Over the past 3 decades, hematopoietic stem cell transplantation has become a lifesaving art that is applied to a variety of malignant and nonmalignant disorders. In the 1970s, several groups demonstrated that advanced leukemia and aplastic anemia patients were cured using sibling-matched allogeneic bone marrow transplantation. By the 1980s, many published reports confirmed that relapsed and refractory lymphoma patients could attain long-term disease-free survival as a result of utilizing autologous bone marrow transplantation.
In the past decade, stem cell transplants have been increasingly performed in many solid tumor patients, including those with neuroblastoma, breast cancer, germ-cell tumors, and most recently, renal cell cancer. Substantial improvements in technology, rapidly implemented during this time, have greatly enhanced patient outcome. Notable advances include the routine use of recombinant hematopoietic growth factors, a departure from bone marrow in favor of peripheral blood stem cells, expanded use of alternative donors (unrelated, haploidentical, or umbilical-cord blood), and novel, more effective antimicrobial prophylaxis and treatment strategies.
Does Stem Cell Transplantation Improve Outcome?
Many of the data describing improved transplant outcome were generated from single-institution trials, in which highly sophisticated expertise was required. As a result, data supporting the premise that transplantation may enhance therapeutic efficacyespecially when compared to conventional therapieshave not always been embraced by the medical community. Some practitioners and investigators suggest that these findings reflect an inherent patient-selection bias; ie, transplantation is usually offered only to "fitter" patients who have a better prognosis. These observers argue that insufficient numbers of randomized clinical trials have been performed on patients undergoing transplantation. While randomized, phase III clinical trials demonstrating the superiority of transplant have been reported in acute myeloid leukemia, multiple myeloma, non-Hodgkin’s lymphoma, and Hodgkin’s disease, one review pointed out that randomized trials comprised only 16 of 255 reports.[3-7]
Restrictive Eligibility Criteria
On the other hand, some investigators have noted that randomized trials may not be representative of clinical practice since eligibility criteria are often highly restrictive. Patient characteristics (age, performance status), disease characteristics (diagnosis, stage, previous treatment), and transplant characteristics (preparative regimen, graft-vs-host disease prophylaxis regimen, supportive care) may vary greatly. Enrollment in potentially restrictive trials may be more difficult, and in general, may take a longer time to accrue sufficient patients; enrolled patients may also not be representative of the larger patient group. Other limitations include restriction to centers that possess special expertise and where late events are often not addressed. While randomized, controlled trials are thought to yield the highest degree of certainty, complete reliance upon such an approach may be unfounded.
Significant Contributions of the IBMTR and ABMTR
In this article, the authors discuss the organizational structure, activities, and function of the International Bone Marrow Transplant Registry (IBMTR), founded by Dr. Mortimer Bortin in 1972, and the Autologous Blood and Marrow Transplant Registry (ABMTR), established in 1990. These voluntary organizations are an important resource that complement existing transplant organizations and clinical trial groups. Unlike other programs that may practice "exclusivity," membership in these organizations is conferred on centers that voluntarily agree to report data on all consecutive cases and to undergo audits every 3 years.
Based on data collected by the Centers for Disease Control Hospital Surveys[9,10] and the Government Accounting Office,[11,12] approximately half of North American autotransplants and more than 60% of allogeneic transplants worldwide are registered with the ABMTR and IBMTR, respectively. Computerized error checks, physician reviews of submitted data, and onsite audits of participating centers ensure data quality. The IBMTR and ABMTR employ a full staff of highly trained data coordinators and biostatisticians who work closely with onsite and offsite health-care professionals to design, conduct, analyze, and publish important investigations that can have a significant impact on the practice of transplantation.
Such an observational database system complements randomized trials and permits analyses in uncommon diseases as well as transplants performed infrequently for common disorders. Observational databases offer an unbiased estimate of outcome and patient-selection practices. In addition, data obtained via the IBMTR and ABMTR more readily allow comparisons with nontransplant strategies. The expertise of many participating centers enables reports of rapidly changing approaches, such as new transplant preparative regimens, and comparisons of intercenter variability in diagnosis, practice, outcome, and transplant cost.
Observational databases are useful adjuncts that represent an essential complementary approach to randomized, controlled clinical studies. Two trials involving 5 meta-analyses and 19 treatment analyses found no evidence that treatment effects in observational studies reported after 1984 differ qualitatively from those obtained from randomized, controlled trials.[13,14] The results of well-designed observational studies do not systematically overestimate the magnitude of treatment effects, as compared with the findings of controlled investigations on the same topic.
The contributions of both the IBMTR and the ABMTR are substantial and have clearly influenced the practice of transplantation in a positive fashion. Indications for transplantation and anticipated outcome data have been extremely useful for practitioners and third-party payers alike. These analyses may help close gaps in current knowledge and facilitate the development of prioritization for new research initiatives. Especially striking are the data from studies that describe the effects of transplant on long-term survivors, including the risk of late events such as a second malignancy. As a result of their past and ongoing contributions to the field, the IBMTR and ABMTR continue to gain increased acceptance as vital resources.