Changing Trends in Diseases and Patients Treated

The number of patients who may be eligible for hematopoietic cell transplantation (bone marrow, PBSC, or cord blood transplantation — BMT) has expanded in recent years. Some of the more significant trends in the diseases and patients treated with hematopoietic cell transplant are discussed below.

Shifts in diseases transplanted

Diseases commonly transplanted

• For autologous BMT, the diseases most commonly treated with transplant are currently multiple myeloma and lymphoma.
• For allogeneic BMT, the diseases most commonly treated with transplant are currently acute and chronic leukemias, lymphoma and myelodysplastic syndromes.

Newer transplant trends

BMT is being studied as a potential therapy for several diseases not traditionally treated with transplant. Some of the diseases for which recent clinical studies are showing promising results include:

• Renal cell carcinoma and other solid tumors [1]
• Sickle cell disease [2]
• Neuroblastoma [1,3]
• Beta thalassemia major [4]
• Autoimmune disorders (e.g., systemic lupus erythematosus) [5]

Transplant trends in flux — chronic myelogenous leukemia (CML)

Allogeneic transplant as a treatment for chronic phase CML decreased greatly with the FDA's approval of the highly effective therapy imatinib mesylate in 2001. However, more recently the number of transplants for CML has begun to stabilize.

Although imatinib mesylate is increasingly being used as first-line therapy for adult CML patients, hematopoietic cell transplantation is often appropriate for second-line therapy should patients not achieve or maintain a complete cytogenetic response to imatinib. A panel of CML experts recently published recommendations that imatinib mesylate failure be treated by either an increased dose of imatinib mesylate, allogeneic transplantation or investigational treatments. Imatinib mesylate failure was defined as no hematologic response at 3 months, incomplete hematologic response or no cytogenetic response at 6 months, or less than partial cytogenetic response (Ph+ >35%) at 12 months. [6]

Resistance to imatinib mesylate is an emerging problem in the treatment of CML, and occurs at a rate of approximately 4% per year among patients treated in early chronic phase and at higher rates in those treated in advanced stages. A 2006 study of imatinib-resistant patients with Bcr-Abl kinase mutations concluded that allogeneic transplantation remains an important salvage option for these patients who develop resistance to imatinib. [7]

The role and timing of allogeneic transplantation and type of preparative regimen as well as the role of autologous transplants for patients achieving molecular remission after imatinib are being explored. For more information, see Recommended Timing for Transplant Consultation and Transplant Outcomes by Disease and Disease Stage.

Increased transplants for patients age 50 and older

The largest growth in hematopoietic cell transplantation is the increasing use of transplants to treat patients age 50 and older (Figures 1 and 2). Increased use of non-myeloablative transplants and other advances in conditioning regimens that have led to decreased regimen-related morbidity and mortality have made transplant an option for an older population of patients. The eligibility of these patients has contributed to an increase in allogeneic and autologous transplants for diseases more commonly occurring in older adults, such as myelodysplastic syndromes, acute myelogenous leukemia, and non-Hodgkin's lymphomas.

Figure 1.
Trends in Allogeneic Transplantation by Recipient Age, 1987-2006. (CIBMTR data)

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Figure 2.
Trends in Autologous Transplantation by Recipient Age, 1993-2006. (CIBMTR data)

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Increased use of unrelated donors and cord blood for allogeneic transplants

The proportion of allogeneic transplants using unrelated donors or cord blood units has increased steadily. In 2006, more than one-third of allogeneic transplants performed worldwide used unrelated donors. For further discussion of this trend, see Trends in Allogeneic Transplants.

References

1. Gratwohl A, Baldomero H, Demirer T, et al. Hematopoetic stem cell transplantation for solid tumors in Europe. Ann Oncol. 2004; 15(4):653-660.
   http://annonc.oupjournals.org/cgi/content/full/15/4/653
2. Shenoy S. Has stem cell transplantation come of age in the treatment of sickle cell disease? Bone Marrow Transplant. 2007; 40(9):813-821.
   http://www.nature.com/bmt/journal/v40/n9/abs/1705779a.html
3. 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.
   http://www.nature.com/cgi-taf/DynaPage.taf?file=/bmt/journal/v32/n1/abs/1704070a.html
4. 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.
   http://www.bloodjournal.org/cgi/content/full/99/12/4350
5. Tyndall A, Saccardi R. Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: results from phase I/II studies, prospective randomized trials and future directions. Clin Exp Immunol. 2005; 141(1):1-9.
   http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2249.2005.02806.x
6. Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia. recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006; 108(6):1809-1820.
   http://www.bloodjournal.org/cgi/content/abstract/108/6/1809
7. Jabbour E, Cortes J, Kantarjian HM, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation–related imatinib failure. Blood. 2006; 108(4):1421-1423.
   http://bloodjournal.hematologylibrary.org/cgi/content/full/108/4/1421