Locatelli F, Pession A, Bonetti F, Maserati E, Prete L, Pedrazzoli P, Zecca M, Prete A, Paolucci P, Cazzola M
Department of Pediatrics, University of Pavia, Italy.
Leukemia. 1994 May;8(5):844-9.
As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.
作为老年人的典型疾病，骨髓增生异常综合征（MDS）在儿童期相对少见。然而，高达17%的儿童急性髓系白血病病例可能有白血病前期。对于年轻患者，治疗目标是根除白血病前期恶性克隆并重建正常造血功能。异基因骨髓移植（BMT）已被证明能够做到这一点，但实现根除的最佳预处理方案仍有待确定。1989年5月至1993年6月，连续8例儿童MDS患者接受了来自HLA相同、混合淋巴细胞培养（MLC）无反应的同胞的骨髓移植。就诊时的诊断为2例难治性贫血伴原始细胞增多（RAEB），3例转化中的RAEB（RAEB-t），其余3例儿童为青少年慢性粒细胞白血病（JCML，成人慢性粒单核细胞白血病的儿童对应类型）。预处理方案包括白消安、环磷酰胺和美法仑，这三种烷化剂有可能杀死休眠的白血病前期干细胞。预处理方案耐受性良好，所有患者均迅速植入。8例患者中有6例（75%）存活且状况良好，中位观察时间为20个月（范围8 - 34个月）。系列核型监测和分子分析显示，3例患者供体细胞完全嵌合，移植前检测到的三体8完全消失。所有存活患者的卡诺夫斯基评分均为100%。一名患有RAEB-t且7号染色体单体对小剂量阿糖胞苷治疗耐药的男孩，在BMT后11个月复发，进展为急性髓系白血病并死于进行性白血病。另一名RAEB患者在BMT后第95天因病因不明的间质性肺炎死亡。本研究证实异基因BMT是儿童MDS患者的首选治疗方法，并表明所采用的预处理方案是根除白血病前期恶性克隆的安全有效手段。特别值得注意的是，3例JCML患儿获得完全缓解，其中1例现为长期存活者。
