Weiser Mary Ann, Cabanillas Maria E, Konopleva Marina, Thomas Deborah A, Pierce Sherry A, Escalante Carmen P, Kantarjian Hagop M, O'Brien Susan M
Department of General Internal Medicine, Ambulatory Treatment and Emergency Care, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2004 Mar 15;100(6):1179-85. doi: 10.1002/cncr.20071.
Hyperglycemia, which is not uncommon during the treatment of acute lymphocytic leukemia (ALL), has been shown to be an independent predictor of adverse outcomes among hospitalized patients with undiagnosed diabetes; it also may have the potential to affect leukemic cell proliferation through altered metabolism. The purpose of the current study was to determine the prevalence of hyperglycemia during induction chemotherapy for ALL using a regimen comprised of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and to determine its effect on survival, duration of disease remission, and treatment-related complications.
Two hundred seventy-eight adult patients with previously untreated ALL who achieved a complete remission with the hyper-CVAD regimen were evaluated. Hyperglycemia was defined as > or = 2 glucose determinations of > or = 200 mg/dL during the first 30 days of induction chemotherapy. Induction chemotherapy was comprised of fractionated cyclophosphamide at a dose of 300 mg/m2 twice daily on Days 1-3, doxorubicin at a dose of 50 mg/m2 on Day 4, vincristine at a dose of 2 mg on Days 4 and 11, and dexamethasone at a dose of 40 mg on Days 1-4 and Days 11-14 (hyper-CVAD). Hyper-CVAD, given in odd-number courses (Courses 1, 3, 5, and 7), was alternated with methotrexate and cytarabine (MTX/Ara-C), given in even-number courses (Courses 2, 4, 6, and 8). MTX/Ara-C was comprised of MTX at a dose of 200 mg/m2 over 2 hours followed by 800 mg/m2 over 22 hours on Day 1, Ara-C at a dose of 3 g/m2 every 12 hours for 4 doses over 2 days (Days 2 and 3), and intravenous methylprednisolone given at a dose of 50 mg twice daily on Days 1-3. The complete remission duration (CRD), survival, and treatment-related complications were determined for patients with and without hyperglycemia; differences between the two groups were assessed using standard statistical methods.
Hyperglycemia was found to occur in 103 patients (37%). Patients with hyperglycemia had a shorter median CRD (24 months vs. 52 months; P = 0.001) and a shorter median survival (29 months vs. 88 months; P < 0.001); they also were more likely to develop sepsis (16.5% vs. 8.0%; P = 0.03) or any complicated infection (sepsis, pneumonia, or fungal) (38.8% vs. 25.1%; P = 0.016) compared with patients without hyperglycemia.
Patients with hyperglycemia during induction chemotherapy for ALL with the hyper-CVAD regimen were found to have a shorter CRD, experience a significant increase in overall mortality, and be at an increased risk for developing complicated infections.
高血糖在急性淋巴细胞白血病（ALL）治疗期间并不少见，已被证明是未确诊糖尿病住院患者不良预后的独立预测因素；它也可能通过改变代谢影响白血病细胞增殖。本研究的目的是确定使用超分割环磷酰胺、长春新碱、阿霉素和地塞米松（Hyper-CVAD）方案进行ALL诱导化疗期间高血糖的发生率，并确定其对生存、疾病缓解持续时间和治疗相关并发症的影响。
对278例先前未经治疗的ALL成年患者进行评估，这些患者采用Hyper-CVAD方案实现了完全缓解。高血糖定义为诱导化疗的前30天内≥2次血糖测定结果≥200mg/dL。诱导化疗包括第1 - 3天每天2次给予剂量为300mg/m²的分割环磷酰胺，第4天给予剂量为50mg/m²的阿霉素，第4天和第11天给予剂量为2mg的长春新碱，以及第1 - 4天和第11 - 14天给予剂量为40mg的地塞米松（Hyper-CVAD）。奇数疗程（第1、3、5和7疗程）给予Hyper-CVAD，偶数疗程（第2、4、6和8疗程）给予甲氨蝶呤和阿糖胞苷（MTX/Ara-C）。MTX/Ara-C包括第1天2小时内给予剂量为200mg/m²的甲氨蝶呤，随后22小时内给予800mg/m²，第2天和第3天每12小时给予剂量为3g/m²的阿糖胞苷共4剂，以及第1 - 3天每天2次给予剂量为50mg的静脉注射甲泼尼龙。确定有和无高血糖患者的完全缓解持续时间（CRD）、生存情况和治疗相关并发症；使用标准统计方法评估两组之间的差异。
发现103例患者（37%）发生高血糖。高血糖患者的中位CRD较短（24个月对52个月；P = 0.001），中位生存期较短（29个月对88个月；P < 0.001）；与无高血糖患者相比，他们发生败血症的可能性也更高（16.5%对8.0%；P = 0.03）或发生任何复杂感染（败血症、肺炎或真菌）的可能性更高（38.8%对25.1%；P = 0.016）。
发现采用Hyper-CVAD方案进行ALL诱导化疗期间发生高血糖的患者CRD较短，总体死亡率显著增加，发生复杂感染的风险增加。
