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Background: The increase in the incidence of malignancies globally, and the increase in the usage frequency and types of new anti-cancer drugs, have made onconephrology more important in our clinical practice. Paraneoplastic glomerulonephritis constitutes an important part of this approach as well. Purpose: The association of AML-nephrotic syndrome is relatively less defined in the literature compared to other hematological malignancies. Case presentation: In this article, we present a case of acute myelocytic leukemia in a patient who was diagnosed with minimal change disease many years ago. Discussion and Conclusion: Hematological malignancies-MCD association, is one of the best described examples of paraneoplastic glomerulonephritis. We know that cancer can be clinically diagnosed years after the detection of renal disease in paraneoplastic glomerulonephritis. In this case; rationality of follow-up, not only during the diagnosis of glomerulonephritis but also periodically in the long term, especially in clinical situations such as MCD that occur in geriatric patients, should be discussed.
Introducción: El aumento en la incidencia de neoplasias malignas a nivel mundial, y el aumento en la frecuencia de uso y tipos de nuevos medicamentos contra el cáncer, han hecho que la onconefrología sea más importante en nuestra práctica clínica. Asimismo, la glomerulonefritis paraneoplásica también constituye una parte importante de este enfoque. Propósito: La asociación de LMA-síndrome nefrótico está relativamente menos definida en la literatura a comparación de otras neoplasias malignas hematológicas. Presentación del caso: En este artículo presentamos un caso de leucemia mielocítica aguda en un paciente al que se le diagnosticó enfermedad de cambios mínimos hace años. Discusión y Conclusión: La asociación de neoplasias hematológicas malignas-MCD, es uno de los ejemplos mejor descritos de glomerulonefritis paraneoplásica. Sabemos que el cáncer puede diagnosticarse clínicamente años después de la detección de la enfermedad renal en la glomerulonefritis paraneoplásica. En este caso, debe discutirse la racionalidad del seguimiento, no solo durante el diagnóstico de glomerulonefritis, sino también periódicamente a largo plazo especialmente en situaciones clínicas como la ECM que se presenta en pacientes geriátricos.
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The study was conducted to characterize the pharmacokinetics, distribution, metabolism and excretion of CHMFL-FLT3-122 after a single oral dose of 50 mg·kg-1 [14C] labeled CHMFL-FLT3-122 in rats. Isotope tracing techniques were used to analyze drug concentration and identify the distribution of drugs in tissues and metabolites in biological samples. The experiments were approved by the Animal Ethics Committee of XenoBiotic Laboratories-China, Inc. The absolute bioavailability in male and female rats were 45.83% and 50.92% respectively. The parent drug and its metabolites were extensively distributed in the stomach, intestine, liver and lung, and were eliminated completely in 48 h. The majority of radioactivity was excreted through the feces at 92.34% of the dose with a small fraction through urine at 3.99% of the dose. The parent drug was the most significant circulating component, representing 49.23% and 70.65% over the 0-48 h collection time interval in the plasma of male and female. Two major metabolites, M553 (sulfate conjugate) and M457 (N-dealkyl product), were identified in plasma. Metabolites of CHMFL-FLT3-122, including ten phase I and four phase II metabolites, were identified. The metabolic pathways of CHMFL-FLT3-122 were proposed as N-dealkylation, oxidation, amide hydrolysis, sulfate conjugation, and glucuronic conjugation.
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Objective: To explore the mechanism of 3-hydroxymethyl-3-methylglutaryl-CoA synthase 1 (HMGCS1) on drug sensitivity of acute myelocytic leukemia (AML) HL-60 cells. Methods: HL-60 cells were cultured. The negative control group and the HMGCS1 overexpressed group were constructed by infecting the negative control lentivirus and HMGCS1 lentivirus,and the untreated HL-60 cells were set as the blank control group. Real-time quantitative PCR (qPCR) was used to detect the expression of HMGCS1 mRNA in the 3 groups,and to verify whether the cell lines of the HMGCS1 overexpressed group were successfully constructed. The effect of HMGCS1 on the expression of AKT and phosphorylated AKT (p-AKT) in phosphatidylinositol 3 kinase (PI3K) / protein kinase B (PKB / AKT) signaling pathway was detected by Western blotting. CCK8 method was used to detect the effects of HMGCS1 and PI3K/AKT signaling pathway inhibitor LY29400 on the activity of HL-60 cells. The effect of LY29400 on HMGCS1 expression was detected by qPCR and Western blotting. Results: Compared with the negative control group,the HMGCS1 mRNA expression was increased significantly in the HMGCS1 overexpressed group (P=0.000). Compared with the blank control group and the negative control group,the p-AKT protein level in the HMGCS1 overexpression group was significantly increased,while the AKT expression of the 3 groups was not significantly different. CCK8 method showed that compared with the blank control group and the negative control group,HMGCS1 could reduce the effect of adriamycin on cell viability in the HMGCS1 overexpressed group (P=0.003,P=0.006),while LY294002 could inhibit the effect produced by HMGCS1 (P=0.000). The intervention of LY294002 could reduce the expression levels of HMGCS1 and p-AKT protein and HMGCS1 mRNA (both P=0.000) in the negative control group and the blank control group. Conclusion: HMGCS1 can reduce the sensitivity of HL-60 cells to chemotherapy drug adriamycin,while PI3K/AKT signaling pathway inhibitor LY294002 can restore its sensitivity.
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PURPOSE: Parents caring for children with leukemia experience a tremendous challenge to get positive results in overcoming traumatic events with their children. The purpose of this study was to identify predictors of posttraumatic growth in parents of children with leukemia. METHODS: One hundred thirty seven parents (117 mothers and 20 fathers) of children with leukemia participated this study from May to August in 2016. Participants completed self-report measures of posttraumatic growth, core belief, deliberate rumination, resilience and social support. RESULTS: All the variables were positively correlated with posttraumatic growth. Core belief, resilience and social support were significant predictors related to posttraumatic growth in parents of children with leukemia and explained for 54% of the variance in posttraumatic growth. CONCLUSION: The results show that there are several factors affecting posttraumatic growth in parents of children with leukemia. Therefore, nursing intervention programs including strengthening resilience, revising core belief as well as utilizing social support systems should be provided for this population in order to enhance positive psychological change beyond parental traumatic events related to children with leukemia.
Subject(s)
Child , Humans , Leukemia , Leukemia, Myeloid, Acute , Mothers , Nursing , Parents , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Stress Disorders, Post-TraumaticABSTRACT
Midostaurin is an orally administered inhibitor of multiple tyrosine kinase receptors developed by Novartis Pharmaceuti-cals. In May 2017,it was approved in the USA for the treatment of adult patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3) mutation-positive acute myeloid leukaemia (AML). Its pharmacokinetics,pharmacodynamics,clinical trials,adverse effects and drug interactions were introduced in the paper.
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Objective To investigate the relationship of the MTHFRC677T,MTHFRA1298C,and MTRRA66G gene polymorphisms with acute myelocytic leukemia (AML).Methods Mononuclear cells were collected from 63 patients diagnosed with AML,and 60 healthy,non-AML control-group patients.DNA extracted from each sample was screened for the MTHFRC677T,MTHFRA1298C,and MTRRA66G polymorphisms.Results No significant difference was observed in the distribution of the MTHFRC677T,MTHFRA1298C,and/or MTRRA66G polymorphisms between the two patient groups.In contrast,the MTRR G allele was observed to occur 1.935 times more frequently than the MTRR an allele (x2 =4.708,P ＜ 0.05,95％ CI:1.061-3.530).No significant difference was observed in the distribution of a combination of the three gene polymorphisms (MTHFRC677T,MTHFRA1298C,and MTRRA66G)between the AML and the control group.Conclusion The results of the present study suggest that the MTHFRC677T,MTHFRA1298C,and MTRRA66G polymorphisms are not associated with AML.
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Objective To explore the alterations, relationship and clinical significance of CD4 +CD25 +CD127 low/ - regulatory T cells ( Treg ) and lymphocyte subsets in peripheral blood of patients with acute myelocytic leukemia ( AML) . Methods The level of peripheral blood lymphocyte subsets and Treg of untreated AML patients and com-plete remission( CR) patients were tested by flow cytometry,and were compared with that of 30 normal controls. Re-sults The proportions of Treg were much higher in untreated AML patients and CR patients than in normal con-trols, while the mean proportion of Treg in untreated AML patients was higher than that in CR patients(P<0. 05). The proportions of NK( CD3 -CD16 +CD56 +) cells in untreated AML patients and CR patients were both decreased compared with normal controls,and the mean proportion of NK cells in untreated AML patients was lower than that in CR patients(P<0. 05). Compared with the normal controls,the proportions of CD3 +T cell, CD4 +T cell,and the ratio of CD4 +/CD8 + decreased in untreated AML patients ( P <0. 05 ) , but the proportions of CD8 +T cell was higher than in normal controls;the proportions of CD3 +T cell, CD4 + T cell, CD8 +T cell and the ratio of CD4 +/CD8 + in CR patients were close to the proportions in normal controls, but there was significant difference between CR patients and untreated AML patients(P<0. 05). Conclusion The increase of Treg, CD8 +T cell and decrease of NK cells, CD3 +T cell, CD4 +T cell, and the ratio of CD4 +/CD8 + in peripheral blood of patients with AML in-dicate that the immune function of patients with AML is depressed. Treg control the immune response of CD8 +T cells,at the same time inhibit the natural immune response of NK cells, playing a major role in the disorders of CD4 +T cells and CD8 +T cell balance,and closely relate with the development of AML. The immune treatment of patients with AML will be optimised by reducing the amount of Treg or removing the suppression function.
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Granuloma annulare is a granulomatous disorder of the dermis and subcutaneous tissue, with different clinical types. Generalized granuloma annulare is a rarely encountered clinical entity. We describe a 60-year-old woman with a 4-month history of generalized annular lesions. She had a history of myelocytic leukemia and chronic hepatitis B virus infection. To date, both acute myelocytic leukemia and hepatitis B virus infection have been described independently in association with generalized granuloma annulare but have never been described together in association with generalized granuloma annulare. Probable etiological causes of granuloma annulare are discussed in our patient.
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Objective To explore the apoptotic effect of Eqi compound prescription (contained-herb serum) on cute myelocytic leukemia HL-60 cell, which is relative to intracellular Ca2+, Caspase-3 and Bcl-2. Methods According to serum pharmacology, HL-60 cells were exposed to 10% concentrations of contained-herb serum for 24, 48, 72 and 96 hours respectively. Cells were observed under a fluore-scence microscope. SubG1 DNA was examined by flow cytometer. Intracellular Ca2+ concentration was measured by fura-2 fluorescence load method. Caspase-3 enzymatic activity were measured by colorimetry. Bcl-2 gene expression were measured by LSAB. Results The contained-herb serum could induce apoptosis of HL-60 cells. Intracellular Ca2+ concentration of treatment with Eqi was higher evidently than that of control (P
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Cutaneous granulocytic sarcoma are rare extramedullary tumor composed of immature leukemic cells of the myeloid series. It has a characteristic greenish color caused by myeloperoxidase in the granulocytic cells. 58-year-old female patient who had been diagnosed as acute myelocytic leukemia presented multiple, variable sized, tender brown-pigmented nodules, papules and plaques on the abdomen and both upper extremities for about 4 weeks. An incision biopsy of the large subcutaneous nodule on her abdomen showed a dense dermal infiltrate of immature myeloblastic cells with pleomorphic hyperchromatic vesicular nuclei and conspicuous nucleoli. A punch biopsy of the other small papule on her abdomen showed an infiltrate of granulocytic cells with round hyperchromic nuclei and granular acidophilic cytoplasm, between the dermal collagen bundles. We present a case of the cutaneous granulocytic sarcoma (chloroma) with coexistent leukemia cutis in acute myelocytic leukemia developed from myelodysplastic syndrome.
Subject(s)
Female , Humans , Middle Aged , Abdomen , Biopsy , Collagen , Cytoplasm , Granulocyte Precursor Cells , Leukemia , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Peroxidase , Sarcoma, Myeloid , Upper ExtremityABSTRACT
Cutaneous granulocytic sarcoma are rare extramedullary tumor composed of immature leukemic cells of the myeloid series. It has a characteristic greenish color caused by myeloperoxidase in the granulocytic cells. 58-year-old female patient who had been diagnosed as acute myelocytic leukemia presented multiple, variable sized, tender brown-pigmented nodules, papules and plaques on the abdomen and both upper extremities for about 4 weeks. An incision biopsy of the large subcutaneous nodule on her abdomen showed a dense dermal infiltrate of immature myeloblastic cells with pleomorphic hyperchromatic vesicular nuclei and conspicuous nucleoli. A punch biopsy of the other small papule on her abdomen showed an infiltrate of granulocytic cells with round hyperchromic nuclei and granular acidophilic cytoplasm, between the dermal collagen bundles. We present a case of the cutaneous granulocytic sarcoma (chloroma) with coexistent leukemia cutis in acute myelocytic leukemia developed from myelodysplastic syndrome.
Subject(s)
Female , Humans , Middle Aged , Abdomen , Biopsy , Collagen , Cytoplasm , Granulocyte Precursor Cells , Leukemia , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Peroxidase , Sarcoma, Myeloid , Upper ExtremityABSTRACT
BACKGROUND: Post remission therapy is one of the most important issues in the treatment of acute myelocytic leukemia (AML). Recently, autologous peripheral blood stem cell transplantation (PBSCT) has become an accepted procedure to support high dose chemotherapy in children with AML. But collection of PBSC from small pediatric patients provides many challenges not faced when collecting from adult patients. Therefore, the efficient procedures and optimal timing to perform the leukapheresis should be decided. The goal of the present study was to evaluate the practice of PBSC mobilization and collection and establish predictors of the leukapheresis in children with AML. METHODS: From November 1995 to February 1998, PBSC mobilizations were performed in 15 patients with AML. PBSCs were mobilized by high dose of cytosine arabinoside and etoposide plus G-CSF. CBC and peripheral blood smear were performed daily after WBC nadir. Leukapheresis was started when the WBC count recovered to 1,000/microliter from myelosuppression and monocytes appeared on the peripheral blood smear. Leukapheretic products were assayed for mononuclear cells, CD34+ cells and CFU-GM colonies. Correlations between the yields of leukapheresis and patients characteristics were evaluated by Wilcoxon rank sums test and Pearson correlation analysis. RESULTS: Eighteen mobilizations were done in 15 patients. The duration of absolute neutrophil count or = 3,000/microliter/day) during recovery was independent variable correlated to the peak MNCs, average MNCs, peak CD34+ cells and average CD34+ cells (P<0.01). CONCLUSIONS: Mobilization procedures using high dose cytosine arabinoside and etoposide plus G-CSF are tolerable and the leukapheresis can be initiated when WBC count recovers to 1,000/microliter from myelosuppression and monocytes appear on the peripheral blood smear. Sufficient numbers of PBSC can be obtained by three leukapheresis procedures without serious adverse effects in children with AML.
Subject(s)
Adult , Child , Humans , Blood Platelets , Cytarabine , Drug Therapy , Etoposide , Fever , Granulocyte Colony-Stimulating Factor , Granulocyte-Macrophage Progenitor Cells , Leukapheresis , Leukemia, Myeloid, Acute , Monocytes , Neutrophils , Peripheral Blood Stem Cell Transplantation , Sepsis , Stem CellsABSTRACT
Monosomy 7 syndrome is a rare myeloproliferative disorder of children, and has a clinical presentation similar to JCML. Both syndromes present in children younger than 2 years of age. Pallor, lymphaenopathy, hepatosplenomegaly, recurrent infection, facial rash and petechial bleeding are frequently present. The hematologic picture is characterized by leukocytosis with monocytosis, anemia, thrombocytopenia. It is important to distinguish these two disorders because of their different natural courses. The course of JCML is brief, with most patients dying within 9 months. Patients with monosomy 7 syndrome often present initially with repeated bacterial infections and develop AML after a latent period of 3~6 years. We report a case of monosomy 7 syndrome with typical clinical course in a 3-year-old male patient. The patient experienced a malignant transformation into AML. To our knowledge, this is the first case report of malignant transformation in monosomy 7 syndrome of children in Korea.
Subject(s)
Child , Child, Preschool , Humans , Male , Anemia , Bacterial Infections , Exanthema , Hemorrhage , Korea , Leukemia, Myeloid, Acute , Leukocytosis , Monosomy , Myelodysplastic Syndromes , Myeloproliferative Disorders , Pallor , ThrombocytopeniaABSTRACT
We have encountered a rare case of erythema nodosum-like leukemia cutis associated with acute myelocytic leukemia(AML) in a 57-year-old male. He was in good health until about 2 weeks prior to admission, when the systemic symptoms of high fever, anorexia, general weakness and malaise, and subcutaneous nodules developed. The nodules were multiple, red and noted bilaterally on the pretibial areas. Histological findings of his skin lesions showed diffuse cellular infiltrates intermingled with leukemic cells predominantly involving the adipose tissues. The cells displayed negative stainirig to antibodies CD3 and CD20, but positive staining to LCA. The diagnosis of AML(M4) was made by blood and bone marrow studies. He had a rapid downhill course and was discharged after 2 weeks of admission, with no anti-cancer chemotherapy.
Subject(s)
Humans , Male , Middle Aged , Anorexia , Antibodies , Bone Marrow , Diagnosis , Drug Therapy , Erythema , Fever , Leukemia , Leukemia, Myeloid, Acute , SkinABSTRACT
Patients with acute myelocytic leukemia (AML) have varied outlooks for survival after the diagnosis. To identify pretreatment prognostic indicators in AML, we analyzed 132 cases of AML seen at our hospital between June, 1989 and December, 1994. The median age of the patients was 40 years (range, 15-81). There were 63 male and 69 female patients. One hundred eight patients (82%) received induction chemotherapy which was based on cytarabine plus anthracyclines. Sixty six patients achieved complete remission (CR) and the CR rate among the patients given induction chemotherapy was 61%. The median duration of CR was 11.2 months. After median follow up of 6.6 months (range 0.5-51.4), 26 patients (39%) remain in continuous CR. The median duration of overall survival of the patients was 6.7 months. After median follow up of 10.6 months (range, 0.1-52.7), 41 patients (31%) are alive. Variables affecting duration of CR included the age of the patients, performance status of the patients, percentage of blast in the peripheral blood, hemoglobin level, percentage of blast in the bone marrow, FAB subtype, and CD7 marker positivity. Variables affecting survival duration included age of the patients, performance status of the patients, absolute blast count (ABC) in the peripheral blood, bone marrow cellularity, the percentage of blast in the bone marrow, and CD5 marker positivity. Multivariate analysis showed that the age of the patients and percentage of blast in the bone marrow were significant independent indicators for overall survival of the patients. Further studies utilizing cytogenetics and molecular characteristics of leukemic cell are warranted to better define the prognostic factors of patients with AML.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Age Factors , Leukemia, Myeloid, Acute/mortality , Middle Aged , Multivariate Analysis , Prognosis , Survival RateABSTRACT
Myelodysplastic syndrome is a heterogeneous disease complex which is basically a clonal disorder and has characteristics of cytopenia of one or more cell series in peripheral blood and of dyspoiesis of precursors in bone marrow. Since the nature of this disease in childhood is very different from that in adults, retrospective clinical study was performed with 17 confirmed patients who were admitted to the Department of Pediatrics, Seoul National University Children's Hospital from June 1986 till October 1992. The results were as follows: 1) Themost frequent occurrence was found in preschool age group (76.5%), and male predominance was noted. 2) Hepatosplenomegaly was the most frequent clinical finding, and in view of laboratory findings, anemia waas found in all cases, and leukopenia in 5 cases, thrombocytopenia in 13cases were observed. Bone marrow aspiration revealed dyspoiesis of 3 cell series in almost all cases. The percentage of myeloblasts more than 5% of total bone marrow nucleated cells was seen in 8 cases on bone marrow study. 3) Subtypes of the disease were found to be 3 cases of RA, 6 cases of RAEB, 3 cases of RAEB-T, 4 cases of JCML, and 1 case of monosomy 7 syndrome. Chromosomal study was performed in 8 cases, and 6 of them were detected to be abnormal. 4) Supportive management was performed for almost all cases, and combined therapy with prednisolone and one-alpha for 3 cases, combined chemotherapy with various anticancer drugs for 7 cases, and low dose cytarabine therapy (10 mg/m2/12 hr) for 6 cases were performed. 5) There were 3 cases of drop out, 8 cases followed up on not remitted state, 5 cases of death, and 2 cases followed up on complete remission state. Two cases in complete remission were one of RA patients, and one of JCML patients, to whom prednisolone with one-alpha, and combined chemotherapy with A-Triple-V regimen were applied as treatment modalities, respectively. 6) Average duration of follow up for 10 survival cases was 18.2 months and a significant difference of 2 year survival rate was found in between the group composed of RA, RAEB and the other group composed of remained subtypes.