OBJECTIVE: To investigate the prognostic significance of dynamic detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) by 8-color flow cytometry. METHODS: MRD of 282 AML patients who achieved remission after initial therapy was detected by 8-color flow cytometry. MRD threshold for predicting recurrence was determined by receiver operating characteristic (ROC) curve, and time from MRD-positive to clinical recurrence was analyzed. The differences in overall survival (OS) time and relapse-free survival (RFS) time of patients with different MRD-changes were compared, and the related factors of recurrence in patients with MRD-negative were analyzed by univariate and logistic regression analysis. RESULTS: ROC curve determined that the MFC-MRD threshold for predicting the recurrence of AML was 0.105%, and the recurrence rate of MRD-positive patients was significantly higher than that of MRD-negative patients [52.45% (75/143 cases) vs 35.97% (50/139 cases), P=0.005]. The patients in MRD persistent positive group and negative to positive group recurred earlier than those in positive to negative group and negative-positive fluctuation group (P<0.005). Survival analysis showed that OS and RFS time of patients with MRD persistent positive were significantly shorter than those of patients with MRD persistent negative, positive to negative, and negative-positive fluctuation (P<0.005). There was no significant difference in OS and RFS between MRD negative to positive group and MRD persistent positive group (P>0.005), either between MRD persistent negative group and MRD positive to negative group (P>0.005). Among 139 MRD-negative patients, 50 recurred. Univariate and logistic regression analysis showed that the risk of recurrence increased with the increase of white blood cells level (95%CI: 1.000-1.013, P=0.045). The risk of recurrence in patients without hematopoietic stem cell transplantation (HSCT) was 9.694 times higher than that in patients who received HSCT (95%CI: 1.720-54.651, P=0.010), and in the high-risk group was 5.848 times higher than that in the low-risk group (95%CI: 1.418-24.121, P=0.015). CONCLUSION The prognosis of AML patients with different MRD changes is significantly different. No matter MRD-positive or MRD-negative at the initial remission, dynamic detection of MRD after treatment is more helpful to accurately guide treatment.
Flow Cytometry ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Neoplasm, Residual/diagnosis* ; Prognosis ; Recurrence ; Transplantation, Homologous

OBJECTIVELeukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment.

DATA SOURCESWe searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML. Clinical trial information was obtained from ClinicalTrials.gov. For the major purpose of this review that is to outline the latest therapeutic development of AML, we only listed the ongoing clinical trials for reference. However, the published results of complete clinical trials were also mentioned.

STUDY SELECTIONThis article reviewed the latest developments related to the diagnosis and treatment of AML. In the first portion, we provided some novel insights on the molecular basis of AML, as well as provided an update on the classification of AML. In the second portion, we summarized the results of research on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/Fms-like tyrosine kinase 3 (FLT3) inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. We will also highlight ongoing research and clinical trials in pediatric AML.

RESULTSWe described clonal evolution and how it changes our view on leukemogenesis, treatment responses, and disease relapse. Pediatric-specific genomic mapping was discussed with a novel diagnostic method highlighted. In the later portion of this review, we summarized the researches on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/FLT3 inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents.

CONCLUSIONGene sequencing techniques should set the basis for next-generation diagnostic methods of AML, and target therapy should be the focus of future clinical research in the exploration of therapeutic possibilities.

Antibodies, Monoclonal ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; fms-Like Tyrosine Kinase 3 ; antagonists & inhibitors

PURPOSE: To study the treatment outcomes in patients who were administered multiple intravitreal ganciclovir injections more than 10 times alone without systemic anti-cytomegalovirus therapy for cytomegalovirus retinitis. CASE SUMMARY: A 64-year-old man who underwent immunosuppressive therapy after thymectomy due to an invasive thymoma and pure red-cell aplasia, a 60-year-old woman who underwent chemotherapy after diagnosis of diffuse large B-cell lymphoma, a 49-year-old man with a history of bone marrow transplantation due to acute myeloid leukemia, a 29-year-old woman with dermatomyositis treated with oral steroids and cyclosporine, and a 47-year-old woman who received intravitreal dexamethasone implant injections, intravitreal and subtenon steroid injections due to Behcet's disease were diagnosed with cytomegalovirus retinitis. All patients showed systemic complications such as pancytopenia after systemic anti-cytomegalovirus therapy, and therefore, they were administered multiple intravitreal ganciclovir injections alone. Best-corrected visual acuities improved in all patients, except in one case, where viral lesions were observed in the fovea. Retinal hemorrhaging and infiltrative lesions decreased in all patients. No severe complication was observed during the injection and in the follow-up period. CONCLUSIONS: Multiple intravitreal ganciclovir injections alone can be used as a treatment modality for cytomegalovirus retinitis to avoid the systemic side effects of systemic anti-cytomegalovirus therapy.
Adult ; Bone Marrow Transplantation ; Cyclosporine ; Cytomegalovirus Retinitis* ; Cytomegalovirus* ; Dermatomyositis ; Dexamethasone ; Diagnosis ; Drug Therapy ; Female ; Follow-Up Studies ; Ganciclovir* ; Humans ; Intravitreal Injections ; Leukemia, Myeloid, Acute ; Lymphoma, B-Cell ; Middle Aged ; Pancytopenia ; Red-Cell Aplasia, Pure ; Retinaldehyde ; Steroids ; Thymectomy ; Thymoma ; Visual Acuity

Myeloid sarcoma (MS) is an extramedullary involvement of immature myeloid proliferation. An isolated MS is defined as a myeloblastic tumor when it arises without any concomitant circulating disease. A diagnosis of MS is established using pathologic features including infiltration of myeloblasts and strong myeloperoxidase expression with negative cytokeratin immunohistochemical staining. We report a rare case of colonic MS without any peripheral blood abnormality. If the affected patient were left untreated, the MS could evolve into acute myeloid leukemia (AML) within one year. Several studies recommend the same regimens of chemotherapy as used for circulating AML to treat isolated MS. We focused on the diagnosis of MS in this study. The correct diagnosis of MS is important for adequate treatment. In conclusion, MS should be considered in the differential diagnosis of intestinal tumor.
Colon ; Colonic Neoplasms ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Granulocyte Precursor Cells ; Humans ; Intestines* ; Keratins ; Leukemia, Myeloid, Acute ; Peroxidase ; Sarcoma, Myeloid*

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.
Adolescent ; Antineoplastic Agents/therapeutic use ; Central Nervous System Neoplasms/diagnosis/drug therapy/radiotherapy ; Child ; Child, Preschool ; Disease-Free Survival ; Hospitals ; Humans ; Infant ; Leukemia, Myeloid, Acute/diagnosis/epidemiology/mortality/therapy ; Myelodysplastic Syndromes/diagnosis/epidemiology/mortality/therapy ; Neoplasms, Second Primary/*diagnosis/epidemiology/mortality/therapy ; Osteosarcoma/diagnosis/epidemiology ; Retrospective Studies ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Autologous ; Young Adult

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.
Adolescent ; Antineoplastic Agents/therapeutic use ; Central Nervous System Neoplasms/diagnosis/drug therapy/radiotherapy ; Child ; Child, Preschool ; Disease-Free Survival ; Hospitals ; Humans ; Infant ; Leukemia, Myeloid, Acute/diagnosis/epidemiology/mortality/therapy ; Myelodysplastic Syndromes/diagnosis/epidemiology/mortality/therapy ; Neoplasms, Second Primary/*diagnosis/epidemiology/mortality/therapy ; Osteosarcoma/diagnosis/epidemiology ; Retrospective Studies ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Autologous ; Young Adult

PURPOSE: To report a case of an 82-year-old male with acute myeloid leukemia presenting with bilateral isolated conjunctival and eyelid masses. CASE SUMMARY: An 82-year-old male presented with a bilateral conjunctival mass and right eyelid mass occurring 10 days prior. He was diagnosed with prostate cancer 8 years ago and complete recovery was achieved using selective mass chemotherapy. He experienced a stroke 4 years ago and was treated using a carotid artery stent insertion and medication. In the initial laboratory test, hemoglobin was 13.7 g/dL and leukocyte count 5,530/mm3(neutrophil 74.4%, lymphocyte 10%, monocyte 11.8%). Light reflex, movement of extraocular muscle and fundus examination were all normal. Biopsy was performed 1 week after the first visit. Seven days after biopsy, he complained of sudden dyspnea and febrile sense and was admitted to the intensive care unit via the emergency room (ER). The laboratory tests performed in the ER showed hemoglobin was 9.6 g/dL and leukocyte count was 78,020/mm3(neutrophil 0%, lymphocyte 7%, monocyte 5%, promyelocyte 1%, metamyelocyte 4%, myelocyte 6%, blast 67%). The biopsy revealed diffuse proliferation of atypical plasmacytoid cells, consistent with leukemic infiltration. Under the diagnosis of acute myeloid leukemia, chemotherapy was administered. However, the patient died due to aggravated pneumonia. CONCLUSIONS: Even if non-specific findings appear on the peripheral blood tests, eyelid and conjunctival masses should be considered as possible tumors in acute myeloid leukemia.
Aged, 80 and over ; Biopsy ; Carotid Arteries ; Conjunctiva* ; Diagnosis ; Drug Therapy ; Dyspnea ; Emergency Service, Hospital ; Eyelids* ; Granulocyte Precursor Cells ; Hematologic Tests ; Humans ; Intensive Care Units ; Leukemia, Myeloid, Acute* ; Leukemic Infiltration ; Leukocyte Count ; Lymphocytes ; Male ; Monocytes ; Pneumonia ; Prostatic Neoplasms ; Reflex ; Sarcoma, Myeloid ; Stents ; Stroke

Acute myeloid leukemia (AML) is a heterogeneous malignancy that comprises 25-30% of pediatric leukemias in Korea. Several inherited diseases, such as Down syndrome and Fanconi anemia, predispose towards AML leukemogenesis. Subgrouping of AML is a key diagnostic step, previously done with the French-American-British (FAB) classification and recently complemented by that of the World Health Organization (WHO). An important feature of AML is the possibility of chloroma at diagnosis, which, if detected, requires follow-up evaluation to determine treatment response. Numerous genetic abnormalities with prognostic relevance have recently been found, the most important of which include those of the core-binding factor (CBF) leukemias, and FLT3-ITD mutation. These genetic abnormalities, combined with patient response to initial treatment, allow for a scheme of risk stratification, and the current consensus is to treat low risk patients with chemotherapy only, whereas high risk patients may receive allogeneic transplant in first remission, although the benefits of transplant remain inconclusive. Overall, the outcome of children and adolescents with AML has improved significantly so that many clinical trials now report event-free survival of around 60%. However, much of this improvement stems from better supportive care and transplant methods, and the genetics-based diagnostic advances in AML have yet to result in enhanced treatment. New therapeutics, including possibly targeted therapy, are necessary to further improve the outcome of pediatric AML.
Adolescent ; Child ; Classification ; Complement System Proteins ; Consensus ; Core Binding Factors ; Diagnosis ; Disease-Free Survival ; Down Syndrome ; Drug Therapy ; Fanconi Anemia ; Humans ; Korea ; Leukemia ; Leukemia, Myeloid, Acute ; Sarcoma, Myeloid ; World Health Organization

No abstract available.
Antineoplastic Agents/*adverse effects/*therapeutic use ; Bone Marrow Cells/metabolism ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/*chemically induced/*diagnosis/genetics ; Leukemia, Promyelocytic, Acute/*drug therapy ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Remission Induction ; Tretinoin/therapeutic use

This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 ± 0.40)×10(9)/L] was obviously lower than that in DA group [(0.99 ± 0.67)×10(9)/L] (P < 0.05); neutrophil minimum value in IA group [(0.19 ± 0.09)×10(9)/L] was significantly lower than that in DA group [(0.21 ± 0.16)×10(9)/L] (P < 0.05); the neutropenia duration in IA group (12.59 ± 5.31)d was much longer than that in DA group (9.17 ± 7.04)d (P < 0.05). The median survival time of patients in IA group was 36.67 months, which was obviously longer than that of patients in DA group (21.45 months) (P < 0.05). The lactate dehydrogenase (LDH) value and chemotherapy regimens were the independently risk factor affecting the prognosis of AML-M2a patients. It is concluded that as compared with DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult