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注册: 2008-06-06
专业: 呼吸系统肿瘤

[交流] 【转帖】研究称捐献干细胞和骨髓并不增加癌症风险

ORLANDO (EGMN) – Donors of bone marrow or peripheral blood stem cells can rest assured that their generous acts are unlikely to have any lingering negative consequences to their own health, investigators reported at the annual meeting of the American Society of Hematology.

A survey collecting 55,228 observation-years of health data on 12,559 donors of bone-marrow and/or peripheral blood stem cells (PBSC) to unrelated recipients suggests that despite receiving granulocyte–colony-stimulating factor (G-CSF), donors are not at increased risk for hematologic malignancies or other significant health problems down the road, said Dr. Alexander H. Schmidt of the DKMS German Bone Marrow Donor Center in Tübingen, Germany.

Looking at standard incidence ratios (SIR) for leukemias, lymphomas, plasmocytoma, and lung cancer, the authors found no evidence of increased risk associated with donation.

Although bone marrow donors (but not PBSC donors) had a threefold higher incidence of malignant melanoma compared with the general German population, this finding was likely a statistical artifact, “because there is no mechanism available that would explain how bone marrow donation could increase the risk of development of malignant melanoma,” Dr. Schmidt said at a media briefing where DKMS was described as the largest bone marrow donation center in the world.

In addition, the incidence of lung cancer was lower than expected among donors, who may be more focused on health concerns than nondonors and thus less likely to smoke.

“We found no evidence that bone marrow or PBSC donation might be unsafe procedures, so there’s no need to change policies from our point of view,” he said.

A handful of studies has suggested that hematopoietic agents such as G-CSF may increase risk for hematologic malignancies among healthy donors who receive them, Dr. Schmidt said.

For example, Dr. Charles L. Bennett and colleagues at the Northwestern University Feinberg School of Medicine in Chicago reviewed findings on donors who developed hematologic malignancies 1-5 years after receiving hematopoietic agents. The authors found that “while a causal relationship with hematological malignancies cannot be demonstrated, long-term follow-up among healthy individuals who receive hematopoietic growth factors is needed.” (Br. J. Haematol. 2006;135:642-50).

But to tease out potentially harmful effects with any degree of certainty requires a large sample of donors who are willing to participate in a survey, Dr. Schmidt said. To capture as many donors as possible, he and his colleagues devised a simple survey asking donors about their general health, hospitalizations or long-term medical therapy (and the underlying disease) since donation, prescription drugs they took regularly or for a minimum of 4 weeks since donating, and whether they were willing to donate again.

They received replies from 81.3% of the 15,456 donors to whom they mailed the questionnaires, for a total of 12,559 completed and returned responses. That translated into 30,777 observation-years for 8,730 PBSC donors, 23,037 observation-years for 3,556 bone marrow donors, and 1,414 observation-years for 273 donors of both marrow and PBSC. Median follow-up time since donation was 3.3 years.

Overall, 95.1% of PBSC donors rated their health as very good or good, as did 96.0% of marrow donors, and 92.2% of those who gave both PBSC and marrow (comparison of PBSC and marrow donors, chi-squared test, P = .03)

PBSC donors had significantly fewer hospitalizations or new prescriptions than did bone marrow donors in a univariate analysis (chi-square tests, P less than .001), but this difference did not hold up in multivariate analysis. Because there were significantly more men and younger PBSC donors than bone marrow donors, the differences detected in health-related problems between the donor groups in the univariate analysis may be attributable to differences in sample characteristics, the investigators said.

A total of 85 malignancies were reported: 50 among 48 stem-cell donors, 31 in marrow donors, and 4 in donors of both. Six of these malignancies were hematologic: two cases of Hodgkin’s disease, both occurring in PBSC donors; one plasmocytoma in a PBSC donor; one acute myeloid leukemia in a bone marrow donor; one non-Hodgkin’s lymphoma in a bone marrow donor; and one chronic myeloid leukemia in a dual donor. (In addition, the investigators said they learned of 21 more donor malignancies in reports from donor centers; 5 of these were hematologic.)

The SIR for all malignancies among all donors was 0.99. There were no significant differences in the incidences of leukemia, non-Hodgkin lymphoma, plasmocytoma, or Hodgkin’s disease from those of age- and gender-adjusted incidences in the German population.

Dr. Schmidt said that the data exclude the possibility of a threefold or greater risk for leukemia in PBSC donors.

The authors said they had no relevant conflicts of interest.

奥兰多(EGMN)——德国图宾根DKMS骨髓捐赠中心Alexander H. Schmidt博士在美国血液学会年会上报告称，尽管骨髓和(或)外周血干细胞(PBSC)非亲属捐献者需接受粒细胞集落刺激因子(G-CSF)治疗，但这并不增加其将来发生血液系统恶性肿瘤或其他重大健康问题的风险，这一慷慨行为不会给自身健康遗留任何负面后果。

此前有少数研究显示健康捐献者接受G-CSF等造血制剂可增加造血系统恶性肿瘤的风险，为确定捐献骨髓和(或) PBSC对捐献者可能产生的有害影响，研究者设计了一份简明问卷调查表，以便使尽可能多的捐献者参与调查。问卷涉及一般健康、捐献后住院或长期药物治疗(以及疾病)、捐献后经常或至少4周服用处方药物，以及是否愿意再次捐献等情况。研究者向15,456位捐献者寄去问卷调查表，共计收回12,559份回答完整的问卷，占81.3%。经换算后，该调查结果包括8,730 位PBSC捐献者30,777观察年，3,556位骨髓捐献者23,037观察年和273位骨髓和PBSC均捐献者1,414观察年。捐献后中位随访时间为3.3年。

总体而言，95.1% 的 PBSC捐献者对自身健康的评价为很好或良好，骨髓捐献者为96.0%，PBSC和骨髓均捐献者为92.2%(与PBSC和骨髓捐献者比较，卡方检验P = 0.03)。单变量分析显示，PBSC捐献者住院及新处方药物使用显著少于骨髓捐献者(P <0 .001)，但因为PBSC捐献者中男性和年轻人明显多于骨髓捐献者，多变量分析结果未见显著差异。

共报告85例恶性肿瘤，50例来自PBSC捐献者，31例来自骨髓捐献者，4例来自PBSC和骨髓均捐献者。6例为血液系统肿瘤，其中2例霍奇金病，1例浆细胞瘤，均来自PBSC捐献者；1例急性髓系白血病， 1例非霍奇金淋巴瘤，均来自骨髓捐献者；1例慢性髓系白血病，来自PBSC和骨髓均捐献者。(此外，研究者从捐献中心报告中得知另外21例捐献者发生恶性肿瘤，其中5例为血液系统肿瘤。)所有捐献者的白血病、淋巴瘤、浆细胞瘤和肺癌总体标化发病率(SIR)为0.99，白血病、非霍奇金淋巴瘤、浆细胞瘤或霍奇金病发病率与校正年龄、性别后的德国人总体发病率无显著差异，而肺癌发生率低于预期值，可能与捐献者更加关注身体健康、吸烟者较少有关。

虽然骨髓捐献者(而非PBSC捐献者)的恶性黑色素瘤发病率是德国一般人群的3倍，但因为没有任何机理可以解释骨髓捐献增加恶性黑色素瘤风险，研究者推测该结果很可能是统计假象。上述研究结果排除了PBSC捐献者白血病风险高出3倍或以上的可能性。

研究者认为，没有证据显示捐献骨髓或PBSC与癌症风险增加有关，因而没有必要改变目前的捐献政策。

研究者声称无利益冲突披露。

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