Tsimberidou Apostolia-Maria, Younes Anas, Romaguera Jorge, Hagemeister Fredrick B, Rodriguez Maria A, Feng Lei, Ayala Ana, Smith Terry L, Cabanillas Fernando, McLaughlin Peter
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2005 Jul 15;104(2):345-53. doi: 10.1002/cncr.21151.
Myelosuppression and immunosuppression occur with purine analogs. The objective of the current study was to investigate the effects of combined fludarabine, mitoxantrone, and dexamethasone (FND) followed by interferon/dexamethasone on myelosuppression (absolute neutrophil counts), immunosuppression (CD4 and CD8 counts), and infectious complications in patients with previously untreated, Stage IV indolent lymphoma.
Seventy-three patients were treated. All patients received Pneumocystis carinii pneumonia (PCP) prophylaxis. CD4 and CD8 counts, serum immunoglobulin (Ig) levels, and neutrophil counts were correlated with infectious complications.
The median follow-up was 6.1 years. Sixty of 73 patients had CD4, CD8, or Ig measurements. The median baseline CD4 count was 764/microL. This CD4 level decreased to 238/microL at 1 year and to 264/microL at 2 years; and it rose to 431/microL by 3 years and to 650/microL at 4 years. CD8 counts did not change significantly. The median baseline serum IgG level was 989 mg/d, decreased to 536 mg/dL at 1 year and to 693 mg/dL at 2 years, and it rose to 949 mg/dL at 3 years and to 1080 mg/dL at 4 years. Fourteen patients (19%) developed Grade 3-4 infections, the majority during FND therapy with neutropenia and/or accompanied by CD4 counts < 200/microL. CD4, CD8, and neutrophil counts did not differ between patients who developed Grade 3-4 infections, Grade 1-2 infections, or no infections.
Most infections with FND occurred during FND, in the setting of neutropenia, often with concurrent low CD4 counts. The overall safety profile for FND was good. However, patients should be monitored for opportunistic infections, and prophylactic antibiotics are recommended, particularly against PCP.
嘌呤类似物会导致骨髓抑制和免疫抑制。本研究的目的是调查氟达拉滨、米托蒽醌和地塞米松联合用药（FND）后使用干扰素/地塞米松对既往未经治疗的IV期惰性淋巴瘤患者的骨髓抑制（绝对中性粒细胞计数）、免疫抑制（CD4和CD8计数）以及感染并发症的影响。
对73例患者进行了治疗。所有患者均接受了卡氏肺孢子虫肺炎（PCP）预防。将CD4和CD8计数、血清免疫球蛋白（Ig）水平以及中性粒细胞计数与感染并发症进行关联分析。
中位随访时间为6.1年。73例患者中有60例进行了CD4、CD8或Ig测量。基线CD4计数的中位数为764/μL。该CD4水平在1年时降至238/μL，在2年时降至264/μL；在3年时升至431/μL，在4年时升至650/μL。CD8计数无显著变化。基线血清IgG水平的中位数为989mg/d，在1年时降至536mg/dL，在2年时降至693mg/dL，在3年时升至949mg/dL，在4年时升至1080mg/dL。14例患者（19%）发生3-4级感染，多数发生在FND治疗期间，伴有中性粒细胞减少和/或CD4计数<200/μL。发生3-4级感染、1-2级感染或未发生感染的患者之间，CD4、CD8和中性粒细胞计数无差异。
FND相关的大多数感染发生在FND治疗期间，处于中性粒细胞减少的情况下，通常同时伴有CD4计数较低。FND的总体安全性良好。然而，应监测患者是否发生机会性感染，建议使用预防性抗生素，尤其是针对PCP的抗生素。
