Immunotherapy is changing the therapeutic landscape of many hematologic diseases, with immune checkpoint inhibitors, bispecific antibodies, and CAR-T therapies being its greatest expression. Unfortunately, immunotherapy in acute myeloid leukemia (AML) has given less brilliant results up to now, and the only approved drug is the antiCD33 antibody-drug conjugate gemtuzumab ozogamicin. A promising field of research in AML therapy relies on anti-leukemic vaccination to induce remission or prevent disease relapse. In this review, we analyze recent evidence on AML vaccines and their biological mechanisms. The principal proteins that have been exploited for vaccination strategies and have reached clinical experimental phases are Wilm’s tumor 1, proteinase 3, and RHAMM. the majority of data deals with WT1-base vaccines, given also the high expression and mutation rates of WT1 in AML cells. Stimulators of immune responses such as TLR7 agonist and interleukin-2 have also proven anti-leukemic activity both in vivo and in vitro. Lastly, cellular vaccines mainly based on autologous or allogeneic off-the-shelf dendritic cell-based vaccines showed positive results in terms of T-cell response and safety, also in elderly patients. Compared to other immunotherapeutic strategies, anti-AML vaccines have the advantage of being a less toxic and a more manageable approach, applicable also to elderly patients with poorer performance status, and may be used in combination with currently available therapies. As for the best scenario in which to use vaccination, whether in a therapeutic, prophylactic, or preemptive setting, further studies are needed, but available evidence points to poorer results in the presence of active or high-burden disease. Given the poor prognosis of relapsed/refractory or high-risk AML, further research is urgently needed to better understand the biological pathways that sustain its pathogenesis. In this setting, research on novel frontiers of immunotherapy-based agents, among which vaccines represent important actors, is warranted to develop new and efficacious strategies to obtain long-term disease control by immune patrolling.

Checkpoint inhibitors (CPI) represent a novel therapeutical strategy with a high efficacy both in solid and hematological cancers. They act by reactivating the immune system against neoplastic cells but may, in turn, cause immune-related adverse events (IRAEs) involving several organs with variable frequency and severity. Up to 10% of CPI-treated patients experience hematological IRAEs, mainly cytopenias. The differential diagnosis is challenging due to underlying disease, previous treatments and the variable liability of available tests (i.e., the direct antiglobulin test, anti-platelet antibodies, etc.). Among extra-hematological IRAEs, cutaneous and endocrine ones are the most frequent (up to 30–50%), ranging from mild (pruritus, eczema and thyroid dysfunctions) to severe forms (bullous disorders, hypophysitis and diabetes), mostly requiring topic or replacement therapy. Gastroenteric and kidney toxicities occur in about 5% of patients, biopsies may support the diagnosis, and immunosuppressive treatment is required in severe cases. Finally, neurologic and cardiologic IRAEs, although rare, may be life-threatening and require prompt intervention. By reviewing the most recent literature on post-CPI IRAEs, it emerged that clinical suspicion and monitoring of laboratory markers of organ damage is pivotal to a prompt diagnosis. In severe cases, CPI should be discontinued and immunosuppressive therapy started, whilst rechallenge is anecdotal and should be carefully evaluated.

Hodgkin lymphoma (HL) is traditionally considered one of the hematological malignancies with the highest rate of cure, ranging from 70 to 90% depending on the disease and patient features