Pediatric chronic myeloid leukemia in myeloid blast crisis

ABSTRACT Chronic myeloid leukemia (CML) accounts for 2-3% of childhood leukemias. About 5% of cases present in a blastic phase of CML which clinically and morphologically mimics more common acute leukemias of childhood. We report a case of a 3-year-old male who presented with gradual onset swelling of the abdomen and extremities along with generalized weakness. Examination revealed massive splenomegaly, pallor, and pedal edema. Initial workup showed anemia, thrombocytopenia, and leukocytosis (120,000/uL) with a blast percentage of 35%. Blasts were positive for CD13, CD33, CD117, CD34 and HLA-DR, and stained negative for Myeloperoxidase and Periodic Acid Schiff. Fluorescence in situ hybridization was positive for b3a2/e14a2 junction BCR-ABL1 transcript and negative for RUNX1-RUNX1T1/t(8;21), clinching the diagnosis of CML in myeloid blast crisis. The patient expired within 17 days of diagnosis and initiation of therapy.

Interleukin 6 and disease transformation in chronic myeloid leukemia: A Northeast Indian population study

Objective: Growth factor independence 1 (GFI1), a transcriptional repressor, is required for hematopoietic stem cell maintenance and self-renewal in addition to controlling differentiation and proliferation of myeloid cells. As murine studies have demonstrated that this transcription factor has a notable role in the initiation and progression of acute myeloid leukemia (AML) disease, the aim of the current study was to investigate and review the influence of GFI1 in human AML cells. Methods: GFI1 expression levels were measured by means of real-time polymerase chain reaction in 96 primary AML samples which were then compared to gene expression levels observed in 18 healthy subjects. Moreover, GFI1 expression patterns were analyzed based on specific AML subtypes including acute promyelocytic leukemia (APL). Finally, leukemic cells were stained to measure levels of myeloperoxidase (MPO) activity. Results: This study reports that AML patients have significantly higher GFI1 mRNA levels in comparison to healthy subjects and that, when considering AML subtypes, patients with APL have higher GFI1 expression than non-APL patients. Conclusion: It is also concluded that GFI1 overexpression in patients with high MPO levels, such as those of the APL subtype, is correlated with favorable disease prognosis as supported by other studies which demonstrate that increased peroxide activity and GFI1 are independently correlated with a favorable prognosis

Bilineage T‑lymphoblastic/myeloid extramedullary blast crisis in chronic myelogenous leukemia.

The blast crisis of chronic myelogenous leukemia (CML) can be hematological or extramedullary. About 25% of these cases fulfill the criteria for mixed phenotype acute leukemia. We here report a case of a second blast crisis of CML which was extramedullary and was immunophenotypically bilineage T/myeloid.

Gen de fusión AML-1/ETO y mutación NPM-1A en leucemia mieloide crónica en crisis blástica mieloide / AML-1/ETO fusion gene and mutation NPM-1A in myeloid chronic leukemia in myeloid blast crisis

La leucemia mieloide crónica es una neoplasia mieloproliferativa de naturaleza clonal que generalmente y de manera progresiva transita por tres fases: crónica, acelerada y crisis blástica. Alrededor del 80 por ciento de los enfermos con leucemia mieloide crónica son diagnosticados durante la fase crónica, 10 por ciento en fase acelerada y otro 10 por ciento durante la crisis blástica. A la presencia del cromosoma Filadelfia y la formación del gen de fusión BCR/ABL, que se traduce en la proteína quimérica pBCR/ABL, le sigue una gran inestabilidad genómica y la adquisición de alteraciones cromosómicas y moleculares adicionales. Algunas alteraciones moleculares, que suelen estar presentes en otras hemopatías malignas, pueden ser adquiridas durante la progresión de la leucemia mieloide crónica a crisis blástica. Se presenta el caso de un paciente que debutó con una leucemia mieloide crónica en crisis blástica, con positividad del gen de fusión BCR/ABL, el gen de fusión AML-1/ETO y la mutación NPM-1A(AU)

Chronic myeloid leukemia is a clonal myeloproliferative neoplasm which generally and progressively goes through three phases: chronic, accelerated and blast crisis. About 80 percent of patients with chronic myeloid leukemia are diagnosed in chronic phase, 10 % in accelerated phase and 10 percent in blast crisis. The presence of Philadelphia chromosome and the formation of BCR/ABL fusion gene, resulting in the chimeric protein pBCR/ABL, generates a large genomic instability and the acquisition of additional chromosomal and molecular alterations. Some molecular alterations, which are usually present in other hematological malignancies, could be acquired during the progression of chronic myeloid leukemia to blast crisis. This report presents the case of a patient with de novo chronic myeloid leukemia in blast crisis, with positivity of BCR/ABL fusion gene, AML-1/ETO fusion gene and mutation NPM-1A(AU)

Imatinib resistance in chronic myelogenous leukemia: an emerging challenge.

Resistance to imatinib is a significant clinical issue, and the underlying mechanism of this resistance is multifactorial. The efficacy of imatinib in chronic myeloid leukemia (CML) in achieving a high remission rate and improving prognosis has seriously been challenged by the development of mutants of BCR-ABL gene, which resist the action of imatinib, which is a tyrosine kinase inhibitor. We present here a case of a 35-year-old male, a known case of CML on imatinib therapy, the patient eventually landed in blast crisis and succumbed to the disease and secondary infections.

Imatinib mesylate as first‑line therapy in patients with chronic myeloid leukemia in accelerated phase and blast phase: A retrospective analysis.

INTRODUCTION: Imatinib is a bcr‑abl tyrosine kinase inhibitor which has revolutionized the treatment for chronic myeloid leukemia (CML). Even though there is much data on CML chronic phase, there is limited data on imatinib‑naïve advanced phase CML. MATERIALS AND METHODS: We retrospectively analysed 90 patients with advanced phase CML (accelerated phase [AP]: 51 and blast crisis [BC]: 39), patients who received imatinib as frontline therapy. RESULTS: The median age of presentation in CML‑AP and CML‑BC were 32 years (12‑61) and 39 years (8‑59), respectively. Imatinib at 600 mg/day was initiated within 2 weeks of diagnosis. Median time to complete hematological response in both CML‑AP and CML‑BC was 3 months (CML‑AP: 1‑9 months and CML‑BC: 1‑14 months). At 6 months 30 (59%) CML‑AP and 15 (38%) CML‑BC patients achieved major cytogenetic response (MCyR), of them 24 (47%) and 10 (25.6%) being the complete cytogenetic response, respectively. At a median follow‑up of 41 months, the median overall survival in CML‑AP was 61 months, but in CML‑BC it was 14 months. The median progression‑free survival and event‑free survival were 30 months and 23 months in CML‑AP and 14 and 12 months in CML‑BC, respectively. On univariate analysis, performance status (PS), spleen size, and MCyR predicted survival in AP, whereas in BC, platelet count, PS, and early MCyR were predictive. Non‑hematologic and hematologic adverse events were observed in 80% and 60% of patients, respectively. Dose was reduced in 10% of patients for grade IV toxicity and interrupted in 30% for grade III toxicity. CONCLUSION: Front‑line imatinib is an option in advanced phases of CML especially in CML‑AP in low‑resource countries, where stem cell transplantation and alternate TKIs are not available.

Allogeneic hematopoietic stem cell transplantation for the treatment of chronic myeloid leukemia in blast crisis / 白血病·淋巴瘤

The treatment for chronic myeloid leukemia is still a challenge,at present.Tyrosine kinase inhibitors can partially control chronic myeloid leukemia in blast crisis (CML-BC),but the effect is not durable.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way that can cure CML-BC.This paper presents a review of the treatment before allo-HSCT for CML-BC,the selection of condition regimen,donor and hematopoietic stem cell,the monitoring of MRD post-transplant,the prophylaxis and intervention of relapse.

Extramedullary B Lymphoblastic Crisis of CML, Presenting as a Leptomeningeal Tumor: A Case Report

We report here on a rare case of a patient who presented with an extramedullary B lymphoblastic crisis as an initial manifestation of chronic myelogenous leukemia (CML). A 71-year-old man visited the emergency room due to suddenly developed dysarthria and right side weakness. Emergency craniotomy was done under the presumptive diagnosis of subdural hemorrhage. During the operation, a poorly demarcated firm mass was identified in the leptomeningeal space. Microscopically, the majority of the tumor was composed of monotonous immature cells with blast morphology, and these cells were immunoreactive for TdT, CD34, CD10 and CD20, indicating the precursor B-cell phenotype. The peripheral area of the tumor consisted of myeloid cells in various stages of maturation, and these cells were reactive for myeloperoxidase, chloroacetate esterase, CD43 and CD15. FISH analysis using the LSI bcr-abl dual color probe showed gene fusion signals in both the B-lymphoblasts and myeloid cells. The peripheral blood and bone marrow findings were consistent with CML with no evidence of a blast crisis. Cytogenetic study of the bone marrow demonstrated the 46, XY, t(9;22)(q34;q11) chromosome. A diagnosis of extramedullary B lymphoblastic blast crisis in a patient with Philadelphia chromosome-positive CML was made. Despite treatment, the patient died 3 months after he was diagnosed.

Tumor Lysis Syndrome in Lymphoblastic Crisis of CML

Tumor lysis syndrome (TLS) defines the metabolic derangements that occur with tumor breakdown following the initiation of cytotoxic therapy. TLS results from the rapid destruction of malignant cells and the abrupt release of intracellular materials and their metabolites into the extracellular space. The syndrome causes hyperuricemia, hyperkalemia, hyperphosphatemia, secondary hypocalcemia and uremia. It can result in acute renal failure and be fatal. Early recognition of patient at risk and preventive measures are important. There is a high incidence of TLS in tumors with high proliferative rates and large burden such as acute lymphoblastic leukemia and Burkitt's lymphoma. It less commonly occurs in solid tumors such as testicular cancer, breast cancer and small cell lung cancer. There are only a few reports on TLS complicated in CML in blast crisis. So we report a 45-yr-old woman presenting with TLS associated with CML in lymphoblastic crisis after the initiation of cytotoxic chemotherapy.

Erythroleukemic Blast Crisis of Chronic Myeloid Leukemia / 대한진단검사의학회지

Erythroleukemic blast crisis of chronic myeloid leukemia (CML) is very rare. We report two cases of erythroleukemic blast crisis of CML resistant to imatinib treatment. Both patients made a rapid progression to blast crisis 6 and 4 months after diagnosis while being treated with imatinib 400 mg/day. Bone marrow aspiration revealed predominant erythroid precursors with 65.4% and 54.8% each. There were significant proportions (more than 20%) of myeloblasts among non-erythroid cells. Immunophenotyping revealed expression of glycophorin A confirming erythroleukemic blast crisis. The karyotyping result of patient 1 was 46,XX,t(9;22)(q34;q11.2)[3]/52,idem,+8,+12,+18,+21,+22,+der(22)t(9;22)[17] and that of patient 2 was 46,XX,inv(3)(q21q26.2),t(9;22)(q34;q11.2)[20]. Patient 1 showed no response to imatinib and BMS-354825 in the following bone marrow study. She died of septic shock as a complication of an infection after 69 days of blast crisis. Patient 2 received allogeneic bone marrow transplantation (BMT) in the cytogenetically no response state, but she also died of graft-versus-host disease 9 weeks after BMT. The poor prognosis and rapid progression of disease in both cases were correspondent to most of the reported cases. During the course of the disease of the two patients, we monitored the BCR-ABL chimeric mRNA with real-time quantitative polymerase chain reaction (RT-PCR), and it was found useful in predicting the imatinib response and progression to blast crisis of CML. Although both of our cases showed the typical bad prognosis and findings of erythroleukemic blast crisis of CML, the karyotypes were different from the expected type of t(3;21)(q26;q22). But the relationship between additional changes of EVI1 on chromosome 3q26 shown in case 2, and progression to the erythroleukemic blast crisis need further investigation.

A Case of Myeloid Blast Crisis of Atypical Chronic Myelogenous Leukemia / 대한혈액학회지

Atypical chronic myelogenous leukemia (aCML) has dysplastic as well as proliferative features in most instance and rarely evolves to blast crisis, so it is considered as a distinct clinical entity to classical BCR-ABL (+) CML. We experienced a patient who are diagnosed aCML and transformed to myeloid blast crisis after 17 months. Monosomy 7 and deletion of 12p were found on conventional cytogenetics.

Mantle Cell Lymphoma, Blastoid Variant, Diagnosed on the Basis of Cytomorphology and Flow Cytometric Immunophenotyping of the Lymph Node Aspirate and Peripheral Blood

Mantle cell lymphoma, blastoid variant (B-MCL), is a very rare type of non-Hodgkin 's lymphoma exhibiting an aggressive clinical course. We describe a case of B-MCL showing generalized lymphadenopathy and leukemic conversion in a 62-yr-old man. The case was diagnosed and subclassified as B-MCL on the basis of cyto-morphology and immunophenotype. Microscopic examination of the peripheral blood (PB) showed a spectrum of cells ranging from small mature lymphocytes to medium- and large-sized lymphocytes with blast-like chromatin and prominent nucleoli. The lymphoma cells were monoclonal B cells with moderately intense surface IgM. They were CD5 positive, cyclin D1 positive, CD10 negative, and CD23 negative. The flow cytometric immunophenotyping and DNA ploidy analysis of the PB and material obtained by aspiration cytology supported the diagnosis of B-MCL. These findings underline the utility of aspiration cytology in diagnosing B-MCL when cytomorphologic examination is combined with flow cytometric analysis of immuno-phenotype and demonstration of proliferation markers.

Two Cases of Erythroleukemic Blast Crisis in Chronic Myelogenous Leukemia / 대한임상병리학회지

The erythroleukemic blast crisis in chronic myelogenous leukemia (CML) is rarely reported. We present two cases of erythroleukemic blast crisis of CML. In both cases, they had been treated with interferon and hydroxyurea prior to a blast crisis of CML. On blastic transformation, one patient underwent an acute clinical transformation marked with fever and hematochezia but the other showed no clinical deterioration. The blasts appeared in the peripheral blood. The bone marrow aspirates revealed megaloblastic erythroid hyperplasia (about 72%, 54% of all nucleated cells), increasing the number of myeloblasts (about 46%, 59% of all non-erythroid cells), and erythroblasts with a positive PAS stain. The cytogenetic studies revealed Philadelphia chromosomes with additional chromosomal abnormalities, t(3;21)(q26;q22) and the FISH studies revealed bcr-abl fusion signals in bone marrow cells. One case expired 8 months later despite of hydroxyuria therapy. The other case received allogeneic bone marrow transplantation (alloBMT) without complete remission but expired 34 weeks after alloBMT due to GVHD.

The incidence of ABL Deletion on Derivative 9 Chromosome in Chronic Myelogenous Leukemia by Interphase Fluorescence In Situ Hybridization and its Association with Progression to Blast Crisis / 대한임상병리학회지

BACKGROUND: Philadelphia(Ph) chromosome is found in about 95 percent of chronic myelogenous leukemia(CML) patients. Ph chromosome results from a reciprocal translocation between the long arms of chromosomes 9 and 22, and the fusion gene, BCR-ABL contribute to oncogenesis. Three to five years after first diagnosis, CML progresses to the blast crisis, and is accompanied by secondary cytogenetic changes in about 85% of cases. In this study, we investigated the incidence of ABL deletion of derivative 9 chromosome in CML and evaluated the association between this deletion and progression to the blast crisis by interphase fluorescence in situ hybridization(FISH). METHOD: The subjects included in this study were a consecutive series of 58 patients who were diagnosed as CML at Seoul National University Hospital between January 1997 and April 2000. On 90 archival bone marrow aspirate samples from these 58 CML patients, interphase FISH was performed with a commercially available probe. RESULTS: The ABL deletion of derivative 9 chromosome was detected in 17(29.3%) of 58 patients with CML. Eighteen of 58 patients progressed to blast crisis in this period. ABL deletion was found in 7 of 18 patients with blast crisis, and not in 11 remainders. The mean duration from the diagnosis to blast crisis was 37.1 months in 7 patients with the ABL deletion, while the mean duration was 74.2 months in 11 patients without the ABL deletion. The mean duration from the diagnosis to blast crisis in patients with ABL deletion was significantly shorter than in patients without ABL deletion(P=0.043). CONCLUSIONS: We found that 29.3% of patients with CML had the ABL deletion on derivative 9 chromosome. In these patients, the time taken for evolution to blast crisis was significantly shorter than that of the patients without ABL deletion.

ider (9) (q10)t (9;22) (q34;q11.2) as Secondary Karyotypic Aberration of Chronic Myelogeous Leukemia / 대한임상병리학회지

Although occasional patients with chronic myeloid leukemia (CML) have chromosomal changes other than Philadelphia chromosome early in the disease, in typical cases the 9;22 translocation remains the sole abnormality throughout the disease course in chronic phase. When disease progression occurs, however, 75-80% develop additional chromosome aberrations. These secondary changes sometimes precede the more aggressive manifestations hematologically and clinically and thus may serve as valuable prognostic indicators. ider (9) (q10)t (9;22) (q34;q11.2) is very rare and a recurrent chromosomal abnormality associated with acute lymphoblastic leukemias (ALL) and lymphoblastic crisis of CML. And ider (9) (q10)t (9;22) (q34;q11.2) is a lymphoid-specific rearrangement and the patients with this abnormality are of older age on average. They commonly show pre-B cell lineage immunophenotype and L2 morphology. We report a case of ider (9) (q10)t (9;22) (q34;q11.2) as secondary aberration in a patient with lymphoblastic crisis of CML.