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Research Snapshot: Seeking complete remission prior to allogeneic hematopoietic transplantation in patients battling AML

Allogeneic hematopoietic transplantation (allo-HCT) is one of the most advanced cell-based therapies available in the fight against complex conditions that can damage or disrupt bone marrow or immune system function.

The procedure, which involves a transplant of blood-forming stem cells from a donor with genetic similarities, provides patients a chance for remission in the fight against conditions like multiple myeloma, non-Hodgkin lymphoma and several types of acute and chronic leukemias, to name a few.

The procedure also remains one of the most effective treatments for most patients with acute myeloid leukemia (AML).

But what conditions should physicians see in their patients before employing allo-HCT?

In a new study recently published in the journal Bone Marrow Transplantation, researchers from the Masonic Cancer Center, University of Minnesota, examined the effectiveness of allo-HCT and tried to determine how to prevent relapse in patients undergoing reduced-intensity conditioning (RIC) allo-HCT. In RIC, physicians use lower doses of chemotherapy or radiation to kill cancer cells while the immune system is suppressed prior to transplant. This may be most effective for older patients or those with other complicating medical conditions.

“AML remains one of the deadliest forms of blood cancer, but fortunately allo-HCT can cure at least half of these patients,” said Celalettin Ustun, M.D., a University of Minnesota Physicians hematologist/oncologist who specializes in cancer of the blood. “But allo-HCT is a harsh and toxic treatment so we often use reduced-intensity conditioning regimens. However, since we’ve only done this in the last 20 years, we don’t yet know if we’re compromising the efficacy of allo-HCT in AML patients by reducing the intensity of therapy.”

According to Ustun, who partnered on the study with University of Minnesota experts Daniel J. Weisdorf, M.D., Michael A. Linden, M.D., Ph.D., and Sophia Yohe, M.D., the success of allo-HCT in AML patients depends on both killing leukemic cells with chemotherapy and radiation and then killing remaining leukemic cells through the patient’s transplant. The concern has always been that decreasing the intensity of therapy could compromise some of the effect, leading to relapse.

“In our latest study we looked at whether or not we’re compromising efficacy of allo-HCT in AML by reducing the intensity of initial treatment, and if so in whom?” said Ustun. “The study showed interesting results: RIC is very effective if a patient’s disease is well-controlled before allo-HCT, meaning the patient is in complete remission according to bone marrow samples examined using microscopic testing. Yet the study indicated we need to be also relying on more refined flow cytometry results, which can detect even smaller numbers of leukemic cells.”

Ustun said the results showed that even small amounts of leukemic cells – often not picked up using morphology alone – can lead to persistent AML which could cause allo-HCT treatments to fail, yet almost half the patients with no evidence of leukemia enjoyed long term survival post-transplant.

Therefore complete remission should be confirmed using flow cytometry before launching an attack with reduced-intensity conditioning allo-HCT.

“Although this study’s results have to be confirmed by other centers and larger studies, the work suggests limitations of RIC allo-HCT if we don’t reach complete remission prior to treatment,” said Ustun.

The remaining question is if these patients’ outcome would have been better if they could have received intensive chemotherapy/radiation therapy or modified approaches to enhance the potency of the transplant. Masonic Cancer Center researchers are actively investigating that particular question now.

Stay tuned to Health Talk for more.

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