Analysis of Infection-Related Mortality in Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Refractory/Relapse Acute Leukemia

Infection-related mortality (IRM) is a major cause of transplant-related mortality (TRM) in recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT). However, the data about IRM in refractory/relapse acute leukemia patients undergoing allo-HSCT was scarce. We conducted a retrospective study to describe the incidence, causes and risk factors for IRM in recipients with refractory/relapse acute leukemia at a single center.

Clinic datas of 127 cases received transplant for refractory/relapse acute leukemia between January 1997 and August 2011 were reviewed. There were 67 cases died at the end of follow-up. In this 67 cases, 27 patients were female and 40 were male; the media age was 31 years (range, 11–61).Uderlying disease was acute myeloid leukemia (AML) in 37 cases, acute lymphoblastic leukemia (ALL) in 21 and acute leukemia of ambiguous lineage in 9. Status of underlying diseases was CR in 19 cases, PR in 15 and NR in 33. There were 25 cases with residual infection diseases before HSCT, including 21 in stable state and 4 in active state with effective control. A total of 59 cases received the conditioning regimen which is 4.5Gy TBI for 2 days and CTX 60mg·kg⁻¹·d⁻¹ for 2 days and 8 patients received busulfan 3.2 mg·kg⁻¹·d⁻¹ for 4 days and CTX 60mg·kg⁻¹·d⁻¹ for 2 days. Patients with PR and NR status of underlying diseases also received fludarabine 50mg·d⁻¹ for 5 days and cytarabine 2 g·d⁻¹ for 5 days as the conditioning regimen. Forty-two cases received related-donor transplant and 25 received unrelated-donor transplant; 30 cases had HLA typing (HLA-A, B and DR) matched-family donor, 12 cases has mismatched-family donors and 25 cases had unrelated-donors. The most common source of stem cells for HSCT was the peripheral blood (n=49), followed by bone marrow plus peripheral blood (n=10) and bone marrow (n=8). Cyclosporine A (CsA) with methotrexate (MTX) (on days +1, +3 and +6) was administered for GVHD prophylaxis in patients undergoing HLA-matched sibling donor transplantation. CsA only or CsA with MTX (on days +1 and +3) was administered for GVHD prophylaxis in patients not received CR before transplant. Patients receiving an unrelated donor or HLA-mismatched sibling donor transplant received CsA + MTX and human antithymocyte globulin (ATG 6–7.5 mg/kg) as GVHD prophylaxis. Logistic regression was used for the identification of risk factors of IRM.

Within a median 23 months follow-up for patients alive, 67 cases died including 36 died of leukemia relapse and 31 died of TRM. The incidence of 5-years overall survival was 35.2% whereas disease-free survival was 30.8%. Of the 127 cases, 36 cases occurred IRM and the 2-year cumulative incidence of IRM was 36.6%. Fungal infections were responsible for a major proportion of the cases of IRM followed by virus and bacteria infections. Multivariate analyses showed II∼IV°aGVHD (OR=3.017, 95%CI 1.007–9.041, P=0.049) and IFI (OR=3.223, 95%CI 1.103–9.421, P=0.032) were the risk factors of IRM.

As a common cause of transplant-related mortality, IRM occurred more frequently in refractory/relapse acute leukemia than in the standard-risk patients. Reduction of IRM will require effective prophylaxis and treatment of severe GVHD.

No relevant conflicts of interest to declare.