Diagnosis Of Acute Myeloblastic Leukemia Research Articles

Optical Genome Mapping Combined with High-Throughput Sequencing Is Effective for the Diagnostic and Prognostic Genomic Classification of Acute Myeloid Leukemia and Myelodysplastic Neoplasms

Cytogenetic and molecular analyses are crucial for the diagnosis, choice of treatment and prognostic evaluation of acute myeloblastic leukemia (AML) and myelodysplastic neoplasms (MDS). Optical genome mapping (OGM) is a recent technology enabling a genome-wide high-resolution detection of structural abnormalities (SVs) and copy number variations (CNV) developed by the Bionano® company. The clinical value of OGM in AML and MDS and its positioning in relation to conventional karyotype and FISH (K&F) and targeted high throughput panel sequencing (HTS) has been little evaluated. Here, the primary objective was to evaluate prospectively the ability of OGM to apply the diagnosis (WHO 2022) and prognostic cytogenetic classification of AML (ELN 2022) and MDS (IPSSm) in comparison with K&F and HTS. The secondary objectives were to evaluate the proportion of informative cases in intention-of-analysis and among them the level of concordance of OGM versus K&F, the amount of additional information (OGM vs KF), and the potential reclassification (OMS 2022, ELN 2022, IPSSm) in addition to K&F and a targeted HTS panel (i.e. including ASXL1, CEBPA, DNMT3A, IDH1, IDH2, FLT3, KRAS, NPM1, NRAS, RUNX1, SRSF2, TP53, WT1) used in real-life. A two-stage prospective selection of bone marrow or blood samples was carried out at Nantes University Hospital between May 2022 and June 2023. A 1st collection of samples from 67 patients (pts) with AML (n=58) or MDS (n=9) was selected and cryopreserved according to pre-analytical criteria (cell count, time after collection). A 2nd final selection of 39 pts including 34 AML and 5 MDS was carried out according to their cytogenetic and/or molecular data, in order to evaluate the performance of OGM in different profiles of clinical interest (Table 1). Of these 39 intention-to-analyze patients, 35 were informative for OGM comparison with K&F (3 OGM failures, 1 K not realized). Interpretation criteria with Bionano access software considered SVs and CNVs >200 and >500 kbp respectively, or smaller if a gene of interest was found. Further details will be presented at the conference. OGM showed concordance with K&F in 30/35 (86%) of informative pts, but 5 had subclonal (<20%) gains undetected i.e. +8, +21, +6p or poorly detected i.e. t(1;15) with centromeric break. None of these OGM false negatives modify the diagnosis or prognosis. Additional information was found with OGM in 19/35 pts, with a median of 1 cryptic anomaly/patient (range = 1-13). Cryptic abnormalities were identified in 9/18 pts with normal K (7 AML, 2 MDS), including 5 pts with pathogenic SV, notably KMT2A with partial tandem duplication (PTD) and TET2 deletion, and 4 pts with SV of unknown significance (-6p, +4q, +15q, +19p, +20q). Finally, the WHO diagnosis was confirmed with OGM in all informative pts but not modified in any of them. OGM confirmed ELN prognostic classification of all the AML cases without modification. Two AML cases had >3 anomalies with OGM (range = 5-6) of which >2 were cryptic without complex karyotype (CK) (size = 226-1221 kbp, VAF% = 3-100) including gains (3q, 11q, Xp) or losses (3p, 4p, 21q) of undetermined or pathogenic ( RUNX1 deletion) significance. In this context of multiple cryptic anomalies, there is no precise definition of abnormal or CK with OGM. One is a MDS-related AML cases that also had MDS-associated somatic mutations (i.e. ASXL1, SRSF2 ELNadverse) and the other was an AML with NUP98 rearrangement and FLT3-ITD mutation (i.e ELN intermediate). OGM confirmed the IPSSm prognostic cytogenetic category in 3 pts and modified it in 2/5 MDS pts (40%). Among the two latter, K was normal (e.g. favorable) but OGM identified cryptic KMT2A- PTD of poor prognosis. These two SMD-IB2 changes the IPSSm risk category from Moderate-High or High to Very-High risk group. The combination of OGM and HTS techniques provided a more accurate prognostic classification of MDS cases. Confirmations of cryptic pathogenic anomalies detected by OGM using a 2nd technique will be presented at the congress. OGM technology is powerful for identifying pathogenic anomalies, but the criteria for abnormal K and CK need to be clarified in order to apply international diagnosis and prognosis classifications. To this end, the OGM+HTS combination is highly effective. The positioning of OGM as a complement and/or replacement for conventional cytogenetic and molecular tools, and its impact on therapeutic choice, still needs to be evaluated in AML and MDS.

The prognostic role of C-KIT, TET1 and TET2 gene expression in Acute Myeloid Leukemia

Aimwas to assess the role of C-KIT, TET1 and TET2 expression in the diagnosis and prognosis of acute myeloblastic leukemia (AML).MethodsThe expression levels of C-KIT, TET1 and TET2 were assessed in the bone marrow (BM) aspirate of 152 AML patients compared to 20 healthy control using quantitative real-time polymerase chain reaction (qRT-PCR). Data were correlated with the clinico-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall survival (OS) rates.ResultsC-KIT, TET1 and TET2 were significantly upregulated in AML patients [0.25 (0–11.6), 0.0113 (0–3.301), and 0.07 (0–4); respectively], compared to the control group [0.013 (0.005–0.250), P < 0.001, 0.001 (0–0.006), P < 0.001, and 0.02 (0.008–0.055), P = 0.019; respectively]. The sensitivity, specificity, and area under curve of of C-KIT were (48.7%, 100%, 0.855; respectively, P = 0.001), and that of TET1 were (63.4%, 100%, 0.897; respectively, P = 0.001), while that of TET2 were (56.8%, 100%, 0.766; respectively, P = 0.019). When combining the three markers, the sensitivity was 77.5%, however it reached the highest sensitivity (78.6%) and specificity (100%) when combining both c-KIT + TET1 together for the diagnosis of AML. C-KIT overexpression associated with shorter DFS (P = 0.05) and increased incidence of relapse (P = 0.019). Lymph nodes involvement [HR = 2.200, P = 0.005] is an independent risk factor for shorter OS rate of AML patients. Increased BM blast % [HR = 7.768, P = 0.002], and FLT3-ITD mutation [HR = 2.989, P = 0.032] are independent risk factors for shorter DSF rate of the patients.ConclusionC-KIT, TET1, and TET2 could be used as possible useful biomarkers for the diagnosis of AML.

Immune Reconstitution Inflammatory Syndrome Associated with Hepatosplenic Candidiasis in a Patient with Acute Myeloblastic Leukemia: Possible Pathogenesis and Treatment in the Light of Current Knowledge

Acquired immune deficiencies caused by different etiologies, promote invasive fungal infections. When this immunity begins to improve, it can induce an excessive inflammatory response defined as Immune Reconstitution Inflammatory Syndrome (IRIS). Hepatosplenic Candidiasis (HSC) can be considered a form of IRIS syndrome as it occurs following neutrophil recovery in patients treated for acute leukemia. Differentiating IRIS from a single fungal infection or treatment failure due to a similar clinical picture is a real diagnostic problem. Misdiagnosis and subsequently ineffective treatment with antifungal therapy instead of anti-inflammatory drugs, may lead fatal course of the disease. A deep and prolonged neutropenia developed after the first induction chemotherapy in our two and a half-year-old male patient who was followed up in our clinic with the diagnosis of Acute Myeloblastic Leukemia (AML). Our patient had fever, abdominal pain as well as his Gamma Glutamyl Transferase (GGT) and Alkaline Phosphatase (ALP) levels increased during neutropenia recovery. He was diagnosed with hepatosplenic candidiasis, by observing ‘target like abscesses’ on dynamic Magnetic Resonance Imaging (MRI) taken for his newly developing symptoms and laboratory findings while recovering neutropenia. After his first and third induction chemotherapy courses, his fever persisted although antifungal therapy, steroid treatment was initiated considering IRIS. After his re-intensification course, because of the same flare-up symptoms, we started immunglobulin in addition to steroid. With methylprednisolone and intravenous immunoglobulin, his symptoms improved and significant regression was observed in the lesions ‘target-like abscesses’ on MRI and in the laboratory values. Result: IRIS should be considered for patients with hepatic candidiasis whose have persistent fever despite appropriate antifungal therapy. Glucocorticoid should be started first for an anti-inflammatory effect.

ÇOCUKLUK ÇAĞI AKUT MYELOBLASTİK LÖSEMİLERDE KAN ÜRÜNÜ KULLANIMININ KEMOTERAPİ BLOKLARINA GÖRE DAĞILIMI

Aim : This study evaluates the association of total erythrocyte, random platelet and apheresis platelet suspension given to children receiving chemotherapy (CT) blocks with a diagnosis of acute myeloblastic leukemia (AML) with the chemotherapy (CT) block the patient received in that period. Material and Methods: The transfusion need of a total of 146 patients followed with a diagnosis of AML were determined as erythrocyte, random platelet and platelet suspension as number and type in bags from the moment the patients were diagnosed to the period the treatment ended by entering the blood bank data base records. Results: The number of total per patient average erythrocyte use of a total of 37 patients during the process from the moment they were diagnosed to the period the treatment ended was 27 (100-102). Of the CT blocks, the block in which both erythrocyte and apheresis platelet use was the highest was Aie block. While the average per person erythrocyte use was 8 (2-20) in this block, apheresis platelet use was found as 8,5 (1-28). While the number of average per person random platelet use was 20 (7-139), the number of average per person random platelet use was as 27 (1-102) in the Maintenance block, which is the CT block in which the most random platelet was used. Conclusion: In children with AML, a great number of blood and blood product transfusions are needed during CT. The efficiency of these transfusions can depend on a great number of factors such as the type of acute leukemia, patient age, patient gender, the CT block the patient is receiving, the CT drugs the patient is receiving in that period and whether the patient has a clinical picture such as infection, sepsis, intense consumption coagulopathy during that period.

A Rare Case of Acute Myeloblastic Leukemia With Blast Count Less Than 20% in Bone Marrow

One of the diagnostic criteria for Acute Myeloblastic Leukemia (AML) is the presence of 20% myeloid blasts in peripheral blood or bone marrow. Some cases with recurrent cytogenetic abnormalities also fall in this category with blast cell count less than 20%. Thus, in the presence of these genetic abnormalities, the patients are classified as AML regardless of blast cell count. One of these genetic heterogeneities is t(8; 21) (q22, q22.1) which is more commonly seen in children and young adults. In this study, a 14-year-old boy is reported with a final diagnosis of AML, which was presented with fever and bicytopenia, clinically suspicious for acute leukemia. Laboratory results reported less than 20% blasts in bone marrow aspiration smears but genetic alteration t(8; 21) (q22, q22.1) was detected by molecular exams.

The effectiveness of the information system for managing data from a registration study of acute myeloid leukemia in children

The article presents the results of the development and implementation of tools for an integrated approach to the formation of a single information space in the field of organizing the registration study Primary diagnosis of acute myeloblastic leukemia in children, organized in the National Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev Ministry of Health of the Russian Federation. On the example of this study the advantages of using the methods of optimization of information flows of data obtained in the medical technological process in the development of specialized information systems are shown. The conceptual model of the study data Primary diagnosis of acute myeloid leukemia in children and the model of interpretation of the data structures obtained as a result of high-tech medical care in the structure of the study data model are presented. On the basis of the proposed conceptual data model and its details, an information system for data flow management of the study Primary diagnosis of acute myeloid leukemia in children was developed and the prospect of its development in accordance with the need to transform the tasks of the registration study into the task of creating a unified therapeutic approach within the framework of the introduction of a single Protocol of therapy in hospitals.

5q- Syndrome in Transformation to the Philadelphia Chromosome Positive Acute Myeloblastic Leukemia

Background: A rare 5q- syndrome subtype (OMIM:153550) of the myelodysplastic syndrome (MDS) evolved to the Philadelphia (Ph) chromosome positive acute myeloblastic leukemia (AML) is presented. The MDS is an acquired clonal stem cell disorder frequently associated with a variety of chromosomal abnormalities. The most common karyotype abnormalities in MDS are del(5q), -7 and +8. The t(9;22)(q34;q11) results in the formation of the Ph chromosome and generates an active chimerical BCR-ABL tyrosine kinase most commonly associated with chronic myelogenous leukemia (CML) and adult precursor B-acute lymphoblastic leukemia (B-ALL). The Ph chromosome positive MDS and AML are uncommon with only 1-2% of newly diagnosed cases. Case report: We present a 72-year old woman with MDS. The HG-banding technique applied on unstimulated bone marrow cells showed 46,XX,del(5)(q13q33)[10]/46,XX. Ten months later, the white blood cell (WBC) count increased to 72×109/l, with 60% of myeloblasts in the formula. The bone marrow aspirate was hypercellular with 50% blasts. The cytogenetic study demonstrated the presence of Ph chromosome together with the initial del(5q) in the same cellular clone. Chemotherapy with hydroxyurea and low-dose cytosine arabinoside was followed by an increase in WBC count to 98×109/l. The dosage of cytosine arabinoside was escalated to 100 mg/m2, for 7 days resulting in a drop in the WBC count to 12×109/l. The follow-up bone marrow aspirations showed a further progression of disease with >70% of myeloblasts in the myelogram. The patient lived 10 months after the initial diagnosis of MDS was made and another 4 months after the diagnosis of secondary AML. Conclusion: The karyotype evolution from the solely 5q- to the 5q- and Ph-positive clone in the MDS in transformation to secondary AML (sAML) is a rare event. To our knowledge, this is a second such case reported in the literature. Based on current literature, we discuss possible links between the 5q- syndrome, BCR/ABL-negative chronic myeloproliferative neoplasms and the BCR/ABL-positive leukemias.

Circulating miR-150 and miR-342 in plasma are novel potential biomarkers for acute myeloid leukemia

BackgroundMicroRNAs (miRNAs) are small (19-22-nt) single-stranded noncoding RNA molecules whose deregulation of expression can contribute to human disease including the multistep processes of carcinogenesis in human. Circulating miRNAs are emerging biomarkers in many diseases and cancers such as type 2 diabetes, pulmonary disease, colorectal cancer, and gastric cancer among others; however, defining a plasma miRNA signature in acute myeloblastic leukemia (AML) that could serve as a biomarker for diagnosis or in the follow-up has not been done yet.MethodsTaqMan miRNA microarray was performed to identify deregulated miRNAs in the plasma of AML patients. Quantitative real-time RT-PCR was used to validate the results. Receiver-operator characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of the highly and significantly identified deregulated miRNA(s) as potential candidate biomarker(s).ResultsThe plasma expression level of let-7d, miR-150, miR-339, and miR-342 was down-regulated whilst that of let-7b, and miR-523 was up-regulated in the AML group at diagnosis compared to healthy controls. ROC curve analyses revealed an AUC (the areas under the ROC curve) of 0.835 (95% CI: 0.7119– 0.9581; P<0.0001) and 0.8125 (95% CI: 0.6796–0.9454; P=0.0005) for miR-150, and miR-342 respectively. Combined ROC analyses using these 2 miRNAs revealed an elevated AUC of 0.86 (95% CI: 0.7819–0.94; P<0.0001) indicating the additive effect in the diagnostic value of these 2 miRNAs. QRT-PCR results showed that the expression level of these two miRs in complete remission AML patients resembled that of healthy controls.ConclusionsOur findings indicated that plasma miR-150 and miR-342 are novel important promising biomarkers in the diagnosis of AML. These novel and promising markers warrant validation in larger prospective studies.

High-dose Glucocorticoid for the Treatment of Myeloid Sarcoma

Myeloid sarcoma is a tumor of myeloblast or poorly differentiated myeloid cells that can occur in extramedullary sites, as isolated tumor, concomitantly with or after the diagnosis of acute myeloblastic leukemia. Despite considerable improvement achieved in the outcome of patients with acute myeloblastic leukemia by using intensive chemotherapy and/or hematopoietic stem cell transplantation, it is generally considered to be poor in patients with myeloid sarcoma. The aim of this review is to indicate the potential therapeutic effects of high-dose glucocorticoid treatment which induce differentiation and apoptosis of myeloid leukemic cells, as a new treatment approach for patients with myeloid sarcoma. We have shown that short-course (3 to7 days) high-dose methylprednisolone treatment that might also induce differentiation and apoptosis of leukemic cells in the extramedullary sites resulted in dramatic decreases in the size of myeloid sarcoma in children with or without marrow infiltration. From the results of our long-term clinical studies, we suggest that to use short- course high-dose glucocorticoids combined with intensive chemotherapy protocol would be a promising treatment strategy for patients with myeloid sarcoma. However, in further studies, the prognostic significance of different localization of myeloid sarcoma and the long term effect of the addition of highdose glucocorticoid to intensive AML chemotherapy protocols should be explored in larger series.

Analyses of karyotypic characteristics and prognosis in pediatric acute myeloblastic leukemia

Acute myeloblastic leukemia (AML) accounts for 15 to 25 percent of childhood acute leukemias. Cytogenetic information is important for diagnosis, classification and prognosis of AML. Our aim was to analyze the relationship between karyotypic characteristics and prognosis of childhood AML. According to karyotypic characteristics, 128 newly diagnosed children AML were separated into 4 subgroups: patients with t(15;17) (group APL), patients with t(8;21)/inv(16) (group A), patients with -7/t(9;22)/complex karyotypes (group C) and the others (group B). Prognoses of these patients were analyzed. The ages ranged from 1 to 16 years with the mean age of 7 years. 85 boys and 43 girls were included in this study. The 4-year event-free survival (EFS) and overall survival (OS) rates were (55.9 ± 4.7)% and (69.3% ± 4.5)%, respectively. The 4-year EFS and OS of non-M(3)-AML patients were (49.9 ± 5.2)% and (57.1 ± 6.0)%, respectively. The probabilities of 4-year EFS of the four subgroups were (72.2 ± 1.1)%, (66.3 ± 7.7)%, (38.5 ± 9.1)% and (20.1 ± 12.3)%, respectively (P = 0.000). The probabilities of 4-year OS were (92.6 ± 5.1)%, (69.4 ± 7.9)%, (55.6 ± 8.6)% and (30.0 ± 12.3)%, respectively (P = 0.000). Cytogenetic aberrations seen in pediatric AML had a significant impact on prognosis.

Commentary to ‘Granulocytic sarcoma of the urinary bladder in a pediatric patient’

The authors report, to my knowledge, the first case of granulocytic sarcoma of the bladder in children. Although a rare tumor, it must be kept in mind in the differential diagnosis of urinary bladder tumors with undifferentiated round cell morphology. A biopsy of the mass was considered unnecessary, since blasts in the urine were found and a prompt decrease in tumor size with antileukemic therapy was observed on ultrasound. They did not perform other imaging studies such as PET, MRI and CT. The approach of the authors does not allow a definitive diagnosis of granulocytic sarcoma of the bladder, because that comes from biopsy only. Instead, they made a probabilistic and presumptive diagnosis, but did not rule out with certitude other more common etiologies of vesical masses in this population of young patients. They state that a biopsy of the mass is necessary only when the tumor antedates the hematologic evidence of leukemia or when the tumor does not promptly decrease in size with antileukemic therapy. On the contrary, several other authors report that a biopsy of an extramedullary mass suspected to be a granulocytic sarcoma is recommended in order to avoid misdiagnosis and be able to start treatment promptly and appropriately [1Aki H. Baslar Z. Uygun N. Ozguroglu M. Tuzuner N. Primary granulocytic sarcoma of the urinary bladder: case report and review of the literature.Urology. 2002; 60: 345Abstract Full Text Full Text PDF PubMed Google Scholar, 2Suh Y.K. Shin H.J. Fine-needle aspiration biopsy of granulocytic sarcoma: a clinicopathologic study of 27 cases.Cancer. 2000; 90: 364-372Crossref PubMed Scopus (61) Google Scholar, 3Orucevic A. Reddy V.B. Selvaggi S.M. Green L. Spitz D.J. Gattuso P. Fine-needle aspiration of extranodal and extramedullary hematopoietic malignancies.Diagn Cytopathol. 2000; 23: 318-321Crossref PubMed Google Scholar, 4Tao J. Wu M. Fuchs A. Wasserman P. Fine-needle aspiration of granulocytic sarcomas: a morphologic and immunophenotypic study of seven cases.Ann Diagn Pathol. 2000; 4: 17-22Abstract Full Text PDF PubMed Scopus (14) Google Scholar]. In conclusion, the choice not to perform a biopsy of a vesical mass in a child is questionable, even more when a rare entity, whose imaging and clinical presentation are non-specific, is suspected. Where clinical conditions and coagulative patterns are favourable, it seems wise to perform a biopsy in order to establish with certitude the nature of a vesical mass in a child and to offer the most appropriate treatment with no delay. Granulocytic sarcoma of the urinary bladder in a pediatric patientJournal of Pediatric UrologyVol. 9Issue 1PreviewGranulocytic sarcoma (GS) is a rare tumor consisting of immature cells of granulocytic lineage. It is also called chloroma, referring to the green color of the tumor caused by high levels of myeloperoxidase in the cells. GS is often associated with acute myeloblastic leukemia. We report the case of a 4-year-old boy with a diagnosis of acute myeloblastic leukemia. Abdominal ultrasonography demonstrated a solid, vascularized, heterogeneous, polypoid formation involving the posterior wall of the bladder. Full-Text PDF

Granulocytic sarcoma of the urinary bladder in a pediatric patient

Granulocytic sarcoma (GS) is a rare tumor consisting of immature cells of granulocytic lineage. It is also called chloroma, referring to the green color of the tumor caused by high levels of myeloperoxidase in the cells. GS is often associated with acute myeloblastic leukemia. We report the case of a 4-year-old boy with a diagnosis of acute myeloblastic leukemia. Abdominal ultrasonography demonstrated a solid, vascularized, heterogeneous, polypoid formation involving the posterior wall of the bladder. Further studies confirmed the etiology of the tumor. On control ultrasonography, a marked decrease in tumor size 15 days after treatment was revealed. We describe the imaging findings in this patient and review the literature about this infrequent entity. Although imaging findings are not specific and considering that extramedullary involvement in leukemia is very sensitive to treatment, inclusion of GS in the differential diagnosis and awareness of the possible sites of occurrence and imaging features is essential to avoid unnecessary therapeutic measures.

Autologous Hematopoietic Recovery with Aberrant Antigen Expression after Allogeneic Bone Marrow Transplantation

A 50-year-old woman was admitted in December 2006 with progressive petechiae. Bone marrow (BM) aspiration showed massive proliferation of leukemic myeloblasts with myeloperoxidase staining. Three-color flow cytometry (FCM) with a CD45 gate for the BM cells was performed in our laboratory ; the blasts were positive for CD7, CD11c, CD13, CD15, CD33, myeloperoxidase and HLA-DR and negative for CD34 and CD117. Karyotypes of the BM cells were normal. A diagnosis of acute myeloblastic leukemia (AML)M2 was made on the basis of French-American-British classification. The patient needed standard induction chemotherapy twice to achieve complete remission. Refractoriness to platelet transfusions due to anti-HLA antibody developed. She received an allogeneic BM transplant from an ABOmatched and HLA-DR-mismatched unrelated female donor in September 2007. The conditioning regimen consisted of total body irradiation (2 Gy twice daily for 3 days) followed by cyclophosphamide (60 mg/kg/day for 2 days). On day 0, 4.0 × 10 BM cells per recipient body weight were infused. Tacrolimus and short-course methotrexate were used as prophylaxis for graft-versus-host disease. After BM transplantation, severe pancytopenia persisted. BM aspiration on day 22 revealed marked hypocellularity, suggesting graft rejection. Peripheral blood neutrophils gradually increased from day 50. BM aspiration smears on day 75 showed recovery of the BM cells, especially myeloid cells, without significant morphologic abnormalities and proliferation of myeloblasts, indicating that complete remission was maintained. Chromosomal analysis of the BM cells showed various cytogenetic abnormalities (Table 1). A chimerism-based analysis of the BM cells using short tandem repeat-polymerase chain reaction showed that 100% of the cells originated from the recipient. A diagnosis of autologous (recipient) hematopoietic recovery after graft rejection was made. Multiparametric FCM based on a four-color method (ReproCELL, Yokohama, Japan), which had been approved by the Jichi Medical University Institutional Review Board (no. 06-70), did not show the abnormal expression of antigens in the blasts in the BM on days 75 and 183. However, it showed small populations of CD34CD7 cells and CD34CD15 cells in the blasts on day 253 (Fig. 1). The latter cells were characterized by a high intensity of CD34, which indicates abnormal expression of the antigen. BM aspiration was performed every three to six months ; various chromosomal abnormalities of BM cells were found in each sample (Table 1). After day 253, routine three-color FCM instead of the multiparametric FCM was conducted to analyze phenotypes of the blasts in the BM. This FCM can detect CD34CD7 cells but not CD34CD15 cells because of antibody combinations. The proportions of CD34CD7 cells among the blasts of the BM were as follows : on day 323, 37.2% ; on day 421, 30.9% ; on day 603, 35.5% ; on day 785, 21.5% ; on day 975, 49.2% ; on day 1,149, 36.0% ; and on day 1,232, 24.5%. Although chromosomal abnormalities were detected on and after day 75, obvious dysplastic features associated with myelodysplastic syndrome (MDS) were not found. The patient is clinically well with normal peripheral blood cell counts. There are several reports on autologous (recipient) hematopoietic recovery after allogeneic hematopoietic stem cell transplantation. All patients received total body irradiation

In Memoriam, Dr. Abhijit Guha, 1957-2011

Dr. Abhijit (Ab) Guha passed away peacefully in the early morning hours of November 8, 2011. For 3 years, Ab had been courageously fighting his diagnosis of acute myeloblastic leukemia (AML). He was 54 years old​old.

Trisomy 9 in a Patient with Acute Myelogenous Leukaemia FAB Type M2: A Rare Occurrence

Complete trisomy 9 is a rare cytogenetic abnormality in haematological malignancies. Here we present the case history of a patient with clinical diagnosis of acute myeloblastic leukaemia (FAB type M2) and having trisomy 9 with adverse outcome.

Inversion 16 Leukemia Possible Associated With Familial Sinus Bradycardia And Bridging Of Ribs

Tumor predisposition syndromes might account for a larger percentage of childhood cancers than currently estimated. A 61 years old man admitted for frequent epistaxis attacks in the last 15 days. The patient’s heart rate was 40 beats/min. Sinus bradycardia rhythm was seen in the electrocardiography (ECG) examination and non-specific T waves were present on D3, AVF derivations of ECG. Chest radiography showed only bridging between anterior portion of second and third ribs. The diagnosis of acute myeloblastic leukemia (AML) with recurrent genetic abnormalitiesinv 16( according to WHO classification) was confirmed by bone marrow biopsy, flow cytometry and genetic evaluation. Constitutional genetic defects should be important for leukemogenic potential.

Population pharmacokinetic analysis of vancomycin in patients with hematological malignancies.

This study determines vancomycin (VAN) population pharmacokinetics (PK) in adult patients with hematological malignancies. VAN serum concentration data (n = 1,004) from therapeutic drug monitoring were collected retrospectively from 215 patients. A one-compartment PK model was selected. VAN pharmacokinetics population parameters were generated using the NONMEM program. A graphic approach and stepwise generalized additive modeling were used to elucidate the preliminary relationships between PK parameters and clinical covariates analyzed. Covariate selection revealed that total body weight (TBW) affected V, whereas renal function, estimated by creatinine clearance, and a diagnosis of acute myeloblastic leukemia (AML) influenced VAN clearance. We propose one general and two AML-specific models. The former was defined by CL (liters/h) = 1.08 x CL(CR(Cockcroft and Gault)) (liters/h); CV(CL) = 28.16% and V (liters) = 0.98 x TBW; CV(V) =37.15%. AML models confirmed this structure but with a higher clearance coefficient (1.17). The a priori performance of the models was evaluated in another 59 patients, and clinical suitability was confirmed. The models were fairly accurate, with more than 33% of the measured concentrations being within +/-20% of the predicted value. This therapeutic precision is twofold higher than that of a non-customized population model (16.1%). The corresponding standardized prediction errors included zero and a standard deviation close to unity. The models could be used to estimate appropriate VAN dosage guidelines, which are not clearly defined for this high-risk population. Their simple structure should allow easy implementation in clinical software and application in dosage individualization using the Bayesian approach.

多剤併用化学療法により完全寛解が得られ1年間生存した分化型骨髄芽球性白血病の猫の1例

A Japanese domestic cat being FeLV-possitive and suffering from depression, anorexia, and vomiting showed severe pancytopenia. Examination of bone-marrow and cytochemical staining led to a diagnosis of acute myeloblastic leukemia with maturation (M2). Combination chemotherapy using vincristine, daunorubicin, cytosine arabinoside, and prednisolone resulted in a complete remission. Thereafter the cat had been kept in a good condition by a low dose administration of cytosine arabinoside. On the 346th day, however, anemia, thrombocytopenia, and leukocytosis of the blast cells appeared. Because the blast cells were negative for both peroxidase and nonspecific esterase, and flow-cytometry analysis of cellular surface markers revealed that the blast cells belonged to the T-cell line, a diagnosis of acute lymphoblastic leukemia had been made. Though treated with vincristine, the cat died on the 368th day.

Rearrangement of MLL in a patient with congenital acute monoblastic leukemia and granulocytic sarcoma associated with a t(1;11)(p36;q23) translocation

Band 11q23 is known to be involved in translocations and insertions with a variety of partner chromosomes. In most cases, they lead to MLL rearrangements, resulting in a fusion with numerous genes. We report here a newborn girl who had disseminated intravascular coagulation and cutaneous tumors (granulocytic sarcomata) in whom a diagnosis of acute myeloblastic leukemia (AML) FAB-M5 was made. Conventional cytogenetics using R-banding showed 11 of the 17 metaphases observed to have a 46,XX,t(1;11)(p36.2;q23) karyotype. FISH analysis confirmed the disruption of the MLL gene. Two adult patients solely have been found to have a t(1;11)(p36;q23); however, no FISH analysis with a MLL probe was performed in both cases. Since the diagnosis was made at birth, this implies that the MLL rearrangement and the onset of the disease occurred in utero. Twenty children, including 3 newborns, have been reported to have granulocytic sarcoma associated with 11q23/MLL rearrangement. To the best of our knowledge, this is the first report of a case of congenital AML with GS arising in a patient with proven MLL rearrangement.

Life-threatening neurological complications after bone marrow transplantation in children

Neurological complications may occur in BMT recipients (11-59%), frequently contributing to morbidity or mortality. They are the main causes of death in 10-15%. Life-threatening neurological complications were seen in 11 out of 113 (9.7%) children who underwent BMT from HLA-matched family (n=7) or mismatched donors (n=4) at our institution. Diagnoses of patients with neurological complications were acute myeloblastic leukemia (AML) (five), thalassemia major (two), Fanconi anemia (two), Omenn syndrome (one) and leukodystrophy (one), and the neurological events were seen between days +13 and +85 after transplantation. Minor symptoms including reversible, nonrepetitive seizures were excluded. Cyclosporine A toxicity was diagnosed in six children. The rest of the complications were brain abscess/meningoencephalitis (two), severe hypomagnesemia (one), busulfan toxicity (one), sustained hypertension (three), and intracranial hemorrhage (three). Six patients with neurological complications suffered from >grade II graft-versus-host disease (GvHD), and all were high risk for transplant-related complications. In this study, risk status of the underlying disease, mismatched transplantation, a diagnosis of AML (advanced stage), older age and >grade II GvHD were important adverse factors for the development of severe life-threatening neurological complications.