Neutrophilic leukemoid reaction may occur in many situations, including hemolysis, malignancy, infection, and exposure to certain toxins. It usually shows morphological overlap with chronic myeloid leukemia in which promyelocytes are not majorly associated. Here, we present a case of promyelocytic leukemoid reaction in a patient with sepsis. A 28-year-old man was admitted for renal stone removal. After percutaneous nephrolithotomy, his condition deteriorated with fever (37.8℃), tachycardia (130/min), acute renal failure, pleural effusion, and pulmonary edema. Complete blood count indicated a white blood cell count of 73.39×10⁹/L including 82% promyelocytes, hemoglobin 8.9 g/dL, and platelet count of 85×10⁹/L. A bone marrow aspirate showed that promyelocytes accounted for 73.8% of all nucleated cells. Following bone marrow examination, treatment with all-trans retinoic acid (ATRA) was started immediately. Reverse transcription polymerase chain reaction (RT-PCR) study revealed the absence of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) and other RARA (retinoic acid receptor alpha) rearrangements. Once the chromosome analysis of bone marrow cells demonstrated the normal karyotype, ATRA was discontinued.
Acute Kidney Injury ; Adult ; Blood Cell Count ; Bone Marrow ; Bone Marrow Cells ; Bone Marrow Examination ; Fever ; Granulocyte Precursor Cells ; Hemolysis ; Humans ; Karyotype ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Promyelocytic, Acute ; Leukemoid Reaction* ; Leukocyte Count ; Nephrostomy, Percutaneous ; Neutrophils ; Platelet Count ; Pleural Effusion ; Polymerase Chain Reaction ; Pulmonary Edema ; Reverse Transcription ; Sepsis* ; Tachycardia ; Tretinoin

Cyclophosphamide-induced cardiotoxicity is an uncommon complication especially in patients who have never undergone mediastinal irradiation or cardiotoxic chemotherapy and do not have underlying cardiac diseases. Here, we describe the case of a 19-year-old female with chronic myeloid leukemia. She was previously treated with oral tyrosine kinase inhibitors and developed cardiomyopathy after receiving infusion of 60 mg/kg intravenous cyclophosphamide for two days with a conditioning regimen for allogenic hematopoietic stem cell transplantation. Severe thickening of the left ventricle and reduced ejection fraction without triggering agents were characteristic for cyclophosphamide-induced cardiomyopathy. Her NT-pro BNP and troponin T concentrations surged to >70,000 pg/mL (0=130 pg/mL) and 2,031 pg/mL (0-14 pg/mL), respectively, during the course of the therapy and multiple organ failure seemed imminent evidenced by unresponsive decline in blood pressure. However, with close monitoring and persistent conservative management which consisted of intravenous hydration, continuous hemodialysis, and mechanical ventilation, her condition recovered.
Blood Pressure ; Cardiomyopathies* ; Cardiotoxicity ; Cyclophosphamide* ; Drug Therapy ; Female ; Heart Diseases ; Heart Failure* ; Heart Ventricles ; Heart* ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Multiple Organ Failure ; Protein-Tyrosine Kinases ; Renal Dialysis ; Respiration, Artificial ; Troponin T ; Young Adult

Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients’ peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.
Apoptosis ; Blood Cells ; Blotting, Western ; Cell Proliferation ; Drug Resistance ; Humans ; Imatinib Mesylate* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Luciferases ; Phenotype ; RNA ; RNA, Long Noncoding*

We describe two cases of pulmonary arterial hypertension (PAH) that occurred under dasatinib treatment and were resolved after dasatinib discontinuation. Two patients with chronic phase chronic myeloid leukemia (CML) were switched to dasatinib therapy because of hematological progress while receiving imatinib. These patients had New York Heart Association (NYHA) functional class II dyspnea with elevated right ventricular systolic pressure (RVSP), which progressed under dasatinib treatment. After dasatinib treatment was discontinued, subjective symptoms were improved to NYHA functional class I and the follow-up transthoracic Doppler echocardiography showed improved RVSP. Treatment with an alternate tyrosine kinase inhibitor was initiated and had been continued without development of dyspnea or elevation of RVSP. This report suggests that dasatinib can cause the reversible PAH, therefore, routine cardiopulmonary evaluation before and during treatment with dasatinib may be needed in CML patients with clinical manifestations.
Blood Pressure ; Dyspnea ; Echocardiography, Doppler ; Follow-Up Studies ; Heart ; Humans ; Hypertension* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Protein-Tyrosine Kinases

BACKGROUNDThere are limited eligible clinical markers at present to monitor the progress of chronic myeloid leukemia (CML). Heme oxygenase-1 (HO-1), as one of the most important oxidation-regulating enzymes in vivo, suggests the onset and progression of cancer when highly expressed. Furthermore, HO-1 level is related with the occurrence and development of hematological diseases. But the relationship between HO-1 expression and progression/relapse of CML has seldom been studied hitherto. This study aimed to investigate the relationship between them to find out a new molecular marker for prediction.

METHODSA total of 60 peripheral blood and bone marrow (BM) samples from 25 CML patients in different phases were collected respectively to detect the expressions of HO-1 and bcr/abl using real-time PCR. Routine blood test was performed to detect the changes of leukocyte and platelet counts. The proportion of primitive cells in BM was detected by flow cytometry. The relationship between high HO-1 expression and CML progression and relapse was explored by the analysis of variance by Wilcoxon test and linear regression analysis. The diagnostic accuracy and cutoff values were determined by receiver operating characteristic curve.

RESULTSRelative expression of HO-1 mRNA in CML patients peripheral blood was significantly higher than that of donors (P < 0.0001), which were 0.57±3.78 and (1.417±1.125)×10(-6), respectively. HO-1 expression level in CML patients was 0.061 5±0.062 4, which decreased to 0.009 4±0.006 7 upon CMoR, and remained remarkably higher 0.016 3±0.017 5 than that of normal donors (1.417±1.125)×10(-6), P < 0.001. When relapse occurred, HO-1 expression significantly increased from 0.020 6±0.021 0 to 3.852±10.285 in CMoR stage and undergoing relapse. According to progression of CML, HO-1 expression level in CML patients increased from CP (0.009 5±0.017 6) to AP (0.028 0±0.055 7) and then to BP (0.276 7 ± 0.447 0). And there was a linear correlation between HO-1 expression and proportion of primitive CML cells. The diagnostic accuracies and cutoff values of HO-1 expression for CML-CP, CML-AP, and CML-BP were 1.0, 0.748, and 0.965, respectively, as well as 0.000 070, 0.001 917, and 0.020 696, respectively.

CONCLUSIONHO-1 may be a potential molecular indicator for the progression and relapse of CML.

Bone Marrow ; metabolism ; Female ; Flow Cytometry ; Gene Expression ; Heme Oxygenase-1 ; blood ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; enzymology ; pathology ; Male ; Predictive Value of Tests ; Real-Time Polymerase Chain Reaction

OBJECTIVETo measure the levels of hormones in chronic myelogenous leukemia (CML) patients receiving imatinib mesylate (IM) and evaluate the effects of IM on endocrine system.

METHODS69 patients with CML while taking IM were enrolled and a total of 86 peripheral blood samples were detected. The levels of total triiodothyronine (TT3), total tetraiodothyronine (TT4), thyroid stimulating hormone (TSH), testosterone, progesterone, estradiol (E2), plasma total cortisol (PTC) at 8:00-10:00 am measured. Concentration of hormones in different groups were measured to evaluate the effects of IM on endocrine system and relationships with its administration duration, plasma concentration and clinical symptoms.

RESULTS(1) Of the 7 types of hormones, an elevation of TSH level was found in 14 patients (20.3%), a decrease of TT3 and testosterone in 8 patients (11.6%) and 8 males (18.6%), respectively. (2) A significant decline of TT3 and testosterone was observed in all patients divided by different administration duration. Negative correlation was seen between TT3 level and duration of administration (r=-0.273, P=0.010), which was also found for testosterone (r=-0.302, P=0.025). (3) There was no correlation between serum levels of the seven hormones and concentration of IM.

CONCLUSIONIM affect the levels of thyroid and sex hormones in some patients with clinical manifestations: a decrease of TT3, testosterone and testosterone, an increase of TSH, which have relationship with the duration of administration.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Benzamides ; administration & dosage ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; administration & dosage ; blood ; therapeutic use ; Pyrimidines ; administration & dosage ; blood ; therapeutic use ; Thyrotropin ; blood ; Triiodothyronine ; blood ; Young Adult

OBJECTIVETo understand the predictive value of early monitoring BCR-ABL transcripts in patients with chronic myeloid leukemia (CML) after treatment with tyrosine kinase inhibitor (TKI), and to provides the information for early assessment of prognosis and treatment options.

METHODSBCR-ABL transcripts of 53 CML patients before and after TKI treatment were detected by using real-time quantitative RT-PCR. The relationship between BCR-ABL transcripts level after TKI treatment for 3 months and the later molecular response, progression and mutation was analyzed.

RESULTSThe median values of BCR-ABL transcripts in peripheral blood samples from 30 newly diagnosed patients were 43.99%, which was used as a baseline of BCR-ABL transcripts for molecular response evaluation. Of 53 patients, 31 (58.49%) had a BCR-ABL mRNA ≤ 4.40% (reduced more than 1 log) and 22 (41.51%) greater than 4.40% (reduced to less than 1 log) after 3 months of TKI treatment. The former 31 patients had a significantly higher 18-months cumulative incidence of major molecular response (MMR) (90.32% vs 18.18%, P=0.000) and 3-year cumulative incidence of complete molecular response (CMR) (48.39% vs 0, P=0.000) compared with the latter 22 patients. The lower BCR-ABL level was, the earlier MMR reached. The proportion of patients with a mutation in group of BCR-ABL mRNA>4.40% was significantly higher than that of BCR-ABL mRNA ≤ 4.40% (22.73% vs 0, P=0.021). The incidence of progression increased in group of BCR-ABL mRNA>4.40%, but the difference was not statistically significant (P=0.052).

CONCLUSIONIt is important for the prognosis evaluation of the patients to monitor the level of BCR-ABL transcripts at 3 months after TKI treatment, which might help to early optimization of treatment and to improve curative effect of CML patients.

Adult ; Aged ; Female ; Fusion Proteins, bcr-abl ; blood ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; drug therapy ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Protein Kinase Inhibitors ; therapeutic use ; RNA, Messenger ; genetics ; Treatment Outcome ; Young Adult

The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and to identify factors related to the decreased BMD in childhood cancer survivors. We studied 78 patients (34 boys, 44 girls) treated for childhood cancer. Twenty (25.7%) patients had lumbar BMD (LBMD) standard deviation score (SDS) lower than -2. Nineteen (24.4%) patients had femur neck BMD (FNBMD) SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17 +/- 1.39 vs -0.43 +/- 1.33, P = 0.025). The risk of having LBMD SDS < -2 was higher in the patients treated with glucocorticoid (GC) for graft-versus-host disease (GVHD) (36.6% vs 13.5%; odds ratio [OR], 3.7; P = 0.020). In multivariate logistic regression analysis, longer duration of GC treatment for GVHD (OR, 1.12; 95% confidence interval [CI], 1.05-1.20) and lower body mass index (BMI) SDS (OR, 0.59; 95% CI, 0.36-0.95) were associated with decreased LBMD SDS. These findings suggest that prolonged GC use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.
Adolescent ; Body Mass Index ; Bone Density/*drug effects ; Bone Diseases, Metabolic/*chemically induced ; Child ; Female ; Glucocorticoids/*adverse effects/*therapeutic use ; Graft vs Host Disease/drug therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hormones/blood ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Leukemia, Myeloid, Acute/pathology ; Male ; Osteoporosis/*chemically induced ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Risk Factors ; Survivors

This study was aimed to evaluate the efficacy and safety of dasatinib in BCR/ABL positive leukemia patients with primary or secondary resistance to imatinib. 27 patients with primary or secondary imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph(+) ALL) received 100 - 140 mg/d dasatinib orally. Their overall survival and tolerance were evaluated. The results showed that the median duration of dasatinib therapy was 8 (1-66) months in the 27 imatinib-resistant BCR/ABL positive leukemia cases, with a median follow-up of 54 (3-75) months. After the dasatinib treatment, 88.8% of all the 27 cases achieved complete hematologic response (CHR), 29.6% of them achieved major cytogenetic response (mCyR), 37% of all achieved complete cytogenetic response (CCyR) and 18.5% cases achieved major molecular response (MMR). Patients who received dasatinib in progress of disease (CML-AP, CML-BC and bone marrow relapse Ph(+) ALL) had a lower CCyR rate than those in stable disease (CML-CP and bone marrow remission Ph(+) ALL) (P = 0.0377), and 3 - 4 grade adverse events occurred more frequently in progress of disease than that in stable disease. Overall survival of the patients who achieved CCyR after dasatinib therapy was statistically longer than those who did not achieve CCyR (63 m vs 9 m, P = 0.0126). The most common grade 3 - 4 adverse events during dasatinib therapy including hematology events such as thrombocytopenia (51.8%), neutropenia (48.1%), anemia (33.3%), and non-hematologic events such as pleural effusion (18.5%), pulmonary infection (18.5%), pericardial effusion (11.1%). The 3-4 grade adverse events occurred within 12 months from dasatinib therapy, and were mainly observed in patients with progress of disease. It is concluded that dasatinib is an effective drug in imatinib-resistant BCR/ABL positive leukemia patients, the better curative effect and better tolerance has been observed in patients who received dasatinib in stable disease.
Adult ; Aged ; Benzamides ; therapeutic use ; Dasatinib ; Drug Resistance, Neoplasm ; Female ; Fusion Proteins, bcr-abl ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Pyrimidines ; therapeutic use ; Thiazoles ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.

METHODSPlasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.

RESULTS(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.

CONCLUSIONThere was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Benzamides ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult