Marin G H, Porto A, Prates V, Napal J, Etchegogen O, Rubens L, Bordone J, Castelletto R, Buschiazzo H, Morales V, Milone J
Catedra de Farmacologia, Facultad de Medicina, Universidad Nacional de La Plata, Argentina.
J Exp Clin Cancer Res. 1999 Jun;18(2):201-8.
Relapse remains the major cause of mortality in haematological malignancies treated with autologous stem cell transplantation (ASCT). Graft versus tumour reaction (GVT) associated to autologous graft versus host disease (GVDH) may contribute to eliminate minimal residual disease (MRD) after ASCT. Eighty patients with several diagnostics were submitted to ASCT. After stem cell infusion, patients randomised in 4 groups. Groups were treated as follows: Group A received either a IFN (alpha Interferon--1,000,000 U/d), Cyclosporine A (CSA--1 mg/-kg/d intravencus) for 28 days, and granulocyte-macrophage colony stimulating factor (GM-CSF-250/m2/d) until engraftment; B: CSA (same dose and way) and GM-CSF; C: CSA (1 mg/kg/d orally) and GM-CSF and D: only GM-CSF. Patients were inspected daily and if skin rash was detected, a skin biopsy was obtained at that moment, otherwise biopsies were obtained at day 21 after ASCT. GVHD was positive in 23 patients (13 from group A and 10 from group B). All cases were grades I and II. A majority of CD4+ T lymphocytes was seen in skin infiltrates. No significant differences were seen in WBC and platelets engraftment times, antibiotic administration or hospitalisation days required among the four groups. With a median follow up of 18 months, there were no differences in disease free survival (DFS) or overall survival (OS) between the patients who developed GVHD and the others. However, considering that myeloma cells do not express antigen MCH II, which is necessary for GVT effect, we excluded patients with multiple myeloma (MM) from survival analysis, thus obtaining a significant difference in OS results between patients who developed GVHD and those in whom this reaction was not observed (81% vs 58% p:0.05). We conclude that pharmacological induction of GVHD in ASCT is possible with CSA administration (1 mg/kg/d i.v.). Development of GVHD showed a better outcome for patients in our study except for those patients with MM. This results must be confirmed by a longer follow up of our patients and further studies.
复发仍然是接受自体干细胞移植（ASCT）治疗的血液系统恶性肿瘤患者死亡的主要原因。与自体移植物抗宿主病（GVDH）相关的移植物抗肿瘤反应（GVT）可能有助于清除ASCT后的微小残留病（MRD）。80例患有多种诊断疾病的患者接受了ASCT。干细胞输注后，患者被随机分为4组。分组治疗如下：A组接受α干扰素（100万U/天）、环孢素A（CSA，1mg/kg/天静脉注射），持续28天，以及粒细胞巨噬细胞集落刺激因子（GM-CSF，250/m²/天）直至植入；B组：CSA（相同剂量和方式）和GM-CSF；C组：CSA（1mg/kg/天口服）和GM-CSF；D组：仅GM-CSF。每天对患者进行检查，若检测到皮疹，则立即进行皮肤活检，否则在ASCT后第21天进行活检。23例患者发生GVHD阳性（A组13例，B组10例）。所有病例均为I级和II级。在皮肤浸润中可见大多数CD4 + T淋巴细胞。四组之间在白细胞和血小板植入时间、抗生素使用或住院天数方面未见显著差异。中位随访18个月，发生GVHD的患者与未发生GVHD的患者在无病生存期（DFS）或总生存期（OS）方面无差异。然而，考虑到骨髓瘤细胞不表达GVT效应所必需的抗原MCH II，我们将多发性骨髓瘤（MM）患者排除在生存分析之外，从而在发生GVHD的患者与未观察到这种反应的患者之间的OS结果上获得了显著差异（81%对58%，p = 0.05）。我们得出结论，通过静脉注射CSA（1mg/kg/天）在ASCT中进行GVHD的药理学诱导是可行的。在我们的研究中，除MM患者外，GVHD的发生对患者显示出更好的结果。这一结果必须通过对我们的患者进行更长时间的随访和进一步研究来证实。
