General AML

Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with CD7-positive AML – a retrospective analysis from Japan

Anti-thymocyte globulins (ATGs) have been shown in previous trials to decrease the incidence of Graft versus Host Disease (GvHD) after allogeneic stem cell transplantation (allo-SCT). Additionally, ATGs demonstrate anti-tumor effects in vitro, but evidence of patient benefit is absent. Kiyosumi Ochi and colleagues from the National Cancer Center Hospital, Tokyo, Japan, retrospectively analyzed the clinical impact of ATGs on the outcomes of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) who underwent allo-SCT. The results of the study were reported in Bone Marrow Transplantation in February 2018.1

CD7, a lymphoid marker, is aberrantly expressed in approximately 30% of AML cases and has been shown to be associated with poor clinical outcomes.2 Ochi et al. observed in a relapsed CD7-positive AML patient that administration of ATGs led to a significant reduction of AML blasts. Thus, in this retrospective study, the authors assessed the effects of ATG against CD7-positive AML in allo-SCT.1

In total, 132 R/R AML patients (median age at SCT = 50, range 19­–68) who underwent allo-SCT between 2000 and 2015 at the National Cancer Center Hospital were divided into four groups according to CD7 positivity and the use of ATGs as part of the conditioning regimen: CD7-positive ATG group (n = 15), CD7-positive no-ATG group (n = 32), CD7-negative ATG group (n = 19), and CD7-negative no-ATG group (n = 66).

Key findings:
  • Survival
    • 2-year overall survival (OS) in the CD7-positive ATG and CD7-positive no-ATG groups: 50.9% (95% CI, 23.6–72.9) vs5% (95% CI, 2.8–24.4), P < 0.01
    • 2-year OS was not significantly different in the CD7-negative ATG and CD7-negative no-ATG groups: 12.0% (95% CI, 2.1–31.5) vs8% (95% CI, 18.3–40.2), P = 0.20
    • 2-year relapse free survival (RFS) in the CD7-positive ATG and CD7-positive no-ATG groups: 26.7% (95% CI, 8.3–49.6) vs2% (95% CI, 1.1–18.1), P < 0.01
    • 2- year RFS in the CD7-negative ATG and CD7-negative no-ATG groups: 10.5% (95% CI, 1.8–28.4) vs6% (95% CI, 6.7–23.0), P = 0.62
    • The use of ATGs significantly associated with superior OS (HR = 0.31, P < 0.01) and RFS (HR = 0.37, P < 0.01) in patients with CD7-positive AML
  • Relapse/progression
    • 2-year relapse/progression rates in the CD7-positive ATG and CD7-positive no-ATG group: 60.0% (95% CI, 29.6–80.7) vs1% (95% CI 57.8–89.5), P = 0.05
    • 2-year relapse/progression rates in the CD7-negative ATG and CD7-negative no-ATG group: 68.4% (95% CI, 40.0–85.4) vs2% (95% CI, 52.1–75.5), P = 0.77
    • The use of ATGs was associated with lower relapse/progression rates in patients with CD7-positive AML: HR = 0.20, (95% CI, 0.08–0.52), P < 0.01
  • GvHD
    • Extensive cGvHD was significantly lower in the CD7-negative ATG group compared with the CD7-negative no-ATG group: 5.3% (95% CI, 0.2–23.8) vs3% (95% CI, 22.1–45.0), P = 0.01

In conclusion, these results showed a possible anti-leukemic effect of ATGs against CD7-positive AML cells. Furthermore, this data indicated that the use of ATGs is beneficial and leads to superior survival outcomes in CD7-positive patients. The key limitations of this study included its retrospective nature and the small number of CD7-positive AML cases. The authors stated that further larger prospective studies are required.

  1. Ochi K. et al. The putative anti-leukemic effects of anti-thymocyte globulins in patients with CD7-positive acute myeloid leukemia. Bone Marrow Transplant. 2018 Feb 19. DOI: 10.1038/s41409-018-0115-7. [Epub ahead of print].
  2. Röhrs S. et al. CD7 in acute myeloid leukemia: correlation with loss of wild-type CEBPA, consequence of epigenetic regulation. J Hematol Oncol. 2010; 3: 15. DOI: 10.1186/1756-8722-3-15.