Rodriguez-Galindo C, Poquette C A, Marina N M, Head D R, Cain A, Meyer W H, Santana V M, Pappo A S
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
J Pediatr Hematol Oncol. 2000 Jul-Aug;22(4):321-9. doi: 10.1097/00043426-200007000-00008.
Current treatment of the Ewing sarcoma family of tumors (ESFT) includes intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating agents, and granulocyte colony-stimulating factor (G-CSF). This treatment approach has been associated with myelodysplasia and acute myeloid leukemia. Because macrocytosis and thrombocytopenia are distinctive features of myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to determine the degree and duration of macrocytosis and thrombocytopenia and their relation with the development of therapy-related hematologic malignancies.
The study group consisted of 73 patients with ESFT treated on two consecutive protocols (EW92 and EW87). Both chemotherapy regimens incorporated the same agents but differed in cumulative drug dose, dose per course, and the use of G-CSF. Platelet counts and the mean corpuscular volume (MCV) of erythrocytes were determined at diagnosis and during follow-up visits after completion of treatment.
Patients in the EW92 group had significantly greater MCVs after treatment than did the less intensively treated EW87 group. These changes persisted throughout the 40-month observation period. Patients in the EW92 group also had lesser mean platelet counts after treatment than those in the EW87 group. MCV differences (from baseline) were inversely related to platelet counts. The cumulative incidence of treatment-related acute myeloid leukemia was 7.8%+/-4.7% at 4 years in the EW92 group and zero in the EW87 group.
Patients treated for ESFT with intensive chemotherapy that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF characteristically have persistently elevated MCVs and decreased platelet counts after completion of therapy. These hematologic abnormalities may represent stem cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia, but further study is needed to establish this relation.
尤因肉瘤家族性肿瘤（ESFT）的当前治疗包括使用拓扑异构酶II抑制剂、烷化剂和粒细胞集落刺激因子（G-CSF）进行强化多药化疗。这种治疗方法与骨髓发育异常和急性髓系白血病有关。由于大细胞性贫血和血小板减少是骨髓发育异常的显著特征，作者评估了一组接受ESFT治疗的患者，以确定大细胞性贫血和血小板减少的程度及持续时间，以及它们与治疗相关血液系统恶性肿瘤发生的关系。
研究组由73例接受两个连续方案（EW92和EW87）治疗的ESFT患者组成。两种化疗方案都使用相同的药物，但在累积药物剂量、每疗程剂量以及G-CSF的使用方面有所不同。在诊断时以及治疗完成后的随访期间测定血小板计数和红细胞平均体积（MCV）。
EW92组患者治疗后的MCV显著高于治疗强度较低的EW87组。这些变化在整个40个月的观察期内持续存在。EW92组患者治疗后的平均血小板计数也低于EW87组。MCV差异（相对于基线）与血小板计数呈负相关。EW92组在4年时治疗相关急性髓系白血病的累积发生率为7.8%±4.7%，EW87组为零。
接受包括大剂量烷化剂、拓扑异构酶II抑制剂和G-CSF的强化化疗治疗ESFT的患者，在治疗完成后通常会持续出现MCV升高和血小板计数降低。这些血液学异常可能代表干细胞损伤，使患者易患骨髓发育异常和急性髓系白血病，但需要进一步研究来证实这种关系。
