Incidence Of Hematologic Malignancies Research Articles

Hematologic malignancies in Li-Fraumeni syndrome.

10613 Background: Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome caused by mutations in the tumor suppressor gene TP53. Since its discovery, a growing list of cancers have been described in association with LFS, predominantly solid tumors. However, hematologic malignancies (HMs) cumulatively account for 4-10% of cancer diagnoses in LFS. In this study, we present the largest series of HMs in families with LFS with detailed clinical courses. Methods: This was a two-center retrospective observational cohort study conducted at the University of Utah and the University of Wisconsin-Madison with IRB approval. Cancer genetics clinic registries were reviewed to identify all families with LFS who also had a confirmed diagnosis of a HM. To meet criteria for LFS, the patient had to have a confirmed germline pathologic or likely pathologic TP53 variant. Patients with a TP53 variant of unknown significance (VUS) were also included if they met classical LFS testing criteria. Data was gathered by manual chart review of both the families’ histories and electronic health records. Results: Among the 121 families identified with LFS, 35 (29%) families had one or more HM. Of these, 17 individuals from 16 families (13%) had confirmed germline TP53 mutations. The most frequent HMs found were acute lymphoblastic leukemia (ALL) (n=6), non-Hodgkin lymphoma (NHL) (n=5), myelodysplastic syndromes (MDS) (n=3), and chronic lymphocytic leukemia (CLL) (n=2). Acute myeloid leukemia (AML), Langerhans cell histiocytosis (LCH), and chronic myeloid leukemia (CML) were each diagnosed once. Most cases were identified in adulthood (n=12, 71%). Of the 19 total HMs, the minority (n=5, 26%) were diagnosed post-cytotoxic therapy and only six (35%) individuals had received a diagnosis of LFS prior to HM diagnosis. The MDS/AML cohort (n=4) all exhibited bi-allelic inactivation of TP53. Two of these four patients achieved long term survival after matched-unrelated donor (MUD) hematopoietic stem cell transplant (HSCT). All three patients who underwent MUD donor HSCT had immune-mediated adverse events. Conclusions: In this study we found a significantly higher incidence of HMs in LFS than previously described, with a predominance of lymphoid over myeloid malignancies. The majority of patients had excellent outcomes after standard of care therapy pointing towards more favorable outcomes for patients with LFS and HMs than previously reported. We also report several unusual immune-mediated adverse events in our patients indicating possible immunogenicity of some TP53 variants. Most patients did not have prior exposure to cytotoxic treatments and were diagnosed with the HM prior to their LFS diagnosis. We also show that 38% of individuals with an HM have multiple family members with an HM, consistent with a familial HM pattern. This underscores the importance of detailed family and personal histories in HM patients found to carry a somatic TP53 variant.

Abstract 6152: Genetic associations with hematologic malignancies: An evaluation of CLL polygenic risk score and MBL status in the Mayo Clinic Biobank Cohort

Abstract Chronic Lymphocytic Leukemia (CLL) exhibits a substantial familial risk that extends beyond CLL to other B-cell lymphomas (including follicular lymphoma and diffuse large B-cell lymphoma). Monoclonal B-cell Lymphocytosis (MBL), a precursor to CLL, is also associated with a significant risk for hematologic malignancies overall and for lymphoid malignancies, specifically. Moreover, previous research has shown an association between the CLL polygenic risk score (CLL-PRS) and common lymphoma subtypes. This study aims to further evaluate CLL-PRS associations with hematological cancer overall and by lineage while also considering MBL status a strong risk factor for lymphoid malignancies. Utilizing the Mayo Clinic Biobank, we selected individuals aged 40 years or older, residing in proximal counties, who had no prior hematologic malignancies, and with available biospecimens. MBL screening was done using 8-color flow cytometry, and MBL with CLL (CD5+/CD20dim) or atypical CLL (CD5+/CD20+) immunophenotype were included. CLL-PRS was calculated from 41 known susceptibility variants, with weights being the log of the odds ratios from the largest CLL genome-wide association study. Incident hematologic malignancies were ascertained through ICD codes and confirmed via medical record review. Hazard ratios (HR) and 95% confidence intervals (CIs) for associations with hematologic malignancies were estimated through Cox regression. Of 7,332 participants, 1,150 (16%) screened positive for MBL; median age was 67 years (range 40-101), and 37% male. Median follow-up was 2.9 years (range 0-13), and 56 hematologic cancers were identified. After adjusting for age and sex, the CLL-PRS was associated with increased risk of developing hematologic (HR=1.49, 95%CI=1.12-1.98, P=0.006) which was all attributable to lymphoid cancers (HR=1.79, 95%CI=1.26-2.56, P=0.001). When adjusting for baseline MBL status in the models, the CLL-PRS associations remained significant but were attenuated for hematological (HR=1.33, 95%CI=0.99-1.79, P=0.058) and lymphoid (HR=1.56, 95%CI=1.07-2.26, P=0.020) malignancies, while MBL status was also significantly associated with risk of hematologic (HR=2.76, 95%CI=1.55-4.91, P=0.001) and lymphoid (HR=3.61, 95%CI=1.78-3.32, P<0.001) malignancies. In this prospective cohort study of individuals screened for MBL, CLL-PRS was associated with an elevated risk of hematologic malignancies overall and within the lymphoid lineage, underscoring a shared genetic etiology across many B-cell lymphomas. However, the associations between CLL-PRS and hematologic malignancies were attenuated when accounting for MBL status or when analyzing among MBL-positive individuals, highlighting the role of MBL status in these associations. Further research with expanded cohorts is needed to unravel these complex genetic and clinical interactions. Citation Format: Raphael Mwangi, Dennis P. Robinson, Sara J. Achenbach, Geffen Kleinstern, Aaron D. Norman, Kari G. Rabe, Janet E. Olson, Neil E. Kay, Rosalie Griffin, Nicholas J. Boddicker, Esteban Braggio, Sameer A. Parikh, Curtis A. Hanson, Celine M. Vachon, James R. Cerhan, Tait D. Shanafelt, Susan L. Slager. Genetic associations with hematologic malignancies: An evaluation of CLL polygenic risk score and MBL status in the Mayo Clinic Biobank Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6152.

Clonal Hematopoiesis Associated with Rheumatoid Arthritis

Introduction: Clonal hematopoiesis (CH) becomes common with age and can play a role in the pathophysiology of inflammatory diseases by modifying immune cell function. CH is characterized by the presence of somatic mutations in genes such as DNMT3A and TET2 (CH of indeterminate potential, CHIP), and as mosaic chromosomal alterations (mCAs). While CHIP, particularly in the context of TET2 mutations, can promote inflammation in cardiovascular diseases, the association between clonal hematopoiesis and autoimmunity has not been comprehensively studied to date. Rheumatoid arthritis (RA) is one of the most common autoimmune diseases primarily affecting joints. Seropositive RA is defined by the presence of anti-cyclic citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF), whereas seronegative RA is a more heterogeneous inflammatory disease entity involving patients with clinical RA manifestations in the absence of ACPA and RF. Understanding of the association between CH and inflammatory processes may yield novel insights into prevention and management of autoimmune diseases. Methods: To comprehensively evaluate the association between CH and autoimmune diseases, we identified CHIP variants in whole exome sequencing (WES) data from the FINRISK study (N=10 129). We also detected mCAs and CHIP in the nationwide FinnGen study (N=340 173), where we manually identified CHIP carriers as outliers in SNP intensity plots at known CHIP loci in DNA microarray data. Only known CHIP loci with variant prevalence comparable to UK Biobank WES data and significant positive associations with age and hematological malignancies were included for downstream analyses. To further characterize the link between CHIP and RA phenotypes, we performed targeted panel sequencing of 69 myeloid driver genes in 675 RA patient blood samples (91% collected at diagnosis) and 60 healthy controls. We studied the association between CH and RA in multivariable models excluding participants with prevalent hematologic malignancies and adjusting for sex, age, smoking, and principal components of ancestry. We performed uni- and multivariable analyses to evaluate the link between CHIP and RA patient phenotypes. Results: We identified CHIP in 381 (3.8%) FINRISK participants. As expected, the prevalence of CHIP increased with age, and CHIP variants were associated with prevalent and incident hematologic malignancies. C-reactive protein values were higher in participants with CHIP (P<0.001). In multivariable models, CHIP status (OR 1.98, 1.13-3.45, P=0.017) was more common in participants with questionnaire-based history of RA (N=151) (Fig 1A). In the FinnGen study, CHIP carrier status was associated with prevalent autoimmune diseases (OR 1.26, 1.05-1.53, P=0.015). We validated the association between prevalent RA (N=10 990) and CHIP carrier status (N=2 393) in the FinnGen study (OR 1.58, 1.18-2.13, P=0.002) (Fig 1A). In particular, CHIP (OR 2.17, 1.40-3.36, P<0.001), and GNB1 variants (OR 4.71, 1.87-11.82, P=0.001) were associated with the seronegative RA, whereas DNMT3A was associated with seropositive RA (OR 1.83, 1.08-3.09, P=0.024). We observed no association between autosomal mCAs and RA. Using targeted panel sequencing, we found CHIP in 22% (146/675) of RA patients. RA patients with CHIP variants were older than those without a CHIP variant (median, 69 vs 63 years, P<0.001). Erythrocyte sedimentation rate (ESR) was higher in those with CHIP (median, 42.5 vs 26.0 mm/h, P=0.043). RA patients with TET2 variants were more likely to have seronegative disease compared with TET2 wild-type patients (proportion of seronegative patients, 56% vs 33%, OR 2.62; P=0.008) (Fig 1B). The association remained significant (OR 2.38, 1.14-4.96, P=0.02) when adjusting for age, sex, and smoking. Evaluation of longitudinal disease outcomes by CHIP status are currently ongoing. Conclusion: CHIP variants were more common in participants with prevalent RA in two population-level cohorts, and the association was specific to seronegative RA in the large FinnGen cohort. In newly diagnosed RA patients, TET2 mutations were more common in seronegative than in seropositive RA. While the causality and the functional basis of these observations remain to be explored in future studies, our results provide additional evidence for the association between CHIP and inflammation in various disease contexts, including autoimmune diseases.

Challenges associated with living with haematological malignancies in sub-Saharan Africa

The incidence of haematological malignancies is growing in sub–Saharan Africa. It currently account for about 10% of all cancers diagnosed in region. The management of these malignancies in the region is not as optimized as in most developed economies. There are several challenges associated with the effective management of these malignancies in the region; population-based cancer registries in the region is underdeveloped, suboptimal research on these malignancies, challenges with early diagnosis and appropriate treatment, suboptimal professional human and infrastructural endowment. Patients with these malignancies face several challenges, lack of optimum and safe blood transfusion support, huge cost of chemotherapeutic remedies including radiotherapy and iron chelation agents and lack of laboratory investigation for monitoring response to treatment. Success and management of haematological malignancies in Sub-Saharan Africa, need the collaboration of the entire cancer community, medical experts, teamwork, and advocacy.

Hematologic Malignancy Risk in Inflammatory Arthritis Patients Treated with TNF Inhibitors: The Real-Life Data from the HUR-BIO Registry.

This study aimed to assess the incidence of hematologic malignancy (HM) among inflammatory arthritis (IA) patients receiving tumor necrosis factor inhibitors (TNFi) compared with the general Turkish population. HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center biological disease-modifying anti-rheumatic drug(bDMARD) registry since 2005. Patients with IA, including rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis who had at least one visit after the TNFi were screened from 2005 to November 2021. Standardized incidence rates (SIR) were calculated after adjustment for age and gender and compared with the 2017 Turkish National Cancer Registry (TNCR). Of the 6139 patients registered in the HUR-BIO, 5355 used any TNFi at least once. The median follow-up duration was 2.6years for patients receiving TNFi. Thirteen patients developed a HM on follow-up. In these patients, the median age at the IA onset was 38 (range, 26-67), and the median age at the HM diagnosis was 55.5 (range, 38-76). Patients using TNFi had an increased HM incidence (SIR 4.23, 95% confidence interval (CI) 2.35-7.05). Ten patients with HM were under 65years of age. In this group, there was a higher incidence of HM in both men (SIR 5.15, 95% CI 1.88-11.43) and women (SIR 4.76, 95% CI 1.74-10.55). The risk of HMs in inflammatory arthritis patients receiving TNFi was four times higher than in the general Turkish population.

Expression variations of DNA damage response genes ATM and ATR in blood cancer patients.

Hematological malignancies (HM) constitute a variety of cancers originating in blood, bone marrow (BM), and lymphatic systems. During the last two decades, the incidence of HM has dramatically increased worldwide. The etiology of HM is still debatable. Genetic instability is a major risk factor for HM. DDR network is a complex signal transduction cellular machinery that detects DNA damage and activates cellular repair factors, thus maintaining genomic integrity. DDR network detects a variety of DNA damage and triggers the activation of cell cycle control, DNA repair, senescence, and apoptosis. Among the DNA repairing pathways, the DNA damage response (DDR) pathway includes DNA damage signaling apparatus such as ATM and ATR genes. ATM tends to detect double-strand breaks (DSBs) while ATR detects single-strand DNA (ssDNA). The study was conducted to observe the expression deregulations of DNA damage response (DDR) pathway genes (ATM, ATR) at mRNA level in 200 blood cancer patients and 200 controls. The real-time PCR was used to analyze the expression of the target genes. The expression results showed statistically significant downregulation of ATM (p < 0.0001) and ATR (p < 0.0001) genes in blood cancer patients vs. controls. Moreover, a significant downregulation of ATM (p < 0.0001) and ATR (p < 0.0001) was obtained in chemotherapy-treated patients vs. healthy controls. The results suggest that dysregulation in ATM and ATR genes may be associated with increased blood cancer risk.

Priapism on Chronic Myeloid Leukemia with BCR-ABL1 Fusion gene Identified by Molecular Test: A Case Report

The incidence of hematological malignancies has elevated in recent decades. Chronic Myeloid Leukemia (CML) is a hematopoietic stem cell malignant clonal disorder resulting in elevation of erythroid cells and platelets in peripheral blood and clear myeloid hyperplasia in the bone marrow. Priapism is one of a rare clinical manifestation and serious complication in Chronic Myeloid Leukemia (CML). It is cause due to hematological disorder is most likely due to venous obstruction as well as hyperviscosity due to an increased number of circulating leukocytes mature and immature forms. We report a 30-year-old male came to the emergency room, presented with priapism caused by Chronic Myeloid Leukemia (CML) with hyperleukocytosis. The rarity of this case reiterates the importance of thorough morphological, cytogenetic examination along with radiology in diagnosing, treatment and follow up of patients. Starting leukemia therapy to reduce the leukocyte count immediately, can solve the problem in hyperleukocytosis that caused priapism in Chronic Myeloid Leukemia (CML).

Acute lymphoblastic leukemia after COVID-19 infection: a coincidence or a second hit

Since the advent of COVID-19 in 2019, the virus has affected all age groups and has a very wide clinical spectrum, ranging from asymptomatic infection to serious life-threatening complications including multi-organ dysfunction syndrome in children. The virus tends to affect all organ systems including the hematological system. There are many contradictory views on the effect of the COVID-19 pandemic on the incidence of hematological malignancies. Some studies have shown an increased incidence of acute lymphoblastic leukemia (ALL) after COVID-19 infection supporting the Greaves two-hit hypothesis of leukemogenesis, while others have shown a decline in the incidence of ALL postulated to be due to widespread lockdown and decreased exposure to environmental pathogens. We report the cases of three children who were diagnosed with acute lymphoblastic leukemia shortly after the initial diagnosis of multisystem inflammatory syndrome in children (MIS-C) or COVID related transient erythroblastopenia of childhood.

Epidemiological and Disease Burden Profiles of Leukemias and Malignant Lymphomas: Overview and Trends in the Republic of Moldova and Worldwide

Introduction: Hematological malignancies (HM) are relatively frequent nosological entities within the structure of morbidity by malignant tumors, exhibiting a severe evolution, restrained prognosis and negative socio-economic impact in the advanced stages and phases. Objective: The objective of the study was to identify the epidemiological patterns, and to evaluate the epidemiological trends and disease burden issues of HM in the Republic of Moldova and worldwide. Materials and Methods: The following research methods were used: epidemiological, descriptive statistics, clinico-analytic. The diagnosis was proved in all cases by histopathological, cytological, cytogenetic, molecular and immunophenotyping examinations. The qualitative type researches were performed and enriched by the narrative synthesis of the data. From the specialized international bibliographic sources and official statistics concerning HM. The narrative review of the reference sources was fulfilled in the form of a synthesis. Results: The number of newly diagnosed and followed-up patients with HM at the Institute of Oncology in 2016, 2017, 2018, 2019, 2020 and 2021 amounted respectively to 725, 802, 613, 628, 536 and 528, the incidence (new cases per 100,000 population) being 17.6, 19.5, 14.9, 17.7, 15.1 and 20.3. In 2021 HM constituted 6.2% of all newly-diagnosed cases with malignant tumors in the Republic of Moldova. In the same year Hodgkin lymphoma was diagnosed in 10.04% of cases, non-Hodgkin’s lymphomas—in 31.63%, multiple myeloma and plasma cells neoplasms—in 7.77%, lymphoid leukemias—in 17.42%, myeloid leukemias—in 12.31%, monocytic leukemias—in 0.95%, and other leukemias—in 16.29%. In 2019 the male rate was 51.5%, and the female rate—48.5%. Within 2 years males were 266 (50.4%), females—262 (49.6%). The age of 50 - 79 years prevailed in both genders (males—65%, females—72.5%). The children constituted 4.0% of the newly diagnosed cases, 4.8% of those under the follow-up at the end of the year 2019 and 6.4% of the newly diagnosed cases in 2021. The disease span from the onset to diagnosis ranged between 1 - 24 months and constituted on average 5.63 months, without a significant difference as compared to 2019 (5.76 months). The incidence of HM in Western countries is 14 - 19 new cases per 100,000 population (4% of all cases with malignant tumors). The incidence of non-Hodgkin’s lymphomas increased by 45% between 2006 and 2016, from 319,078 to 461,000 cases. Between 2006 and 2016, the incidence of leukemias increased by 26%, from 37,000,000 to 467,000 cases. Conclusions: The epidemiological study revealed slightly lower morbidity by HM in the Republic of Moldova as compared to the West European countries mainly due to the migration of a workable population. The patients with malignant lymphomas, male gender and age categories of 50 - 79 years proved to be commonly registered epidemiological patterns. The narrative analysis of the literature revealed that patients with HM may experience a considerable disease burden with a negative impact on their employment status, working productivity and annual household income.

Integrating Mosaic Chromosomal Alterations and Single-Nucleotide Variants to Predict Evolution of Clonal Hematopoiesis

Background: Clonal hematopoiesis (CH) is an age-related expansion of mutated hematopoietic stem cells. Multiple studies have previously described distinct types of CH, CHIP (mutations in genes commonly associated with myeloid malignancies) as well as mosaic chromosomal alterations (mCA), that have been associated with increased risk of hematologic malignancies and cardiovascular morbidity. We hypothesized that the presence of both mCA and CHIP mutations may have an additive impact vis-à-vis risk of hematologic malignancy. Methods: Data on 91,335 patients from the BioVU repository, a Vanderbilt University Medical Center biobank with linked de-identified EHRs, spanning 2006 to 2021 were included in the analysis. Peripheral blood-derived DNA of 91,335 subjects from BioVU were genotyped on the Illumina Multi-Ethnic Global Array (MEGAEX) platform, which contains more than 2 million SNPs. CHIP mutation calls (DNMT3A R882/JAK2 V617F) were made by deconvoluting the MEGAEX array intensity data. Predetermined array intensity scores greater than a defined threshold for DNMT3A R882 and JAK2 V617F mutations were highly predictive of the corresponding mutation, so these mutations were included in the analysis. Individuals with a diagnosis of hematologic malignancy (HM) prior to blood draw were excluded, while those that went on to develop HM post-blood draw were included in the analyses. The relationship between independent variables and disease progression and death was assessed using Cox proportional hazards model. All statistical analyses were performed using R. Results: In this large cohort (n=91,335), CH is strongly age-related with an increased frequency in the elderly, as has been previously shown (eg., Bick et al, Nature 2021; Jaiswal et al NEJM 2014). In total, we identified mCA in 765 (0.8%) patients. DNMT3A R882 and JAK2 V617F SNV/indels were identified in 1167 (1.3%) and 347 (0.4%) patients, respectively. Most frequent mCA detected in this cohort include 9p CN-LOH (n=105, 6.9%), del (5q) (n=99, 6.5%), del (20q) (n=98, 6.4%), del (7q) (n=94, 6.2%), and del (13q) (n=67, 4.4%). Combined mCA and DNMT3A R882/JAK2 V617F mutations were reported in 147 (0.2%). Co-occurring JAK2 and 9p CN-LOH (n= 100, OR=5658, q<0.001) are consistent with the well-known mechanisms of biallelic alterations involved in the pathogenesis of HM. There were significant correlations between abnormal blood counts and CH lesions, for example, high platelet count had a higher frequency of JAK2 V617F and 9p CN-LOH (OR=2.57, q=3.41e-141). Individuals with mCA are associated with lower WBC and platelet count, and any blood count abnormality (Figure 1A). Finally, we looked at how presence of both mCA and JAK2/DNMT3A impact the risk of HM. In total, 1615 cases in the entire BioVU cohort were reported to develop HM: 947 myeloid, AML (n=210), CML (n=73), MDS (n=315), MPN (n=349) and 668 lymphoid, ALL (n=72), B-NHL (n=252), T-NHL (n=22), MM (n=322). The presence of mCA was associated with a higher incidence of HM (hazard ratio (HR) = 6.85, 95% confidence interval (CI) = 5.9-7.95, P < 0.001), and DNMT3A/JAK2 was associated with higher incidence of HM ( HR=5.7, 95% CI= 4.75-6.85, P<0.001), and presence of both (mCA and DNMT3A/JAK2) were significantly associated with higher incidence of HM (HR=26.67, 95% CI= 19.48-36.5, P<0.001) than observed in no CH patients (Figure 1B). Conclusion: In this large cohort of patients, the presence of CH (both mCA and DNMT3A/JAK2) in apparently healthy individuals positively correlated with blood count abnormalities and increased incidence of hematologic malignancy. The results from this large cohort of patients emphasize the significance of detecting both mCA and SNV/indels in clonal hematopoiesis. These results should be validated in large datasets to determine if detecting both mCAs and CH can augment clinical care and outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A comprehensive study of the epidemiology of haematological malignancies in North Queensland.

There is an absence of clinically relevant epidemiological data in regional Australia pertaining to haematological malignancies. To determine the incidence and geographical variation of haematological malignancies in North Queensland using a clinically appropriate disease classification. Retrospective, observational study of individual patient data records of all adults diagnosed with a haematological malignancy between 2005 and 2014 and residing within The Townsville Hospital Haematology catchment region. We report descriptive summaries, incidence rates and incidence-rate ratios of haematological malignancies by geographic regions. One thousand, five hundred and eighty-one haematological malignancies (69% lymphoid, 31% myeloid) were diagnosed over the 10-year study period. Descriptive data are presented for 58 major subtypes, as per the WHO diagnostic classification of tumours of haemopoietic and lymphoid tissues. The overall median age at diagnosis was 66 years with a male predominance (60%). We demonstrate a temporal increase in the incidence of haematological malignancies over the study period. We observed geographical variations in the age-standardised incidence rates per 100 000 ranging from 0.5 to 233.5. Our data suggest an increased incidence rate ratio for haematological malignancies in some postcodes within the Mackay area compared with other regions. The present study successfully reports on the incidence of haematological malignancies in regional Queensland using a clinically meaningful diagnostic classification system and identifies potential geographic hotspots. We advocate for such contemporary, comprehensive and clinically meaningful epidemiological data reporting of blood cancer diagnoses in wider Australia. Such an approach will have significant implications towards developing appropriate data-driven management strategies and public health responses for haematological malignancies.

Association between maternal breastfeeding and risk of systemic neoplasms of offspring

BackgroundBreastfeeding might prevent childhood cancer by stimulating the immune system.MethodsThe following databases, including PubMed, Embase, and Cochrane Library, were searched from inception to January 10, 2021.ResultsIn dose-dependent manner, there was a statistically significant inverse association between any breastfeeding and the incidence of childhood cancer. There was no evidence that breastfeeding was inversely related to childhood cancer of the skeletal, reproductive, or sensory systems. However, breastfeeding was inversely associated with the incidence of hematological malignancies and cancers of the nervous and urinary systems. Among hematological malignancies, the relationship was significant for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), but not for acute non-lymphocytic leukemia (ANLL), Hodgkin’s lymphoma (HL), or non-HL.ConclusionsThe evidences demonstrated that breastfeeding have a potential protective role in preventing selective childhood cancer growth, especially for ALL, AML, cancer of nervous and urinary systems. This study recommended that breastfeeding be extended for as long as possible or maintained for at least 6 months to prevent selective childhood cancer growth.

Association of antibiotic-consumption patterns with the prevalence of hematological malignancies in European countries

Hematological malignancies are considered the fifth most common cancer in the world. Several risk factors and probable etiological agents have been suspected in the pathomechanism of those malignancies as infections, chemicals, irradiation, etc., and recently, the contribution of the altered gut flora, dysbiosis, was identified also as a possible additional factor to the existing ones. Host, and external factors, like antibiotics, which were identified as a major disruptor of the "normal" gut flora, influence the composition of the microbiome. Considering the several-fold differences in antibiotic consumption patterns and the incidence of hematological malignancies in European countries, the hypothesis was raised that the dominant consumption of certain antibiotic classes might influence the incidence of different hematological malignancies through the modification of gut flora. Comparisons were performed between the average antibiotic consumption databases reported yearly by ECDC (2009–2019) and the incidence rate of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia (LEU) estimated for 2020 in 30 European countries. Applying Spearman calculations, significant positive correlation has been found between the incidence of HL and tetracycline (J01A) consumption (r = 0.399, p = 0.029), NHL and narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.580, p = 0.001), MM and tetracycline (r = 0.492, p = 0.006), penicillin (J01C) (r = 0.366, p = 0.047), narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.574, p = 0.001), while strong, significant negative correlation has been recorded between NHL and cephalosporin (r = − 0.460, p = 0.011), and quinolone (r = − 0.380, p = 0.038). The incidence of LEU did not show any positive or negative association with any antibiotic classes using Spearman calculation. Multivariate ordinal logistic regression (OR) indicated increased risk between HL and the total consumption of systemic antibiotics (J01 p: 0.038), and tetracyclin (J01A p: 0.002). Similarly, increased risk has been detected between the MM and tetracyclin (J01A p: 0.02), and narrow spectrum, beta-lactamase resistant penicillin (J01CF p: 0.042) and decreased risk between cephalosporin and MM (J01D p:0.022). LEU showed increased risk with the consumption of macrolides (p: 0.047).

Cancer incidence in healthy Swedish peripheral blood stem cell donors

Granulocyte colony-stimulating factor (G-CSF) has been used for over 20 years to obtain peripheral blood stem cells from healthy donors for allogeneic stem cell transplantation. Concerns have been raised about a potentially increased cancer incidence in donors after donation, especially regarding haematological malignancies. In a prospective Swedish national cohort study, we studied the cancer incidence after donation in 1082 Swedish peripheral blood stem cell donors, donating between 1998 and 2014. The primary objective was to evaluate if the cancer incidence increased for donors treated with G-CSF. With a median follow-up time of 9.8 years, the incidence of haematological malignancies was 0.85 cases per 1000 person-years, and did not significantly differ from the incidence in age-, sex- and residence-matched population controls (hazard ratio 1.70, 95% confidence interval (CI) 0.79–3.64, p value 0.17), bone marrow donors or non-donating siblings. The total cancer incidence for peripheral blood stem cell donors was 6.0 cases per 1000 person-years, equal to the incidence in matched population controls (hazard ratio 1.03, 95% CI 0.78–1.36, p value 0.85), bone marrow donors or non-donating siblings. In this study of healthy peripheral blood stem cell donors, the cancer incidence was not increased after treatment with G-CSF.

Hematological Malignancies and the Kidney.

The incidence of hematologic malignancies is on the rise worldwide. Kidney disease is ubiquitous in patients with hematologic malignancies, encompassing a wide spectrum of disorders involving each kidney compartment, including the vasculature, tubules, interstitium, and glomerulus, and there is significant overlap of kidney involvement with each hematologic malignancy. Vascular disorders include both microvascular and macrovascular damage, via thrombotic microangiopathy, hyperleukocytosis, hyperviscosity, and cryoglobulinemia. The tubulointerstitial compartment may be affected by prerenal azotemia and acute tubular injury, but malignant infiltration, tumor lysis syndrome, extramedullary hematopoiesis, cast nephropathy, granulomatous interstitial nephritis, and lysozymuria should be considered in certain populations. Obstructive uropathy may occur due to nephrolithiasis or retroperitoneal fibrosis. Glomerular disorders, including membranoproliferative, membranous, minimal change, and focal segmental glomerulosclerosis, can rarely occur. By understanding how each compartment may be affected, care can best be optimized for these patients. In this review, we summarize the widely varied etiologies of kidney diseases stratified by kidney compartment and hematologic malignancy, focusing on demographics, pathology, pathophysiology, mechanism, and outcomes. We conclude with common electrolyte abnormalities associated with hematologic malignancies.

Fertility preservation in women with haematological malignancies

The incidence of haematological malignancies is increasing in women of childbearing age. Survival rates accompany this increase, making it essential to assess the impact of treatments on their future quality of life, evaluate the impact of each treatment on ovarian reserve and define the fertility preservation techniques used by women with haematologic malignancies. A retrospective study was conducted after data collection from 61 women diagnosed with haematological malignancies and followed-up in a fertility preservation centre between January 2008 and June 2019. Cancer treatments caused a decrease in ovarian reserve, demonstrated by an increase in FSH levels and a decrease in AMH levels. When assessing which treatments have the greatest impact on AMH levels, we found that the BEACOPP regimen, and the agents vincristine, etoposide, procarbazine, prednisone and the haematopoietic stem cell transplantation were mainly responsible. Regarding pregnancy after oncological treatments, of the eleven women who became pregnant, ten did so spontaneously. This study reinforces the importance of referring patients to a fertility preservation consultation before starting oncological treatment, as most of them opt to preserve fertility. This work also helps to clarify the impact of each chemotherapeutic agent on the ovarian reserve.

Noble metal nanomaterials for the diagnosis and treatment of hematological malignancies.

Recently, the incidence of hematological malignancy, such as various leukemias, multiple myeloma and lymphoma, has revealed an increasing tendency, exhibiting a major impact on human health. Most of the available anti-cancer drugs, however, possess high non-targeted accumulation, dosage-associated toxicity, fast elimination, and lack specificity towards tumors, which restrict their utilization in clinical therapy. This extends also to cancer diagnosis where there is a lack of predictive biomarkers. Noble metal nanomaterials (NM NMs) have the potential to overcome these shortcomings due to several characteristics including ease of synthesis, ultra-small size, easy surface modification and specific physicochemical properties. At present, gold-, silver- and platinum-based nanomaterials have been employed in the tracing and treatment of hematopoietic tumors through direct individual endocytosis or in innovative drug delivery systems (DDS) by conjugation with other targeting biomolecules. In this mini review, we focus on the use of localized surface plasmon resonance (LSPR)-/surface-enhanced Raman scattering (SERS)- and fluorescence-based diagnosis of NM NMs in the hematological malignancies. Furthermore, the treatment of hematological malignancies utilized the NM NMs or NM NMs-based therapy technology in the chemotherapy, targeted therapy, and photothermal therapy are depicted in depth. The construction of effective and promising NM NMs or NM NMs- dependent theranostic methodology has the potential to provide interdisciplinary knowledge in the development of clinical tracing, diagnosis and treatment of refractory hematological diseases.

Связь активности Солнца и дыма с трендами гемобластозов в России

ematological malignancies, which include leukemia, Hodgkin's lymphoma (HL), non-Hodgkin's lymphomas (NHL) and multiple myeloma, amount 6.6% of the global incidence of malignant ne-oplasms, and 4.7% in Russia. A significant number of studies indicate the involvement of envi-ronmental factors in the occurrence of hematological malignancies. The role of electromagnetic waves in the origin of NHL is indicated by data on the increased risk of developing them in occu-pations associated with electricity. Leukemia in children is positively associated with vehicle smoke. There are indications of a role in the emergence of HL of tobacco smoke. Previously, the authors established a links between the incidence of NHL and leukemia in cohorts of young chil-dren with the activity of the Sun, and in leukemia a correlation with the smoke of forest fires was also found. In this work has been investigated the relations between the trends in the incidence of hematological malignancies in the population of Russia in 1993-2018 with smoke and solar activity. There was a tendency towards an increase in the incidence of hematological malignancies (p&lt;0.001) by 2.8% per year. The incidence of leukemia (p=0.004), NHL (p&lt;0.001), and multiple myeloma (p&lt;0.001) significantly increased. This trend is presumably related to the increase in the number of cars in the country. The incidence of HL, on the contrary, is characterized by a downward trend (p=0.019). A link was found between the activity of the Sun and the incidence of leukemia (r=0.708, p=0.010, lag 2 years), NHL (r=0.689, p=0.013, lag 2 years), multiple myeloma (r=0.657, p=0.020, lag 2 years) and LH (r=0.606, p=0.037, lag 7 years). The data obtained sug-gest a significant contribution of smoke and solar activity to the occurrence of hematological ma-lignancies in children and adults. Based on the role of environmentally related oxidative stress in oncogenesis, it is recommended for the prevention of hematological malignancies to consume a sufficient amount of vitamins, regularly include in the diet fresh vegetables, fruits, foods to stimulate autophagy and Transfer Factor.

Chronic myeloid leukemia coexisting with non-Hodgkin’s lymphoma: An uncommon presentation of bilineage hematological malignancy

The incidence of hematological malignancies is on the rise particularly in developing countries as a result of newer diagnostic technologies and skills. However, the coexistence of chronic myeloid leukemia (CML) and non-Hodgkin lymphoma (NHL) in a single patient simultaneously is extremely rare, with an overall incidence of less than 1%, while the majority of cases (66%) have sequential presentations. We report a 36-year old Nigerian man, who was diagnosed in our facility initially in chronic phase CML, but progressed through accelerated phase to blastic phase CML and was subsequently diagnosed with NHL within weeks of starting hydroxyurea. He also received cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (CHOP) for the NHL. However, he subsequently succumbed to the disease. CML is a triphasic disease with the tendency to acquire new cytogenetic abnormalities particularly transformation to extramedullary disease during its blastic phase. These events may be associated with NHL in the setting of blast crisis. Our case report adds to the growing literature on the coexistence of two separate hematological malignancies in a single patient.

Twenty-year incidence trend of hematologic malignancies in the Republic of Korea: 1999-2018.

BackgroundIn this study, we presented the national cancer statistics on the incidence of hematologic malignancies in the Republic of Korea (ROK) over a period of 20 years, from 1999 to 2018.MethodsWe obtained data on the incidence of hematologic malignancies using the Korean Statistical Information Service (KOSIS). For each hematologic malignancy, the number of cases, crude incidence rate, and age-standardized incidence rate were calculated, and the statistical trends were confirmed by Poisson regression and Joinpoint regression analysis.ResultsAll the investigated hematologic malignancies showed a statistically significant increase in incidence over 20 years. The 20-year trend of the age-standardized incidence rate was as follows non-Hodgkin lymphoma [average annual percent change (AAPC)=2.26%, P-trend <0.05], leukemia (AAPC=0.94%, P-trend <0.05), myeloid leukemia (AAPC=1.44%, P-trend <0.05), multiple myeloma (AAPC=3.05%, P-trend <0.05), myeloproliferative disorders (AAPC=9.87%, P-trend <0.05), myelodysplastic syndrome (AAPC=7.59%, P-trend <0.05), malignant immunoproliferative diseases (AAPC=11.82%, P-trend <0.05), lymphoid leukemia (AAPC=2.21%, P-trend <0.05), and Hodgkin lymphoma (AAPC=4.04%, P<0.05).ConclusionIt was confirmed that the incidence of hematologic malignancies has increased significantly in the ROK over the past 20 years. This study can be used as foundational data source for future studies. In addition, it can aid in the necessary actions of predicting future incidences and establishing future healthcare policies.