THE STRUCTURE OF THE INCIDENCE OF ONCOHEMATOLOGICAL DISEASES IN ECOLOGICALLY DISADVANTAGED REGIONS OF THE DNIPROPETROVSK REGION FOR THE PERIOD 2006-2017. / СТРУКТУРА ЗАХВОРЮВАНОСТІ НА ОНКОГЕМАТОЛОГІЧНІ ХВОРОБИ В ЕКОЛОГІЧНО НЕБЛАГОПОЛУЧНИХ РЕГІОНАХ ДНІПРОПЕТРОВСЬКОЇ ОБЛАСТІ ЗА ПЕРІОД 2006­2017 РОКІВ).

OBJECTIVE: to conduct a comparative analysis of the incidence of malignant oncohematological diseases structure among the population of the 4 most ecologically disadvantaged cities of the Dnipropetrovsk region, taking into account the possible influence of various adverse environmental factors (radiation and chemical pollution of air, water and soil) for the period 2006-2017. MATERIALS AND METHODS: 1948 cases of acute myeloblastic and lymphoblastic leukemia, chronic myeloid and lymphocytic leukemia in residents of 4 cities of the Dnipropetrovsk region were analyzed, taking into account the possible influence of adverse environmental factors (radiation, air pollution, etc.). We used clinical and hematological data per patient and statistic information on these diseasis incidence in the region. RESULTS: An analysis of the oncohematological patients incidence structure, namely: acute lymphoblastic (C91.0) and myeloblastic leukemia (C92.0), chronic lymphocytic (C91.1) and myeloid (C92.1) leukemia, over 12 years in environmentally disadvantaged cities of Dnipropetrovsk region have been conducted. A comparative analysis of the incidence of these diseases among the population of 4 cities of the Dnipropetrovsk region was carried out, taking into account the possible influence of adverse environmental factors (radiation, air pollution, etc.). An excess of the incidence rates of the above-mentioned oncohematological diseases for the period 2006-2017 was revealed in the cities of Dnipro, Kryvyi Rih, Kamianske and Zhovti Vody, where environmental factors significantly affect the increase in morbidity due to pollution mainly by radioactive and chemical substances.

Risk of mortality and second malignancies in primary myelofibrosis before and after ruxolitinib approval.

BACKGROUND: Primary myelofibrosis (PMF) is associated with morbidity and mortality. Ruxolitinib gained US FDA approval for treatment of intermediate/high-risk PMF in November 2011. We evaluated differences in survival and second primary malignancy (SPM) incidence among US PMF patients in the years before and after ruxolitinib approval. METHODS: We conducted a retrospective study utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-18 database for PMF patients. We divided patients into five-year cohorts pre- (2007-2011) and post-ruxolitinib (2012-2016) approval and compared relative survival rates (RSRs) to the standard population and standardized incidence rates (SIRs) of SPMs between cohorts. RESULTS: We included 2020 patients diagnosed with PMF from 2007-2016 in this study. There was no difference in the four-year RSRs between cohorts (54 % vs. 57 %, p = 0.776). More patients developed SPMs in the post-ruxolitinib cohort (8% vs. 6%, p = 0.041). The majority of SPMs were hematologic with higher incidence of AML transformation in the post-ruxolitinib cohort (SIR 125.29 vs. 70.55). CONCLUSIONS: PMF prognosis remains poor in the years following ruxolitinib's approval. SPM incidence including AML transformation is higher in the years after approval. Further studies are needed to determine the true impact of ruxolitnib on population outcomes.

Long-term outcomes following the addition of granulocyte colony-stimulating factor-combined high-dose cytarabine to total body irradiation and cyclophosphamide conditioning in single-unit cord blood transplantation for myeloid malignancies.

An intensified myeloablative conditioning regimen, involving the addition of granulocyte colony-stimulating factor (G-CSF)-combined high-dose cytarabine (12 g/m2) to standard total body irradiation and cyclophosphamide, has been performed for adult patients with myeloid malignancies in single-unit cord blood transplantation (CBT) since 1998 in our institute. We update the results of CBT, as the first allogeneic hematopoietic cell transplantation after this conditioning regimen, in 169 patients with a median long-term follow-up of 10.4 years. The median age was 43 years (range, 16 to 59 years). Ninety-four patients (56%) were in non-remission at the time of CBT, and 124 patients (73%) were acute myeloid leukemia. The median cryopreserved cord blood total nucleated cell dose and CD34+ cell dose was 2.40 × 107/kg and 0.93 × 105/kg, respectively. The cumulative incidence of neutrophil recovery at 42 days was 94.4% (95% confidence interval [CI]: 88.6-97.3%). Among the whole cohort, 105 patients were still alive at the end of the study period. The cumulative incidences of relapse and non-relapse mortality at 10 years were 26.0% (95% CI: 19.5-33.0%) and 16.9% (95% CI: 11.4-23.4%), respectively. There was an overall survival probability of 62.5% (95% CI: 54.3-69.7%) at 10 years. Higher disease risk index alone significantly affected higher overall mortality (hazard ratio 2.21, P = 0.003) in multivariate analysis. These outcomes demonstrate that G-CSF-combined myeloablative conditioning could have favorable long-term remission rates for adult patients with myeloid malignancies undergoing single-unit CBT.

Treating Acute Leukemia During the COVID-19 Pandemic in an Environment With Limited Resources: A Multicenter Experience in Four Latin American Countries.

PURPOSE: The COVID-19 pandemic is a colossal challenge for global health; nonetheless, specific subgroups face considerably higher risks for infection and mortality. Among patients with malignant diseases, those with hematologic neoplasms are at a higher risk for poor outcomes. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and their short-term consequences in Latin America. METHODS: Multicenter, prospective, observational, cohort study including patients older than 14 years from 14 centers in four countries (Mexico, Peru, Guatemala, and Panama) who had a confirmed diagnosis of acute leukemia, and who were undergoing active treatment since the first COVID-19 case in each country until the cutoff on July 15, 2020. RESULTS: We recruited 635 patients. Treatment modifications because of the COVID-19 pandemic were reported in 40.8% of cases. The main reason for such modifications was logistic issues (55.0%) and the most frequent modification was chemotherapy delay (42.0%). A total of 13.1% patients developed COVID-19 disease, with a mortality of 37.7%. Several factors were identified as independently associated with mortality, including a diagnosis of acute myeloid leukemia (odds ratio 2.38 [95% CI, 1.47 to 3.84]; P < .001), while the use of telemedicine was identified as a protective factor (odds ratio 0.36 [95% CI, 0.18 to 0.82]; P = .014). CONCLUSION: These results highlight the collateral damage of COVID-19 in oncology patients.

Association of elevated vitamin B12 with oncohematological diseases in a cohort of 79,524 patients from Latvia.

AIM: Currently there are some large-scale studies of elevated total vitamin B12 in relation to diseases and their prognosis. Aim of this retrospective study was to determine association of increased B12 as an additional diagnostic marker of oncohematological diseases by a statistical analysis of clinical data of 79,524 patients. MATERIALS AND METHODS: Overall Latvian population representative data on B12  testing in 79,524 patients were obtained from laboratory database. The following exclusion criteria were applied: fluctuating B12 results within a three-month period, elevated (> 100 U/L) alanine transaminase or aspartate transaminase, hepatitis (HAV, HBV, and HCV) infection, reduced glomerular filtration rate (< 45 mL/min/1.73 m2). As a control group, individuals with normal B12 level and any oncologic diagnosis (solid cancer or hematological malignancies) were selected. RESULTS: After application of step-by-step exclusion filters, 1,373 patients were left with significantly increased level of plasma B12 (> 1,700 pg/mL). Odds ratios for oncohematological diseases in total and myeloid leukemia (including acute, chronic and unspecified) in patient group with elevated B12 were found to be 6.0 (95% CI 4.7-7.6; p < 0.0001) and 19.2 (95% CI 13.1-28.0; p <0.0001), respectively, as compared to the control group. CONCLUSION: Elevated total B12 could be considered as a potential marker for oncohematological disorders.

Second malignancies in patients treated for Ewing sarcoma: A systematic review.

The therapies used to treat Ewing sarcoma are associated with a risk of second malignant neoplasm (SMN). We conducted a systematic review to pool available evidence on the risks, types, and outcomes after SMN. We obtained 52 articles that met inclusion criteria. Cumulative incidence rates of SMN ranged from 0.9 to 8.4% and 10.1 to 20.5% at 5 and 30 years after initial diagnosis. Of the 327 reported SMNs, 63.6% were solid tumors, although acute myeloid leukemia /myelodysplastic syndrome was the single most commonly diagnosed SMN, with generally poor outcomes. Patients treated for Ewing sarcoma are at substantial risk of SMN, with a broad range of reported secondary cancers.

Myeloid malignancies-related somatic mutations in aging individuals.

We search for the presence of somatic mutations in 12 genes related to MDS, MPN, and AML in a Brazilian cohort composed of 609 elderly individuals from a census-based sample.

The incidence of hematological neoplasms morbidity on radiation-contaminated territories in Cherkasy region. / ZAKhVORIuVANIST' NA GEMATOLOGIChNI NOVOUTVORENNIa V RADIATsIY̆NO ZABRUDNENYKh REGIONAKh ChERKAS'KOÏ OBLASTI.

OBJECTIVE: The main goal was to analyze the incidence of the morbidity in 1980, 1989, 2001, 2014 years and the structures of the absolute number of hematopoietic and lymphoid neoplasms cases during the period 1980-2014 on radiation contaminated and not contaminated territories in Cherkasy region. MATERIALS AND METHODS: The epidemiological indecies of hematological neoplasms were analyzed on radiation con taminated and not contaminated territories in Cherkasy region during the period from 1980 to 2014. Referring the territory in Cherkasy region to radiation contaminated is based on settlements dosimetry certification of Ukraine after the Chornobyl accident. 63 settlements were enrolled to radiation contaminated areas in Cherkasy region and 11 settlements assigned as not contaminated areas. RESULTS: The first positions in the list of the hematological neoplasms structure and frequency among new cases during 1980-2014 on not contaminated territories in Cherkasy region occupied by lymphoid leukemia, Hodgkin's lymphoma and myeloid leukemia and on the radiation contaminated territories - chronic, acute lymphoid and myeloid leukemia and lymphoma, diffuse large cell lymphoma. In the structure of hematological neoplasms record ed on the contaminated territories in Cherkasy region, there is a smaller proportion of Hodgkin's lymphoma cases (C81) than 0.84 fold (RR = 0.84; 95 % CI = 0.75-0.93) and more than 1.15 times (RR = 1.15; 95 % CI = 1.02-1.30) other unspecified malignant lymphoid and hematopoietic neoplasms. In 2001 on the radiation contaminated terri tories in Cherkasy region increase the incidence of acute and chronic myeloid leukemia in 2.46 times (p = 0.024) observed compared to non contaminated areas there (5.30 per 100 000, 95% CI = 3.03-8.33 versus 2.15 per 100,000, 95 % CI = 0.66-3.64). It was calculated that RR of acute and chronic myeloid leukemia (C92) in 2001 on radiation contaminated areas in Cherkasy region is 1.40 (95 % CI = 1.12-1.17) and Hodgkin's lymphoma (C81) on condition ally clean areas Cherkasy region - 1.70 (95 % CI = 1.36-2.12).

Sepsis and Acute Myeloid Leukemia: A Population-Level Study of Comparative Outcomes of Patients Discharged From Texas Hospitals.

BACKGROUND: In the United States, approximately 750,000 cases of sepsis occur annually, and 28% to 50% of affected people die. Treatment is costly, often involving admission to the intensive care unit and prolonged hospitalization. We evaluated outcomes of patients with acute myeloid leukemia (AML) and sepsis in Texas. PATIENTS AND METHODS: We conducted a population-based cohort study of adults discharged from Texas hospitals during 2011, using ICD-9-CM codes and the Texas Inpatient Data Collection. RESULTS: A total of 2,173,776 adults were discharged from hospitals in Texas, and 5501 (0.25%) had a diagnosis of AML. Among patients with AML, 40% were ≥ 65 years old, and 52% were men. The rate of sepsis for AML patients was 16% compared to 4% for non-AML patients. Among patients with AML, sepsis was associated with pneumonia, acute renal failure, and hematologic dysfunctions in 34%, 32%, and 29% of discharges, respectively. Median length of stay, intensive care unit admission rate, and median hospital charges per stay for patients with AML and sepsis were 13 days (range, 1-133 days), 72%, and $122,333, respectively. Among in-hospital deaths due to sepsis, mortality was 30% in AML patients compared to 21% in non-AML patients. CONCLUSION: Patients with AML had a higher sepsis incidence and higher mortality rates overall, especially in relation to stem-cell transplant recipients and those with other types of cancer. Clinical trials are needed to determine whether early intervention or treatment in specialized centers could improve outcomes and reduce costs of care, particularly in the management of serious complications such as sepsis.

Spatial clustering of childhood leukaemia in Switzerland: A nationwide study.

The aetiology of childhood leukaemia remains largely unknown. Several hypotheses involve environmental exposures that could implicate spatial clustering of cases. The evidence from previous clustering studies is inconclusive. Most of them used areal data and thus had limited spatial resolution. We investigated whether childhood leukaemia tends to cluster in space using exact geocodes of place of residence both at the time of birth or diagnosis. We included 1,871 leukaemia cases diagnosed between 1985 and 2015 at age 0-15 years from the Swiss Childhood Cancer Registry. For each case, we randomly sampled 10 age and sex matched controls from national censuses closest in time. We used the difference of k-functions, Cuzick-Edwards' test and Tango's index for point data to assess spatial clustering and Kulldorff's circular scan to detect clusters. We separately investigated acute lymphoid leukaemia (ALL), acute myeloid leukaemia (AML), different age groups at diagnosis (0-4, 5-15 years) and adjusted for multiple testing. After adjusting for multiple testing, we found no evidence of spatial clustering of childhood leukaemia neither around time of birth (p = 0.52) nor diagnosis (p = 0.51). Individual tests indicated spatial clustering for leukaemia diagnosed at age 5-15 years, p k-functions = 0.05 and p Cuzick-Edwards' = 0.04 and a cluster of ALL cases diagnosed at age 0-4 years in a small rural area (p = 0.05). This study provides little evidence of spatial clustering of childhood leukaemia in Switzerland and highlights the importance of accounting for multiple testing in clustering studies.

Treatment results in children with myeloid leukemia of Down syndrome in Saudi Arabia: A multicenter SAPHOS leukemia group study.

Despite the high incidence of Down syndrome (DS) in Arab countires, the incidence and outcomes of myeloid leukemia of DS (ML-DS) have not been studied. We evaluated 206 pediatric acute myeloid leukemia (AML) patients diagnosed between 2005 and 2012 and identified 31 (15%) ML-DS. The incidence of ML-DS was 48 per 100,000 compared to 0.6 per 100,000 for AML in non-DS children. Thus, patients with DS had 80-fold increased risk of ML-DS compared to AML in non-DS children. The median age at diagnosis was 1.8 years, male/female ratio was 1.2, majority (84%) of patients had FAB-M7 subtype, and the cytogenetic abnormalities were normal karyotype (constitutional trisomy 21) in 48%, additional trisomy in 23%, and other aberrations in 29%. Complete remission, cumulative incidences of relapse (CIR), toxic-death, and 5-year event-free survival (EFS) rates were 96.8%, 19.4%, 13.1%, and 67.7±8.4%; respectively. In the present study, multivariate analysis revealed favorable outcome (5-year EFS 86.7±8.8%) for patients with normal karyotype. The incidence and clinical characteristics of ML-DS in Saudi patients were comparable to other reports. However, there is a need to optimize risk stratification and treatment intensity to reduce CIR and toxic death rates to further improve outcomes of patients with ML-DS.

[Myeloproliferative masks of multiple myeloma: A review of literature and clinical case reports]. / Mieloproliferativnye «maski¼ mnozhestvennoi mielomy (obzor literatury i opisanie klinicheskikh nabliudenii).

Concurrences of multiple myeloma with myeloproliferative diseases or secondary myeloid leukemoid reactions are rather rare. The paper describes 3 cases of multiple myeloma: the first case concurrent with neutrophilic leukocytosis; the second case with secondary erythropoetin-dependent erythrocytosis, and the third case with chronic myeloid leukemia. In such cases, an accurate diagnosis requires molecular testing, besides routine clinical and laboratory studies. The paper discusses therapeutic strategy in cases of a concurrence of 2 competing tumors of the blood system: to treat them simultaneously or the most aggressive tumor now, as well as a relationship between multiple myeloma and chronic myeloid leukemia, other myeloproliferative disorders, and secondary myeloid leukemoid reactions.

Pneumonia diagnosis in childhood and incidence of leukaemia, lymphoma and brain cancer: a Danish nationwide cohort study.

OBJECTIVES: There is an ongoing debate on the possible association between infections in early childhood and subsequent cancer risk, but it remains unclear if a hospital admission for infection is associated with risk of childhood cancer diagnosis. We examined if a hospital-based diagnosis of pneumonia was a clinical marker of the three most common childhood cancers. DESIGN: Population-based cohort study. SETTING: Denmark, hospital diagnoses, 1994-2013. METHODS: Using national health registries, we compared the observed incidence of leukaemia, lymphoma and brain cancer among 83 935 children with a hospital-based pneumonia diagnosis with that expected among children in the general population. We calculated absolute cancer risks and standardised incidence ratios (SIRs) as a measure of relative risk. RESULTS: The cancer SIRs were substantially increased during the first 6 months of follow-up; lymphoid leukaemia: 6.2 (95% CI 3.5 to 10.3); myeloid leukaemia: 14.8 (95% CI 6.0 to 30.6); Hodgkin's lymphoma: 60.8 (95% CI 26.2 to 120), non-Hodgkin's lymphoma: 15.9 (95% CI 5.2 to 37.2) and brain cancer: 4.4 (95% CI 1.9 to 8.7). The 6-month absolute risks of leukaemia, lymphoma and brain cancer were all low, reaching 0.05% when combined. An increased risk persisted beyond 5 years for non-Hodgkin's lymphoma and brain cancer. However, the 5-year absolute cancer risk was 0.14%. CONCLUSIONS: The short-term incidence of leukaemia, lymphoma and brain cancer was higher than expected and persisted beyond 5 years for non-Hodgkin's lymphoma and brain cancer. However, the absolute cancer risk was low.

Therapy-related myeloid neoplasms.

PURPOSE OF REVIEW: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis. RECENT FINDINGS: Fifteen percent of t-AML patients present with favorable risk fusion genes, whereas 50% have adverse cytogenetics. The most frequent molecular aberration in t-AML and t-MDS affects TP53 (33%). Selection of a pre-existing treatment-resistant hematopoietic stem cell clone with TP53 mutation has been shown as an important mechanism in the development of t-MNs and explains the high frequency of TP53 mutations in these patients. Following previous cytotoxic therapy, patients develop specific vulnerabilities, which become especially evident as high nonrelapse mortality of t-MN patients after allogeneic hematopoietic cell transplantation. SUMMARY: Patients are treated according to their genetic risk profile. Assessment of minimal residual disease helps to guide allogeneic transplantation for patients with favorable risk and genetic markers.

Cancer Incidence in Workers Exposed to Styrene in the Danish-reinforced Plastics Industry, 1968-2012.

BACKGROUND: Occupational exposure to styrene is widespread and has been suggested to be carcinogenic. The aim of this study was to investigate whether occupational exposure to styrene increases the risk of cancer, in particular lymphohematopoietic cancers. METHODS: We established a study population of 72,292 workers employed in 443 small and medium-sized companies producing reinforced plastics 1964-2007 by utilizing several national registries, expert assessment, and worker survey data. We identified incident cancer cases from 1968 to 2012 in the national Danish cancer registry and computed standardized incidence rate ratios (SIRs) with 95% confidence intervals (95% CI) based on national rates. RESULTS: Increasing SIRs of Hodgkin lymphoma, myeloid leukemia, and cancer of nasal cavities and sinuses were inconsistently associated with increasing duration of employment, early year of first employment, or styrene exposure probability. No such trends were observed for cancer of the esophagus, pancreas, lung, kidney, or urinary bladder, which have previously been associated with styrene exposure. Lung cancer showed an overall increased risk that decreased by duration of employment. CONCLUSION: Occupational styrene exposure may be associated with Hodgkin lymphoma, myeloid leukemia, and cancer of nasal cavities and sinuses. Further studies are needed to evaluate if the observed associations are likely to be causal.

[Leukemia cutis: clinical features of 27 mexican patients and a review of the literature]. / Leucemia cutis (LC): características clínicas de 27 pacientes mexicanos y una breve revisión de la literatura.

BACKGROUND: Leukemia Cutis (LC) consists in neoplastic leukocytic infiltration of the skin and is strongly associated with the presence of extramedullary disease and poor prognosis. However, there are few studies in the literature regarding this entity. We perform a retrospective study of 27 mexican patients in order to analyze the clinical features and prognosis of LC in Mexico, and a brief review of the literature. METHODS: Cases diagnosed as LC by skin biopsy were selected from the database of the Department of Dermatology of National Institute of Medical Science and Nutrition Salvador Zubirán. Cases were searched between the dates of January 1993 and December 2013. RESULTS: Twenty-seven cases which were histologically confirmed with cutaneous leukemic infiltrate were included. Of these patients 60% were male and the mean age at diagnosis was 42 yr (19 to 80 yr). The predominant tipe of LC was acute myeloid leukemia (AML) with 48% of the cases. Nodular neoformations were the main clinical manifestation with 63% of the cases. The mean interval between the diagnosis of LC and death was 10 months (CI 95%). CONCLUSIONS: The presence of LC is a marker of poor prognosis and can precede the relapse of systemic leukemia. Cutaneous infiltration may be the first or the only sign of progression, so doctors should be familiar with the clinical manifestations of this disease.

Reproductive outcomes after hydatiform mole and gestational trophoblastic neoplasia.

Gestational trophoblastic disease includes complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) and gestational trophoblastic neoplasia (GTN). Given the very high-curability rate of trophoblastic disease, the risk of further molar pregnancy after CHM or PHM as well as the risk of second primary tumors and fertility compromise after chemotherapy for GTN represent major concerns. The incidence of subsequent molar pregnancy ranges from 0.7 to 2.6% after one CHM or PHM, and is approximately 10% after two previous CHMs. Among patients who have received chemotherapy, there is an increased risk of myeloid leukemia which is mainly related to the cumulative dose of etoposide. Resumption of normal menses occurs in approximately 95% of women treated with chemotherapy, but menopause occurs 3 years earlier compared with those non-treated with chemotherapy. Term live birth rates higher than 70% without increased risk of congenital abnormalities have been reported in these women, and pregnancy outcomes are comparable to those of general population, except a slightly increased risk of stillbirth. Fertility-sparing treatment for placental site trophoblastic tumor is a therapeutic option reserved to highly selected, young women who do not present markedly enlarged uterus or diffuse multifocal disease within the uterus.