Chronic Hematologic Malignancies Research Articles

Living with a chronic hematological malignancy: Perspectives on PRO-based management of symptoms

PurposeTo explore study participants’ experiences with chronic hematologic malignancies and their perspectives on symptom management based on patient-reported outcomes during follow-up care. MethodsThis qualitative descriptive study used semi-structured telephone interviews conducted from May 2022 to February 2023. A purposeful sample was recruited, with participants invited consecutively. Participants were adults ≥18 years diagnosed with a chronic hematological malignancy and participating in a symptom management intervention. Reflexive thematic analysis, as described by Braun and Clarke, was used to perform an inductive analysis of the interview data. ResultsA total of 19 telephone interviews were conducted with 17 participants. Participants had nuanced perspectives on managing life with a chronic and uncommon hematological malignancy reflected in the following themes: not allowing the disease to dominate, struggling to understand and manage the disease, navigating everyday life with the disease, and evaluating impact and tailoring of patient reported outcome-based symptom management. ConclusionThis study emphasizes the ambiguity of living with a chronic hematological malignancy. Participants strive to prevent the disease from dominating their lives, despite their struggles to understand and manage the disease. The use of patient-reported outcomes in dialogue and targeted symptom management helped participants navigate daily life challenges. These findings underscore important considerations for enhancing follow-up care for patients with chronic hematological malignancies.

Assessment of Molecular Response to Treatment of Chronic Myeloid Leukemia at Kigali University Teaching Hospital of Kigali

Abstract Introduction/Objective Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm that gives proliferation advantage to the granulocytes, it is one of the commonest chronic hematological malignancies and it is a burden to the world especially Rwanda. Since the introduction of Tyrosine Kinase Inhibitors (TKIs) especially the first line Imatinib in 2001, the outcomes of CML have been much improved and currently, in developed world, the life expectancy of patients with CML is almost the same as general population. However, it is not the case in developing world especially Rwanda due to limitation on access of all TKIs. The aim of this study is to assess molecular response on Imatinib of patients with CML. Methods/Case Report This was a one arm open label prospective cohort study that recruited 31 patients with CML and on Imatinib for at least three months and followed for 11 months. The clinical features at diagnosis and recruitment were captured from the hospitals filing systems and investigator’s own assessment at the time of recruitment respectively. Information was filled to a well-structured questionnaire. Lab results at the time of diagnosis was obtained from laboratories reporting systems. Samples for full blood count and BCR-ABL1/ABL1 were withdrawn from the patients at the time of diagnosis and they were run at University Teaching Hospital of Kigali (CHUK). Data analysis was performed using Statistical Package for the Social Sciences (SPSS 28) and South Texas Art Therapy Association (STATA 15.0). Results (if a Case Study enter NA) Better response according to European LeukemiaNet (ELN) defined as optimal response was found among only 38.7% and resistance to imatinib defined by ELN as Failure and warning was found in 45.2% and 16.1% respectively. The eleven months survival rate was 93.5% in which it is 85.7% among those in treatment failure group. Late presentation showed by presence of very high White Blood Cells above 100x109/L and massive splenomegaly at diagnosis, and poor adherence to Imatinib according to Morsiky Medication Adherence Scale (MMAS-8) are associated with poor molecular response to Imatinib. Conclusion CML is a serious disease especially to those who suffer from it; on time diagnosis, access to all available lines of TKIs and better follow up are crucial for patients with CML to access the same life expectancy as general population as it is in developed world.

Examining psychosocial vulnerability in caregivers of individuals with a chronic haematological malignancy. A cross sectional survey.

ObjectiveTo investigate psychosocial vulnerability in informal caregivers of chronic haematological cancer patients and determine the level of psychosocial vulnerability among carers of people living with a CHM. MethodsAn international cross – sectional study including caregivers of individuals with a chronic haematological cancer (n=64) from Ireland (n=29), Australia (n=21), the UK (n=4), the USA (n=4), and India (n=6). Caregivers completed scales for loneliness, resilience, stress and caregiver strain using the UCLA scale, BRS scale, PSS scale and MCSI scale. Descriptive statistics and non-parametric techniques were used. ResultsThe results show that younger carers (aged between 18-40) report higher levels of loneliness, stress and caregiver strain. Carers who have left their paid employment due to caregiving and are in receipt of carers’ allowance or social welfare report high levels of loneliness and caregiver strain. Lower stress levels were reported in those who received paid professional caring support. Finally, higher levels of loneliness in carers were associated with the patient currently being on some form of treatment and higher levels of caregiver strain were associated with caring for someone for more than 8 hours per day and having all social, mental, and financial areas of life affected ConclusionCaregivers of patients with chronic haematological cancers experience psychosocial vulnerability, which is associated with their age, socioeconomic status, gender and health and wellbeing.

Pathways of patients with chronic haematological malignancies: a report from the UK’s population-based HMRN

Pathways of patients with chronic haematological malignancies: a report from the UK’s population-based HMRN

Qualitative Insights into the Factors Impacting Information Sharing in People with Chronic Haematological Malignancies

Background. There are many different haematological malignancy subtypes. Most follow chronic pathways that are uncertain and unpredictable, which may lead to feelings of anxiety and distress. The provision of information can ameliorate such difficulties, but patients are known to have unmet needs in this regard. The aim of this study is to explore experiences of information sharing among patients with chronic blood cancers and the factors impacting this process. Methods. The study is set within a UK cohort of blood cancer patients, where care is provided across 14 hospitals according to national clinical guidelines. Purposive sampling was used to identify expert participants (based on experience), and in-depth qualitative interviews were conducted with 35 patients, 10 with a relative present. The study was intended to inform practice and utilised qualitative description, with thematic content analysis and systematic data coding. Results. Experiences of information sharing varied. Most patients described this positively, but not all. Several barriers and facilitators were identified, which are discussed within five themes: (1) shock affects ability to process information, (2) the importance of time to facilitate information exchange, (3) personal relationships have an impact on meeting information needs, (4) HCP interpersonal skills are central to good information sharing, and (5) communication skills and terminology. Conclusions. Patients with chronic blood cancers prefer to engage in information sharing when they are not in a state of shock, and when they have adequate time to process material that is effectively and sensitively delivered, by HCPs they know and trust.

Clinical Features and Long-Term Outcomes of a Pan-Canadian Cohort of Adolescents and Young Adults with Myeloproliferative Neoplasms: A Canadian MPN Group Study.

Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.

Cutaneous malignancies in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that is associated with an increased risk of developing cutaneous malignancies. Clinical outcomes for these malignancies, including melanoma and keratinocyte cancers (KC), are worse for patients with CLL. Individuals with CLL develop an immunodeficiency of both the adaptive and innate immune system, which plays a role in the increased prevalence of skin cancers. This review focuses on the complex interplay between genetics, immunity, and pathogens that influence the cellular composition and biology of skin tumors and their microenvironment in CLL patients, and in comparison with other chronic hematological malignancies. It is paramount for dermatologists to be aware of the association between CLL (and chronic hematological malignancies more broadly) and cutaneous malignancies. This is a high-risk population who require regular and vigorous dermatologic follow-up.

Multiple Myeloma in 2023 Ways: From Trials to Real Life.

Multiple myeloma is a chronic hematologic malignancy that obstinately tends to relapse. Basic research has made giant strides in better characterizing the molecular mechanisms of the disease. The results have led to the manufacturing of new, revolutionary drugs which have been widely tested in clinical trials. These drugs have been approved and are now part of the therapeutic armamentarium. As a consequence, it is essential to combine what we know from clinical trials with real-world data in order to improve therapeutic strategies. Starting with this premise, our review aims to describe the currently employed regimens in multiple myeloma and compare clinical trials with real-life experiences. We also intend to put a spotlight on promising therapies such as T-cell engagers and chimeric antigen receptor T-cells (CAR-T) which are proving to be effective in changing the course of advanced-stage disease.

The Efficacy and Safety of Selinexor in Combination with Ruxolitinib in Ruxolitinib-Treated Myelofibrosis Patients： the Interim Analysis of a Prospective, Open-Label, Multicenter, Parallel-Cohort, Phase 2 Study

Background: Myelofibrosis is a chronic hematologic malignancy characterized by constitutional symptoms, bone marrow fibrosis, extramedullary hematopoiesis resulting in splenomegaly and a propensity toward leukemic progression. Although JAK inhibitors have improved patients' splenomegaly and symptom burden, the clinical management of MF is still challenging for its limited treatment options, especially when patients become less responsive or intolerable to Ruxolitinib (RUX) treatment. Selinexor (SEL) is a novel, first-in-class, oral selective inhibitor of nuclear export agent that binds the karyopherin protein exportin 1 (XPO1). Preclinical studies showed SEL decreased viable cells and colony formation both in newly diagnosed and RUX-exposed MF cells. ESSENTIAL trial showed SEL's sustained spleen responses as a single agent in JAKi refractory MF. Besides, a phase I study reported, with SEL plus RUX in treatment-Naïve MF, 92% patients(pts) achieved SVR35, 69% had symptom response and 65% had stable or improved Hgb levels. We have presented promising efficacy and safety data in real-world setting of SEL plus RUX regimen in MF patients in 2023 EHA. Here we are to report the efficacy and safety of the regimen in RUX-treated patients in a prospective clinical trial. Methods: This is a prospective, open-label, multi-center, parallel-cohort phase 2 study, examining SEL plus RUX regimen in RUX-treated MF pts. The study includes MF pts with suboptimal RUX responses or intolerable to RUX treatment. Pts are given SEL 40mg or 60mg QW plus RUX (dosage per investigator judgement, RUX intolerable pts will receive reduced dose of RUX). A total of 40 pts will be included into the study. The primary endpoint is spleen response assessed by palpation or CT/MRI scan per IWG-MRT and ELN response criteria. Key secondary endpoints include anemia response, symptom response defined as symptom resolution or alleviation according to TSS or physician's judgement, and safety. Results: Characteristics As of July 2023, 28 pts had received at least one dose of oral weekly SEL, including 12 suboptimal RUX responses pts and 16 RUX intolerable pts. The median age was 65 years old. Mean duration of prior RUX treatment was 24.5 months (range: 4-77). 18 pts had primary MF, 4 had post-PV MF, and 6 had post-ET MF. Median time from MF diagnosis to study enrollment was 5 years (0.25-29). JAK2, CALR and MPL mutations were present in 18 (64.28%), 5 (17.85%) and 1 (3.57%) pts respectively. All pts presented constitutional symptoms, 25 (89.29%) had splenomegaly, and 7 (25.00%) had packed red blood cell (PRBC) transfusion-dependent anemia. DIPSS risk category was intermediate 23 (82.14%), high risk 3 (10.71%) and unknown 2 (7.14%). Median treatment duration was 134 days (14-525) (Table 1). 15 pts (53.57%) discontinued SEL. Reasons for treatment discontinuation were death in 4 pts (3 from covid-19, 1 sepsis), participation in clinical trial in 2 pts, unsatisfactory response in 2, transplantation in 1, toxicity in 2, economic burden in 1 patient and lost to follow-up in 3. Efficacy Analysis The analysis of spleen response included 21 pts with spleen length assessment data by either palpation or CT/MRI. Spleen response is defined as length reduction more than 50% per IWG-MRT and ELN response criteria. 15 (71.42%) pts had a reduction in spleen volume and 8 (38.09%) achieved spleen response ( Figure 1). For symptom response, 27 pts are with available data. 23 (85.18%) pts had symptom alleviation, 9 (33.33%) achieved ≥50% reduction in TSS or symptom response assessed by physician, of which 1 achieved symptom resolution. There are 12 pts with PRBC transfusion-independent anemia (Hgb≤100g/L) at baseline and had received study treatment for at least 28 days. 10 (83.33%) pts had maintained stable or improved Hgb levels at the last follow up. 5/7 (71.42%) PRBC transfusion-dependent pts became transfusion independent (1 pt) or had reduced transfusion frequency (4 pts), and 2 pts remained stable. Safety The most common TEAEs were nausea 14 (50.00%), vomiting 9 (32.14%), decreased appetite 8 (28.57%), and anemia 7 (25.00%). The most frequent TEAEs ≥ Grade 3 were anemia 3(10.71%) and thrombocytopenia 2(7.14%). Conclusion: In this preliminary analysis, the combination of SEL and RUX showed encouraging efficacy and manageable safety in RUX-treated pts with myelofibrosis.

Patient experiences of living with chronic haematological malignancies and their interactions with Primary Care: qualitative investigation.

Haematological malignancies are the fifth most common cancer in the UK. Aggressive subtypes are potentially curable; chronic variants (the most frequent diagnoses) are incurable, although can be successfully managed for many years with observation, interspersed with treatment if required, or with long-term oral therapy. Chronic subtypes involve uncertain pathways, long-term symptoms and psychological distress, which may emerge in primary care. To explore the experiences of patients living with chronic haematological malignancies, specifically regarding interactions with primary care. Fifty-two people with chronic haematological malignancies, including chronic lymphocytic leukaemia, myeloma and chronic myeloid leukaemia, were purposively sampled from the Haematological Malignancy Research Network; a population-based study set-up for research purposes, to improve clinical care. In-depth interviews were conducted, then analysed using thematic analysis. Patients spoke positively about diagnostic efficiency in primary care and trusting relationships shared with their GPs. However, some described GPs as lacking knowledge about their cancer and having limited involvement in their on-going management; along with problems accessing GPs and continuity of care. Many praised hospital clinicians, but could find it difficult to discuss their ongoing physical and psychosocial symptoms, and medication non-adherence with them. Given the rising prevalence of haematological malignancies, pressure on acute services and UK survivorship policy, care may be increasingly shared between secondary and primary care-settings. Challenges include complex shared-care models that lack guidance, workforce issues, and knowledge of haematological malignancies. However, the value patients placed on primary care, coupled with difficulties experienced in hospital clinics, indicate shared care could succeed.

Gatekeepers in research: the experience of recruiting carers of people with chronic blood cancers.

Gatekeepers play a crucial role in successfully recruiting participants to nurse-led qualitative research, particularly in clinical settings. To present the authors' experience of recruiting and conducting qualitative interviews during the COVID-19 pandemic with the carers of patients who have chronic haematological malignancies, and the effects that gatekeepers had on recruitment. The authors had to adapt and adjust their research plan because of difficulties in accessing their target population. Establishing and maintaining relationships with gatekeepers and a Patient and Public Involvement (PPI) panel was integral in successfully collecting data. Ongoing reflexivity and feedback from supervisors, gatekeepers and PPI members in addition to developing research experience can help researchers to overcome challenges in recruiting difficult-to-access populations. Researchers need to be prepared for challenges to their research plans and carefully consider the options available for addressing these challenges. Reaching out to others is integral in expanding researchers' ideas.

The hidden psychosocial impact of caregiving with chronic haematological cancers: A qualitative study

People living with a chronic haematological malignancy (CHM) are living longer due to the continued emergence of novel treatments. Their care is mostly delivered in an outpatient setting, and little is known about their experience of this disease trajectory. The aim of this qualitative study was to explore carers' experiences, expressed needs and psychosocial vulnerability. In-depth interviews with a purposive sample of carers (n=11) explored their experiences of caring for someone with a CHM and the impact it had on their lives. Reflexive thematic analysis guided data analysis. Two main themes were developed from the interview data: 1) restructured living, and 2) sustaining caring, with six subthemes: shrinking world, constant carer, healthcare professional support, needing information, particularly in the early days, peer support, and taking control. Caregivers of patients with a CHM undergo a significant life change which is often invisible to others. Identifying carers at risk of psychosocial vulnerability and recognising the caregiver as a member of the care team are significant steps towards addressing the support needs of this population.

The Clinical and Prognostic Significance of Ribonucleotide Reductase Subunits RRM1 and RRM2 mRNA Levels in Patients with Chronic Lymphocytic Leukemia

Ribonucleotide Reductase (RNR) converts ribonucleotides to deoxyribonucleotides required for DNA replication and repair. RNR consists of subunits M1 and M2. It has been studied as a prognostic factor in several solid tumors and in chronic hematological malignancies, but not in chronic lymphocytic leukemia (CLL). Peripheral blood samples were collected from 135 CLL patients. M1/M2 gene mRNA levels were measured and expressed as a RRM1-2/GAPDH ratio. M1 gene promoter methylation was studied in a patients’ subgroup. M1 mRNA expression was higher in patients without anemia (p = 0.026), without lymphadenopathy (p = 0.005) and 17p gene deletion (p = 0.031). Abnormal LDH (p = 0.022) and higher Rai stage (p = 0.019) were associated with lower M1 mRNA levels. Higher M2 mRNA levels were found in patients without lymphadenopathy (p = .048), Rai stage 0 (p = 0.025) and Trisomy 12 (p = 0.025). The correlation between RNR subunits and clinic-biological characteristics in CLL patients demonstrate RNR’s potential role as a prognostic factor.

COVID-19 Vaccination Outcomes in Children, Adolescents, and Young Adults with Acute Lymphoblastic Leukemia

Background:While several studies have shown that less than half of adults on active therapy for chronic hematological malignancies develop an immune response to COVID-19 vaccination, little is known about the efficacy of COVID-19 vaccines in the midst of active therapy for acute lymphoblastic leukemia (ALL). Furthermore, COVID-19 vaccine outcomes in pediatric leukemia remain uncharacterized. Given the differences in the intensity of chemotherapy regimens between pediatric ALL and adult chronic hematological malignancies as well as age related immune differences, there is a need to specifically define vaccination outcomes in pediatric ALL. This study aims to define the safety and efficacy of COVID-19 vaccination in children and adolescents and young adults with ALL, the most common pediatric leukemia. Methods: We conducted a prospective single center Institutional Review Board approved study. Eligible patients were ages 5-25 years with a diagnosis of ALL or receiving ALL-like therapy who had received COVID-19 vaccination. Pediatric oncology patients at our center undergo universal surveillance for COVID-19 via nasopharyngeal PCR regardless of symptom status, prior to any sedation or hospitalization. Labs were drawn at 3,6-, and 12-months post-vaccination for anti-COVID-19 spike (S) and nucleocapsid (N) IgG ELISA and anti S neutralizing antibody assays, in vitro COVID-19 peptide stimulation T-cell response studies, and T-cell receptor (TCR) sequencing for COVID specific TCR. These tests were validated in healthy COVID-19 infection convalescent and healthy post-vaccination cohorts. Results: Between April 2021 and April 2022, the study enrolled 21 patients (median age 12.5 years). Diagnoses included high risk B-ALL (n=13), mixed-phenotype acute leukemia (MPAL) (n=2), and standard risk B-ALL (n=6). Three had relapsed ALL. All were in complete remission and receiving chemotherapy at the time of vaccination (17 receiving maintenance therapy and 4 in an intensive chemotherapy phase). Twenty received the BNT162b2 mRNA vaccine (10mcg dose n=11 and 30mcg dose, n=9); one received the Ad26.COV2.S vaccine. One patient received one dose (excluded from efficacy analysis), 17 received 2 doses, and 2 received three doses (i.e. a booster dose) of BNT162b2. Vaccinations were well tolerated with no patient experiencing anaphylaxis or an allergic reaction, including 10 patients with PEG-asparaginase allergy (BNT162b2 contains PEG). Three patients presented to the emergency department with fever; one of those was hospitalized for hypotension. Thirteen of 20 patients (65%) were positive for spike (S) anti-COVID-10 IgG following two doses of BNT162b2 (n=12) or one dose of Ad26.COV2.S (n=1). Eleven of these 13 were negative for N IgG, an antibody profile (S IgG+, N IgG-) consistent with an immune response to vaccination rather than a prior undiagnosed COVID-19 infection. All three patients with ≥ 6 months post-vaccination data continue to be positive for S IgG. Notably, 6 of 12 lymphopenic patients (absolute lymphocyte count <500 at the time of vaccination) and 3 of 4 patients in an intense phase of therapy during vaccination showed an immune response. Six of 8 patients with PEG-allergy had an immune response. All patients with positive S IgG showed presence of neutralizing anti-S antibodies. There was no difference in immune response based on vaccine dose. Five of 20 patients (3 of 13 patients who were S IgG+ following vaccination) developed COVID-19 infection following vaccination; one of these occurred after the third dose. Hospitalization was needed in one of five cases of COVID-19. All infections occurred during the omicron wave and included 3 sequencing confirmed omicron infections (variant testing not done for 2). Conclusions: In our study, two doses of COVID-19 vaccination induced a neutralizing antibody response in over half of the children and AYA actively receiving ALL chemotherapy including those who were receiving intensive chemotherapy or had PEG allergy. Adverse events were uncommon. Omicron infections occurred in our study, a finding consistent with the occurrence of breakthrough omicron variant infections in immunocompetent vaccinated individuals. T-cell response studies for our cohort are ongoing. Additional long-term follow-up and larger studies are needed to investigate durability of immune response and optimal vaccine frequency especially in the setting of omicron variants. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Molecular Pathogenesis of Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are chronic hematological malignancies characterized by increased proliferation of MPN stem and myeloid progenitor cells with or without bone marrow fibrosis that typically lead to increased peripheral blood cell counts. The genetic and cytogenetic alterations that initiate and drive the development of MPNs have largely been defined, and we summarize these here. In recent years, advances in understanding the pathogenesis of MPNs have defined a long-preclinical phase in JAK2-mutant MPN, identified genetic loci associated with MPN predisposition and uncovered mechanistic insights in CALR-mutant MPN. The integration of molecular genetics into prognostic risk models is well-established in myelofibrosis and ongoing studies are interrogating the prognostic implications of concomitant mutations in ET and PV. Despite all these advances, the field is deficient in clonally selective therapies to effectively target the MPN clone at any stage of disease, from pre-clinical to advanced. Although the biological understanding of the pathogenesis of MPNs has progressed quickly, substantial knowledge gaps remain, including in the molecular mechanisms underlying MPN progression and myelofibrotic transformation. An ongoing goal for the MPN field is to translate advances in biological understanding to improved treatments for patients.

Priapism in Chronic Myeloid Leukemia: A Rare Case

Causes of CML not clear with a important role from gen and environment factors, such as pesticide use. Priapism in CML around 5%. The report from this case is a man 40 years old with erection complaint in 4 days, patient feel a painful and weak. Patient as a farmer. In the physical check. There is anemic palpebral conjunctiva, hepatosplenomegaly, erection. In the laboratory result, Hb 4,3, Leukocyte 354.300, peripheral blood picture suggests chronic hematological malignancy myeloid series, BMP showed chronic phase CML, cavernous sinus blood gas analysis pH 7.567 pCO2 33.7 HCO3 31.0. In the first control Hb 8.7 Leukocyte 3000, BCR ABL detected. In the second control, leukocyte 22.500. Then, patient is aspirated and winter procedure for priapism management. Patient get transfuse PRC leukodeplected with the Hb target 10, Terbutaline tab 5 mg/12 hours, Allopurinol tab 300 mg/24 hours, hydroxyurea tab 1.500 mg/24-night hours. Giving Tyrosine Kinase inhibitor was delayed when controlling time because there is leukopenia so the blood should be monitor in two weeks routinely, then, in the second control, patient given nilotinib 1x150 mg and hydroxyurea was stopped. The conclusion is patient with priapism is clinical from leukocytosis in CML. Monitoring blood routinely is more important to assess the response to therapy, in addition, it is necessary to carry out a cytogenic and molecular evaluation.

Diagnostic Testing of Hematology Analyzer Equipped with WPC Channel Scattergram in Determining Strains of Hematological Malignancies

Determination of myeloid and lymphoid strains of hematological malignancies is often difficult when determination is solely based on morphology. ADVIA hematology analyzer and WPC channels are said to have the ability to differentiate acute leukemia strains. There is no data regarding the diagnostic values of WPC channels in determining the strain of both acute and chronic hematological malignancies. This study aims to analyze the diagnostic value of WPC channels in determining myeloid and lymphoid strains in both acute and chronic hematological malignancies in comparison to immunophenotyping, which is considered as the gold standard in strain identification. Peripheral blood and BMA specimens from patients with suspected acute and chronic hematological malignancies were subjected to immunophenotyping and testing using WPC Sysmex XN-1000 simultaneously. The strains of hematological malignancies produced from the two examinations were then statistically analyzed to determine their sensitivity and specificity. There was a total of 86 samples of hematological malignancies used in this research. With WPC channel-based strain interpretation, results showed that 54 samples were in accordance with the results obtained from immunophenotyping, meanwhile 25 samples could not be interpreted/inconclusive. Inconclusive samples were further analyzed by examining the dominant abnormal population contained in the WPC scattergram, which resulted in a lower number of inconclusive samples, namely 5 samples. After further analysis was carried out on the inconclusive samples, the results of the diagnostic test for WPC channel-based strain identification showed sensitivity of 85.71% and specificity of 91.89% in determining hematological malignancies of myeloid and lymphoid strains, with diagnostic accuracy reaching 91.65% in comparison to immunophenotyping. In conclusion, the WPC channels have the ability determine strains of both acute and chronic hematological malignancies with high diagnostic value in comparison to strain identification using immunophenotyping.

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies.

Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which were originally discovered in 1980 as enzymes involved in glucose metabolism via inhibitory phosphorylation of glycogen synthase. Differently from other proteins kinases, GSK-3 isoforms are constitutively active in resting cells, and their modulation mainly involves inhibition through upstream regulatory networks. In the early 1990s, GSK-3 isoforms were implicated as key players in cancer cell pathobiology. Active GSK-3 facilitates the destruction of multiple oncogenic proteins which include β-catenin and Master regulator of cell cycle entry and proliferative metabolism (c-Myc). Therefore, GSK-3 was initially considered to be a tumor suppressor. Consistently, GSK-3 is often inactivated in cancer cells through dysregulated upstream signaling pathways. However, over the past 10–15 years, a growing number of studies highlighted that in some cancer settings GSK-3 isoforms inhibit tumor suppressing pathways and therefore act as tumor promoters. In this article, we will discuss the multiple and often enigmatic roles played by GSK-3 isoforms in some chronic hematological malignancies (chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B-cell non-Hodgkin’s lymphomas) which are among the most common blood cancer cell types. We will also summarize possible novel strategies targeting GSK-3 for innovative therapies of these disorders.

Fecal Microbial Community Composition in Myeloproliferative Neoplasm Patients Is Associated with an Inflammatory State.

ABSTRACTThe capacity of the human microbiome to modulate inflammation in the context of cancer is becoming increasingly clear. Myeloproliferative neoplasms (MPNs) are chronic hematologic malignancies in which inflammation plays a key role in disease initiation, progression, and symptomatology. To better understand the composition of the gut microbiome in patients with MPN, triplicate fecal samples were collected from 25 MPN patients and 25 non-MPN controls. Although most of the variance between the microbial community compositions could be attributed to the individual (permutational analysis of variance [PERMANOVA], R2 = 0.92, P = 0.001), 1.7% of the variance could be attributed to disease status (MPN versus non-MPN). When a more detailed analysis was performed, significantly fewer reads mapping to a species of Phascolarctobacterium, a microbe previously associated with reduced inflammation, were found in MPNs. Further, our data revealed an association between Parabacteroides and tumor necrosis factor alpha (TNF-α), an inflammatory cytokine elevated in MPNs. Taken together, our results indicate a significant difference in the microbiome of MPN patients compared to non-MPN controls, and we identify specific species which may have a role in the chronic inflammation central to this disease.IMPORTANCE MPNs are chronic blood cancers in which inflammation plays a key role in disease initiation, progression, and symptomatology. The gut microbiome modulates normal blood development and inflammation and may also impact the development and manifestation of blood cancers. Therefore, the microbiome may be an important modulator of inflammation in MPN and could potentially be leveraged therapeutically in this disease. However, the relationship between the gut microbiome and MPNs has not been defined. Therefore, we performed an evaluation of the MPN microbiome, comparing the microbiomes of MPN patients with healthy donors and between MPN patients with various states of disease.

Managing Infectious Complications in the Immunocompromised Stage D Heart Failure Patient: A Case of Left Ventricular Assist Device Placement in a Patient with Chronic Lymphocytic Leukemia

<h3>Introduction</h3> Little is known about placement and management of a durable left ventricular assist device (LVAD) in patients with chronic hematologic malignancies. We describe the inherent challenges and complications of a case of LVAD implantation in a patient with chronic lymphocytic leukemia (CLL). <h3>Case Report</h3> A 77-year-old man with CLL, stage D heart failure and placement of a HeartMate 3 LVAD one month prior returned to the hospital after a recent hospitalization to the intensive care unit (ICU) for respiratory failure and sepsis secondary to an empyema. The patient returned with dyspnea, altered mentation, and was again admitted to the ICU for septic shock and respiratory failure requiring mechanical ventilation. The patient's presenting white blood cell count was 77,500 K/uL and concerning for infectious etiology though confounded by the patient's known CLL. His presenting heart rate was 103 beats per minute and blood pressure was 70/50 mmHg with a respiratory rate of 17. The patient was found to be septic from multiple sources. Blood cultures were positive for <i>Klebsiella Pneumoniae</i>, tracheal aspirate was positive for <i>Burkholderia Cepacia</i> and urine culture was positive for <i>Citrobacter Freundii</i> and <i>Candida Albicans</i>. The infections were treated successfully with ceftazidime and fluconazole for 2 weeks with a prolonged duration determined by clinical response given chronic leukocytosis in the setting of CLL. <h3>Summary</h3> We present a patient with known CLL who experienced multiple ICU admissions within 3 months of LVAD placement and required treatment for distinct infectious sources as a cause of the critical illness during each admission. This case demonstrates the immunocompromised state of chronic hematologic malignancies and the necessity to maintain a high suspicion for infection despite chronic leukocytosis confounding workup in the post-operative course. We emphasize the need to consider these increased risks when determining candidacy for durable devices and to discuss these risks with patients who have chronic hematologic malignancies and stage D heart failure considering LVAD implantation.