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Mini-Transplants

Age no longer barrier to stem cell transplants for older patients

(From Center News Weekly; November 7, 2011; By Dean Forbes)

Age alone should no longer be considered a defining factor when determining whether an older patient with blood cancer is a candidate for stem cell transplantation. That's the conclusion of the first study summarizing long-term outcomes from a series of prospective clinical trials of patients age 60 and over who were treated with the mini-transplant, a "kinder, gentler" form of transplantation developed at Fred Hutchinson Cancer Research Center. The findings were published Nov. 2, 2011 in the Journal of the American Medical Association (JAMA).

The five-year rates of overall and disease-progression-free survival among mini-transplant patients were 35 percent and 32 percent, respectively. Patients in three age groups: 60 to 64, 65 to 69, and 70 to 75 had comparable survival rates, which suggested that age played a limited role in how patients tolerate the mini-transplant.

Increased medical problems unrelated to cancer (comorbidities) and a higher degree of cancer aggressiveness were the two factors that affected survival among those older patients. For example, patients who had less-aggressive cancer and fewer comorbidities had a five-year survival rate of 69 percent, while patients with more aggressive cancer and a significant number of comorbidities had a survival rate of 23 percent, regardless of age.

Although a long-term survival rate of one-third of patients may seem low, these patients all would have died of their diseases within a matter of months without a transplant. "The majority of patients were referred for a transplant after they had exhausted all forms of conventional therapy," said corresponding author Dr. Mohamed Sorror of the Clinical Research Division at the Hutchinson Center. Sorror, who works in the research group led by Dr. Rainer Storb, who developed the mini-transplant.

Conventional vs. mini-transplants

"While there is much room for improvement, particularly with regard to relapse, these results are encouraging given the poor outcomes with nontransplantation treatments, especially for patients with high-risk AML (acute myeloid leukemia), fludarabine-refractory CLL (chronic lymphocytic leukemia), or progressive lymphoma," the authors wrote.

The mini-transplant, also known as nonmyeloablative transplantation, was developed by researchers at the Hutchinson Center for older and medically sicker patients who otherwise could not tolerate the standard, more-toxic, high-dose regimens used to prepare patients for transplantation.

Conventional transplants, which are generally not performed on people over age 60 or others who are medically unfit, use high doses of total-body irradiation and potent chemotherapy to eliminate leukemic cells. The intense treatment destroys the blood and immune system and is fatal unless the patient is rescued by infusion of donor bone marrow or stem cells isolated from peripheral blood.

The mini-transplant, in contrast, relies on the ability of donor immune cells to target and destroy the cancer without the need for high-dose chemotherapy and radiation. Instead, low-dose radiation and chemotherapy is used to suppress the immune system rather than destroy it. This helps the body accept the donor stem cells, which then go to work to attack cancer cells—called the graft-vs.-leukemia effect—and rebuild the immune system.

The study involved 372 patients ages 60 to 75 who were enrolled in prospective clinical trials between 1998 and 2008 at 18 collaborating U.S. and European cancer centers known as the "Seattle Consortium." All patients at these centers were treated with the same regimen, which was developed at the Hutchinson Center. The patients in the study were treated for acute and chronic leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes (which can progress to acute myeloid leukemia if not treated) and myeloproliferative diseases such as chronic myelogenous leukemia.

Relapse rates

In addition to survival and the impact of comorbid conditions, the study examined rates of relapse, hospitalization, acute and chronic graft-vs.-host disease, and the toxicity of the treatment to internal organs.

For example, two-thirds of patients five years after their transplants who were affected by chronic GVHD had complete resolution of their symptoms and were able to discontinue immunosuppressive medications after a median time of 2.5 years from diagnosis. This was comparable to the duration reported by previous studies on younger patients who were treated with high-dose radiation and chemotherapy. Half of the patients never required hospitalization after transplant.

"These findings, together with the normal to near-normal performance status of surviving patients, should help allay reluctance in entering older patients with hematologic cancers on nonmyeloablative transplantation protocols," Sorror said. The lack of a matched sibling donor also should no longer be a limitation given that transplants with matched unrelated donor grafts had comparable outcomes, he said.

Disease relapse risks and comorbidities, but not increasing age, were associated with worse outcomes. The Seattle Consortium investigators continue to explore novel approaches to be combined with the mini-transplant to reduce the relapse rate, particularly among patients with more aggressive blood cancers.