B淋巴细胞白血病骨髓B细胞CD34^+CD38^+和CD34^+CD38^(low/-)细胞亚群的临床意义

Clinical Significance of CD34^+CD38^+ and CD34^+CD38^(low/-) Subgroups in Bone Marrow of Patients with B Lymploblastic Leukemia

本研究比较发病时免疫表型为CD34+CD38+和CD34+CD38low/-两组B淋巴细胞白血病(B-ALL)的生物学特性,并探讨其临床意义。选取54例初发B-ALL并经多参数流式细胞术检测为CD34+的B-ALL患者,根据CD38表达不同将其分为CD34+CD38+组(n=35)和CD34+CD38low/-组(n=19)。利用实时定量PCR的方法分别进行BCR-ABL,TEL-AML1和WT1基因的检测。随访标本利用7色流式细胞术检测微量残留病(MRD),平均随访时间12个月(1-28个月),平均随访间隔2个月(1-5个月)。结果表明,两组患者发病时WBC,血小板和血红蛋白水平及BCR-ABL,TEL-AML1和WT1基因阳性表达的比例均无统计学差异(P>0.05)。在诱导缓解后,CD34+CD38+组微量残留病阳性(MRD+)为28.57%(10/35),CD38low/-组MRD+为68.42%(13/19),CD34+CD38low/-组MRD+的检出率明显高于CD34+CD38+组(P<0.01)。在复发率上,CD34+CD38+组有2例,分别在第94天和第245天复发,复发率为5.71%(2/35)。CD34+CD38low/-组有7例复发,复发率为36.84%(7/19),中位复发时间263 d(46-468 d),两组间具有明显统计学差异(P<0.01)。本研究以16岁为年龄分界点,CD34+CD38+组16岁以上患者为8人(8/35),CD34+CD38low/-组16岁以上患者为10人(10/19),两组间有统计学差异(P<0.05)。结论:CD34+CD38low/-患者在成人中比例较高,且CD34+CD38low/-组在治疗后更易出现MRD+和复发。

This study was purposed to investigate the biological characteristics of B lymphoblastic leukemia（B-ALL） between CD34 positive CD38 positive（ CD34^＋ CD38^＋ ） and CD34^＋ CD38^low/- subgroups and their clinical significance. Immunophenotyping of B cells in bone marrow of 54 patients with newly diagnosed CD34^＋ B-ALL were analyzed by 4 color multiparametric flow cytometry （FCM）. According to the different expression of CD38, the newly diagnosed patients with B-ALL were divided into two groups： CD34^＋ CD38^＋ subgroup and CD34^＋ CD38^low/- subgroup. BCR- ABL, TEL-AML1 fusion genes and WT1 gene were detected by real time RT-PCR simultaneously. After chemotherapy, minimal residual desease （MRD） was monitored by one tube of 7 color FCM. The average follow-up time was 12 months （ range 1 - 28 ）, the average follow-up interval was 2 months （ range 1 - 5 ）. The results showed that there was no significant differences such as WBC, Plt count and Hb level between the two groups at diagnosis, the positive rate of BCR-ABL, TEL-AML1 and WT1 gene was also no significantly different. After clinical complete remission（ CR）, MRD positive （MDR^＋） case rates were 28.57% （10/35） in CD34^＋ CD38^＋ subgroup and 68.42% （13/19） in CD34^＋ CD38^low/- subgroup （P 〈 0.01 ）. The relapse rate between the two groups was 5.71% （2/35） in CD34^＋ CD38^＋ subgroup （relapse time at 94 and 245 d respectively） and 36.84% （7/19） in CD34^＋ CD38^low/- group [ median relapse time was 263 d （range 46-468）, P 〈0.01]. The age distribution was analyzed in these two subgroups （ 〉 16 or ≤〈16 years old） ,there was 8 （8/35） adult patients （ 〉 16 years old） in CD34^＋ CD38^＋ group and 10（10/19） adult patients in CD34^＋ CD38^low/- group （P 〈 0.05 ）. It is concluded that CD34^＋ CD38^low/- phenotype is more often presented in adult patients and the CD34^＋ CD38^low/- patients with B-ALL are more likely to have MRD^＋ and relapse after treatment.