Betticher D C, Huxol H, Müller R, Speck B, Nissen C
Department of Internal Medicine, University of Basel, Switzerland.
Exp Hematol. 1993 Nov;21(12):1517-21.
The recovery of colony-forming cell numbers after curative treatment for leukemia and severe aplastic anemia (SAA) was studied. We examined 191 patients (85 acute myeloid leukemia [AML], 48 acute lymphocytic leukemia [ALL], 32 chronic myeloid leukemia [CML], 17 SAA, and nine myelodysplastic syndrome [MDS]) who were in hematologic remission 6 months to 13 years after either curative chemotherapy (n = 69) or allogeneic bone marrow transplantation (BMT) (n = 122) by culturing their precursor cells from bone marrow (BM) (n = 548) and peripheral blood (PB) (n = 529) in methylcellulose. Thirty-six BM donors and 25 PB donors served as controls. BM colony-forming cell numbers were abnormally low in all patients (p < 0.002) irrespective of underlying disorder and type of treatment (chemotherapy or irradiation). These numbers did not normalize with time--colony-forming cells were still strongly reduced up to 10 years after therapy, whether or not the patient had received an allogeneic bone marrow graft (p < 0.002). We also compared patients who remained in stable hematologic remission with those who later relapsed (6 months to 2 years after treatment). BM colony-forming cell numbers were significantly lower in patients who subsequently relapsed (p = 0.004). In contrast to BM cultures, we found normal colony-forming capacity by PB precursors in all patients. We conclude that (1) after chemotherapy or BMT, colony-forming cell numbers of BM in culture are permanently reduced; (2) this defect is probably due to a dysfunction of the BM environment rather than to a numerical reduction of the precursor cell pool; and (3) very low colony-forming capacity may be related to relapse.
我们研究了白血病和重型再生障碍性贫血（SAA）根治性治疗后集落形成细胞数量的恢复情况。我们检测了191例患者（85例急性髓系白血病[AML]、48例急性淋巴细胞白血病[ALL]、32例慢性髓系白血病[CML]、17例SAA和9例骨髓增生异常综合征[MDS]），这些患者在接受根治性化疗（n = 69）或异基因骨髓移植（BMT）（n = 122）后6个月至13年处于血液学缓解期，通过在甲基纤维素中培养他们骨髓（BM）（n = 548）和外周血（PB）（n = 529）中的前体细胞进行检测。36例BM供体和25例PB供体作为对照。无论潜在疾病和治疗类型（化疗或放疗）如何，所有患者的BM集落形成细胞数量均异常低（p < 0.002）。这些数量并未随时间恢复正常——无论患者是否接受了异基因骨髓移植，治疗后长达10年集落形成细胞仍显著减少（p < 0.002）。我们还比较了血液学缓解稳定的患者与后来复发的患者（治疗后6个月至2年）。随后复发的患者BM集落形成细胞数量显著更低（p = 0.004）。与BM培养不同，我们发现所有患者PB前体细胞的集落形成能力正常。我们得出结论：（1）化疗或BMT后，培养的BM集落形成细胞数量永久性减少；（2）这种缺陷可能是由于BM环境功能障碍而非前体细胞池数量减少；（3）极低的集落形成能力可能与复发有关。
