TABLE 5.

Analysis of Studies Included in the GRADE Profile Question: Among Individuals With Bone Marrow Failure After Exposure to Ionizing Radiation, Does Bone Marrow Transplantation vs No Transplantation Affect Overall Survival?

Accident	Design	Estimated Whole-Body Doses Received	Bone Marrow Transplantation Technique Used	Outcome in Patients Treated With Bone Marrow Transplantation	Outcome in Patients Not Treated With Bone Marrow Transplantation	Other Considerations and Limitations	Summary of Findings	Effects	Quality	Importance
Vinca, Yugoslavia,35 criticality accident during an experiment at the Boris Kidrich Institute	Case series report of treatment of 5 patients with bone marrow failure	Not known with a reasonable degree of precision Original clinical case report gave following ranges (in Sv) for the total doses received: 10–12, 7–10, 7–10, 7–10, 6–8, and 3–5 Reconstruction of the incident provides evidence that actual doses received were lower than initial estimates IAEA Vinca Dosimetry Experiment 35 suggested following dose exposures (in Gy): 4.36, 4.26, 4.19, 4.14, 3.23, and 2.07 (reports quoted gave these values in rad/rem and the conversion factors of 1Sv 100 rem and 1 Gy = 100 rad were used)	HLA-unmatched bone marrow transplants	4/5 patients survived with good hematological recovery	No untreated patients	No evidence of engraftment, and hematological recovery may have been caused by either spontaneous recovery of patient’s own bone marrow or engraftment	Case series in which 4/5 patients survived with good hematological recovery in an incident in which the dose exposure is uncertain and no markers of engraftment are available to identify whether HLA-unmatched bone marrow transplantation was responsible for survival of those treated	4/5 exposed people who survived after exposure to doses of radiation that may not have inevitably produced lethal bone marrow damage whose treatment included bone marrow grafting	Low quality: significant uncertainty of dose exposure No evaluation of severity of hematological injury to establish need for treatment No clear evaluation of an engraftment endpoint to demonstrate unequivocally the role of bone marrow transplantation in their treatment	Limited importance
Pittsburgh, PA,36 industrial linear accelerator accident	Case report of treatment of 1 patient with bone marrow failure	3 patients affected, only 1 reported to have received a radiation dose likely to have caused severe hematological injury, which was estimated as 6.0 Sv; dose was heterogeneous (feet 27 Sv and hands 59 Sv)	Bone marrow transplant from genetically identical twin	1/1 patient survived with good hematological recovery	No untreated patients	Evidence of complete bone marrow destruction not established Dose significantly heterogeneous Graft taken from genetically identical twin and no definitive marker of engraftment therefore available	Single case in which 1/1 patients survived with good hematological recovery following transplantation from a genetically identical twin Uncertain evidence of degree of bone marrow failure and no evidence of engraftment	1/1 patients exposed to radiation dose that may be expected to impart significant bone marrow impairment survived whose treatment included bone marrow graft	Low quality: single case with significantly heterogeneous dose and uncertain evidence of bone marrow failure Not possible to identify engraftment endpoint to demonstrate unequivocally role of bone marrow transplantation in treatment	Limited importance
Chernobyl, former Soviet Union,34 criticality accident with significant release of radioactive materials into environment from an industrial electricity-generating reactor	Case series report of treatment of 13 patients with bone marrow failure treated with bone marrow grafting; limited reporting of outcome in 14 cases of similar dose exposure that did not receive transplants	Biological marker estimated doses (in Gy): 6.6, 9.2, 12.1, 11.9, 4.4, 5.2, 9.6, 5.6, 10.2, 13.4, 8.3, 6.4, and 8.7	Histocompatibility (H = haplotype; H1 = haplotype and 1 locus; Id = identical): H1 (father), Id (brother), Id (sister), H1 (mother), H1 (sister), Id (brother), Id (brother), H (sister), H (mother), H (brother), Id/H1 (brother),* Id (sister), H (sister)	Outcomes reported at day 1187 after accident: died (burns), died (GI/burns/pneumonitis), died (GI/burns), died (burns), died (ARF/ARDS), died (GvH/infection), died (GI/burns), survived, died (GvH/interstitial pneumonia), died (burns/GI complications/interstitial pneumonia), died (GvH/hepatic failure/interstitial pneumonia), died (GvH/infection/ARF), survived, 2/13 survived who had dose exposures of 5.6 and 8.7 Gy Survival stratified by dose in patients who received grafts was ≥9 Gy 0/6, <9 Gy 2/7	15 patients were selected for transplantation with criteria of dose ≥6 Gy, full or partial HLA-typed donor availability, predicted absence of irreversible lethal damage to other organs No sib/parent donor could be found for 2 cases; HLA-matched nonfamilial donors were found for these cases; outcomes of these cases were 1 case subsequently developed organ damage judged to be likely lethal; 1 case refused consent for transplantation; limited data reported on 14 people who did not receive transplants with similar dose exposure Survival stratified by dose in patients who did not receive grafts was ≥9 Gy 0/6, <9 Gy 6/8	Radiation injury judged to be relatively homogeneous in all cases Severity of other organ injuries dominant as cause of death Initial engraftment identified in 8 cases, of whom 7/8 survived for at least 14 d after transplantation Graft-vs-host disease identified in 4/8 of cases in which initial engraftment identified Interstitial pneumonitis identified in 4/13 cases in which grafting undertaken Engraftment probably transient in both survivors	Case series in which 2/13 patients survived with good hematological recovery after transplantation Evidence of bone marrow failure is good Grafting from donors with partial or complete HLA typing was undertaken Of the 2 survivors, engraftment was probably transient Adverse effects of adjunctive treatment to enable grafting to occur are present in 5/11 patients who died (GvH/interstitial pneumonitis, or both) Cause of death in all cases complicated by significant damage to other organs	2/13 patients exposed to a dose of radiation that may be expected to impart significant bone marrow impairment survived whose treatment included bone marrow grafting 6/14 patients exposed to dose of radiation that may be expected to impart significant bone marrow impairment survived whose treatment did not include bone marrow grafting Adverse effects of treatment potentially significant in 5/11 deaths	Moderate quality: reporting of intervention group is to a high standard and all relevant information can be elicited Reporting of a control group is poor with no matching data available Negative effects of intervention significantly intermingled with organ damage from radiation	Critical

ARF-ARDS=adult respiratory distress syndrome/acute respiratory failure; GI=gastrointestinal; GvH=graft-vs-host disease; HLA=human leukocyte antigen. Principal criterion for inclusion: All studies with an observational outcome regarding the use of bone marrow transplantation in irradiated individuals with bone marrow failure. Additional criteria for exclusion: radiation exposure was in a nontherapeutic setting; reporting of the clinical details of the incident is in the public domain; reported cases had no other clinical reason to experience bone marrow injury; report contained sufficient clinical information to establish clear evidence of bone marrow injury; report contained sufficient clinical information to establish clear evidence of consequent survival; and information on the radiation doses received was available.

^*Unresolved laboratory testing disparity.