Whether autologous or allogeneic stem cells are used for an HCT depends on the underlying disease and the planned treatment strategy. When an immune anti-cancer effect is wanted, or when an inherited bone marrow defect in the patient needs correction, or when a cancer-free autologous graft can not be harvested from the patient, an allogeneic transplant becomes the primary choice. Performing an allogeneic HCT depends upon finding a suitable donor, ideally an HLA-identical relative. Such a donor is unfortunately only available for about a third of patients in the US [8
]. The next best option is an HLA-identical or minimally HLA-mismatched unrelated donor transplant, using cells collected from a healthy adult volunteer donor or previously collected and stored UCB cells made available for public use. In some centers UCB transplantation is now the preferred choice for unrelated donor HCT in children who do not have an HLA-identical related donor [14
]. During the years selected for this study, about 25% of allogeneic HCTs performed used adult or cord blood unrelated donors [CIBMTR data]. Despite these alternative sources of grafts, more than half of patients in need of transplantation still do not have an available donor.
The average annual number of HCTs, either autologous or allogeneic, which we calculated for the US (about 17,000 under Scenario 3, assuming universal donor availability, ), is similar or higher than the average annual number of other generally accepted medical procedures in the US, e.g., kidney transplantation, with an average of about 15,000 per year [15
] and surgery for cleft palate / cleft lip, with an average of about 5,000 per year [16
When calculating the lifetime probabilities, several assumptions were made that deserve discussion. Under Scenario 1, CIBMTR data indicate that the lifetime probability of undergoing an autologous HCT in the US is about 1:400 if the indications for autologous HCT do not change much during the next 70 years. This, of course, may not be true. Advances in HCT technology may lead to its use for new indications, new pharmaceutical developments may replace HCT for some diseases, or both may occur; the effect of these advancements could increase, decrease or leave unchanged the lifetime probabilities estimated in this study. Under Scenarios 2 and 3, the lifetime probabilities are 1:400 and 1:200, respectively, for undergoing allogeneic HCT or either autologous or allogeneic HCT. Those probabilities are partly speculative, because of the assumption of universal donor availability. However, these probabilities may be realized with increased numbers of donors and/or UCB units and/or strategies to accommodate greater degrees of donor-recipient HLA disparity. A bank with sufficient allogeneic UCB units could provide suitable transplants for most US patients in need, because of the possibility of using UCBs with 1 or 2 HLA mismatches [17
], and when strategies become available to overcome limitations of low cell numbers [18
]. The size required for such a donor bank is discussed elsewhere [23
] and must take into account differences, if any, in outcome with varying degrees of HLA matching and varying cell doses [24
Under Scenario 4, the calculated probability of almost 1:100 is based on the speculation that many changes in current practice will enable more widespread use of HCT in the future in patients with diseases where efficacy has already been demonstrated. A comparison of the probabilities under Scenarios 3 and 4 shows how much a change in scenario can affect the lifetime probability of undergoing an HCT. At the moment about 17% of patients who are diagnosed with diseases potentially treatable with HCT actually undergo HCT (as outlined in the Materials and Methods
section), in contrast to the 50% we empirically selected as an “upper limit”. It is unlikely that the percentage would be higher than this since patients may not require transplantation, may be treated with other therapies, may have comorbidities that would preclude transplantation or may have socio-economic barriers to transplantation. The usage of HCT is limited by consideration of the risk to benefit ratio of this therapy, which carries significant treatment-related mortality, versus other (less aggressive) therapies [4
]. Major improvements in safety and efficacy of HCT are required to realize Scenario 4. It is of interest that during the study period, we estimated that 40–45% of patients diagnosed with multiple myeloma up to age 70 years received HCT (>95% autologous HCT). During this time, there was general consensus that autotransplant was the preferred therapy (though more recent studies have brought this into question) and that the procedure could be safely done even in older patients.
Regardless of scenario or transplant practice, yearly HCT rates would increase if uninsured Americans, which included 11% of children and 15% of non-elderly adults in 2003 [25
], had full access to health care. Unequal access to health care may account for some of the discrepancy between the proportion of HCTs received by African-Americans (9%, , Scenario 3) and their representation of about 13% in the US population [26
As stated in the Materials and Methods
section, our adjustment for under-reporting assumed that transplants reported to the CIBMTR are a simple random sample of patients receiving transplant. There may be inherent differences in the types of patients treated by centers reporting versus not reporting to the CIBMTR, which would result in a biased adjustment for under-reporting. However, inspection of data reported to NMDP, BMTInfoNet and the EBMT, suggest that CIBMTR is representative. A similar bias could occur from the use of group-level data from SEER.
In conclusion, whatever the future developments in HCT practice, our results show that the lifetime probability of undergoing HCT is much higher than the probabilities previously reported by others [27
], which ranged from 1:2700 to 1:200,000. These results are important for planning donor registries, UCB banks and health insurance policies.