The use of ATG abrogates the antileukemic effect of cytomegalovirus reactivation in patients with acute myeloid leukemia receiving grafts from unrelated donors.
Several studies provided evidence of a consistent antileukemic effect induced by cytomegalovirus (CMV) replication in acute myeloid leukemia (AML) patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), however the use of antithymocyte globulin (ATG) as graft-versus-host disease prophylaxis, may potentially abrogate the protective effect of CMV infection. To address this issue, we retrospectively analyzed the risk of relapse in a cohort of 101 patients with AML who received grafts from an unrelated donor after a conditioning regimen including ATG. The cumulative incidence of CMV reactivation, evaluated by RT qPCR, was 59% at 12 months, and 93% of CMV reactivations occurred within the first 100 days post HSCT. The 5-year cumulative incidence of relapse in patients with CMV reactivation was 29% compared with 37% for patients without CMV reactivation, and the only factor associated with a reduced 5-year cumulative incidence of relapse was the disease status at HSCT (P < 0.001). In the multivariable model adverse cytogenetics (HR 2.42, 95% CI 1.02-5.72; P = 0.044) and acute GVHD (HR 3.36, 95% CI 1.32-8.54; P =  0.011) were independent risk factors for reducing overall survival (OS), while the presence of chronic GVHD was associated with a better OS (HR 0.37, 95% CI 0.15-0.89; P = 0.027). CMV replication was not an independent risk factor for OS (HR 1.06, 95% CI 0.07-15.75; P = 0.965). In Conclusion, the results of present study suggest that relapse prevention in patients with AML receiving T-cell depleted HSCT using ATG do not benefit from CMV reactivation.
Department of Oncology and Hematology, Stem Cell Transplant Center, AOU Città Della Salute E Della Scienza, Turin, Italy.
Alessandro
A
Busca
Division of Nuclear Medicine, AOU Città Della Salute E Della Scienza, Turin, Italy.
Roberto
R
Passera
Department of Hematology, AO Nazionale Alessandria, Alessandria, Italy.
Massimo
M
Pini
Department of Hematology, AO Nazionale Alessandria, Alessandria, Italy.
Francesco
F
Zallio
Department of Oncology and Hematology, Stem Cell Transplant Center, AOU Città Della Salute E Della Scienza, Turin, Italy.
Chiara
C
Dellacasa
Department of Oncology and Hematology, AOU Città Della Salute E Della Scienza, Turin, Italy.
Ernesta
E
Audisio
Department of Oncology and Hematology, Stem Cell Transplant Center, AOU Città Della Salute E Della Scienza, Turin, Italy.
Luisa
L
Giaccone
Department of Oncology and Hematology, AOU Città Della Salute E Della Scienza, Turin, Italy.
Enrico
E
Maffini
Microbiology and Virology Unit, Laboratory of Virology, AOU Città Della Salute E Della Scienza, Turin, Italy.
Cristina
C
Costa
Microbiology and Virology Unit, Laboratory of Virology, AOU Città Della Salute E Della Scienza, Turin, Italy.
Rossana
R
Cavallo
Department of Oncology and Hematology, Stem Cell Transplant Center, AOU Città Della Salute E Della Scienza, Turin, Italy.
Benedetto
B
Bruno
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects*; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D061349:Unrelated Donors; D014775:Virus Activation / Q000502:physiology*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents