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Assessing the suitability of older adults with acute myeloid leukemia (AML) for intensive chemotherapy or stem cell transplantation remains a long-standing challenge. Geriatric assessment, which involves the evaluation of multiple dimensions of health, may influence a patient's ability to tolerate intensive or mild-intensity approaches, including treatment-related mortality. Prospective studies are required to validate different fitness criteria, in addition to making it possible to compare the effectiveness of geriatric assessment-based fitness against other criteria, in order to identify which aspects of geriatric assessment are linked to treatment tolerance. It is hoped that validation studies will include different groups of patients receiving either intensive or lower-intensity chemotherapy. At a minimum, geriatric assessment should involve the measurement of the comorbidity burden, cognition, physical function, and emotional health—factors previously associated with mortality in AML. These assessments should be conducted before starting chemotherapy in order to minimize the treatment's impact on the results. While treatment tolerance has traditionally been evaluated through toxicity rates in solid tumor patients, AML treatment often results in high toxicity rates regardless of the intensity. Therefore, early mortality should be the primary endpoint for assessing treatment tolerance, given its significant and clear implications. Other important endpoints might include declines in functional status and quality of life and treatment adjustments or discontinuation due to toxicity. Validating these fitness criteria is essential for guiding treatment choices, improving supportive care, determining trial eligibility, interpreting study outcomes, and informing drug labeling. [ABSTRACT FROM AUTHOR]

High-risk acute myeloid leukemia has been associated with a poor outcome. Hematopoietic stem cell transplantation (HSCT) represents the only curative option for eligible patients. Relapse after HSCT is a dramatic event with poor chances of survival. With the aim of reducing the rate of post-HSCT relapse, maintenance treatment has been investigated in this setting. Results from clinical trials suggest an advantage in the use of a maintenance strategy; however, standardized guidelines are not yet available due to the lack of prospective clinical trials. In this review, we have reported the most important strategies adopted as post-HSCT maintenance, highlighting their efficacy, but the current research also opens questions. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplant (ASCT) remains the only treatment option for patients with high-risk acute myeloid leukemia (AML). Recurrence of leukemic cells after ASCT represents a dramatic event associated with a dismal outcome, with a 2-year survival rate of around 20%. Adoptive cell therapy (ACT) is a form of cell-based strategy that has emerged as an effective therapy to treat and prevent post-ASCT recurrence. Lymphocytes are the principal cells used in this therapy and can be derived from a hematopoietic stem cell donor, the patient themselves, or healthy donors, after being engineered to express the chimeric antigen receptor (CAR-T and UniCAR-T). In this review, we discuss recent advances in the established strategy of donor lymphocyte infusion (DLI) and the progress and challenges of CAR-T cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Compared to the resounding success demonstrated in the field of B-cell leukemia, lymphoma, and multiple myeloma, in the field of acute myeloid leukemia, CAR-T-cell-therapy slows down its application in clinical practice. Yet, immunotherapy and/or cell therapy could be curative in certain high-risk AML subtypes refractory to classical chemotherapy approaches. Several CAR-T constructs targeting different antigens have been tested and have shown promising results. This review illustrates the main results obtained with the use of CAR-T in AML. Chimeric antigen receptors (CAR)-T-cell therapy represents the most important innovation in onco-hematology in recent years. The progress achieved in the management of complications and the latest generations of CAR-T-cells have made it possible to anticipate in second-line the indication of this type of treatment in large B-cell lymphoma. While some types of B-cell lymphomas and B-cell acute lymphoid leukemia have shown extremely promising results, the same cannot be said for myeloid leukemias—in particular, acute myeloid leukemia (AML), which would require innovative therapies more than any other blood disease. The heterogeneities of AML cells and the immunological complexity of the interactions between the bone marrow microenvironment and leukemia cells have been found to be major obstacles to the clinical development of CAR-T in AML. In this review, we report on the main results obtained in AML clinical trials, the preclinical studies testing potential CAR-T constructs, and future perspectives. [ABSTRACT FROM AUTHOR]

The median age of I ZNF384-r i patients was 43 years (range 18-64), 47% were female and 53% male; the median WBC count was 4.82 × 10 SP 9 sp /L (range 1-54.9), while the median platelet count was significantly higher in I ZNF-384 i -r patients compared to the remaining cases (176 B × b 10 SP 9 sp /L vs 49 × 10 SP 9 sp /L, I p i <.001) (Table S2, Supplemental Material). We identified 17 (9.2%) patients with I ZNF384- i r, involving different partner genes: the most frequent fusion was I ZNF384-EP300 i ( I n i = 9), followed by I ZNF384-TAF15 i ( I n i = 4) I ZNF384-TCF3 i ( I n i = 2) and I ZNF384-ARID1B i ( I n i = 1). Rearrangements involving I ZNF384 i ( I ZNF384-r i ) were described in B/myeloid mixed phenotype acute leukemia (B/MPAL) [[9]] and in Ph- B-ALL; in the latter, at least 15 partner genes were identified ( I EWSR1 i , I TAF15 i , I TCF3 i , I EP300 i , I SYNRG i , I CREBBP i , I BMP2K i , I SMARCA2, CLLORF74, CCAR1, CLTC, DUX4, NIPBL, SEC24B and ARID1B i ) [[10]]. ZNF384 rearrangement is the most frequent genetic lesion in adult PH-negative and Ph-like-negative B-other acute lymphoblastic leukemia. [Extracted from the article]

The article presents a study which aims at assessing rate of response in cohort of chronic phase chronic myeloid leukaemia (CML) patients treated with second‐generation tyrosine kinase inhibitors (TKIs). It mentions that having a higher body mass index (BMI) at diagnosis is a risk factor in terms of response achievement and time of response to treatment in CML patients treated with imatinib frontline. It states that high BMI has been observed in patients receiving nilotinib or dasatinib.

A letter to the editor is presented which discusses a case study of a 30-year-old Caucasian female who had an isolated ovarian relapse after undergoing an allogeneic stem cell transplant for the treatment of acute lymphoblastic leukemia.

The article presents a case study of a 9-year old female diagnosed with acute promyelocytic leukemia (APL) and treated through chemotherapy-free protocol. Topics discussed include an overview of the medical history of the patient, the diagnosis of her APL, her clinical trials, and the treatment options for the patient.

Competing Interests: The authors declare no conflict of interest.

Early recognition of Ph-like acute lymphoblastic leukemia cases could impact on the management and outcome of this subset of B-lineage ALL. To assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)-driven trial, we screened 88 B-lineage ALL cases negative for the major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the BCR/ABL1-like predictor - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission (CR) rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs 91.5%, p=0.044); ii) at time point 2 (TP2), decisional for transplant allocation, 52.9% of Ph-like cases vs 20% of non-Ph-like were MRD-positive (p=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at TP2 (p=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs 66.2%, p=0.005 and 45.5% vs 72.3%, p=0.062, respectively). This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies.