It is a new and exciting time for acute lymphoblastic leukemia (ALL). While nearly 50 years ago, only one in nine children with ALL survived with chemotherapy, nowadays nearly 90% of children have a chance of long-term survival. Adults with ALL, as well as the special category of adolescents and young adult (AYA) patients, are catching up with the new developments seen in children, but still their prognosis is much worse. A plethora of factors are regarded as responsible for the differences in treatment response, such as age, ethnicity, disease biology, treatment regimens and toxicities, drug tolerance and resistance, minimal residual disease evaluation, hematopoietic stem cell transplantation timing and socio-economic factors. Taking these factors into account, bringing pediatric-like protocols to adult patient management and incorporating new agents into frontline treatment could be the key to improve the survival rates in adults and AYA.

Checkpoint inhibitors were a major breakthrough in the field of oncology. In September 2014, based on the KEYNOTE-001 study, the Food and Drug Administration (FDA) approved pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, for advanced or unresectable melanoma. Up until now, seven PD-1/PD-ligand(L)-1 inhibitors are approved in various solid cancers and hundreds of clinical studies are currently ongoing. In hematology, PD-1 inhibitors nivolumab and pembrolizumab were approved for the treatment of relapsed/refractory (R/R) classic Hodgkin lymphoma, and later pembrolizumab was approved for R/R primary mediastinal large B-cell lymphoma. In acute myeloid leukemia (AML), the combination of hypomethylating agents and PD-1/PD-L1 inhibitors has shown promising results, worth of further investigation, while other combinations or single agent therapy have disappointing results. On the other hand, rather than in first line, these therapies could be useful in the consolidation or maintenance setting, for achieving minimal residual disease negativity. Furthermore, an interesting application could be the use of PD-1/PD-L1 inhibitors in the post allogeneic hematopoietic stem cell transplantation relapse. There are several reasons why checkpoint inhibitors are not very effective in treating AML, including the characteristics of the disease (systemic, rapidly progressive, and high tumor burden disease), low mutational burden, and dysregulation of the immune system. We here review the results of PD-1/PD-L1 inhibition in AML and discuss their potential future in the management of this disease.

Macrophages are terminally differentiated innate immune cells. Through their activation, they can be polarized towards the pro-inflammatory M1 type or the wound healing-associated, anti-inflammatory M2 type macrophages. In the tumor microenvironment (TME), M2 is the dominant phenotype and these cells are referred to as tumor-associated macrophages (TAMs). TAMs secrete cytokines and chemokines, exerting an antiapoptotic, proliferative and pro-metastatic effect on the tumor cells. TAMs can be found in many cancers, including chronic lymphocytic leukemia (CLL), where they are called nurse-like cells (NLCs). Despite the generally indolent behavior of CLL, the proportion of treatment-refractory patients is significant. As with the majority of cancers, despite significant recent progress, CLL pathogenesis is poorly understood. The emerging role of the TME in nurturing the neoplastic process warrants the investigation of macrophages as a significant pathogenetic element of tumors. In this paper, we review the current knowledge on the role of stromal macrophages in CLL.

Tumor cells promote the suppression of host anti-tumor type 1 T cell responses by various mechanisms, including the upregulation of surface inhibitory molecules such as programmed death ligand (PD-L)-1, and the production of immunosuppressive cytokines such as interleukin-10 (IL-10). There are over 2000 trials investigating PD-L1 and/or its receptor programmed-death 1 (PD-1) blockade in cancer, leading to the approval of PD-1 or PD-L1 inhibitors in several types of solid cancers and in hematological malignancies. The available data suggest that the molecule PD-L1 on antigen-presenting cells suppresses type 1 T cell immune responses such as cytotoxicity, and that the cytokine IL-10, in addition to downregulating immune responses, increases the expression of inhibitory molecule PD-L1. We hypothesize that the manipulation of both the co-inhibitory network (with anti-PD-L1 blocking antibodies) and suppressor network (with anti-IL-10 blocking antibodies) is an attractive immunotherapeutic intervention for acute myeloid leukemia (AML) patients ineligible for standard treatment with chemotherapy and hematopoietic stem cell transplantation, and with less severe adverse reactions. The proposed combination of these two immunotherapies represents a new approach that can be readily translated into the clinic to improve the therapeutic efficacy of AML disease treatment.

This study aimed to explore the associations between the TP53 rs1042522 (TP53 Arg72Pro), MDM2 rs2279744 (MDM2 309T>G), rs3730485 (MDM2 del1518), MDM4 rs4245739 (MDM4 34091 C>A) variants and odds of developing acute myeloid leukemia (AML) in a cohort of 809 adult subjects, consisting of 406 healthy controls and 403 AML patients. Model-based multifactor dimensionality reduction (MB-MDR) framework was used to identify the interactions of the mentioned variants and their association with AML risk. Associations of the mentioned variants with clinical features of AML, somatic mutations, and response to treatment were also evaluated. Significant associations between TP53 rs1042522 and MDM4 rs4245739 variants and AML susceptibility were noticed. MB-MDR and logistic regression analysis revealed an interaction between MDM2 rs2279744 and TP53 rs1042522, between MDM4 rs4245739 and MDM2 rs3730485, as well as significant associations with AML susceptibility. Several associations between the mentioned variants and clinical features of AML and somatic mutations were also noticed. Individually, the variant genotypes of TP53 rs1042522 and MDM4 rs4245739 were associated with AML susceptibility, but their interaction with MDM2 rs2279744 and rs3730485 modulated the risk for AML. The variant genotypes of TP53 rs1042522 were associated with adverse molecular and cytogenetic risk and also with NPM1 mutations.

Despite a plethora of studies demonstrating significant morbidity and mortality due to community-acquired respiratory viral (CRV) infections in intensively treated hematology patients, and despite the availability of evidence-based guidelines for the diagnosis and management of respiratory viral infections in this setting, there is no uniform inclusion of respiratory viral infection management in the clinical hematology routine. Nevertheless, timely diagnosis and systematic management of CRV infections in intensively treated hematology patients has a demonstrated potential to significantly improve outcome. We have briefly summarized the recently published data on CRV infection epidemiology, as well as guidelines on the diagnosis and management of CRV infections in patients intensively treated for hematological malignancies. We have also assessed available treatment options, as well as mentioned novel agents currently in development.