点击显示 收起
德国研究者报告一项首次进行的全球随机研究时表示，治疗性血小板输注是安全可行的，且可以降低费用。不过，此研究只包括171名病患，专家认为在做出安全性与运用的定论前需要更多资料。
这项试验由德国纽伦堡Klinikum Nuremberg Nord的Hannes Wandt医师发表于美国血液学会(ASH)第50届年会暨展览会中，研究对象是最近接受高剂量化疗、全身放射线治疗或者自体干细胞移植治疗各种血液恶性病，如多发性骨髓瘤、非何杰金氏淋巴瘤、何杰金氏症与急性骨髓性白血病的患者。
这类病患通常会发生血小板减少，目前的实务是，当血小板计数低于10,000/uL时，以预防性血小板输注治疗这些病患；Wandt医师等人比较了此一标准实务与治疗性血小板输注这两种方法，后者为病患发生临床相关出血时才进行输注(比淤血或微量黏膜出血更严重时)。
这个新策略显著降低了需要的血小板输注数量— 从预防组的152单位降低到治疗组的118单位，减少率为27% (P?= .004)。Wandt医师报告指出，预防组有14例达到启动输血的临界值，但是未输血；如果把这些也纳入，减少率更高(33%)。
此外，Wandt医师建议，藉由治疗策略，46%的病患不需要血小板输注，几乎是预防组(22%)的两倍。
本研究中治疗组减少的血小板输注数量可以换算成庞大的费用节省。Wandt医师估计，如果把这策略运用到接受自体移植的病患，根据欧美这类病患的官方统计资料，粗估每年可以省下16,460单位的分离术血小板，也就是每年可以省下800万欧元或者1,000至1,100万美元。
【治疗组发生比较多出血事件】
Wandt医师表示，治疗组比预防组发生比较多的临床相关出血事例，分别是37%与7%，但这属于预期发生的效应。他表示，所有的出血事件都是轻微到中度(等级2或3)且都使用输血加以安全的治疗。
Wandt医师表示，虽然出血事件增加，但这些是启动输血的设定，若遵照此策略就得接受它。不过，没有严重的致命出血。
两组在住院、输红血球、白血球减少等没有差异；相对的，治疗组的血小板减少期间(指血小板数量 ≦20,000/uL)明显比预防组长(平均值分别为5 天与3天；P= .004)，Wandt医师表示，这也是预料中的。
Wandt医师向与会听众表示，我们结论是，治疗性血小板输注对于自体干细胞移植病患有经济效益且是安全的；他指出，尽管会有比较多的微量出血，但都可以用血小板输血安全地控制，防止发生严重出血。
不过，听众里有许多医师对“此一策略是安全”的结论进行争论，认为研究病患数太少，难以侦测出两组之间严重出血的差异。
Wandt医师回应表示，强调本研究中没有严重致命的出血事件，在他们之前发表的140名自体干细胞移植病患的研究中也没有严重事件(Bone Marrow Transplant. 2006;37;387-392)。他的团队目前正对急性骨髓性白血病患者进行一个小型随机试验，所以很快就有更多资料。
但是，他也指出，目前为止的病患数的确太少，而无法侦测出严重出血的差异，这类差异也可能相当小。他的团队之前估算，此一差异需要每一组有2,000名病患的临床试验才可以获得。
ASH现任总裁、加州大学圣地牙哥分校医学教授Kenneth Kaushansky医师在被邀请对此治疗性血小板输注策略提出评论时表示，这很有趣，但是要改变临床实务则为时尚早；我们需要更多资料。
华盛顿Puget Sound血液中心的血小板输血专家Sherrill Slichter医师同意需要更多资料，特别是不同的病患族群。在她的经验中，有最多资料的是自体移植组，这一组的出血发生率比其他组低。她指出，在她于此会议所发表的PLADO研究(Medscape Oncology已经报导)中，自体移植病患有54%的出血率，而化疗病患有68%、异体移植病患有72%。她表示，期待看到Wandt医师可望于明年ASH会议中发表的有关急性骨髓性白血病患者的研究结果。
本研究接受德国癌症基因会赞助资金。 Wandt医师宣称没有相关资金上的往来。
美国血液学会(American Society of Hematology (ASH))第50届年会暨展览会：摘要286发表于2008年12月8日。
ASH 2008: Therapeutic Instead of Prophylactic Platelet Transfusions Are Feasible and Reduce Costs
By Zosia Chustecka
Medscape Medical News
Therapeutic instead of prophylactic platelet transfusions are safe, feasible, and would reduce costs considerably, say German researchers reporting the first worldwide randomized study comparing the 2 different strategies. However, the study was conducted in 171 patients, and experts believe more data are needed before conclusions can be drawn about safety and the new strategy is implemented.
The trial was presented here at the American Society of Hematology (ASH) 50th Annual Meeting and Exposition by Hannes Wandt, MD, from the Klinikum Nuremberg Nord, in Nuremberg, Germany. It was conducted in patients who had recently received high-dose chemotherapy, total-body irradiation, or autologous stem-cell transplant for a variety of hematological malignancies, including multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's disease, and acute myeloid leukemia.
Such patients often become thrombocytopenic. Current practice is to treat patients with prophylactic platelet transfusions, which are triggered when the platelet count falls below 10,000/uL. Dr. Wandt and colleagues compared this standard practice to an experimental strategy of therapeutic platelet transfusions, where patients received a transfusion only when they experienced a clinically relevant bleed (more than petechias or minimal mucosal bleeding).
This new strategy significantly reduced the number of platelet transfusions that were administered — from 152 in the prophylactic group to 118 in the therapeutic group, a reduction of 27% (P?= .004). There were 14 instances in the prophylactic group where the trigger was reached but a transfusion was not given; if these are included, the reduction is even greater (33%), Dr. Wandt reported.
In addition, with the therapeutic strategy, 46% of patients did not need a platelet transfusion, which is nearly double the 22% in the prophylactic group, Dr. Wandt commented.
The reduction in platelet transfusions seen in the therapeutic group of this study could translate into huge cost savings. Dr. Wandt estimated that if this strategy was implemented only for patients who receive autologous transplants, based on figures from official registries of such patients in the United States and Europe, an estimated 16,460 apheresis platelet units could be saved each year. This translates to cost savings of €8?million or $10?million to $11?million each year.
More Bleeding Episodes in Therapeutic Group
There were more instances of clinically relevant bleeding in the therapeutic group than in the prophylactic group (37% vs 7%), although this is to be expected with a strategy that has bleeding as the trigger for transfusion, Dr. Wandt commented. "All of the bleeding events were of minor to moderate severity (grade?2 or 3) and were safely treated with transfusions," he said.
"It is clear that bleeding episodes are increased, but these are triggers for transfusion, and if you follow this strategy, you have to accept this," Dr. Wandt commented. However, there were no severe or fatal bleeds, he added.
There was no difference between the 2 groups in hospitalization, number of red-blood-cell units transfused, or leukocytopenia. In contrast, the duration of thrombocytopenia (platelet count of ?20,000/uL) was significantly longer in the therapeutic-transfusion group than in the prophylactic group (median of 5 days vs 3 days; P?= .004), as would be expected with this strategy, Dr. Wandt commented.
"We conclude that our therapeutic platelet-transfusion strategy is cost effective and safe in patients after autologous stem-cell transplantation," Dr. Wandt told the meeting. Despite more minor hemorrhages with the experimental strategy than with the traditional prophylactic strategy, all bleeding events could be safely controlled by consecutive platelet transfusion, and development of major bleeding could be prevented, he added.
However, several clinicians in the audience took issue with the conclusion that this strategy was safe, saying that the patient numbers were too small to detect a difference in severe bleeding between the 2 groups.
Dr. Wandt countered by emphasizing that no major life-threatening bleeds were seen in this study, nor in a previous study that his group conducted in 140 patients with autologous stem-cell transplants (Bone Marrow Transplant. 2006;37;387-392). His group is currently conducting a similar randomized trial in patients with acute myeloid leukemia, so more data will be available soon.
But he did acknowledge that the patient numbers so far may be too small to detect a difference in severe bleeds, and he pointed out that such a difference may be extremely small. His group previously calculated that to detect such a difference, a clinical trial would need to have 2000 patients in each group.
Asked to comment on this therapeutic platelet-transfusion strategy, current ASH president Kenneth Kaushansky, MD, professor of medicine at the University of California, San Diego, said that this was interesting but it was too early to change clinical practice. "We need more data," he said.
Sherrill Slichter, MD, an expert on platelet transfusions from the Puget Sound Blood Center, in Seattle, Washington, agreed that more data are needed, particularly in different patient populations. The group for which there are the most data is autologous transplants and, in her experience, this subgroup has a lower incidence of bleeding than other groups. She noted that in the PLADO study that she presented at the meeting, already reported by Medscape Oncology, patients who received autologous transplants had a 54% rate of bleeding, compared with 68% in patients who received chemotherapy, and 72% in patients who received an allogeneic transplant. She said it will be interesting to see results from the ongoing study in acute myeloid leukemia patients, which Dr. Wandt hopes to present at the ASH meeting next year.
The study was funded by a grant from the German Cancer Foundation. Dr. Wandt has disclosed no relevant financial relationships.
.
American Society of Hematology (ASH) 50th Annual Meeting and Exposition: Abstract 286. Presented December 8, 2008.