Latest articles in this journal
Hemato, Volume 2, pp 645-659; https://doi.org/10.3390/hemato2040042
Non-native immunoglobulin light chain conformations, including aggregates, appear to cause light chain amyloidosis pathology. Despite significant progress in pharmacological eradication of the neoplastic plasma cells that secrete these light chains, in many patients impaired organ function remains. The impairment is apparently due to a subset of resistant plasma cells that continue to secrete misfolding-prone light chains. These light chains are susceptible to the proteolytic cleavage that may enable light chain aggregation. We propose that small molecules that preferentially bind to the natively folded state of full-length light chains could act as pharmacological kinetic stabilizers, protecting light chains against unfolding, proteolysis and aggregation. Although the sequence of the pathological light chain is unique to each patient, fortunately light chains have highly conserved residues that form binding sites for small molecule kinetic stabilizers. We envision that such stabilizers could complement existing and emerging therapies to benefit light chain amyloidosis patients.
Hemato, Volume 2, pp 635-644; https://doi.org/10.3390/hemato2040041
(1) Background: The purpose of this study is to retrospectively compare CT, MRI, and PET/CT in detecting lymphadenopathies and extra-nodal lesions in lymphoma and in disease staging. (2) Methods: Inclusion criteria were the availability of TB (Total Body) CT and/or PET/CT performed before treatment; MRI performed no later than 2 weeks after TBCT; histological confirmation of lymphoma; clinical-diagnostic follow-up. Using these criteria, we included 64/353 patients with TBCT and MRI performed at our hospital; 20/64 had PET/CT performed in other hospitals. Histology and follow-up were gold standard. (3) Results: The sensitivity, specificity, and accuracy in lymph nodes detection was 84.5%, 94.4%, and 91% for CT and 95%, 98.9%, and 95.6% for MRI. High agreement was observed between CT and MRI regarding the number and size of positive lymph nodes and for disease staging. MRI identified eight more extra-nodal lesions than CT. In the subgroup of 20 patients, PET/CT did not show a significant superiority in sensitivity, specificity, accuracy, and staging ability than CT and MRI. (4) Conclusions: Our study demonstrates a mild superiority of MRI over CT in lymphoma staging. Although PET/CT remains the reference standard, MRI demonstrated a similar diagnostic accuracy, with the added value of being radiation-free.
Hemato, Volume 2, pp 628-634; https://doi.org/10.3390/hemato2040040
In the UK, approximately 5820 new cases of multiple myeloma (MM) are diagnosed each year. This number has increased by a third since the early 1990s. Considerable progress has been achieved in our ability to treat MM as a result of the development of new chemotherapeutic agents. MM is a disease more commonly seen in elderly individuals who frequently have pre-existing co-morbidities and are subject to social pressures that impact adversely on their quality of life (QOL). As their lives are extended by more effective treatment of MM, there is a greater need to address such issues. This review will focus on the holistic needs of a patient with MM, and how all members of the multidisciplinary team have a role. The aim is to advocate for centres to support MM patients to live well with their condition.
Hemato, Volume 2, pp 607-627; https://doi.org/10.3390/hemato2030039
In vitro culture is widely used for characterization of primary human acute myeloid leukemia (AML) cells, but even when using optimized handling and culture conditions the AML cells show spontaneous in vitro apoptosis with a gradual decrease in cell viability during culture. The extent of this stress-induced apoptosis varies between patients, and a high degree of apoptosis is associated with high pre-culture BCL2 levels together with low levels of BAX and Heat Shock Proteins 30 and 90. We compared the global proteomic profiles during ongoing in vitro apoptosis for patients with high and low AML cell viability (i.e., less extensive versus extensive spontaneous apoptosis) after 48 h of culture. We identified 7902 proteins, but only 276 proteins differed significantly between patients with high (i.e., >25% viable cells; 192 upregulated and 84 downregulated peptides) and low viability after in vitro culture. Protein interaction network analysis based on these 276 protein identified three protein networks that included 18 proteins; most of these proteins were localized to the endoplasmic reticulum and several of them are involved in or are altered during the process of endoplasmic reticulum stress/unfolded protein stress response. To conclude, primary AML cells are heterogeneous with regard to degree of apoptosis in response to cellular stress, and this difference in regulation of apoptosis is associated with differences in the induction of and/or response to the unfolded protein stress response.
Hemato, Volume 2, pp 596-606; https://doi.org/10.3390/hemato2030038
To clarify the prognostic value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in Neurolymphomatosis (NL), we retrospectively reviewed medical records of all NL patients who had undergone 18F-FDG PET/CT from 2007 to 2020 at Kameda Medical Center and Tokyo Medical and Dental University Hospital. The clinical data of patients were compared with 18F-FDG PET/CT findings of number of nerve lesions and presence of non-nerve extranodal lesions (ENL). Subsequently, we calculated recurrence-free survival (RFS) and overall survival (OS) using the Kaplan–Meier method. A total of 28 patients (mean age 70.1 years, range 44–87 years; 15 women) were included in the study and 7 patients (25.0%) relapsed NL. The number of nerve lesions detected by 18F-FDG PET/CT ranged from 1 to 5, with an average of 2.02. ENL was observed in 18 cases (64.3%). The comparison between the findings revealed that the more the lesions detected by 18F-FDG PET/CT, the higher the probability of recurrence (χ2 = 13.651, p = 0.0085) and there was significantly shorter RFS for the patients with 3 or more nerve lesions (p = 0.0059), whereas the presence of ENL was not significantly associated with any clinical findings. The present study revealed that the more nerve lesions detected by 18F-FDG PET/CT, the poorer the recurrence rate and RFS.
Hemato, Volume 2, pp 586-595; https://doi.org/10.3390/hemato2030037
Anaplastic large cell lymphoma (ALCL) is a histological subtype of non-Hodgkin lymphoma, largely characterized by anaplastic lymphoma kinase (ALK) positivity, resulting from the chromosomal translocation t(2;5). We report a pediatric case of ALK-positive ALCL with primary concomitant involvement of bone and central nervous system (CNS); thereafter, a literature review about pediatric primary bone and primary CNS ALCL was conducted. According to the analyzed data, our case is unique because it is characterized by the contemporary involvement of the spine and CNS. During and after chemotherapy, our patient was monitored by detecting minimal residual disease (MRD) through the analysis of fusion transcript nucleophosmin-ALK. MRD assessment, not only in bone marrow but also in peripheral blood, seems to be a very powerful tool for predicting the prognosis of pediatric ALCL patients, as already described in the literature. Moreover, as shown in our case, it could be used during the follow-up for early recognition of relapse.
Hemato, Volume 2, pp 572-585; https://doi.org/10.3390/hemato2030036
Plasmacytoid dendritic cells (PDC) constitute a small subset of normal bone marrow (BM) cells but have also been shown to be present, sometimes in large numbers, in several hematological malignancies such as acute myeloid leukemia with RUNX1 mutation, chronic myelomonocytic leukemia or, obviously, blastic plasmacytoid dendritic cell neoplasms. These cells have been reported to display somewhat variable immunophenotypic features in different conditions. However, little is known of their plasticity within individual patients. Using an unsupervised clustering tool (FlowSOM) to re-visit flow cytometry results of seven previously analyzed cases of hematological malignancies (6 acute myeloid leukemia and one chronic myelomonocytic leukemia) with a PDC contingent, we report here on the unexpectedly high variability of PDC subsets. Although five of the studied patients harbored a RUNX1 mutation, no consistent feature of PDCs could be disclosed as associated with this variant. Moreover, the one normal single-node small subset of PDC detected in the merged file of six normal BM could be retrieved in the remission BM samples of three successfully treated patients. This study highlights the capacity of unsupervised flow cytometry analysis to delineate cell subsets not detectable with classical supervised tools.
Hemato, Volume 2, pp 556-571; https://doi.org/10.3390/hemato2030035
Acute myeloid leukaemia (AML) is a haematological cancer with poor outcomes due to a lack of efficacious targeted therapies. The Nuclear Factor of Activated T Cells (NFAT) family of transcription factors is well characterised as a regulator of the cell cycle and differentiation in the myeloid lineage. Recent evidence has demonstrated that NFAT family members may have roles in regulating AML leukemogenesis and resistance to targeted therapy in myeloid leukaemia. Furthermore, gene expression data from patient samples show that some NFATs are more highly expressed in poorly differentiated AML and after disease relapse, implying that the NFAT family may have roles in specific types of AML. This review outlines the evidence for the role of NFAT in healthy myeloid tissue and explores how NFAT might regulate AML pathogenesis, highlighting the potential to target specific NFAT proteins therapeutically in AML.
Hemato, Volume 2, pp 545-555; https://doi.org/10.3390/hemato2030034
Myelodysplastic syndromes are clonal disorders with morphological dysplasia, a variable degree of cytopenia and a risk of transformation to acute myeloid leukemia. Prognosis is very variable and is defined by blast count, cytopenia, cytogenetics and more recently by somatic mutations, with IPSS or revised IPSS score being the most widely used to assess disease risk. HSCT remains the only curative treatment to date, with high-risk patients obtaining the biggest benefit. However, NRM should be carefully assessed before indicating the transplant in this usually old population, where organ toxicity and comorbid conditions are to be considered. Multi-domain assessment tools, such as CGA (comprehensive geriatric assessment) and EBMT score, are useful in this context and might guide physician decisions regarding the transplant. Indeed, with the development of reduced intensity conditioning regimens, the number of patient candidates for an HSCT has increased. Regarding pre-transplant treatment, patients with a blast excess > 10% might be treated with HMAs or chemotherapy, although there are no randomized trials confirming the benefit of this approach, even when achieving a complete response. Concerning donor choice, matched sibling donors continue to be the first option, although matched unrelated donors, and more recently haploidentical donors, have proven to be valid options and should be offered in the absence of a related donor. Relapse remains the main cause of transplantation failure. MRD assessment and pre-emptive or prophylactic use of HMA or other targeted inhibitors with or without DLI are accepted strategies to reduce relapse risk, but the prognosis in this context remains dismal, and is the subject for several ongoing clinical protocols.
Hemato, Volume 2, pp 515-544; https://doi.org/10.3390/hemato2030033
Acute myeloid leukemia (AML) is a heterogeneous aggressive hematologic malignancy derived from malignant clones that promote their own growth and survival at the expense of normal hematopoiesis resulting in life-threatening bleeding and infections. Traditional initial AML therapy has been centered on a backbone of intensive chemotherapy often composed of an anthracycline and cytarabine. This strategy has proven most effective in patients less than 60 years of age due to both patient-related tolerability factors as well as changes in AML biology centered on chemotherapy refractory mutational profiles that are seen with advancing age. Recent improvements in frontline AML therapy have been seen in patients 60 years of age and over, a population most typically referred to as “older” adult AML. Herein, we describe the characteristics of “older” adult AML, review the differences in outcomes amongst those 60–75 and those over 75 years of age, and cite challenges in delivering frontline therapies within this group based not only on therapeutic toxicity but also on the patient’s overall level of “fitness” and inherent biology. We also discuss the role of targeted therapies that inhibit specific mutations and have the potential to deliver improved efficacy with less side effects while also recognizing that some selected older AML patients still benefit from intensive induction therapy.