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Expanded Patient SelectionDue to advances that make hematopoietic cell transplantation (bone marrow, PBSC, or cord blood transplantation — BMT) better tolerated and more effective at treating underlying diseases, patient selection has changed dramatically, especially for older patients or those with co-morbidities who would otherwise be excluded from receiving a transplant. [1] Treating older patientsNon-myeloablative or reduced-intensity conditioning regimens, which focus on immunosuppression rather than disease eradication, have allowed more patients to receive hematopoietic cell transplants. As shown in Figure 1, the number of transplants for patients older than 50 years increased more than in any other patient age group between 1987 and 2004. Between 2001 and 2004, patients older than 50 years received 19% of all allogeneic transplants for AML, ALL, and CML. [CIBMTR data]Figure 1. Trends in Allogeneic Transplants Recipient Age, 1987-2004. (CIBMTR data)  View larger version A 2005 study of 150 non-myeloablative transplant recipients revealed no significant difference in non-relapse mortality and overall survival between patients older than 55 years and those younger than 55. [2] The best outcomes in non-myeloablative transplants are typically in less aggressive diseases and those with lower proliferative rates. It is hypothesized that these diseases allow more time for a graft-versus-malignancy effect to take place. [1,3] Treating patients with co-morbid conditionsThese reduced-intensity conditioning regimens have also made transplant a suitable option for many patients with co-morbid conditions who would have not previously been eligible for transplantation. Although transplant-related mortality (TRM) varies with diagnosis, age, and performance status of patients, newer conditioning regimens using low doses of agents such as fludarabine, cyclophosphamide, and intravenous busulfan have significantly lower toxicities than the dose-intense regimens used in the past. [4,5] In addition, new comorbidity indices are being developed to better judge the suitability of transplantation for patients with comorbidities. [6]In a 2005 retrospective study of 152 patients older than 50 who underwent allogeneic transplantation, the 100-day TRM was significantly lower for patients receiving non-myeloablative transplants (n=71) than for recipients of myeloablative conditioning (n=81): 6% versus 30%, respectively. Overall and progression-free survival was also not significantly different between the two groups, despite the significantly higher likelihood that the non-myeloablative patients had unrelated donors, were recipients of a prior transplant, and had active disease at transplantation. [7] Applying transplant to more diseasesOngoing clinical trials have suggested both the safety and efficacy of using hematopoietic cell transplantation for diseases that have not been traditionally treated with transplants:
Ongoing clinical trials are testing the efficacy of transplantation in these diseases. For more information, see Diseases Treatable by Hematopoietic Cell Transplant. Treating patients earlier in the course of the diseaseStudies on the outcome of hematopoietic cell transplantation have revealed that transplant success can be highly dependent upon transplant timing. For example, in a 2007 study of 3,857 unrelated donor transplants, patients with intermediate-stage disease had a 38% greater risk of mortality than patients with early-stage disease. Patients with advanced disease had approximately twice the mortality risk as patients with early-stage disease. [14]In another study, disease-free survival (DFS) in adults with high-risk acute lymphoblastic leukemia is significantly better when allogeneic transplantation is performed in first complete remission. [15] In the same study, a multivariable analysis showed that shorter interval from diagnosis to transplantation was independently associated with better DFS. A study of 1,423 patients with chronic myelogenous leukemia (CML) who received transplants using NMDP donors found an increase in survival for chronic phase CML patients transplanted within 1 year of diagnosis. [16] Using the results of this and several other large-scale studies on transplantation, the NMDP, together with the ASBMT (http://www.asbmt.org/policystat/policy.htm) have developed Recommended Timing for Transplant Consultation guidelines that identify the optimal timing for transplant referral and consultation. Consideration of transplant therapy earlier and identification of possible donors may expand treatment choices for patients and their physicians. References
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