Robak T, Błasińska-Morawiec M, Błoński J, Hellmann A, Hałaburda K, Konopka L, Kotlarek-Haus S, Potoczek S, Hansz J, Dmoszyńska A, Urasiński I, Zdziarska B, Dwilewicz-Trojaczek J, Hołowiecki J, Skotnicki A B
Department of Hematology, Medical University of Lòdź, Poland.
Eur J Haematol. 1999 Jan;62(1):49-56. doi: 10.1111/j.1600-0609.1999.tb01114.x.
Between January 1991 and December 1997, 103 patients, 97 with typical hairy cell leukemia (HCL) and 6 with HCL-variant (HCL-V) were treated with 2-chlorodeoxyadenosine (2-CdA) given as 2-h infusion for 5 consecutive d at a daily dose 0.12 mg/kg. To our knowledge this is the largest cohort of HCL patients treated with this type of regimen. Median follow-up amounted to 36 months. Fifty-six of 97 patients with typical HCL were newly diagnosed and 41 were relapsed after previous treatment. Splenectomy as a first-line therapy was performed in 23 patients and 18 remaining patients received prednisone, chlorambucil or interferon-alpha (IFN-alpha) alone or in combinations. Seventy-five (77.3%) patients entered CR and 18 (18.6%) achieved PR, giving an overall response rate of 95.9%. The mean time of first CR duration amounting to 32 months (range 3-72) did not correlate to the number of 2-CdA cycles. 2-CdA was equally effective in treatment of newly diagnosed patients and patients who relapsed after previous therapeutic procedures. Relapse of the disease occurred in 20 of 75 patients who achieved CR after 2-CdA and was usually manifested by very discrete changes in peripheral blood counts (neutropenia and/or relative lymphocytosis). The mean progression-free survival (PFS) time in this group was 37.4 (range 10-66) months. Ten of 20 relapsed patients were retreated with 2-CdA given an identical course to the first one. Seven patients entered second CR lasting 19+ (range 8-47) months and 3 experienced PR. This confirms the previous observations that 2-CdA gives no resistance to leukemic clone. Ten remaining patients have not required retreatment so far and remain in a good clinical and hematological state. The results of HCL-V treatment with 2-CdA were poor. Only 2 patients achieved PR and 4 patients did not respond to this drug. Seven patients (5 with typical HCL and 2 with HCL-V) died, 3 of causes unrelated to the disease. Second neoplasms were noted in 5 patients. 2-CdA-related side effects resulted mainly from myelosuppression and infectious complications. In conclusion we confirm the effectiveness of 2-CdA in inducing CR in patients with typical HCL, but this drug is unable to completely eradicate the leukemic clone which results in the relapse of the disease. The real incidence of the relapse rate may be underestimated unless bone marrow biopsy is performed. The results of our study indicate that a 2-h infusion of 2-CdA in HCL patients is at least as effective as a 24-h infusion but more convenient to the patients, and may be given on an outpatient basis.
1991年1月至1997年12月期间，103例患者接受了2-氯脱氧腺苷（2-CdA）治疗，其中97例为典型毛细胞白血病（HCL）患者，6例为变异型毛细胞白血病（HCL-V）患者。给药方式为连续5天每天2小时静脉输注，剂量为0.12mg/kg。据我们所知，这是接受此类治疗方案的最大规模HCL患者队列。中位随访时间为36个月。97例典型HCL患者中，56例为初诊患者，41例为先前治疗后复发患者。23例患者接受了脾切除术作为一线治疗，其余18例患者单独或联合使用泼尼松、苯丁酸氮芥或α-干扰素（IFN-α）治疗。75例（77.3%）患者达到完全缓解（CR），18例（18.6%）患者达到部分缓解（PR），总缓解率为95.9%。首次CR持续时间的平均时长为32个月（范围3 - 72个月），与2-CdA疗程数无关。2-CdA对初诊患者和先前治疗后复发患者的治疗效果相同。75例接受2-CdA治疗后达到CR的患者中有20例疾病复发，通常表现为外周血细胞计数的非常细微变化（中性粒细胞减少和/或相对淋巴细胞增多）。该组患者的无进展生存期（PFS）平均时间为37.4个月（范围10 - 66个月）。20例复发患者中有10例再次接受了与首次相同疗程的2-CdA治疗。7例患者进入第二次CR，持续时间为19 +个月（范围8 - 47个月），3例患者达到PR。这证实了先前的观察结果，即2-CdA不会使白血病克隆产生耐药性。其余10例患者目前尚未需要再次治疗，临床和血液学状态良好。2-CdA治疗HCL-V的效果较差。仅2例患者达到PR，4例患者对此药无反应。7例患者（5例典型HCL患者和2例HCL-V患者）死亡，3例死于与疾病无关的原因。5例患者出现了第二肿瘤。2-CdA相关的副作用主要源于骨髓抑制和感染并发症。总之，我们证实了2-CdA在诱导典型HCL患者达到CR方面的有效性，但该药物无法完全根除白血病克隆，这导致疾病复发。除非进行骨髓活检，否则复发率的实际发生率可能被低估。我们的研究结果表明，HCL患者2小时静脉输注2-CdA至少与24小时静脉输注一样有效，但对患者更方便，可以在门诊进行。
