Extramedullary relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcomes

Abstract

Extramedullary relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia is a contributor to post-transplant mortality but risk factors for, and outcomes of, this condition are not well characterized. We analyzed 257 consecutive patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia at our institution to characterize extramedullary relapse, identify predictive variables and assess outcomes. The 5-year cumulative incidence of isolated extramedullary or bone marrow relapse was 9% and 29%, respectively. Extramedullary relapse occurred later than marrow relapse and most frequently involved skin and soft tissue. Factors predictive of extramedullary relapse after transplantation included previous extramedullary disease, French-American-British classification M4/M5 leukemia, high risk cytogenetics, and advanced disease status at the time of transplantation. Children were more likely than adults to develop extramedullary relapse, a finding probably explained by an overrepresentation of extramedullary disease prior to transplantation and M4/M5 leukemia in children. Acute graft-versus-host disease was not protective against relapse. Unlike medullary relapse, chronic graft-versus-host disease was not protective against extramedullary relapse. The survival rate after extramedullary relapse was 30% at 1 year and 12% at 2 years. Extramedullary relapse is a significant contributor to mortality after allogeneic transplantation for acute myeloid leukemia and appears to be resistant to the immunotherapeutic effect of allogeneic grafting. Effective strategies for patients with extramedullary relapse are needed to improve outcomes after transplantation.

Figure 1.

Cumulative incidence of relapse and post-relapse survival. All relapses shown as a solid line, isolated bone marrow relapse as a dotted line, extramedullary ± bone marrow relapse as a dashed line. (A) Cumulative incidence of relapse following HSCT for AML. Any relapse (solid line) – 38% (n=99); isolated bone marrow relapse (dotted line) – 28% (n=73); extramedullary ± bone marrow relapse (dashed line) – 10% (n=26); extramedullary versus isolated bone marrow relapse; P<0.001. (B) Two-year overall survival following AML relapse post-HSCT. Any relapse (solid line) – 6% (n=6/99); isolated bone marrow relapse (dotted line) – 5% (n=4/73); extramedullary ± bone marrow relapse (dashed line) – 15% (n=4/26). Extramedullary versus isolated bone marrow relapse; P=0.03.