Blume K G, Forman S J, Snyder D S, Nademanee A P, O'Donnell M R, Fahey J L, Krance R A, Sniecinski I J, Stock A D, Findley D O
Transplantation. 1987 Mar;43(3):389-92. doi: 10.1097/00007890-198703000-00014.
Patients with acute lymphoblastic leukemia who have poor prognostic features at diagnosis usually have a short disease-free survival in spite of successful remission induction. Those poor risk features are: age over 30 years, a white blood cell count over 25,000/microliter, certain translocations of chromosomes, and requirement for more than six weeks of induction chemotherapy to attain a complete remission. We have used high-dose radiochemotherapy to prepare 39 patients with acute lymphoblastic leukemia in first complete remission (1 infant and 38 adults; median age 23 years) for bone marrow transplantation from histocompatible sibling donors. Thirty-one of the 39 patients in this study had one (n = 23) or more (n = 8) poor risk features: age (n = 7); high white blood cell count (n = 19); translocations (n = 4), or resistance to initial induction therapy (n = 11). Currently, 26 patients are surviving for 4-72 months (median 18 months) following marrow grafting and are in complete remission. One of the surviving patients had two marrow transplant procedures because of recurrent leukemia. Actuarial survival in complete remission is 63% for the entire group of 39 patients and is 60% if the eight patients who had no poor risk features are excluded from analysis. The following causes for failure were observed: leukemic relapse was encountered in four patients between 3 and 17 months after BMT for an actuarial relapse rate of 16%; bacterial sepsis was the cause of death in two patients; graft-versus-host disease and/or interstitial pneumonia led to the demise of seven patients, and one patient died with leukoencephalopathy. It appears that high-dose radiochemotherapy followed by bone marrow transplantation from a histocompatible sibling donor during first complete remission can result in a high disease-free survival rate for younger adults with poor-risk acute lymphoblastic leukemia. This concept needs to be tested in prospective trials comparing bone marrow transplantation with chemotherapy.
急性淋巴细胞白血病患者若在诊断时具有不良预后特征,即便缓解诱导成功,通常也只有较短的无病生存期。这些不良风险特征包括:年龄超过30岁、白细胞计数超过25,000/微升、某些染色体易位,以及需要超过六周的诱导化疗才能达到完全缓解。我们采用大剂量放化疗为39例首次完全缓解的急性淋巴细胞白血病患者(1例婴儿和38例成人;中位年龄23岁)做准备,以便接受来自组织相容性同胞供者的骨髓移植。本研究的39例患者中,有31例具有一项(n = 23)或多项(n = 8)不良风险特征:年龄(n = 7);白细胞计数高(n = 19);易位(n = 4),或对初始诱导治疗耐药(n = 11)。目前,26例患者在骨髓移植后存活4 - 72个月(中位时间18个月),且处于完全缓解状态。其中一名存活患者因白血病复发接受了两次骨髓移植手术。39例患者的总体完全缓解无病生存率为63%,若将8例无不良风险特征的患者排除在分析之外,无病生存率为60%。观察到以下失败原因:4例患者在骨髓移植后3至17个月出现白血病复发,精算复发率为16%;2例患者死于细菌败血症;移植物抗宿主病和/或间质性肺炎导致7例患者死亡,1例患者死于白质脑病。看来,首次完全缓解期间采用大剂量放化疗并继以来自组织相容性同胞供者的骨髓移植,可使具有不良风险的年轻成人急性淋巴细胞白血病患者获得较高的无病生存率。这一概念需要在前瞻性试验中进行检验,比较骨髓移植与化疗的效果。