(also see also see mesenchymal stem cells, granulocyte transfusion, regulatory issues, autoimmune diseases, HIV positive patients, other items)

vi. Acute Radiation Injury

A. Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Weisdorf D, Chao N, Waselenko JK, Dainiak N, Armitage JO, McNiece I, Confer D. Biol Blood Marrow Transplant. 2006;12:672-82.

Evaluation and management of victims of exposure to myelosuppressive radiation in a military, terrorist, or accidental event is challenging. The hematopoietic syndrome with marrow suppression and pancytopenia follows intermediate intensity radiation exposure and as such produces a clinical syndrome similar to that after myelosuppressive chemotherapy or stem cell transplantation. Therefore, hematologists, oncologists, and transplantation physicians have the opportunity and challenge to plan for care of irradiation victims. Management of the hematopoietic syndrome, as a component of acute radiation sickness, requires understanding its manifestations and implementation of clinical biodosimetry to provide appropriate therapeutic support. Hematopoietic growth factors may be of value if administered early as a component of supportive care. Planning for urgent stem cell transplantation for those with intermediate- to high-dose radiation (4-10 Gy) may be required. Establishing contingency plans for triage, assessment, supportive care, and treatment resembles the development of phase II trials, with defined eligibilities, treatment plans, and incorporated data collection to assess results and plan further improvements in care. The hematology/oncology community is most suited to participate in such contingency planning, and the necessary elements for its success are reviewed.

[Comment: We must remember that, when considering the disaster of "9/11", the pertinent year is 2001 – almost five years ago. The obvious need for planning for urgent stem cell transplantation was pointed out in 2002 in a letter to the Editor of the New England Journal of Medicine (see citation B below) but largely ignored. In the event of large-scale exposure, some persons are likely to be exposed to a dose of total-body radiation that would result in death from bone marrow failure without other life-threatening complications. The only effective treatment for bone marrow failure caused by lethal doses of radiation is hematopoietic cell transplantation. It would seem that the first stage in planning for urgent hematopoietic cell transplantation after acute radiation injury would be to be sure that stem cell donors are available. There is no point in developing contingency plans for triage, assessment, supportive care, etc., unless there is a ready source of stem cell products available for transplantation. As was emphasized in 2002, cord blood transplantation seems particularly suited to the task because of the ease and rapidity with which stem cell products can be obtained. The federal government has apparently seen fit to spend >200 million dollars on anthrax and smallpox vaccines for products we hope will never be needed. Had this money been spent on umbilical cord blood banking, we could now (five years later) already have an inventory of cryopreserved cord blood units that could provide high grade HLA matched units for a large majority of potential victims of a radiation disaster. Even if never needed for treatment of radiation disaster victims, the units could be used to save lives of those in need of a hematopoietic cell transplant. Once developed, the inventory could easily be maintained even while being used for ongoing patient needs. The Stem Cell Therapeutic and Research Act of 2005 is welcomed and, if implemented expeditiously, will begin to satisfy the need.

Although stem cell transplantation provided no significant benefit in the Chernobyl disaster, much has changed since then. In particular, one needs to be reminded that, at the time of Chernobyl, HLA typing could not be done on the victims because typing then required lymphocytes whereas the victims were pancytopenic. Therefore, there was no way to select an appropriate donor, and the lack of success of stem cell transplantation for that disaster is easy to understand but no longer relevant. Modern HLA typing is DNA based and can be performed quickly using a small tissue sample from the victim.]

B. Major Radiation Exposure. Forman SJ, Petz LD. New Eng J Med 2002;347:944 (Correspondence)

To the Editor: In their review article on radiation exposure (N Engl J Med 2002;346:1554-1561), Mettler and Voelz did not give adequate consideration to hematopoietic cell transplantation as a potential treatment for persons exposed to radiation. In the event of large-scale exposure, some persons are likely to be exposed to a dose of total-body radiation (approximately 6 to 15 Gy) that would result in death from bone marrow failure without other life-threatening complications. The only effective treatment for bone marrow failure caused by lethal doses of radiation is hematopoietic-cell transplantation.

Since the Chernobyl disaster, there have been substantial advances that make urgent hematopoietic-cell transplantation more practical. Pancytopenia is no longer an impediment to HLA typing, which can now be performed with the use of DNA techniques. HLA-matched donors can be identified among family members or from donor registries, although the latter approach may be too time-consuming to be practical in emergencies, and matched donors are not always available. Moreover, units of cryopreserved umbilical-cord blood can be identified in registries and made available within days for transplantation in children and adults. When umbilical-cord blood is used, less stringent HLA matching is required, so that a bank of approximately 200,000 units could provide 90 percent of the population with a donor matched at four or five of six HLA loci — the type of matches that are commonly used in cord-blood transplantation.

Shortening of the turnaround time for searches of donor registries, providing for an umbilical cord blood bank of appropriate size, and developing a consortium of transplantation programs to care for patients requiring such transplantation should be part of the plan for national preparedness for such a disaster.