Administration of GCSF to granulocyte donors by hospitals on behalf of blood centers

A transfusion medicine physician in the Southeast reports that his local blood center, for a variety of legitimate reasons, is not able to administer GCSF to granulocyte donors, but that the center is willing to identify and refer potential donors to the local hospitals for GCSF stimulation and then collect granulocyte components from the donor after stimulation. Using such a strategy, the hospital transfusion service would manage the GCSF consent, injection, adverse effects etc., as well as arrange for IRB approval, when appropriate. The inquiring physician says that the need to collect granulocytes currently only comes up infrequently, but with a growing stem cell transplant volume, such a strategy seems reasonable. He wonders if any other hospital transfusion service medical directors have similar arrangements with their blood centers, and if so what has been their experience? If so, please share examples of donor consent forms, procedures, etc. for GCSF stimulation.

The following comments have been received.

ADDENDA Feb. 5, 2004

1. Ronald E. Domen, MD, Medical Director, Blood Bank and Transfusion Medicine, Milton S. Hershey Medical Center at Penn State University College of Medicine (attribution used with permission) believes that the proposed approach by the blood center to work with the hospital transfusion service seems like a reasonable one, and one that appears to maximize donor safety. Dr. Domen says: "One of the important roles of the transfusion medicine physician/service is to be an advocate for the donor and to keep their best interests in mind. If the blood center does not have the appropriate staffing or expertise in place to oversee and monitor G-CSF administration then utilizing services available at the hospital-level - along with the approval of the hospital's IRB - seems like a good approach. While we have not given G-CSF in the blood bank for granulocyte collection our nurses have given it to stem cell donors when it was more convenient for the donor. Administering G-CSF is not difficult, but someone needs to be available to handle any side effects or recipient questions. I would also refer you to the only paper that has addressed the ethical issues of administering G-CSF to volunteer granulocyte donors (Volk EE, Domen RE, Smith ML. An examination of the ethical issues raised in the pretreatment of normal volunteer granulocyte donors with granulocyte colony-stimulating factor. Arch Pathol Lab Med 1999;123:508-513)."

ADDENDA Feb. 7, 2004

2. A very experienced transfusion medicine physician in the Midwest is of the opinion that while on the surface a proposal for a hospital to assume GCSF administration, consent, etc. for a donor center sounds appropriate, there may be several problems, from an ethical standpoint.
   • Who is going to obtain the truly informed consent?
   • One can question whether a Transfusion Service medical director can be the donor's advocate if the patient is at his/her hospital.
   • Basically for such an instance with normal donors, there needs to be clear distancing of the counseling/consent processes from those persons with a 'stake' in obtaining the granulocytes.
   He adds that while the immediate risks are low, given the uncertainty about possible long-term risks, he would suggest using a model similar to that for unrelated volunteer live organ donors. He concludes saying; "Obviously, there should be clear lines of legal responsibilities and liabilities for the several parties"

ADDENDA Feb. 9, 2004

3. A colleague from the United Kingdom reports that if a clinician feels that their patient needs granulocytes from G-CSF stimulated donors, they follow a similar approach to that adopted for related stem cell donors. The hospital has a specified program for screening relatives of the intended recipient. The hospital administers G-CSF and dexamethasone. The blood center collects and processes the component issuing it back to the hospital. At present the administration of G-CSF to unrelated volunteer donors for the purpose of granulocyte donation has not been recommended by his transfusion service. This does lead to some logistical and ethical difficulties. The UK colleague would be interested in colleagues' views on this. If anyone uses a similar approach he would be pleased to hear from them. He would also be interested to know how many transfusion services have guidelines regarding the G-CSF stimulation of unrelated volunteer donors for this purpose.

ADDENDA Feb. 13, 2004

4. A Medical Director of a Clinical Laboratory in one of the children's hospitals in the Rocky Mountains reports that at his institution the administration of G-SCF to normal blood donors is done only under an IRB-approved protocol intended to follow the donors for at least 5 years. Their concern is not so much as to where the G-CSF should be administered, but whether anyone should be administering G-CSF to the volunteer donor population. He writes "Donors are extremely trusting and will do almost anything we ask of them, yet, in this case, there are no data to my knowledge of potential long-term adverse effects. I don't feel that good about administering G-CSF to our donors even under IRB approval, as our numbers are too small and we will not be able to follow these donors for the 20 or 30 years we likely need to see if we have set the stage for a bone marrow proliferative event in their distant future. I very much agree with the conclusion in the article by Volk, et al that we need to establish a multi-institutional registry to collect the needed data on the side effects of G-CSF on normal donors. Until we do this, I will continue to be very concerned that we should not be administering growth factors to our donors. I feel I should add also that the overall survival of children who are placed on a course of granulocytes is extremely poor, so that the criteria for use of granulocytes are questionable in the first place, and yet we put donors at some unknown risk to supply these products. If we are going to continue to respond to these clinical requests I suggest that our duty might be to put together a registry of donors for long-term follow up."

ADDENDA Mar. 21, 2004

5. 5.A colleague asks if neupogen injection of donors for granulocyte stimulation is the standard of care when harvesting granulocytes, or does this procedure require an IRB approved protocol? She also wants to know what kind of guidelines do blood banks have in regards to consenting the donors and their follow up. Should the blood donor director obtain the consent? Does anyone have examples of their protocols/guidelines in place at their institutions for this procedure that they would share? The reason she is asking these questions is that her institution no longer has an IRB approved protocol for the stimulation of donors for granulocytes collection, since the institution's pathologist says that it is standard practice to do this stimulation. Some of the institution's oncologists disagree with this point of view, and do not want donors stimulated with GCSF. Apparently, the hospital has no set guidelines other than that the use of GCSF for donor stimulation is considered by the pharmacy as an "off label use of neupogen". The inquiring colleague thinks that it is the standard of care to stimulate donors for stem cell harvest, but she cannot find this for granulocyte harvest.  They currently offer no followup of the stimulated donor other than in the immediate 24 hour period. She is wondering how others view this approach.

ADDENDA Mar. 24, 2004

6. A transfusion medicine physician/lawyer reports that "off label" use of GCSF for donor stimulation in a hospital, at the request of a blood center, presents a tricky situation. He notes, "In general the FDA has tolerated off label use of approved drugs, by individual physicians." He adds that in his experience, off label use of drugs is actually widespread, although he believes that there is potentially increased liability if there is a complication with an off label use. In the case of off label use of GCSF for a donor, he wonders if the ordering physician is documented, so that accountability is clearly defined. Is the ordering physician the transfusion service medical director or the blood center medical director? If the latter, is the blood center medical director on staff at the hospital? If not, this could pose a problem for the hospital, should something go wrong. While in the usual sense, this is not research, having IRB approval would be wise. He concludes saying this situation raises "A lot of questions to decide, wherein the responsibilities need to be assigned both organizationally and individually".

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