Immunology has provided a new avenue of therapy for patients with acute lymphoblastic leukemia (ALL), though matching the right treatment to a patient’s condition is an evolving science. A recent report published in Leukemia described the associations between various aspects of patients’ immunobiology and treatment outcomes.
The authors noted that high rates of treatment success characterize ALL in children but that the outcomes for adults tend to remain poor. However, allowing measurement of minimal residual disease (MRD) to drive treatment has improved results for adults, as has treating younger adults with protocols similar to those used in pediatric treatment. Use of tyrosine kinase inhibitors has also shown increased success for patients with Philadelphia chromosome-positive ALL.
Using multiplexed immunohistochemistry (mIHC), the researchers analyzed bone marrow biopsy specimens from adult patients with precursor B cell ALL (52 patients) compared with samples from a healthy control cohort (14 patients). A total of 30 markers were evaluated for each group, and signals from the markers were visualized and assessed in comparison with clinical data. The researchers validated results with a separate cohort of patients with ALL (31 patients) whose samples were analyzed through flow cytometry.
Some specific immunological patterns in bone marrow emerged, distinguishing the patients with ALL from controls. Patients with ALL showed relatively lower proportions of CD27+ T cells (Benjamini-Hochberg-derived significance level q <.0001 for each comparison), CD8+ granzyme B+ CD57+ T cells (q =.0001), M1-like macrophages (q =.0002), and NK cells (q <.0001) compared with control patients. The authors interpreted these results to indicate more limited costimulatory and cytolytic capacity in patients with ALL.
ALL was associated with relatively higher proportions of M2-like macrophages (q <.0001) and myeloid-derived suppressor cells (q <.0001) compared with healthy controls. Additionally, there was elevated expression of the checkpoint molecules PD1 (q <.0001 for each comparison) and CTLA4 (q <.0001) in patients with ALL.
Multivariate analysis indicated that poorer outcomes were associated with greater proportions of CD4+ PD1+ TIM3+ T cells, more advanced age, and lower platelet counts.
The authors concluded that ALL in adult bone marrow shows a particular immunobiological profile that may contribute to clinical treatment responses, with PD1 emerging as a potentially useful immunotherapy target. They recommended that future research should attempt to elucidate any other connections between ALL immunobiology, survival, and biomarkers linked to treatment.
1. Hohtari H, H, Brück O, Blom S, et al. Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL [published online January 11, 2019]. Leukemia. doi: 10.1038/s41375-018-0360-1