Due to advances that make hematopoietic cell transplantation better tolerated and more effective at treating underlying diseases, patient selection has expanded dramatically. The largest growth area has been in older patients or those with co-morbidities transplanted using reduced-intensity conditioning regimens. 
Two other reasons for expanded patient selection include the use of transplants to treat some types of solid tumors, and a growing trend to transplant patients earlier in their disease course to improve outcomes.
Transplanting more patients >50
Reduced-intensity conditioning regimens (RIC) and better patient care have allowed older patients (in their 50s, 60s, and even 70s) or those with co-morbidities to receive allogeneic transplants. As shown in Figure 1, the percentage of allogeneic transplants for patients older than 60 years increased more than in any other patient age group between 2001-2005 and 2006-2010.
Trends in Allogeneic and Autologous Transplantation by Recipient Age, 2001-2010. (CIBMTR data)
View larger version
Increasing numbers of older patients (>50 years) have received unrelated donor transplants through the National Marrow Donor Program® (NMDP) and its Be The Match Registry®. In 2012, 44% of NMDP transplants, representing 2,550 transplants, were for patients aged 50 and older.
Figure 2 separates the >50 patients into two groups: 51-64 and >64 years.
NMDP Transplants by Year and Patient Age, 2002-2012.
(NMDP data) (NMDP data are fiscal year data through September 30, 2012)
View larger version
The NMDP and its research arm, the Center for International Blood and Marrow Transplant Research® (CIBMTR), collect and study data to learn how to improve patient outcomes. The NMDP also operates Be The Match®.
Several studies show that when older patients undergo RIC transplants, outcomes can be comparable to those attained by younger patients.
A 2005 study of 150 non-myeloablative transplant recipients revealed no significant difference in non-relapse mortality and overall survival in patients older than 55 years and those younger than 55. 
A 2008 study of 141 adults found no significant difference in transplant outcomes between RIC patients and myeloablative patients, despite the RIC group being a median of 6 years older than the myeloablative group (48 years vs. 42 years, respectively) and having significantly more patients with a failed prior autologous transplant (39% vs. 0%, respectively). 
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. [1,4]
Treating patients with co-morbid conditions
RIC 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. [5,6] In addition, new comorbidity indices are being developed to better judge the suitability of transplantation for patients with comorbidities. 
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 in this study 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. 
Applying transplant to more diseases
The development of RIC regimens, which focus on immunosuppression rather than disease eradication, have also been used to treat some types of solid tumors. Ongoing clinical trials have suggested both the safety and efficacy of using hematopoietic cell transplantation for:
- Renal cell carcinoma and other solid tumors 
- Sickle cell disease [10,11]
- Neuroblastoma [9,12]
- Beta thalassemia major 
- Autoimmune disorders (e.g., systemic lupus erythematosus) 
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 disease
Studies 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. 
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.  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 donors from the Be The Match Registry found an increase in survival for chronic phase CML patients transplanted within 1 year of diagnosis. 
Using the results of this and several other large-scale studies on transplantation, the NMDP, together with the ASBMT (http://www.asbmt.org/) 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.
- Giralt S, Logan B, Rizzo D, et al. Reduced-intensity conditioning for unrelated donor progenitor cell transplantation: long-term follow-up of the first 285 reported to the National Marrow Donor Program. Biol Blood Marrow Transplant. 2007; 13(7):844-852.
- Corradini P, Zallio F, Mariotti J, et al. Effect of age and previous autologous transplantation on nonrelapse mortality and survival in patients treated with reduced-intensity conditioning and allografting for advanced hematologic malignancies. J Clin Oncol. 2005; 23(27):6690-6698.
- Tomblyn M, Brunstein C, Burns LJ, et al. Similar and promising outcomes in lymphoma patients treated with myeloablative or nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2008; 14(5):538-545.
- Anagnostopoulos A, Giralt S. Critical review on non-myeloablative stem cell transplantation (NST). Crit Rev Oncol Hematol. 2002; 44(2):175-190.
- Barrett AJ. Conditioning regimens for allogeneic stem cell transplants. Curr Opin Hematol. 2000; 7(6):339-342.
- De Lima M, Couriel D, Thall PF, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004; 104(3):857-864.
- Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8):2912-2919.
- Alyea EP, Kim HT, Ho V, et al. Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. Blood 2005; 105(4):1810-1814.
- Gratwohl A, Baldomero H, Demirer T, et al. Hematopoetic stem cell transplantation for solid tumors in Europe. Ann Oncol. 2004; 15(4):653-660.
- Bernaudin F, Socie G, Kuentz M, et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007; 110(7):2749-2756.
- Shenoy S. Has stem cell transplantation come of age in the treatment of sickle cell disease? Bone Marrow Transplant. 2007; 40(9):813-821.
- Inoue M, Nakano T, Yoneda A, Nishikawa M, et al. Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transplant. 2003; 32(1):103-106.
- La Nasa G, Giardini C, Argiolu F, et al. Unrelated donor bone marrow transplantation for thalassemia: the effect of extended haplotypes. Blood. 2002; 99(12):4350-4356.
- Griffith LM, Pavletic SZ, Tyndall A, et al. Feasibility of allogeneic hematopoietic stem cell transplantation for autoimmune disease: Position statement from a National Institute of Allergy and Infectious Diseases and National Cancer Institute–sponsored international workshop, Bethesda, MD, March 12 and 13, 2005. Biol Blood Marrow Transplant. 2005; 11(11):862-870.
- Lee SJ, Klein J, Haagenson M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007; 110(13):4576-4583.
- Cornelissen JJ, Carston M, Kollman, et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: Strong graft-versus-leukemia effect and risk factors determining outcome. Blood. 2001; 97(6):1572-1577.
- McGlave PB, Shu XO, Wen W, et al. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the National Marrow Donor Program. Blood. 2000; 95(7):2219-25.