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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]

On flow cytometry, HCL cells express brightly mature B-lymphoid cell antigens as CD19, CD20, CD22, CD200, are typically positive for CD11c, CD103, CD123 and CD25, while are usually negative or dim for CD5, CD23, CD10, CD79b and CD27. Three cases (3/71, 4%) - despite expressing CD25, CD11c, and CD200 on all clonal cells (which were 15%, 22% and 37% of total leukocytes, respectively) - had CD103 expressed only on a fraction of leukaemic cells (40%, 27%, and 10.8%, corresponding to 5%, 6% and 4% of total leukocytes) (Figure 1A). Keywords: CD103; flow cytometry; hairy cell leukaemia EN CD103 flow cytometry hairy cell leukaemia e28 e31 4 07/18/22 20220715 NES 220715 Classical hairy cell leukaemia (HCLc) is an uncommon mature B-cell lymphoproliferative neoplasm (MBCLN) comprising about 2% of lymphoid leukaemias. [Extracted from the article]

Simple Summary: Secondary AML (s-AML) including therapy-related acute myeloid leukemia (t-AML) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) represent approximately one quarter of all AML cases. These AML subcategories are predominantly associated with advanced age and present a specific biologic profile including adverse genetics and a multidrug resistance phenotype, which often determine dramatically poor outcomes after conventional chemotherapy. In 2017, the FDA approved CPX-351, a liposomal formulation of cytarabine and daunorubicin at a fixed 5:1 molar ratio, for the treatment of adults with newly diagnosed t-AML and MRC-AML. Since the approval, many trials have been conducted or are still ongoing in order to assess the role of CPX-351 as frontline treatment in different AML subcategories, as a potential bridge to transplant or in combination with target therapies. In this review, we will discuss the current role of CPX-351 in treating these high-risk AML, focusing on how its use may potentially change the treatment paradigms of AML. Therapy-related acute myeloid leukemia (t-AML) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) represent aggressive diseases characterized by a dismal prognosis if compared with de novo acute myeloid leukemia, especially in older patients. In these AML subsets, standard chemotherapy regimens produce poor response rates and unsatisfactory outcomes. Historically, conventional approaches consisted of an anthracycline combined with continuous infusion of cytarabine for 7 days, the "3+7" regimen. Several attempts have been conducted to ameliorate this combination regimen but inconsistent improvements in response rates and no significant changes in overall survival have been observed, until the recent introduction of targeted molecules. A liposomal formulation of traditional chemotherapy agents cytarabine and daunorubicin, termed CPX-351, enhances pharmacodynamics and synergistic effects through the maintenance of the optimal 5:1 molar ratio, which extends the treatment's half-life and increases the bone marrow tropism of the drug. The use of CPX-351 in newly diagnosed AML-MRC and t-AML patients aged 60–75 years has demonstrated superior remission rates compared to conventional chemotherapy and improvements in event-free and overall survival. Recently, published data from a 5-year follow-up highlighted evidence that CPX-351 has the ability to produce and contribute to long-term remission and survival in older patients with newly diagnosed high-risk/secondary AML. Future perspectives include evaluation of dose intensification with CPX-351 in high-risk settings, combining this agent with targeted therapies, and better understanding the mechanism of improved responses in t-AML and AML-MRC. In this review, we will examine the role of CPX-351 inside the new AML therapeutic scenario and how its employment could potentially modify the treatment algorithm of high-risk and elderly patients with AML [ABSTRACT FROM AUTHOR]

In Ph+ acute lymphoblastic leukaemia (Ph+ ALL), minimal residual disease (MRD) is the most relevant prognostic factor. Currently, its evaluation is based on quantitative real‐time polymerase chain reaction (Q‐RT‐PCR). Digital droplet PCR (ddPCR) was successfully applied to several haematological malignancies. We analyzed 98 samples from 40 Ph+ ALL cases, the majority enrolled in the GIMEMA LAL2116 trial: 10 diagnostic samples and 88 follow‐up samples, mostly focusing on positive non‐quantifiable (PNQ) or negative samples by Q‐RT‐PCR to investigate the value of ddPCR for MRD monitoring. DdPCR BCR/ABL1 assay showed good sensitivity and accuracy to detect low levels of transcripts, with a high rate of reproducibility. The analysis of PNQ or negative cases by Q‐RT‐PCR revealed that ddPCR increased the proportion of quantifiable samples (p < 0.0001). Indeed, 29/54 PNQ samples (53.7%) proved positive and quantifiable by ddPCR, whereas 13 (24.1%) were confirmed as PNQ by ddPCR and 12 (22.2%) proved negative. Among 24 Q‐RT‐PCR‐negative samples, 13 (54.1%) were confirmed negative, four (16.7%) resulted PNQ and seven (29.2%) proved positive and quantifiable by ddPCR. Four of 5 patients, evaluated at different time points, who were negative by Q‐RT‐PCR and positive by ddPCR experienced a relapse. DdPCR appears useful for MRD monitoring in adult Ph+ ALL. [ABSTRACT FROM AUTHOR]

Clofarabine (CLO) and cyclophosphamide (CY) combinations were tested in late stage refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) with disappointing results and high-grade toxicity. We designed a sequential 5-day combination of CLO 40 mg/m2/d plus CY 400 mg/m2/d as first salvage for Philadelphia-negative ALL patients refractory or relapsed until 24 months from complete remission (CR). Primary endpoint was an overall response rate (ORR) ≥ 40%. Among 26 study patients (median age 40.5 years) ORR was 57.6% (CR with complete [n = 8] or incomplete [n = 7] hematologic recovery). Despite severe myelotoxicity, no dose-limiting toxicity suggested de-intensification of CLO schedule. With a median follow-up of 17.0 months, median and 1-year overall and disease-free survival were 6.5 months and 28.6%, and 3.7 months and 28.1%, respectively. This association was tolerable and more effective in patients younger than 40 years with B-precursor ALL, longer first CR, not previously transplanted and achieving CR with full hematological recovery. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate differences in clinical results according to age among patients with chronic myeloid leukemia (CML). Methods: 207 consecutive CML patients treated with imatinib frontline were revised, dividing them in young adults (>20 < 45 years) (YA), middle‐aged adults (≥45 < 65 years) (MA) and elderly (≥65 years) (EL). Results: Cumulative incidence of complete cytogenetic response (CCyR) and major molecular response (MMolR) were significantly higher in MA compared with YA and EL (P < .001 for CCyR and P = .001 for MMolR). Number of total events was lower in MA (8 [11.1%] vs 21 [34.4%] in YA and 28 [37.8%] in EL, P = .001): no difference was observed for blastic evolution (P = .478). Number of deaths was higher in the EL (12 [16.2%] vs 2 [3.2%] in YA and 0 in MA, P < .001): however, 11/12 deaths in EL were not related to CML. The PFS curve in MA was significantly longer than in YA and in EL (P = .02). The OS curve in EL was significantly shorter than in YA and in MA (P < .001). Conclusions: Age at diagnosis influences significantly the course of CML patients treated with imatinib: a possible explanation of the counterintuitive worse course in YA is the delayed diagnosis compared to elderly. [ABSTRACT FROM AUTHOR]

Introduction: Recent advances in prognostication as well as management of Follicular Lymphoma (FL) are moving to personalized approach. Areas covered: Prognostic scores as well as consolidated and innovative therapeutic approaches are evaluated according to the various presentation modalities. For asymptomatic, low-tumor burden FL, a 'watch and wait' policy is currently the first-choice approach, although possible alternatives are discussed. Early stage FL may be treated with local radiotherapy although the role of minimal residual disease in possible additional agents should be determined. The first line treatment for symptomatic FL is chemo-immunotherapy followed by two years maintenance therapy with anti-CD20 monoclonal antibodies. A deeper knowledge of FL biology has opened new perspectives regarding the timing of therapy and has offered new targets for the development of novel agents that aim to change the therapeutic scenario of FL management. Expert commentary: The introduction of novel agents could question the incurability of FL and change the therapeutic goal from prolonging the complete remission state to eradicating the disease in young/fit patients, as well as improving quality of life in elderly/unfit patients. In the near future, combining new biologic agents and adoptive cell therapies could help in achieving these aims. [ABSTRACT FROM AUTHOR]

In patients with ITP secondary to lymphoma, treatment with a TPO-RA could be a favourable therapeutic option for symptoms control, if ITP is not responsive to standard therapy. All patients obtained at least a response, thus suggesting that treatment with romiplostim could overcome a life-threatening ITP, eventually postpone splenectomy and/or limit the use of steroids in severely immune-compromised patients and reduce megakaryocyte lineage chemotherapy toxicity. [Extracted from the article]

Infections by Carbapenem-Resistant Enterobacteriaceae (CRE), in particular, carbapenem-resistant Klebsiella pneumoniae (CRKp), are a significant public health challenge worldwide. Resistance to carbapenems in enterobacteriaceae is linked to different mechanisms, including the production of the various types of enzymes like KPC, VIM, IMP, NDM, and OXA- 48. Despite several attempts to control the spread of these infections at the local and national level, the epidemiological situation for CRKp had worsened in the last years in the Mediterranean area. The rate and types of CRKp isolates greatly differ in the various Mediterranean countries. KPC-producing K. pneumoniae is diffused particularly in the European countries bordering the Mediterranean Sea and is endemic in Greece and Italy. On the contrary, OXA-48-producing K. pneumoniae is endemic in Turkey and Malta and diffused at inter-regional level particularly in some North African and Middle East countries. The spread of these multiresistant pathogens in the world and the Mediterranean countries has been related to various epidemiological factors including the international transfer of patients coming from endemic areas. [ABSTRACT FROM AUTHOR]

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.

Long-term survival of relapsed/refractory acute myeloid leukemia (AML) remains a major problem, particularly in patients not eligible for transplantation. We hereby evaluated the feasibility and efficacy of adding Gemtuzumab Ozogamicin to salvage chemotherapy (Ara-C, Idarubicine, Peg-Filgrastim) in relapsed/refractory AML. The main end points were: the rate of complete remissions (CR) and the proportion of patients capable of undergoing a stem cell transplant. Fourty-two patients were enrolled. The overall CR rate was 76% and no induction deaths were reported. In 56% of patients, a transplant procedure could be performed. The treatment schedule proved feasible and well tolerated, providing a high CR rate and a useful bridge to transplant. [ABSTRACT FROM AUTHOR]

The article focuses on the efficacy of the nivolumab-mediated PD-1 blockade with human immunodeficiency virus (HIV) patients. It discusses the patient's treatment with adriblastine, dacarbazine, and bleomicine (ABD), the observation of interim positron emission tomography (PET), the dropping of the CD4 count.

The article presents a case study of a long-term response to daratumumab in a 69-year-old woman with advanced immunoglobulin light-chain (AL) amyloidosis and organ damage. It states that the patient experienced a temporary partial response and the decline in bone marrow plasma cells after receiving dexamethasone and melphalan treatment. It mentions that the woman restarted daratumumab due to pneumonia and is being monitored for infection.