Harnessing Immune Response in Acute Myeloid Leukemia.

Despite the results achieved with the evolution of conventional chemotherapy and the inclusion of targeted therapies in the treatment of acute myeloid leukemia (AML), survival is still not satisfying, in particular in the setting of relapsed/refractory (R/R) disease or elderly/unfit patients. Among the most innovative therapeutic options, cellular therapy has shown great results in different hematological malignancies such as acute lymphoblastic leukemia and lymphomas, with several products already approved for clinical use. However, despite the great interest in also expanding the application of these new treatments to R/R AML, no product has been approved yet for clinical application. Furthermore, cellular therapy could indeed represent a powerful tool and an appealing alternative to allogeneic hematopoietic stem cell transplantation for ineligible patients. In this review, we aim to provide an overview of the most recent clinical research exploring the effectiveness of cellular therapy in AML, moving from consolidated approaches such as post- transplant donor's lymphocytes infusion, to modern adoptive immunotherapies such as alloreactive NK cell infusions, engineered T and NK cells (CAR-T, CAR-NK) and novel platforms of T and NK cells engaging (i.e., BiTEs, DARTs and ANKETTM).

Identification of a novel cord blood NK cell subpopulation expressing functional programmed death receptor-1.

Background: Natural Killer cells (NKs) represent the innate counterpart of TCRαß lymphocytes and are characterized by a high anti-tumor and an anti-viral cytotoxic activity. Recently, it has been demonstrated that NKs can express PD-1 as an additional inhibitory receptor. Specifically, PD-1 was identified on a subpopulation of terminally differentiated NKs from healthy adults with previous HCMV infection. So far it is unknown whether PD-1 appears during NK-cell development and whether this process is directly or indirectly related to HCMV infection. Methods: In this study, we analyzed the expression and function of PD-1 on Cord Blood derived NKs (CB-NKs) on a large cohort of newborns through multiparametric cytofluorimetric analysis. Results: We identified PD-1 on CB-NKs in more than of half the newborns analyzed. PD-1 was present on CD56dim NKs, and particularly abundant on CD56neg NKs, but only rarely present on CD56bright NKs. Importantly, unlike in adult healthy donors, in CB-NKs PD-1 is co-expressed not only with KIR, but also with NKG2A. PD-1 expression was independent of HCMV mother seropositivity and occurs in the absence of HCMV infection/reactivation during pregnancy. Notably, PD-1 expressed on CB-NKs was functional and mediated negative signals when triggered. Conclusion: To our understanding, this study is the first to report PD-1 expression on CB derived NKs and its features in perinatal conditions. These data may prove important in selecting the most suitable CB derived NK cell population for the development of different immunotherapeutic treatments.

Case report: Insulin desensitization as the only option for managing insulin allergy in a Sudanese patient.

Introduction: Allergic reactions to insulin have become very rare with the introduction of human insulin. Anaphylaxis is a life-threatening condition that results from immediate IgE-mediated hypersensitivity. Desensitization to human insulin was reported to control immediate hypersensitivity reactions to insulin. Here, we describe the history and challenges of managing our patient and the development of an insulin desensitization protocol in a resource-limited setup. Case Summary: A 42-year-old Sudanese woman with poorly controlled type 2 diabetes on maximum antidiabetic medications required insulin therapy to achieve reasonable glycemic control. She developed progressive and severe immediate hypersensitivity reactions to insulin, including anaphylaxis. Serum sample analysis demonstrated insulin-specific IgE antibodies. The patient's poor glycemic control and the need for breast surgery indicated insulin desensitization. A 4-day desensitization protocol was delivered in an ICU bed for close observation. Following successful desensitization and 24-h observation, our patient was discharged on pre-meal human insulin, which was tolerated well to the current date. Conclusions: Although insulin allergy is rare, once encountered, it is very challenging in patients who have no other treatment options available. Different protocols for insulin desensitization are described in the literature; the agreed protocol was implemented successfully in our patient despite the limited resources.

International Efforts to Save Healthcare Personnel during COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic is a global challenge. Several governments of the world have decided to take drastic actions in order to combat the spread of the disease, including the closing of air, maritime and land borders, as an extreme measure of isolation of each country/region. However, such measures had not prevented the disease from spreading globally; as COVID-19 has already spread in almost all countries. This virus's main victims are the healthcare personnel (HCP), who are physically and psychologically affected. The HCP serves as the first line of defense against this pandemic, what if we faced a significant loss in their number? And what if our HCP was going through a deep dark depression? The condition would be terrifying not only for now but also in the future. This raises the need for an intensified International collaboration, that mainly supports the HCP. We are throwing by challenging moments, and it is clear that social distancing, cooperation, hygiene awareness and abide by the recommendation and help of all governments, as well as obtaining the support of international organizations could be an excellent tool for preventing an increase in the number of cases, principally in countries and regions were COVID-19 is in the early stage of the epidemic. However, this is not the final solution for the current pandemic. An intensified global program, which mainly supports the HCP, then considers the other aspects of the COVID19 pandemic might bring this pandemic to a peaceful end.

Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia.

STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a de novo STAT3 gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of STAT3 GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.