ORLANDO (FRONTLINE MEDICAL NEWS) – For post–autologous hematopoietic cell transplant (auto-HCT) patients, the 10-year risk of developing a myeloid neoplasm was as high as 6%, based on a recent review of two large cancer databases.

Older age at transplant, receiving total body irradiation, and receiving multiple lines of chemotherapy before transplant all upped the risk of later cancers, according to a study presented by Shahrukh Hashmi, MD, and his collaborators at the combined annual meetings of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society for Blood and Marrow Transplantation.

“The guidelines for autologous stem cell transplantation for surveillance for AML [acute myeloid leukemia] and MDS [myelodysplastic syndrome] need to be clearly formulated. We are doing 30,000 autologous transplants a year globally and these patients are at risk for the most feared cancer, which is leukemia and MDS, for which outcomes are very poor,” said Dr. Hashmi of the Mayo Clinic in Rochester, Minn.

The researchers examined data from auto-HCT patients with diagnoses of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and multiple myeloma to determine the relative risks of developing AML and MDS. The study also explored which patient characteristics and aspects of the conditioning regimen might affect risk for later myeloid neoplasms.

In the dataset of 9,108 patients that Dr. Hashmi and his colleagues obtained from CIBMTR, 3,540 patients had NHL.

“As age progresses, the risk of acquiring myeloid neoplasms increases significantly,” he said, noting that the relative risk (RR) rose to 4.52 for patients aged 55 years and older at the time of transplant (95% confidence interval [CI], 2.63-7.77; P less than .0001).

Patients with NHL who received more than two lines of chemotherapy had approximately double the rate of myeloid cancers (RR, 1.93; 95% CI, 1.34-2.78; P = .0004).

The type of conditioning regimen made a difference for NHL patients as well. With total-body irradiation set as the reference at RR = 1, carmustine-etoposide-cytarabine-melphalan (BEAM) or similar therapies were relatively protective, with an RR of 0.59 (95% CI, 0.40-0.87; P = .0083). Also protective were cyclophosphamide-carmustine-etoposide (CBV) and similar therapies (RR, 0.57; 95% CI, 0.33-0.99; P = .0463).

Age at transplant was a factor among the 4,653 patients with multiple myeloma, with an RR of 2.47 for those transplanted at age 55 years or older (95% CI, 1.55-3.93; P = .0001). Multiple lines of chemotherapy also increased risk, with patients who received more than two lines having an RR of 1.77 for neoplasm (95% CI, 0.04-2.06; P = .0302). Women had less than half the risk of recurrence as men (RR, 0.44; 95% CI, 0.28-0.69; P = .0003).

Among the 915 study patients with Hodgkin lymphoma, patients aged 45 years and older at the time of transplant carried an RR of 5.59 for new myeloid neoplasms (95% CI, 2.98-11.70; P less than .0001).

Total-body irradiation was received by 14% of patients with non-Hodgkin lymphoma and by 5% of patients with multiple myeloma and Hodgkin lymphoma. Total-body irradiation was associated with a fourfold increase in neoplasm risk (RR, 4.02; 95% CI, 1.40-11.55; P = .0096).

Dr. Hashmi and his colleagues then examined the incidence rates for myelodysplastic syndrome and acute myelogenous leukemia in the Surveillance, Epidemiology, and End Results (SEER) database , finding that, even at baseline, the rates of myeloid neoplasms were higher for patients with NHL, Hodgkin lymphoma, or MM patients than for the general population of cancer survivors. “Post NHL, Hodgkin lymphoma, and myeloma, the risks are significantly higher to begin with. … We saw a high risk of AML and MDS compared to the SEER controls – risks as high as 100 times greater for auto-transplant patients,” said Dr. Hashmi. “A risk of one hundred times more for MDS was astounding, surprising, unexpected,” he said. The risk of AML, he said, was elevated about 10-50 times in the CIBMTR data.

The cumulative incidence of MDS or AML for NHL was 6% at 10 years post transplant, 4% for Hodgkin lymphoma, and 3% for multiple myeloma.

A limitation of the study, said Dr. Hashmi, was that the investigators did not assess for post-transplant maintenance chemotherapy.

“We have to prospectively assess our transplant patients in a fashion to detect changes early. Or maybe they were present at the time of transplant and we never did sophisticated methods [like] next-generation sequencing” to detect them, he said.

Dr. Hashmi reported no conflicts of interest.

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