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Auto-Transplant: Therapeutic, Not Prophylactic, Transfusions

Goodwin, Peter

doi: 10.1097/01.COT.0000345891.93261.20

SAN FRANCISCO—A note of controversy was struck at the ASH Annual Meeting here with the announcement that patients who have their hematologic malignancies treated with high-dose chemotherapy and stem cell transplantation—with or without total body irradiation—may be spared toxicity and cost by avoiding routine platelet transfusions.

Hannes Wandt, MD, Professor of Medicine and Head of the Bone Marrow Transplant Unit, at the University of Nuremberg, called therapeutic platelet transfusion safe and feasible, according to the conclusions of his group's multicenter study, with 171 patients randomized either to receive platelet transfusions triggered by a count falling to 10/nL (the “prophylactic” arm of the study), or to have transfusions only if “clinically relevant” bleeding takes place (the “therapeutic” arm).

But ASH's 2008 President, Kenneth Kaushansky, MD, who chaired a news briefing about platelet disorders at which Dr. Wandt's study was featured, noted that patients in the study were relatively free of major complications and were healthy going into the study—except for their underlying disease—and didn't have big anatomical problems, graft-versus-host disease, or sepsis:

“It's certainly worth studying in those kind of settings,” said Dr. Kaushansky, who is the Helen M. Ranney Distinguished Professor and Chair of the Department of Medicine at the University of California, San Diego. “And we did hear about the beginning of a trial in patients with acute myeloid leukemia, who are going to be sicker, and for whom a treatment strategy rather than a prophylactic strategy, is worth studying.”



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Study Details

About two thirds of Dr. Wandt's patients had multiple myeloma, the remainder having either Hodgkin's lymphoma, non-Hodgkin's lymphoma, or acute leukemia.

The primary objective was to achieve a reduction of platelet transfusions by 15% to 25%. And this was met, with a reduction of 27% in the therapeutic arm of the trial in which 46% of the patients did not need platelet transfusions.

Secondary objectives were to assess safety, hospitalizations, the duration of leukopenia and thrombocytopenia, and the number of red cell transfusions required.

Patients in the therapeutic arm received routine platelet transfusions if they had invasive aspergillosis, sepsis, or unexpected headache.

There was no life-threatening or fatal bleeding. One patient had a minor subarachnoid hemorrhage (documented by CT scan) without any clinical sequelae. Although days with any hemorrhage were rare among all patients, there was an increase in the experimental arm (0.69 vs 0.17 days per patient), and the overall incidence of hemorrhage was higher (28.7% vs 9.5% of patients).

Fever, infection, or patient age made no difference in the risk of bleeding, and neither was there any difference between the two arms in the duration of leukocytopenia or the need for hospitalization or for red cell transfusions.

The duration of thrombocytopenia was significantly longer in the therapeutic arm (median 5 vs 3 days), raising the suggestion that temporary low platelet counts are not hazardous per se.

“The conclusion is that you can safely perform a therapeutic platelet transfusion strategy, and this will mean that more than 50% of the patients, especially the myeloma patients, don't need any platelet transfusion at any time during their autologous transplantation,” Dr. Wandt said in an interview. “All in all, you can save about one third of the platelet transfusions with the new strategy.”



And he noted that apart from cost savings running into millions of dollars there are some important clinical gains: “The benefit for patients are the milder transfusion reactions and fever, and you can also reduce very severe side effects, like transfusion-related lung injury, which has a mortality of about 60 to 80 percent.”

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Still, Relatively Small Number of Patients in the Study

And Dr. Kaushansky said that while he was impressed with the findings, he did have reservations about the relatively small number of patients: “I think we'll need a little bit broader experience. This was a study based on [not even] a couple of hundred patients. And again—like so many things in clinical medicine—one wants to see greater numbers of patients treated in a certain way before you change your practice.”

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Concerns about Bleeding Risk

Asked for his opinion for this article, George Canellos, MD, the William Rosenberg Chair and Professor of Medicine at Harvard Medical School and a senior physician in the Department of Hematologic Oncology at Dana-Farber Cancer Institute, said he was concerned about any move towards a therapeutic platelet transfusion strategy, especially because of the risk of a major bleed in the brain or another vital organ, which could not be treated so effectively retrospectively.

“I think the ultimate argument is that you as a physician are responsible for that patient in front of you. And until more of these studies are done we just can't go on the basis of this [one] trial. And I think the doctor is obligated to do the best he can for that patient, and not experiment with him on the basis of this study—which is very well done,” Dr. Canellos said.

He added that he wasn't convinced, personally, that he should adopt the therapeutic strategy over routine transfusions below platelet counts of 10/nL, especially in an older population with leukemia.

“All you have to see is bleeding into the head once, and you would never, never again do the wait-and-see policy. You would prophylactically transfuse them—I speak for myself.”

© 2009 Lippincott Williams & Wilkins, Inc.
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