O'Brien S, Kantarjian H, Beran M, Robertson L E, Koller C, Lerner S, Keating M J
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Blood. 1995 Aug 15;86(4):1298-300.
Many patients with chronic lymphocytic leukemia (CLL) achieve remission after treatment with fludarabine chemotherapy. Most of these patients, however, later experience relapse. In addition, immunologic deficits may persist even in patients in complete remission; lymphopenia, predominantly involving the CD4 population, is universal after fludarabine therapy. We used recombinant alpha interferon (IFN-alpha) maintenance therapy in patients with CLL who achieved remission in response to fludarabine therapy to determine its effect on residual disease, assessed by either bone marrow biopsy or flow cytometry, and on immune restoration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U by subcutaneous injection three times weekly). Twenty-two patients (71%) were in complete remission (CR) and nine (29%) were in partial remission (PR). Of the 22 patients in CR, 21 (95%) had evidence of residual disease at the start of IFN-alpha therapy. Low CD4 levels were noted in 93% of patients, low IgG levels in 45%, and anergy or hypoergy in 52%. Only one patient in PR achieved a CR on IFN-alpha therapy: the only patient who had had no prior fludarabine but had been treated with chlorambucil and prednisone. All patients in CR with minimal residual disease had persistent disease after IFN-alpha treatment. There were no increases in CD4 counts or IgG levels; three patients with borderline responses to skin testing had an increase in the number of positive tests while on IFN-alpha. The time to progression was no different in patients treated with IFN-alpha than in a historical control group of patients who had received no further therapy after fludarabine. In summary, the use of IFN-alpha maintenance did not eradicate residual disease, restore immune function, or prolong remissions in patients with CLL responsive to fludarabine.
许多慢性淋巴细胞白血病（CLL）患者在接受氟达拉滨化疗后可实现缓解。然而，这些患者中的大多数随后会复发。此外，即使是完全缓解的患者，免疫缺陷可能仍然存在；氟达拉滨治疗后普遍存在淋巴细胞减少，主要累及CD4细胞群。我们对接受氟达拉滨治疗后缓解的CLL患者使用重组α干扰素（IFN-α）维持治疗，以确定其对通过骨髓活检或流式细胞术评估的残留疾病以及免疫恢复的影响。31例患者接受IFN-α治疗（皮下注射3×10⁶U，每周3次）。22例患者（71%）完全缓解（CR），9例（29%）部分缓解（PR）。在22例CR患者中，21例（95%）在IFN-α治疗开始时有残留疾病证据。93%的患者CD4水平低，45%的患者IgG水平低，52%的患者无反应或反应低下。仅1例PR患者在IFN-α治疗后实现CR：该患者未曾接受过氟达拉滨治疗，但接受过苯丁酸氮芥和泼尼松治疗。所有残留疾病极少的CR患者在IFN-α治疗后疾病持续存在。CD4计数或IgG水平没有增加；3例皮肤试验反应临界的患者在接受IFN-α治疗期间阳性试验次数增加。接受IFN-α治疗的患者与氟达拉滨治疗后未接受进一步治疗的历史对照组患者相比，疾病进展时间没有差异。总之，对于对氟达拉滨有反应的CLL患者，使用IFN-α维持治疗并不能根除残留疾病、恢复免疫功能或延长缓解期。
