Lauria F, Raspadori D, Ventura M A, Rondelli D, Zinzani P L, Gherlinzoni F, Miggiano M C, Fiacchini M, Rosti G, Rizzi S, Tura S
Istituto di Clinica Medica Generale e Terapia Medica, Università di Siena, Italy.
Bone Marrow Transplant. 1996 Jul;18(1):79-85.
In order to induce a therapeutic immunomodulatory activity, 11 patients with high-grade non-Hodgkin's lymphoma (HG-NHL) at a median of 42 days after autologous bone marrow transplantation (ABMT) received recombinant interleukin-2 (rIL-2) subcutaneously at a dose of 2 international megaunits (IMU)/m2 every other day for 2 weeks and then 3 IMU/m2 twice a week for 1 year. Immunological studies, including T and natural killer (NK) cell subset assessment, together with functional assay, such as NK and CD16-mediated cytotoxic activities, were performed before therapy, after 2 weeks and then monthly. Phenotypic analyses showed a significant and persistant (P = 0.001) increase in the proportion and absolute number of total lymphocytes and, particularly of both CD16 and CD56 NK cells, from pre-treatment values of 14 and 18% to 30 and 38% respectively, recorded after 6 months of therapy. No changes were observed in CD25 (p55)-positive cells, while a significant increase from 13 to 33% (after 6 months) was observed in CD122-positive cells. Furthermore, rIL-2 administration led to an enhancement of NK activity even at the lowest effector:target ratio and of CD16-mediated cytotoxic activity. Clinical tolerance was acceptable with moderate fever and fluid retention observed only at the onset of rIL-2 treatment. None of the patients have progressed with a median follow-up of 22 months (range 10-42 months) after starting therapy. In addition, two patients with a residual disease after ABMT, one in the liver and the second in the lymph nodes, obtained a complete response after 10 and 7 months of rIL-2 therapy, respectively. These preliminary data suggest that the infusion of low-dose rIL-2 s.c. after ABMT is safe and well tolerated and can selectively increase the NK cell number and function. Additional patients are needed in order to assess the impact of these immunological changes on relapse-free survival after ABMT for HG-NHL.
为诱导治疗性免疫调节活性，11例高级别非霍奇金淋巴瘤（HG-NHL）患者在自体骨髓移植（ABMT）后中位42天，接受皮下注射重组白细胞介素-2（rIL-2），剂量为2国际单位（IMU）/m²，隔日1次，共2周，然后3 IMU/m²，每周2次，持续1年。在治疗前、2周后及之后每月进行免疫学研究，包括T细胞和自然杀伤（NK）细胞亚群评估，以及功能测定，如NK和CD16介导的细胞毒性活性。表型分析显示，治疗6个月后，总淋巴细胞比例和绝对数量，特别是CD16和CD56 NK细胞，从治疗前的14%和18%分别显著且持续增加（P=0.001）至30%和38%。CD25（p55）阳性细胞未见变化，而CD122阳性细胞从13%显著增加至33%（6个月后）。此外，即使在最低效应细胞：靶细胞比例下，rIL-2给药也导致NK活性增强以及CD16介导的细胞毒性活性增强。临床耐受性可接受，仅在rIL-2治疗开始时观察到中度发热和液体潴留。开始治疗后中位随访22个月（范围10 - 42个月），无患者病情进展。此外，2例ABMT后有残留病灶的患者，1例在肝脏，另1例在淋巴结，分别在rIL-2治疗10个月和7个月后获得完全缓解。这些初步数据表明，ABMT后皮下注射低剂量rIL-2是安全且耐受性良好的，并且可以选择性增加NK细胞数量和功能。需要更多患者来评估这些免疫变化对HG-NHL患者ABMT后无复发生存的影响。
