Acute Nonlymphocytic Leukemia Research Articles

Second primary cancer risks according to race and ethnicity among U.S. breast cancer survivors.

Breast cancer survivors have an increased risk of developing second primary cancers, yet risks by race and ethnicity have not been comprehensively described. We evaluated second primary cancer risks among 717,335 women diagnosed with first primary breast cancer (aged 20-84 years and survived ≥1-year) in the SEER registries using standardized incidence ratios (SIRs; observed/expected). SIRs were estimated by race and ethnicity compared with the racial- and ethnic-matched general population, and further stratified by clinical characteristics of the index breast cancer. Poisson regression was used to test for heterogeneity by race and ethnicity. SIRs for second primary cancer differed by race and ethnicity with the highest risks observed among non-Hispanic/Latina Asian American, Native Hawaiian, or other Pacific Islander (AANHPI), non-Hispanic/Latina Black (Black), and Hispanic/Latina (Latina) survivors and attenuated risk among non-Hispanic/Latina White (White) survivors (SIRAANHPI = 1.49, 95% CI = 1.44-1.54; SIRBlack = 1.41, 95% CI = 1.37-1.45; SIRLatina = 1.45, 95% CI = 1.41-1.49; SIRWhite = 1.09, 95% CI = 1.08-1.10; p-heterogeneity<.001). SIRs were particularly elevated among AANHPI, Black, and Latina survivors diagnosed with an index breast cancer before age 50 (SIRs range = 1.88-2.19) or with estrogen receptor-negative tumors (SIRs range = 1.60-1.94). Heterogeneity by race and ethnicity was observed for 16/27 site-specific second cancers (all p-heterogeneity's < .05) with markedly elevated risks among AANHPI, Black, and Latina survivors for acute myeloid and acute non-lymphocytic leukemia (SIRs range = 2.68-3.15) and cancers of the contralateral breast (SIRs range = 2.60-3.01) and salivary gland (SIRs range = 2.03-3.96). We observed striking racial and ethnic differences in second cancer risk among breast cancer survivors. Additional research is needed to inform targeted approaches for early detection strategies and treatment to reduce these racial and ethnic disparities.

Role of Radiation Therapy in Management of Isolated Myeloid Sarcoma: Report of a Case and Review of the Literature

Myeloid sarcoma is an infrequent extramedullary tumor originating from immature myeloid cells and is associated with acute non-lymphocytic leukemia or myelodysplastic syndrome. Recent years have seen advancements in the survival rates of leukemia patients, primarily attributed to a deeper comprehension of the genetic underpinnings of the disease and the development of more effective combinations of chemotherapy and targeted therapies. Notably, the ability to achieve lasting control over systemic disease within the blood and bone marrow has markedly contributed to improved survival rates. However, the emergence of extramedullary relapses can present challenging therapeutic situations, where radiation therapy emerges as a crucial intervention. In light of these considerations, we report the case of a 67-year-old patient, with a history of acute leukemia treated in 2019 in remission and who presents an extramedullary blast localization at the level of the left elbow treated locally by radiotherapy and we have conducted a comprehensive literature review aimed at evaluating the potential role of radiotherapy in managing this rare manifestation of leukemia.

Racial and ethnic disparities in risk of second primary malignancies among diffuse large B-cell lymphoma survivors.

7567 Background: Previous studies have shown an increased risk of second primary malignancies (SPMs) among diffuse large B-cell lymphoma (DLBCL) survivors; however, this has not been comprehensively examined by race/ethnicity. We utilized a large population-based database to examine disparities in SPM risk by race/ethnicity. Methods: From 17 United States population-based Surveillance, Epidemiology and End Results (SEER) program cancer registry areas, we identified 57,262 ≥12-month first-primary DLBCL survivors diagnosed between 2000-2019. Standardized incidence ratios (SIRs) and accompanying 95% confidence intervals (CIs) quantified SPM risk by race/ethnicity (non-Hispanic White, Black, Asian/Pacific Islander [API] and Hispanic), compared with the general population. Results: Overall, we observed 4,719 SPMs after DLBCL representing a 1.2-fold significantly increased risk (95% Confidence Interval [CI] = 1.16-1.23) compared to the general population and an excess of 23 cases per 10,000 person-years. SIRs for all second cancers combined varied significantly by race/ethnicity with APIs and Hispanics presenting higher overall SPM risk [SIRAPI: 1.42 (CI = 1.27-1.59), and SIRHispanic: 1.31 (CI = 1.19-1.43)] compared to the White or Black patients [SIRwhite: 1.17 (CI = 1.13-1.21), SIRBlack: 1.16 (CI = 1.03-1.30)] (p-heterogeneity &lt; 0.001). Heterogeneity by race/ethnicity in SIRs was even more pronounced in DLBCL survivors diagnosed at a younger age, those who were ≥5 years into their survivorship, those who had received chemotherapy, or those who had received no radiation as their initial treatment. Although SIRs for SPM was significantly higher for advanced stage DLBCL survivors (compared to those with a localized/regional disease), heterogeneity by race/ethnicity in SPM risk was significant regardless of the stage. Results from site specific analyses reported significantly higher overall SIRs for second hematological malignancies compared to solid cancers [SIRhemat: 3.52 (CI = 3.22-3.85), and SIRsolid: 1.08 (CI = 1.04-1.11)]. Patterns by race/ethnicity also varied significantly by second cancer type, particularly for second primary anal cancer, Hodgkin’s lymphoma (HL), and Acute Non-Lymphocytic Leukemia (ANLL) (p &lt; 0.001 for each). Strikingly elevated SPM risks (SIRs &gt; 10) were observed for second primary anal cancer, HL and ANLL among the Black patients, and HL among the APIs and Hispanic DLBCL survivors, compared to the white patients. Conclusions: Using a large-scale population-based data, we observed substantial disparities in SPM risk by race/ethnicity, with patients belonging to minority groups experiencing higher risks. SPMs have emerged as an important challenge for DLBCL survivors, therefore, further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.

Live birth in woman with premature ovarian insufficiency and 46, XY karyotype after chemotherapy and bone marrow transplant: a case report

BackgroundPremature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian function before the age of 40 years, characterized by elevated serum gonadotropin levels and decreased estrogen levels with menstrual disturbance. POI can be natural or iatrogenic such as after chemotherapy, radiotherapy and surgery.Case presentationIn this study, we describe a successful live birth in a 31-year-old woman with POI and 46, XY Karyotype after being treated with chemotherapy and bone marrow transplant (BMT) for acute non-lymphocytic leukemia when she was 17 years old. With amenorrhea or oligomenorrhea for 11 years, her serum level of FSH was up to 35.0 IU/L and 53.0 IU/L taken 4 weeks apart, which can be diagnosed as POI. After controlled ovarian stimulation treatment for three cycles with different protocols and frozen-thawed embryo transfer (FET), she finally got a successful pregnancy and had a live birth later.ConclusionsThis case report serves as a reminder that karyotype of peripheral blood may mislead the diagnosis as disorders of sex development (DSD). It also demonstrates that it is possible for a woman with chemotherapy and bone marrow transplant induced POI can have successful pregnancy and live birth with appropriate therapy. Furthermore, as age may plays a predominant role in fertility rather than residual ovarian reserve, active treatment may be concerned for women with POI at younger age.

CRISPR-gene-engineered CYBB knock-out PLB-985 cells, a useful model to study functional impact of X-linked chronic granulomatous disease mutations: application to the G412E X91+-CGD mutation.

Chronic granulomatous disease (CGD) is a rare primary immune disorder caused by mutations in one of the five subunits of the NADPH oxidase complex expressed in phagocytes. Two-thirds of CGD cases are caused by mutations in CYBB that encodes NOX2 or gp91phox. Some rare X91+-CGD point mutations lead to a loss of function but with a normal expression of the mutated NOX2 protein. It is therefore necessary to ensure that this mutation is indeed responsible for the loss of activity in order to make a safe diagnosis for genetic counselling. We previously used the X-CGD PLB-985 cell model of M.C. Dinauer obtained by homologous recombination in the original PLB-985 human myeloid cell line, in order to study the functional impact of such mutations. Although the PLB-985 cell line was originally described by K.A. Tucker et al. in1987 as a distinct cell line isolated from a patient with acute nonlymphocytic leukemia, it is actually identified as a subclone of the HL-60 cells. In order to use a cellular model that meets the quality standard for the functional study of X91+-CGD mutations in CGD diagnosis, we developed our own model using the CRISPR-Cas9 technology in a certified PLB-985 cell line from DSMZ-German Collection of Microorganisms and Cell Cultures. Thanks to this new X-CGD model, we demonstrated that the G412E mutation in NOX2 found in a X91+-CGD patient prohibits access of the electron donor NADPH to its binding site explaining the absence of superoxide production in his neutrophils.

Human Leukocyte Antigen-DP in Acute Nonlymphocytic and Acute Lymphoblastic Leukemia

Acute leukemias are characterized by the elonogenic proliferation&#x0D; &#x0D; of haemopoietic progenitor cells arrested in maturation. Clinical&#x0D; manifestations are related to the infiltration of the bone marrow and other&#x0D; tissues by the leukemic blasts.&#x0D; &#x0D; Peripheral blood mononuclear cell (PBMC) from luekemic patients&#x0D; (29)ANLL,(36)ALL and from normal donors(55)were typed for HLA-&#x0D; DP specificities using microlymphocytotoxicity assay.&#x0D; &#x0D; Results showed frequencies of DPw alleles in ANLL patients were&#x0D; not significantly different from controls ,exept that in DPw1 was absent&#x0D; .In contrast ,in ALL,frequencies of DPw2 and DPw5 were significantly&#x0D; increased (p&lt;0.05, relative risk (RR) = 1.95 and p&lt;0.01, RR=4.27,&#x0D; respectively.&#x0D; &#x0D; These results ,therefore ,demonstrate both positive negative&#x0D; associations between major histocompatibility complex (MHC) gene&#x0D; products which are in only very weak linkage with the rest of HLA ,and&#x0D; ALL,ANLL patients.The HLD-DP region could thus contain long sought&#x0D; – after genes influencing susceptibility and resistance to leukeemogenesis.

Efficacy Observation of Pre-Excitation Regimen in the Treatment of Refractory Relapsed Acute Non-Lymphocytic Leukemia

Objective: To explore the clinical effect of applying the pre-excitation regimen in the treatment of patients with refractory relapsed acute non-lymphocytic leukemia (ANLL). Methods: This research work was carried out in our hospital (Shaanxi Provincial People’s Hospital) from September 2021 to September 2022. A total of 50 cases were selected for this study, and all were given a pre-excitation treatment plan, mainly low-dose cytarabine, aclarithromycin, etoposide, granulocyte colony-stimulating factor, and more were implemented. The clinical intervention effect was then analyzed. Results: Among the 50 patients in this study, the results showed that the treatment was very effective for 22 cases, accounting for 44.00%; effective for 14 cases, accounting for 28.00%; and ineffective for 14 cases, accounting for 28.00%. The total rate of effectiveness was 72.00%. The hematopoietic system adverse reactions of the patients were mainly bone marrow suppression. All 50 patients had different degrees of blood count decline, among which some patients’ neutrophils were less than 0.5×109 /L. The median time was 7 days. Among them, 25 patients had infection problems, the incidence rate was 50.00%, the patient’s platelet count PLT &lt; 20 × 109/L, and the median time was 10 days. At the same time, among the 50 patients in this study, 34 (68.00%) patients had symptoms such as loss of appetite, nausea, vomiting, and fatigue, 17 (34.00%) patients showed hair loss, mildly elevated transaminases were observed in 8 (16.00%) patients, and 11 (22.00%) patients had muscle soreness. Conclusion: In the treatment of patients with refractory complex acute non-lymphocytic leukemia, the application of pre-excitation regimen has a significant effect, which can improve the adverse symptoms of patients, reduce the incidence of adverse reactions, and promote the recovery of patients.

Second Primary Malignancy in Waldenström Macroglobulinemia: Insights from a Population-Based Analysis

INTRODUCTION: Waldenström Macroglobulinemia (WM), is a hyper-viscosity syndrome characterized by unrestricted proliferation of lymphoplasmacytic precursors in the bone marrow and monoclonal IgM gammopathy. The development of secondary primary malignancy (SPMs) in WM is a multifactorial phenomenon; the indolent nature of the disease, associated immune dysregulation, environmental factors and therapeutic measures, are responsible for high incidence of SPM in WM. This study was conducted to analyse the site-specific incidence of SPM in WM using data from the US Surveillance, Epidemiology and End Results (SEER) cancer registries. METHODS: A retrospective study was conducted using the SEER-18 dataset. WM patients who were diagnosed between 2000 and 2018, according to the ICD-O-3 = 9761/3 were included. Patients diagnosed on autopsy or through death certificates, and patients with incomplete follow-up data were excluded. SPM was defined as other malignancy appearing at least 1 year after WM diagnosis. Latency was defined as interval between WM and SPM diagnosis. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated using SEER*Stat software (version 8.3.9). P-values and 95% confidence intervals (CI) were generated assuming Poisson distribution of observed incidence of SPM. RESULTS: A total of 4112 WM patients were identified. SPM was reported in 699 (17.0%) patients. The overall risk of developing SPM was significantly higher in WM patients as compared to the general population (SIR= 1.53, 95% CI=1.42-1.65, p <0.05) with an AER of 102.69 per 10,000 population. The risk of developing second primary solid tumors was significantly greater compared to the general population (SIR = 1.12, 95% CI= 1.02-1.23, p >0.05), but significantly increased risks were reported for secondary tumours of the lung and bronchus (SIR = 1.44), skin melanoma (SIR = 1.88), mouth (SIR 3.28), brain (SIR 2.73) and non-melanotic skin tumors (SIR = 4.09). The overall risk of developing secondary hematological malignancies was significantly increased (SIR = 4.95, 95% CI 4.31-5.66, p <0.05). Significantly increased risks were reported for nodal non-Hodgkin lymphoma (NHL) (SIR = 6.62), extranodal NHL (SIR = 11.3), acute lymphocytic leukemia (ALL) (SIR 8.04), acute non-lymphocytic leukemia (ANLL) (SIR = 4.2) and acute myeloid leukemia (AML) (SIR 4.22). Increased risk of SPMs was noted for patients with age 50-74 years (SIR= 1.65, 95%CI=1.44-1.89, p value <0.05) or > 75 years (SIR= 1.3, 95% CI= 1.13-1.49, p value <0.05), but not for patients younger than 50 years. Patients aged 50-74 years had a significantly increased risk of developing SPMs of lungs and bronchus (SIR 2.23), skin (SIR 3.09), vulva (SIR 8.5), thyroid (SIR 3.59), nodal NHL (SIR 6.06), extranodal NHL (SIR 11.87), ANLL (SIR 5.77) and AML (SIR 6.37). Patients aged >75 years had a significantly increased risk of developing SPMs of cecum (SIR 2.50), colon (SIR 1.62), soft tissues (SIR 5.25), nodal NHL (SIR 2.38), extranodal NHL (SIR 7.51), ANLL (SIR 3.69) and AML (SIR 3.63). Risk of SPM was significantly increased in both males (SIR 1.39) and females (SIR 1.59). On subsite evaluation, males had a significantly greater risk of SPMs involving lung and bronchus (SIR 1.71), soft tissues (SIR 4.52), skin (SIR 1.88), nodal NHL (SIR 3.85), extra-nodal NHL (SIR 6.9), ANLL (SIR 5.4) and AML (SIR 5.55). Females reported a significantly increased risk of SPM involving cecum (SIR 3.88), skin (SIR 2.87), vagina (SIR 11.51) nodal NHL (SIR 3.86) and extranodal NHL (SIR 13.57). The risk of SPM was significantly greater in Caucasians (SIR 1.46) but not African Americans or other races. The risk of SPM was significantly greater in patients at all latencies. The risk of SPM of cecum (SIR 2.76) and non-melanotic skin cancer (SIR 5.52) was significantly greater in patients with latency of 12-59 months, but not at subsequent latencies. The risk of melanotic skin cancer (SIR 2.61) was significantly greater in patients with latency of 60-119 months but not other latencies. The risk of thyroid cancer (SIR 6.43) was significantly increased for patients with latency 120+ months only. CONCLUSION: This study showed that 17% of WM patients developed SPM. WM patients were at a 53% greater risk of developing SPM compared to the general population. Caucasians and patients aged greater than 50 years were at particularly high risk of developing SPM. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Mixed-Lineage Leukemia

Introduction: Acute Leukemia with Mixed Lineage phenotype (MLL) is leukemia that consists of cells characterized by mixed lineage markers, both from myeloid and lymphoid cells. The incidence of this leukemia is only 2-5% of all acute leukemias and is considered to have a poor prognosis.Case Presentation: A seven-year-old girl was diagnosed with MLL. The results of immunophenotyping showed two blast populations with the expressions of CD33, CD34, HLA-DR, CD117, CD13, CD19, CD10, CD20, CyMPO, Cy CD79a, and morphological features of Acute Lymphoblastic Leukemia (ALL) and Acute nonLymphocytic Leukemia (AnLL) on bone marrow aspiration. The BCR-ABL examination showed the detected BCR-ABL p210 (Major breakpoint), the majority of which was found in chronic myeloid leukemia (CML) patients. There is no definite pathogenesis of BCR-ABL p210 (MBCR-ABL) in this patient. BCR-ABL can also present in 11–29% of ALL patients but is relatively rare in childhood ALL (1%–3%) and mostly expresses p190 (minor breakpoint (mBCR-ABL)). The p210 BCR-ABL transcript is detected in 30% of adults and 20% of childhood ALL patients with Philadelphia ALL. Conclusions: MLL with BCR-ABL p210 transcript is very rare in acute leukemia. Immunophenotyping tests can detect typical MLL profiles, and WHO has standardized the diagnosis for MLL.

CAGE regimen in the treatment of adult refractory acute non-lymphocytic leukemia

Objective: To observe the effect of CAGE regimen in the treatment of adult refractory acute non-lymphocytic leukemia. Methods: In this experiment, 86 adult patients with refractory acute non-lymphocytic leukemia who were treated between January 2018 and January 2022 were selected as experimental subjects and were divided into two groups, the observation group and the control group, according to different treatment methods, with 43 patients in each group. The observation group was treated with the CAGE regimen, whereas the control group was treated with conventional therapy. The disease remission rate and incidence of adverse reactions were observed. Results: The comparison of disease remission rates between the two groups showed that there was no significant difference in the results of the first course of treatment and the second course of treatment between the two groups (P &gt; 0.05), but the incidence of adverse reactions in the observation group was lower than that in the control group (P &lt; 0.05). Conclusion: The CAGE regimen has a significant therapeutic effect in the treatment of adult refractory acute non-lymphocytic leukemia. It improves the treatment advantage of patients during the treatment process, thus alleviating the condition of patients and improving their quality of life.

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.

Mortality of 196,826 Men and Women Working in U.S.-Based Petrochemical and Refinery Operations: Update 1979 to 2010.

To describe mortality trends of men and women working in various petrochemical and refinery operations of a U.S.-based company. The cohort consists of full-time employees with at least 1 day of service during 1979 through 2010. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated for 111 possible causes of death studied. SMRs for malignant mesothelioma and asbestosis were highest for the 1940s decade of hire. Increased SMRs were observed for malignant melanoma and motor neuron disease with no obvious work patterns. Decreasing mortality patterns were observed for aplastic anemia and acute nonlymphocytic leukemia. Mortality surveillance of this large established cohort aids in assessing the chronic health status of the workforce. Identifying methods for incorporating job-exposure matrices and nonoccupational risk factors could further enhance interpretations for some findings such as motor neuron disease.

Risks of subsequent primary cancers among breast cancer survivors according to hormone receptor status

This study was aimed at examining the risks of subsequent primary cancers (SPCs) among breast cancer survivors by hormone receptor (HR) status and age at diagnosis. Data from 12 Surveillance, Epidemiology, and End Results registries were used to identify 431,222 breast cancer survivors (at least 1 year) diagnosed between the ages of 20 and 84 years from 1992 to 2015. Risks of SPCs were measured as the standardized incidence ratio (SIR) and the excess absolute risk (EAR) per 10,000 person-years. Poisson regression was used to test the difference in SIRs by HR status. In comparison with the general population, the risk of new cancer diagnoses among survivors was 20% higher for those with HR-positive cancers (SIR, 1.20; 95% confidence interval [CI], 1.19-1.21; EAR, 23.3/10,000 person-years) and 44% higher for those with HR-negative cancers (SIR, 1.44; 95% CI, 1.41-1.47; EAR, 45.2/10,000 person-years), with the risk difference between HR statuses statistically significant. The higher risk after HR-negative cancer was driven by acute nonlymphocytic leukemia and breast, ovarian, peritoneal, and lung cancers. By age at diagnosis, the total EAR per 10,000 person-years ranged from 15.8 (95% CI, 14.1-17.5; SIR, 1.11) among late-onset (age, 50-84 years) HR-positive survivors to 69.4 (95% CI, 65.1-73.7; SIR, 2.24) among early-onset (age, 20-49 years) HR-negative survivors, with subsequent breast cancer representing 73% to 80% of the total EAR. After breast cancer, the greatest EARs were for ovarian cancer among early-onset HR-negative survivors, lung cancer among early- and late-onset HR-negative survivors, and uterine corpus cancer among late-onset HR-positive survivors. Risks of SPCs after breast cancer differ substantially by subtype and age. This suggests that more targeted approaches for cancer prevention and early-detection strategies are needed in survivorship care planning.

Treatment of Poor Risk Acute Leukemia With Sequential High-Dose ARA-C and Asparaginase

Resistance of leukemia cells to cytosine arabinoside (ARA-C) may be due to any one or combination of biochemical processes, which in certain instances may be substantially reversed by an appropriate increase in ARA-C dosage. Based on these and other laboratory observations indicating pharmacologic synergy between sequential high-dose ARA-C and asparaginase (HiDAC----ASNase), a therapeutic program was developed for the treatment of patients with acute nonlymphocytic leukemia (ANLL) refractory to conventional doses of ARA-C, as well as patients with high risk ANLL and advanced acute lymphocytic leukemia (ALL). Treatment consisted of 3-hr intravenous infusions of 3 g/sq m of ARA-C given at 12-hr intervals for 4 doses, followed by 6,000 IU/sq m ASNase given i.m. at hour 42. The same schedule was repeated on day 8. In 32 induction attempts, only 4 patients proved to be truly refractory, i.e., failed to achieve substantial leukemia cell cytoreduction. Complete remissions were achieved with HiDAC---- ASNase in 9 of 13 patients with refractory ANLL, 6 of 9 patients with antecedent hematologic disorders, and 3 of 10 patients with advanced ALL. These include 9 of 14 patients who had either failed induction or who had relapsed on active ARA-C therapy and 6 of 8 patients who had had no prior exposure to ARA-C. The median duration of unmaintained remission in ANLL was 5 mo. In a patient with central nervous system (CNS) leukemia, there was clearance of cerebral spinal fluid (CSF) blasts without intrathecal therapy, suggesting a role for HiDAC in CNS prophylaxis. In general, toxicity was tolerable and reversible. These data suggest that HiDAC----ASNase is an exceptionally effective and well tolerated regimen in leukemic patients with antecedent hematologic disorders and in those refractory to conventional doses of ARA-C.

Comparison of Three Remission Induction Regimens and Two Postinduction Strategies for the Treatment of Acute Nonlymphocytic Leukemia: A Cancer and Leukemia Group B Study

Patients with acute nonlymphocytic leukemia were randomized to receive remission induction therapy consisting of seven days of cytosine arabinoside and three days of daunorubicin (“7 + 3”) or to receive the same regimen intensified by either the addition of 6-thioguanine or by extension of the administration of cytosine arabinoside to ten days. Additionally, all patients were randomized to receive or not to receive cotrimoxazole antibacterial prophylaxis during the remission induction phase. Neither an increase in intensity of chemotherapy nor the antibacterial prophylaxis increased the remission rate above the 53% for patients treated with the standard “7 + 3” regimen. The second part of this study addressed the issue of the utility of long-term maintenance chemotherapy. To this end, patients were randomized to discontinue all treatment after 8 months of maintenance chemotherapy or to continue maintenance therapy for a total of 3 years. Although there was a transient increase in the relapse rate for patients who discontinued therapy, the proportion of long-term remitters was identical in the two patient groups. Additionally, there is a suggestion of a survival advantage for patients randomized to discontinue all therapy at 8 months.

Interleukin-4 and Interleukin-5 Map to Human Chromosome 5 in a Region Encoding Growth Factors and Receptors and Are Deleted in Myeloid Leukemias With a del(5q)

Interleukin-4 (IL-4) is a potent mediator of growth and differentiation of cells of several hematopoietic lineages. Interleukin-5 (IL-5) is a lineage-specific hematopoietic growth factor that stimulates the production of eosinophils and eosinophil colonies from normal human bone marrow cells. By using somatic cell hybrids and in situ chromosomal hybridization, we localized the IL-4 and IL-5 genes to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the IL-4 and IL-5 genes were found to be deleted in the 5q- chromosome of four patients with refractory anemia (RA) or therapy-related acute nonlymphocytic leukemia (t-ANLL), who had a del(5q). Thus a small segment of chromosome 5 contains IL-4, IL-5, IL-3, and GM-CSF as well as other genes such as CD14 and EGR1. Our findings that each of these genes was deleted in the 5q- chromosome suggest that loss of function of one or more of these genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).

Nonrandom Chromosomal Abnormalities in Acute Nonlymphocytic Leukemia in Patients Treated for Hodgkin Disease and Non-Hodgkin Lymphomas

Chromosomal analyses of myeloid cells were performed on ten patients who had acute nonlymphocytic leukemia (ANLL) following treatment for malignant lymphoma. Seven patients had Hodgkin disease and three had non-Hodgkin lymphoma, poorly differentiated lymphocytic type. Six patients were treated with radiotherapy and chemotherapy; two had radiotherapy only, and two chemotherapy only. The median time between diagnosis of lymphoma and subsequent leukemia was 58 mo. Four patients had the blast phase of a myeloproliferative syndrome, four had acute myelogenous leukemia, one had acute promyelocytic leukemia, and the tenth, erythroleukemia. None of four patients whose leukemia was treated with intensive chemotherapy responded. Every patient had an abnormal karyotype. Seven of the patients showed hypodiploid cell lines, two a pseudodiploid, and one a hyperdiploid cell line. Cells from every patient except one were lacking a B chromosome; in eight, this could be identified as a No. 5. Five of nine patients were lacking a No. 7. Loss or rearrangement of No. 17 was found in four and of Nos. 6 or 8 in three patients. Many of the karyotypes were bizarre, with marker chromosomes and minute chromosomes. The karyotypic pattern seen in these patients showed no correlation with the nature of the originalmore » lymphoma, the type of leukemia, or the therapy used. The chromosomal pattern of hypodiploid cell lines found in ANLL that arose de novo was similar to that occurring in treated lymphoma. However, in ANLL de novo, less than half of the patients had fewer than 46 chromosomes, and less than 10% had fewer than 45 chromosomes. In this study, 70% of the patients had fewer than 46 and 40% had fewer than 45 chromosomes. The critical question thus concerns the factors, as yet unknown, that predispose to the development of hypodiploid modal numbers in ANLL in lymphoma.« less

Fluorescence In Situ Hybridization: A Sensitive Method for Trisomy 8 Detection in Bone Marrow Specimens

Trisomy 8 is a common anomaly in bone marrow (BM) cells of patients with myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), or acute nonlymphocytic leukemia (ANLL). We studied the efficacy of fluorescence in situ hybridization (FISH) detection of trisomy 8 in patients with MPD, MDS, or ANLL using directly labeled fluorescent alpha-satellite and whole chromosome paint (WCP) DNA probes specific for chromosome 8. Using FISH, we analyzed interphase nuclei and metaphase spreads from randomized series of BM specimens from normal individuals and patients with varying proportions of trisomy 8 as determined by conventional cytogenetic analysis. The BM of all normal donors contained less than or equal to 2.0% nuclei with 3 interphase FISH signals and less than or equal to 1 metaphase with 3 WCP FISH signals. Ninety-five percent and 98% of BM specimens with at least two metaphase cells with trisomy 8 by cytogenetic analysis contained greater than 2.0% nuclei with 3 interphase FISH and greater than 2 metaphases with 3 WCP FISH signals, respectively. Thirteen patients had 1 in 20 or 1 in 30 metaphase cells with trisomy 8 by conventional cytogenetic studies. Of these patients, four had greater than 2.0% nuclei with 3 interphase FISH signals. The BM of all four patients contained positive metaphase FISH results. We then studied the usefulness of FISH analysis to detect occult trisomy 8 by analyzing BM nuclei from 144 patients who had MPD, MDS, or ANLL and either 20 normal metaphase cells or an abnormal karyotype without trisomy 8. Seven patients had greater than 2.0% nuclei with 3 interphase FISH signals (range, 2.10% to 3.40%) and six patients had 2 or more cells with trisomy 8 upon metaphase FISH or extensive conventional cytogenetic analysis. Our results show that interphase and metaphase FISH analyses are useful methods to detect trisomy 8 cells in BM specimens, especially for specimens with normal or uncertain conventional cytogenetic results.

Cyclin A1 Expression in Leukemia and Normal Hematopoietic Cells

Human cyclin A1 is a newly cloned, tissue-specific cyclin that is prominently expressed in normal testis. In this study, we showed that cyclin A1 was highly expressed in a subset of leukemia samples from patients. The highest frequency of cyclin A1 overexpression was observed in acute myelocytic leukemias, especially those that were at the promyelocyte (M3) and myeloblast (M2) stages of development. Cyclin A1 expression was also detected in normal CD34(+) progenitor cells. The expression of cyclin A1 increased when these cells were stimulated to undergo myeloid differentiation in vitro. Taken together, our observations suggest that cyclin A1 may have a role in hematopoiesis. High levels of cyclin A1 expression are especially associated with certain leukemias blocked at the myeloblast and promyelocyte stages of differentiation.

Expressing of linc-223 and miR-125a in Patients with Acute Leukemia and Its Clinical Significance

To determine the expression level of linc-223 and miR-125a in the patients with adult acute leukemia (AL) and explore the relationship between the expression level and the occurrence, development, prognosis of leukemia. Bone marrow samples of 93 patients with AL treated in our hospital from January 2017 to September 2017 were enrolled, including 21 cases of acute lymphoblastic leukemia (ALL) and 72 cases of acute non-lymphocytic leukemia (ANLL). At the same time, bone marrow samples from 20 cases of non-malignant hematopathy patients in the same period were enrolled as control group. Real-time quantitative PCR (qRT-PCR) was used to test the expression level of linc-223 and miR-125a in bone marrow of 93 AL patients and the relationship between the level and the occurrence, development, prognosis of leukemia was analyzed. There was no significant difference in the expression of linc-223 between AL patients (ANLL and ALL) and control group (P>0.05). Moreover, there was no significant correlation between linc-223 and PML-RARα gene or the remission rate of patients after treatment. The expression of miR-125a in ANLL patients was significantly lower than those in the control group (P<0.01), but there was no significant difference between the initial treatment, recurrence and remission group (P>0.05), and also for ALL and control group (P>0.05). In the newly treatment ANLL patients, the expression level of miR-125a showed negatively correlated with LDH level and the ratio of immature cells (r=-0.454, r=-0.400), but not with sex, degree of risk, peripheral blood leukocyte count, platelet count, hemoglobin content, WT1, CRP, etc. (P>0.05). There was a positive correlation between linc-223 and miR-125a in ANLL patients (r=0.296). No abnormal expression of linc-223 was found in the bone marrow of AL patients, but miR-125a expression shows a low level and positively correlate with the expression level of linc-223 in ANLL, which is helpful for the diagnosis.