Universität Berlin, F.R.G.
Leuk Res. 1993 Mar;17(3):277-83. doi: 10.1016/0145-2126(93)90012-a.
Recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-SCF) is currently being tested in clinical trials for the treatment of acute myeloid leukemias with two main intentions: reduction of neutropenia and recruitment of leukemic blasts into cell cycle to enhance cytarabine (ara-C) mediated cytotoxicity. We report a case of a fatal spleen rupture in a patient with acute monocytic leukemia (AML M5b) who was treated according to a clinical phase I/II protocol with rh GM-CSF priming and standard induction chemotherapy TAD 9 (thioguanine/ara-C/daunorubicin). During treatment we observed rapidly rising peripheral blast counts and the development of an acute abdomen. Ultrasound examination revealed splenomegaly due to diffuse cellular infiltration and spleen rupture. The patient died 17 days later due to pneumonia and renewed spleen hemorrhage. Bone marrow progenitor assays before treatment showed exclusive growth of monocytoid blast cell colonies (CFU-L). Colony growth could be stimulated with rh GM-CSF and blocked dose-dependently by a monoclonal anti-GM-CSF antibody. CFU-L proliferation also increased after stimulation with rh interleukin-3 (rh IL-3) and supra-additively with rh granulocyte colony-stimulating factor (rh G-CSF) combined with rh GM-CSF. Furthermore, rh GM-CSF induced surface marker expression of CDw 65 and CD 11b on isolated CFU-L blasts. After short-term suspension culture, rh GM-CSF enhanced the expression of CD 29- and CD 11b-adhesion molecules on peripheral blast cells. In summary, this case represents a fatal spleen rupture occurring during rh GM-CSF priming and induction chemotherapy for acute monocytic leukemia. Although the etiology of this spleen rupture remains uncertain, in view of our data we suggest special caution, when further testing this therapy protocol in acute leukemias with monocytic subtype and high peripheral blast cell counts.
重组人（rh）粒细胞-巨噬细胞集落刺激因子（GM-SCF）目前正在临床试验中用于治疗急性髓系白血病，主要有两个目的：减少中性粒细胞减少症以及促使白血病原始细胞进入细胞周期，以增强阿糖胞苷（ara-C）介导的细胞毒性。我们报告了一例急性单核细胞白血病（AML M5b）患者发生致命性脾破裂的病例，该患者按照I/II期临床方案接受rh GM-CSF预处理和标准诱导化疗TAD 9（硫鸟嘌呤/阿糖胞苷/柔红霉素）治疗。在治疗期间，我们观察到外周原始细胞计数迅速上升以及急腹症的发生。超声检查显示由于弥漫性细胞浸润导致脾肿大和脾破裂。患者17天后因肺炎和再次脾出血死亡。治疗前的骨髓祖细胞分析显示单核样原始细胞集落（CFU-L）单独生长。rh GM-CSF可刺激集落生长，而单克隆抗GM-CSF抗体可剂量依赖性地阻断其生长。用rh白细胞介素-3（rh IL-3）刺激后CFU-L增殖也增加，rh粒细胞集落刺激因子（rh G-CSF）与rh GM-CSF联合刺激后增殖超相加。此外，rh GM-CSF诱导分离的CFU-L原始细胞表面标记CDw 65和CD 11b表达。短期悬浮培养后，rh GM-CSF增强外周原始细胞上CD 29和CD 11b黏附分子的表达。总之，该病例代表了在rh GM-CSF预处理和急性单核细胞白血病诱导化疗期间发生的致命性脾破裂。尽管这种脾破裂的病因仍不确定，但鉴于我们的数据，我们建议在急性单核细胞亚型且外周原始细胞计数高的白血病中进一步测试该治疗方案时要特别谨慎。
