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Planning and Response to Radiation Exposures
1262
Letters to the Editor
Planning and Response to Radiation Exposures The March 11 earthquake and tsunami in Japan has caused the worst radiation disaster since Chernobyl. In the ensuing weeks, dozens of workers have been exposed to radiation while struggling to limit the release of radioactivity from damaged reactor containment vessels and compromised spent-fuel storage pools. Fortunately, no serious immediate injuries have been reported. Exposure monitoring for individual workers enables managers to limit radiation doses, and this relatively controlled situation should prevent, barring further calamity, any dangerous exposures. Nevertheless, some medical professionals including a group of experienced hematologists in Japan advising on safety measures for this catastrophic situation have proposed that, because the bone marrow is known to be the most radiosensitive organ in the body, hematopoietic progenitor and stem cells (HPC) should be collected prophylactically from some or all workers [1]. Then, if a subsequent uncontrolled radiation exposure occurred, a worker who received a marrow-ablative dose of radiation could be rescued with an infusion of his own (autologous) cells. Autologous HPC transplantation has been used therapeutically to treat various cancers for more than 30 years. The procedure makes it possible to deliver otherwise lethal doses of radiation and/or chemotherapy to the cancer and achieve higher tumor cell kill. It works, and works very well. Countless cancer survivors can attest to its effectiveness and safety. But this is a finely tuned delivery of cytotoxic therapy: too little and the autologous HPC are irrelevant; too much and the toxicities to other organs (gut, lung, blood vessels, brain) prove fatal [2]. It is estimated that exposures of whole-body irradiation 4 to 9 Gy (4000-9000 mSv) fall in this range where marrow suppression is the critical factor for survival, but partial-body irradiation, as might occur with workers partially shielded by walls or equipment, may spare some marrow tissue allowing spontaneous hematologic recovery [3-5]. For radiation casualties without radiation monitors, the ability to assign precise radiation dose to each organ is not possible today. Victims with even severe exposures can be medically supported for weeks to months if autologous recovery is possible, but transplantation of HPC for selected cases could accelerate recovery [6]. So, what is the likelihood that a worker in the Fukushima Daiichi nuclear plant will receive that precise dose of radiation that will render autologous HPC rescue a necessary and life-saving procedure? We do not know, but it is probably very low.
Biol Blood Marrow Transplant 17:1261–1263, 2011
In a different scenario, a terrorist nuclear explosion, it is estimated that tens of thousands might be exposed to major doses of radiation [7]. Among these, there could be hundreds or thousands who receive that precise dose wherein marrow destruction is a certainty, but no other organ is irreversibly injured. These victims could conceivably be saved with HPC rescue. But we certainly cannot store autologous cells on every potential victim in major U.S. cities. If victims in this terrible scenario can be rescued with HPC, they will be rescued with donated (allogeneic) HPC from HLA (human leukocyte antigen)-matched relatives, volunteer unrelated donors, or frozen umbilical cord blood units from public cord blood banks [8,9]. In the United States, we have established the Radiation Injury Treatment Network (RITN) (www.ritn.org), a collaboration of the American Society for Blood and Marrow Transplantation (www.ASMBT.org) and the National Marrow Donor Program (NMDP), which in coordination with U.S. government and regional emergency planning programs has plans and procedures for such urgent situations. RITN members include Bone Marrow (HPC) transplant programs plus the marrow, blood stem cell, and umbilical cord bank donor network (www.marrow.org). Transplant physicians understand bone marrow suppression. We know how to manage patients with marrow injury. We can identify those that need allogeneic HPC infusions for rescue and we can recognize multiorgan injury that is unrecoverable. RITN has also established guidelines for advanced planning to outline steps in evaluation of those with marrow injury, shared tools to estimate radiation exposure, supportive care management techniques, and procedures to provide multifaceted treatments for marrow suppressed radiation victims. For some, whose radiation exposure falls in the window of severe marrow injury without otherwise lethal organ toxicity, aggressive supportive care may not be enough. Then HPC replacement with autologous (if available) or more likely, allogeneic donor cells, may be needed. Plans and protocols for such treatments have been proposed. We emphasize that in some, likely limited circumstances, autologous HPC collection and cryopreservation may be appropriate, but careful analysis suggests that very few victims might either need or benefit from such preemptive measures. In a large scale, unanticipated accidental or terrorist radiation incident, autologous HPC will not be available or applicable to the broader public exposed to radiation. Alternatively, education and planning for management of the acute radiation syndrome, prompt application of clinical or laboratory dose estimation algorithms, and administration of marrow-stimulating cytokines or other radiation injury mitigators may be of equal or greater benefit, especially for a large-scale incident.
Biol Blood Marrow Transplant 17:1261–1263, 2011
For carefully selected casualties, marrow replacement with allogeneic matched hematopoietic cells could be their best option. Ongoing support for research into new dosimetry techniques and radiation mitigators along with better medical management approaches could expand the array of useful options to help victims: whether few or many. We also recognize that our U.S. and collaborating overseas network of physicians is small, capable of a limited supportive role for a contained number of victims: such as could have occurred with the recent industrial accident. But the only way that RITN can effectively respond to the unfathomable nuclear explosion is when physicians everywhere devote their efforts to understanding radiation and how to manage its effects. ACKNOWLEDGMENT The authors declare no conflicts of interest. REFERENCES 1. Tanimoto T, Uchida N, Kodama Y, Teshima T, Tanuguichi S. Safety of workers at the Fukushima Daiichi nuclear power plant. Lancet. 2011;377:1489-1490. 2. Haire WD. Multiple organ dysfunction syndrome in hematopoietic stem cell transplantation. Crit Care Med. 2002;30: S257-S262. 3. Weinstock DM, Case C Jr., Bader JL, et al. Radiologic and nuclear events: contingency planning for hematologists/oncologists. Blood. 2008;111:5440-5445. 4. Waselenko JK, MacVittie TJ, Blakely WF, et al. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 1037;140:1037-1051.
Letters to the Editor
1263
5. Weisdorf D, Chao N, Waselenko JK, et al. Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol Blood Marrow Transplant. 2006;12:672-682. 6. Klymenko SV, Belyi DA, Ross JR, et al. Hematopoietic cell infusion for the treatment of nuclear disaster victims: new data from the Chernobyl accident. Int J Radiat Biol. 2011;(Early Online): 1-5. 7. Threats NSSIPCSfPaRtRaN. Planning Guidance for Response to a Nuclear Detonation, 2nd ed. Washington, DC: Government Printing Office; 2010. 8. Brunstein CG, Gutman JA, Weisdorf DJ, et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood. 2010;116:4693-4699. 9. Gooley TA, Chien JW, Pergam SA, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091-2101.
Daniel Weisdorf, M.D.1 David Weinstock, M.D.2 Cullen Case4 Nelson Chao, M.D.3 Dennis L. Confer, M.D.4 1
Masonic Cancer Center University of Minnesota Minneapolis, Minnesota 2 Dana-Farber Cancer Institute Harvard Boston, Massachusetts 3 Duke University Medical Center Durham, North Carolina 4 National Marrow Donor Program Minneapolis, Minnesota
Biol Blood Marrow Transplant 17: 1262–1263 (2011) Ó 2011 American Society for Blood and Marrow Transplantation doi:10.1016/j.bbmt.2011.06.002
Letters to the Editor
Planning and Response to Radiation Exposures The March 11 earthquake and tsunami in Japan has caused the worst radiation disaster since Chernobyl. In the ensuing weeks, dozens of workers have been exposed to radiation while struggling to limit the release of radioactivity from damaged reactor containment vessels and compromised spent-fuel storage pools. Fortunately, no serious immediate injuries have been reported. Exposure monitoring for individual workers enables managers to limit radiation doses, and this relatively controlled situation should prevent, barring further calamity, any dangerous exposures. Nevertheless, some medical professionals including a group of experienced hematologists in Japan advising on safety measures for this catastrophic situation have proposed that, because the bone marrow is known to be the most radiosensitive organ in the body, hematopoietic progenitor and stem cells (HPC) should be collected prophylactically from some or all workers [1]. Then, if a subsequent uncontrolled radiation exposure occurred, a worker who received a marrow-ablative dose of radiation could be rescued with an infusion of his own (autologous) cells. Autologous HPC transplantation has been used therapeutically to treat various cancers for more than 30 years. The procedure makes it possible to deliver otherwise lethal doses of radiation and/or chemotherapy to the cancer and achieve higher tumor cell kill. It works, and works very well. Countless cancer survivors can attest to its effectiveness and safety. But this is a finely tuned delivery of cytotoxic therapy: too little and the autologous HPC are irrelevant; too much and the toxicities to other organs (gut, lung, blood vessels, brain) prove fatal [2]. It is estimated that exposures of whole-body irradiation 4 to 9 Gy (4000-9000 mSv) fall in this range where marrow suppression is the critical factor for survival, but partial-body irradiation, as might occur with workers partially shielded by walls or equipment, may spare some marrow tissue allowing spontaneous hematologic recovery [3-5]. For radiation casualties without radiation monitors, the ability to assign precise radiation dose to each organ is not possible today. Victims with even severe exposures can be medically supported for weeks to months if autologous recovery is possible, but transplantation of HPC for selected cases could accelerate recovery [6]. So, what is the likelihood that a worker in the Fukushima Daiichi nuclear plant will receive that precise dose of radiation that will render autologous HPC rescue a necessary and life-saving procedure? We do not know, but it is probably very low.
Biol Blood Marrow Transplant 17:1261–1263, 2011
In a different scenario, a terrorist nuclear explosion, it is estimated that tens of thousands might be exposed to major doses of radiation [7]. Among these, there could be hundreds or thousands who receive that precise dose wherein marrow destruction is a certainty, but no other organ is irreversibly injured. These victims could conceivably be saved with HPC rescue. But we certainly cannot store autologous cells on every potential victim in major U.S. cities. If victims in this terrible scenario can be rescued with HPC, they will be rescued with donated (allogeneic) HPC from HLA (human leukocyte antigen)-matched relatives, volunteer unrelated donors, or frozen umbilical cord blood units from public cord blood banks [8,9]. In the United States, we have established the Radiation Injury Treatment Network (RITN) (www.ritn.org), a collaboration of the American Society for Blood and Marrow Transplantation (www.ASMBT.org) and the National Marrow Donor Program (NMDP), which in coordination with U.S. government and regional emergency planning programs has plans and procedures for such urgent situations. RITN members include Bone Marrow (HPC) transplant programs plus the marrow, blood stem cell, and umbilical cord bank donor network (www.marrow.org). Transplant physicians understand bone marrow suppression. We know how to manage patients with marrow injury. We can identify those that need allogeneic HPC infusions for rescue and we can recognize multiorgan injury that is unrecoverable. RITN has also established guidelines for advanced planning to outline steps in evaluation of those with marrow injury, shared tools to estimate radiation exposure, supportive care management techniques, and procedures to provide multifaceted treatments for marrow suppressed radiation victims. For some, whose radiation exposure falls in the window of severe marrow injury without otherwise lethal organ toxicity, aggressive supportive care may not be enough. Then HPC replacement with autologous (if available) or more likely, allogeneic donor cells, may be needed. Plans and protocols for such treatments have been proposed. We emphasize that in some, likely limited circumstances, autologous HPC collection and cryopreservation may be appropriate, but careful analysis suggests that very few victims might either need or benefit from such preemptive measures. In a large scale, unanticipated accidental or terrorist radiation incident, autologous HPC will not be available or applicable to the broader public exposed to radiation. Alternatively, education and planning for management of the acute radiation syndrome, prompt application of clinical or laboratory dose estimation algorithms, and administration of marrow-stimulating cytokines or other radiation injury mitigators may be of equal or greater benefit, especially for a large-scale incident.
Biol Blood Marrow Transplant 17:1261–1263, 2011
For carefully selected casualties, marrow replacement with allogeneic matched hematopoietic cells could be their best option. Ongoing support for research into new dosimetry techniques and radiation mitigators along with better medical management approaches could expand the array of useful options to help victims: whether few or many. We also recognize that our U.S. and collaborating overseas network of physicians is small, capable of a limited supportive role for a contained number of victims: such as could have occurred with the recent industrial accident. But the only way that RITN can effectively respond to the unfathomable nuclear explosion is when physicians everywhere devote their efforts to understanding radiation and how to manage its effects. ACKNOWLEDGMENT The authors declare no conflicts of interest. REFERENCES 1. Tanimoto T, Uchida N, Kodama Y, Teshima T, Tanuguichi S. Safety of workers at the Fukushima Daiichi nuclear power plant. Lancet. 2011;377:1489-1490. 2. Haire WD. Multiple organ dysfunction syndrome in hematopoietic stem cell transplantation. Crit Care Med. 2002;30: S257-S262. 3. Weinstock DM, Case C Jr., Bader JL, et al. Radiologic and nuclear events: contingency planning for hematologists/oncologists. Blood. 2008;111:5440-5445. 4. Waselenko JK, MacVittie TJ, Blakely WF, et al. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med. 1037;140:1037-1051.
Letters to the Editor
1263
5. Weisdorf D, Chao N, Waselenko JK, et al. Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol Blood Marrow Transplant. 2006;12:672-682. 6. Klymenko SV, Belyi DA, Ross JR, et al. Hematopoietic cell infusion for the treatment of nuclear disaster victims: new data from the Chernobyl accident. Int J Radiat Biol. 2011;(Early Online): 1-5. 7. Threats NSSIPCSfPaRtRaN. Planning Guidance for Response to a Nuclear Detonation, 2nd ed. Washington, DC: Government Printing Office; 2010. 8. Brunstein CG, Gutman JA, Weisdorf DJ, et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood. 2010;116:4693-4699. 9. Gooley TA, Chien JW, Pergam SA, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091-2101.
Daniel Weisdorf, M.D.1 David Weinstock, M.D.2 Cullen Case4 Nelson Chao, M.D.3 Dennis L. Confer, M.D.4 1
Masonic Cancer Center University of Minnesota Minneapolis, Minnesota 2 Dana-Farber Cancer Institute Harvard Boston, Massachusetts 3 Duke University Medical Center Durham, North Carolina 4 National Marrow Donor Program Minneapolis, Minnesota
Biol Blood Marrow Transplant 17: 1262–1263 (2011) Ó 2011 American Society for Blood and Marrow Transplantation doi:10.1016/j.bbmt.2011.06.002