Stem Cells for Cancer in Older Patients

Older patients with blood disorders may be able to undergo a stem cell transplant without having to first undergo chemotherapy to destroy their own bone marrow cells according to new research published in the Journal of the American Medical Association. The majority of haematologic malignancies (cancers) are diagnosed in patients 65-70yrs old, but current treatment guidelines generally restrict intense cytotoxic conditioning treatment followed by haematopoietic stem cell transplants to those under 55yrs of age. Only younger patients in good physical condition are usually given the intensive treatment which destroys the body’s immune system so as to prevent the rejection of the transplanted material. This leaves many older patients with poor therapeutic options and a gloomy prognosis.

Improved Survival with Stem Cell Transplant

The new data suggests that patients may undergo haematopoietic stem cell transplantation (HSCT) without the intensive chemotherapy to first destroy the immune system cells. This nonmyeloablative allogeneic HSCT was carried out in patients between the ages of sixty and seventy-five and resulted in a 5yr survival rate of 35%, with 32% of patients’ cancers progression-free during that time. Accounting for the patients’ ages and comparing them to their peers in the general population, the increase in survival times was significant following treatment.

Graft-Versus-Host Disease

There were 372 patients involved in the study, with 133 still alive in June 2010 at a median follow-up stage of 55months. At 120days after transplant, there was an incidence of 52% for graft-versus-host-disease and a nonrelapse mortality rate of 7% at 100days after the stem cell transplant. The patients were divided into three age-groups, 60-64, 65-69, and 70 and older. There was no association between older age and poorer outcome or increased incidence of graft-versus-host disease. This is the condition that arises when the body’s immune system detects the donor stem cells as foreign invaders and starts attacking them.

Immunosuppression

The patients involved in the trial had undergone previous therapy for their cancers, but were no longer responsive to chemotherapy or radiotherapy. In this new technique, which was developed in 1997, the patients are given fludarabine and a low-dose total-body irradiation treatment. These are then followed by HSCT, and immunosuppresion treatment with mycophenolate mofetil and a calcineurin inhibitor. The hope is to instigate a graft-versus-tumor effect in the patient so as to destroy the cancer.

Increased Options for Older Cancer Patients

The trial may help to encourage both patients and their physicians to discuss a referral to a transplant center in order to assess their eligibility for a clinical trial using a similar technique. Often, older patients are not aware (or not made aware) of the possible use of such experimental procedures because there is a pervading view that any life extension is undesirable or will be fraught with its own problems of old age. Older patients also have other issues to consider when choosing medical treatments, such as a higher likelihood that they are on Medicare than a younger patient, possible low levels of family support if their spouse has already died or their children or caregivers have their own medical problems.

Extended Life with Stem Cells

More data needs to be collected on the use of nonmyeloablative HSCT treatment in order to see how patients respond to the technique which is still considered experimental. Although some patients do undergo such stem cell therapy outside of a clinical trial, most are enrolled for observation in order to allow scientists to learn more and improve the survival rates of those treated with HSCT. Older patients with haematologic malignancies who are not eligible for a transplant are usually given just months to live, with the likelihood of any surviving past the five year mark being low to non-existent. This nonmyeloablative allogeneic haematopoietic stem cell transplantation treatment led to more than a third of patients living for what could be considered an extra five years or more and the researchers are hopeful of improving this figure further.

References

Sorror ML, Sandmaier BM, Storer BE, Franke GN, Laport GG, Chauncey TR, Agura E, Maziarz RT, Langston A, Hari P, Pulsipher MA, Bethge W, Sahebi F, Bruno B, Maris MB, Yeager A,Petersen FB, Vindeløv L, McSweeney PA, Hübel K, Mielcarek M, Georges GE, Niederwieser D, Blume KG, Maloney DG, Storb R., Long-term Outcomes Among Older Patients Following Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation for Advanced Hematologic Malignancies. JAMA. 2011;306(17):1874-1883; 1918-1920.