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Second Transplant vs Donor Lymphocyte Infusion in Relapsed AML

— Both options viable, benefit more clear in certain groups

Last Updated October 26, 2018
Ƶ MedicalToday

Neither donor lymphocyte infusion (DLI) nor second transplant proved better than the other in the salvage setting for patients with acute myeloid leukemia (AML), according to a retrospective registry study.

Among 418 AML patients who relapsed following an initial allogeneic hematopoietic cell transplant (allo-HCT1), the study found no significant overall survival (OS) difference between those who received a second transplant (allo-HCT2) compared with DLI at either 2 years (26% versus 25%, respectively) or 5 years (19% versus 15%), reported Mohamad Mohty, MD, PhD, of Université Pierre et Marie Curie in Paris, and colleagues.

"Best outcomes seem to be achieved in patients relapsing 6 or more months from an allo-HCT1 or those in complete remission at the time of either allo-HCT2 or DLI," wrote Mohty and colleagues in . "In patients who relapse within less than 6 months or receive an intervention while having active disease, OS rates are low."

Mohty's group noted that heterogeneity of the patient population, as well as various disease and treatment-related characteristics preclude the recommendation of one approach over the other, but pointed out that OS appeared comparable between the two options in this setting.

As noted, there were significantly better survival outcomes following either procedure when patients were in complete remission (hazard ratio 0.55, 95% CI 0.41-0.74, P<0.001). Those with prior chronic graft-versus-host disease (GVHD) also had better OS (HR 0.71, 95% CI 0.53-0.95, P=0.02).

And while patients who were in remission for 6 months or longer had better survival rates:

  • 2-year OS: 34% with allo-HCT2 and 37% for DLI
  • 5-year OS: 24% with allo-HCT2 and 23% for DLI

Those who came out of remission in less than 6 months had poorer survival rates:

  • 2-year OS: 11% with allo-HCT2 and 9% for DLI
  • 5-year OS: 9% with allo-HCT2 and 4% for DLI

The study shows that for patients who relapse following initial transplant, DLI and allo-HCT2 are "reasonable salvage approaches that yield promising long term-survival," Samer Al-Homsi, MD, MBA, of NYU Langone's Perlmutter Cancer Center in New York City, told Ƶ. "This is particularly true in patients with late relapse and who remain responsive to anti-tumor chemotherapy."

Al-Homsi, who was not involved in the study, explained that without randomized trial data, "the study is a welcomed attempt to provide some insights" into the role of these two approaches in this setting.

From November 2015 to May 2017, the researchers assessed 418 adults (mean age 46.2 years, 54.5% men) across 61 centers, who received second transplants or DLI for post-allograft relapsed AML (de novo or secondary). Patient information was collected from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

A higher incidence of grade 2 to 4 acute GVHD was seen in allo-HCT2 patients, regardless of remission status (37% versus 20% with DLI, P=0.004) at 100 days post intervention. But when looking at solely those in complete remission, rates of acute GVHD were similar.

Mohty and colleagues acknowledged that their study had some limitations. The investigators were unable to gather qualitative data on why physicians chose allo-HCT2 or DLI. And the setup of the study prevented them from assessing both the starting dose for DLI and/or the schedule for its administration. Moreover, the researchers were unable to assess the importance of donor chimerism (complete versus less than complete), because the information was not readily available prior to intervention, and noted that "specific clinical scenarios such as the role of allo-HCT2 or DLI in AML relapsing in the central nervous system," could not be assessed.

The authors said that these important questions remain but will require prospective data.

Disclosures

The study was funded by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Mohty disclosed relationships with Sanofi, Janssen, Amgen, Celgene, Takeda, Novartis, Jazz Pharmaceuticals, MolMed, Bristol-Myers Squibb, and the Association for Training, Education and Research in Hematology, Immunology and Transplantation.

Co-authors also reported relationships with Seattle Genetics, Incyte Corp, Alexion Pharmaceuticals, Pharmacyclics, Roche, Kalytera Therapeutics, Astellas Pharma, Merck Sharp & Dohme, Pfizer, Gilead Sciences, and others.

Al-Homsi reported no conflicts of interest.

Primary Source

JAMA Oncology

Kharfan-Dabaja MA, et al "Association of second allogeneic hematopoietic cell transplant vs donor lymphocyte infusion with overall survival in patients with acute myeloid leukemia relapse" JAMA Oncology 2018; DOI: 10.1001/jamaoncol.2018.2091.