Mach-Pascual S, Legare R D, Lu D, Kroon M, Neuberg D, Tantravahi R, Stone R M, Freedman A S, Nadler L M, Gribben J G, Gilliland D G
Division of Hematology/Oncology, Department of Medicine, Brigham and Women's Hospital, the Dana-Farber Cancer Institute, and the Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 021115, USA.
Blood. 1998 Jun 15;91(12):4496-503.
Recent studies have documented an increased risk of therapy-related myelodysplastic syndrome or acute myelogenous leukemia (t-MDS/AML) after autologous bone marrow transplant (ABMT) for non-Hodgkin's lymphoma (NHL). To develop methods to identify patients at risk for this complication, we have investigated the predictive value of clonal bone marrow (BM) hematopoiesis for the development of t-MDS/AML, as defined by an X-inactivation based clonality assay at the human androgen receptor locus (HUMARA), in a group of patients undergoing ABMT for NHL from a single institution (Dana-Farber Cancer Institute, Boston, MA). One hundred four female patients were analyzed. At the time of ABMT, the prevalence of polyclonal hematopoiesis was 77% (80/104), of skewed X-inactivation pattern (XIP) was 20% (21/104), and of clonal hematopoiesis was 3% (3/104). To determine the predictive value of clonality for the development of t-MDS/AML, a subgroup of 78 patients with at least 18 months follow-up was analyzed. As defined by the HUMARA assay, 53 of 78 patients had persistent polyclonal hematopoiesis, 15 of 78 had skewed XIP, and 10 of 78 (13.5%) either had clonal hematopoiesis at the time of ABMT or developed clonal hematopoiesis after ABMT. t-MDS/AML developed in 2 of 53 patients with polyclonal hematopoiesis and in 4 of 10 with clonal hematopoiesis. We conclude that a significant proportion of patients have clonal hematopoiesis at the time of ABMT and that clonal hematopoiesis, as detected by the HUMARA assay, is predictive of the development of t-MDS/AML (P = .004).
近期研究表明，非霍奇金淋巴瘤（NHL）患者接受自体骨髓移植（ABMT）后，发生治疗相关骨髓增生异常综合征或急性髓系白血病（t-MDS/AML）的风险增加。为了开发识别有此并发症风险患者的方法，我们在来自单一机构（马萨诸塞州波士顿达纳-法伯癌症研究所）接受ABMT治疗NHL的一组患者中，研究了克隆性骨髓（BM）造血对于t-MDS/AML发生的预测价值，该克隆性通过基于X染色体失活的人雄激素受体基因座（HUMARA）克隆性分析来定义。分析了104名女性患者。在ABMT时，多克隆造血的患病率为77%（80/104），X染色体失活模式偏斜（XIP）的患病率为20%（21/104），克隆性造血的患病率为3%（3/104）。为了确定克隆性对于t-MDS/AML发生的预测价值，分析了随访至少18个月的78例患者亚组。根据HUMARA分析定义，78例患者中有53例持续多克隆造血，78例中有15例XIP偏斜，78例中有10例（13.5%）在ABMT时已有克隆性造血或ABMT后出现克隆性造血。53例多克隆造血患者中有2例发生t-MDS/AML，10例克隆性造血患者中有4例发生。我们得出结论，相当一部分患者在ABMT时存在克隆性造血，并且通过HUMARA分析检测到的克隆性造血可预测t-MDS/AML的发生（P = 0.004）。
