Concomitant Acute Myeloid Leukemia Research Articles

An unusual case of hepatosplenic T-cell lymphoma-like unclassifiable T/NK-cell lymphoma accompanied by acute myeloid leukemia.

We describe a case of unclassifiable T/NK-cell lymphoma with concomitant acute myeloid leukemia (AML). A 73-year-old Japanese man was diagnosed with AML by bone marrow smear, but the presence of splenomegaly and liver tumor was incompatible with AML. Splenectomy and hepatic resection were performed to resolve the thrombocytopenia and define the diagnosis. The pathological findings showed sinusoidal involvement of abnormal lymphoid cells that were CD3-positive but negative for T-cell receptor (TCR) rearrangement. Our case could not be categorized as hepatosplenic T-cell lymphoma because of the lack of immunohistological expression of TCR, despite the clinical similarity.

Acute myeloid leukemia causing acute thrombosis of the\xa0coronary arteries: a\xa0case report

BackgroundThis case report demonstrates acute myeloid leukemia causing acute thrombosis of coronary arteries with anterolateral ST elevation myocardial infarction and ventricular tachycardia in an otherwise healthy woman. Few case reports have been documented on patients with concomitant conditions of acute myeloid leukemia and acute myocardial infarction, and it is important to note that prognosis for patients with both is worse than that of either condition. While both conditions together are rare, other non-atherosclerotic causes of acute coronary syndromes are likewise important considerations in the context of myocardial ischemia.Case presentationA 59-year-old Caucasian woman with no notable past medical history presented to her primary care provider with 2 weeks of severe fatigue, anorexia, and malaise, associated with chills, night sweats, and myalgias. Peripheral blood smear identified 92% blasts consistent with acute myeloid leukemia and computed tomography identified a right segmental pulmonary embolism and thrombotic infarcts in the spleen, bilateral kidneys, right lung, and liver. Laboratory testing also demonstrated disseminated intravascular coagulopathy. She was admitted to the intensive care unit for treatment and subsequently developed ventricular tachycardia, anterolateral ST segment elevation, acute dysarthria, and nonreactive pupils. Pulseless electrical activity developed with unsuccessful resuscitative measures. The patient died secondary to presumed cerebrovascular and coronary thromboses causing stroke and anterolateral infarct complicated by ventricular tachycardia and pulseless electrical activity.ConclusionThis case is notable as a case of acute myeloid leukemia causing acute thrombosis of coronary arteries with anterolateral ST elevation myocardial infarction, ventricular tachycardia, and pulseless electrical activity. Prognosis of concomitant acute myeloid leukemia and acute myocardial infarction is poor. Management is challenging due to thrombocytopenia, platelet dysfunction, and systemic coagulopathy, and administration of thrombolytic agents can be fatal. This is an extreme presentation of a case of acute myocardial infarction with disseminated intravascular coagulopathy causing acute coronary thrombosis and sudden death with dramatic electrocardiogram and telemetry findings recorded with rapid progression from normal sinus rhythm to acute myocardial infarction to terminal rhythm.

An Unusual Case Of Disseminated Histiocytic Sarcoma Preceded By Myeloid Sarcoma With Concomitant Acute Myeloid Leukemia

Abstract Introduction/Objective Histiocytic sarcoma (HS) is rare (<1% of hematolymphoid neoplasms), and can present extranodally as disseminated disease. Immunophenotypically, the cells express CD163, CD68, lysozyme and CD45. HS often occurs as a secondary event following B-cell lymphomas, acute lymphoblastic leukemia or acute myeloid leukemia (AML) typically with monocytic differentiation retaining the same molecular/cytogenetic abnormalities as the primary tumor. Results Our patient, a 47 year old male was diagnosed with myeloid sarcoma (MS) following FNA of a new neck mass. A bone marrow biopsy revealed AML without monocytic differentiation. Flow cytometric findings of both marrow and neck mass were similar (positive for CD34, CD117, CD33, CD11b, CD13, CD15, CD64, CD7; negative for CD4, CD14, CD56). Karyotypic and FLT3 ITD mutation analysis were normal. CNS involvement was diagnosed 2 months later, while a marrow biopsy (status post therapy) confirmed resolution of AML. A hypermetabolic left perinephric mass noted by PET CT, when biopsied, showed large epithelioid polygonal cells with amphophilic cytoplasm and atypical vesicular nuclei (positive for CD68, PU.1; negative for LCA, CD163, CD34, CD4, pankeratin). A diagnosis of atypical epithelioid neoplasm suggestive of HS was rendered, although negativity for LCA and CD163 was unusual. No treatment was given for HS. A month later, the patient presented with a cheek mass diagnosed again as being suggestive of HS. His AML also relapsed. Next-generation sequencing (37 genes including BRAF) from both marrow and tissue samples detected the presence of a nonsense mutation in exon 7 of WT1 (p.Ser169). Conclusion Our case appears to be the first reported one of disseminated HS preceded by MS and concomitant AML, lacking monocytic differentiation. The findings overall support the hypothesis of origin as being from a common progenitor cell differentiating along both myeloid and histiocytic/other cell lineages at different time points.

Clinicopathological, Cytogenetic, and Prognostic Analysis of 131 Myeloid Sarcoma Patients.

Myeloid sarcoma (MS) is an extramedullary tumor of immature myeloid cells. We analyzed 131 patients with MS, including: (1) de novo MS; (2) MS with concomitant acute myeloid leukemia (AML); (3) MS following myelodysplastic syndrome, myeloproliferative neoplasm, or chronic myelogenous leukemia; and (4) MS as a recurrence of AML. The most common development site was the lymph node. Testicular lesions were statistically more frequent in MS as a recurrence of AML than in other types of MS (P=0.0183). MS tended to lack myeloid markers (myeloperoxidase was present in 63.2%, CD68 in 51.3%, CD13 in 48.7%, and CD33 in 48.7% of patients) and express T-cell markers such as CD3 (20.7%) and CD5 (34.2%). All T-cell marker-positive MS cases were negative for the αβ and γδ T-cell receptors on immunohistochemistry. Underlying myelodysplastic syndrome or myeloproliferative neoplasm was a poor prognostic factor (vs. de novo MS: P=0.0383; vs. MS with concomitant AML: P=0.0143). However, there was no statistical difference in prognosis between de novo MS and MS with concomitant AML (P=0.288). There were no significant differences in prognosis between the prognoses of T-cell marker-positive and T-cell marker-negative MS cases. In addition, CXCR4 expression was a poor prognostic factor in MS (P=0.0229). This study involves the largest MS cohort to date and expands the clinical and pathologic knowledge of the disease.

Determination of D816V mutation in the c-kIt gene in the Slovenian patients with acute myeloid leukemia and systemic mastocytosis

Background: D816V mutation in the C-KIT gene is present in more than 90 % of patients with systemic mastocytosis (SM) and 2–7 % of patients with acute myeloid leukemia (AML). D816V mutation is caused by the substitution of adenine with thymine at 2447 nucleotide sequence in the C-KIT gene. This nucleotide substitution causes the replacment of aspartate acid by valine at codon 816 of the KIT protein. KIT protein with D816V mutation acts as constitutively active tyrosine kinase that promotes cell proliferation and inhibits apoptosis. The purpose of our study was to determine the incidence of D816V mutation in the C-KIT gene in Slovenian patients with AML and in patients with suspected systemic mastocytosis. Patients and methods: In the retrospective study, 71 patients with AML and 25 patients with suspected systemic mastocytosis were included. D816V mutation in the C-KIT gene was determined by polymerase chain reaction (PCR) and the resulting PCR products were analyzed by agarose gel electrophoresis. Results: D816V mutation in KIT protein was determined in 7 % of patients with AML and in 32 % patients with suspected systemic mastocytosis. Conclusions: Identification of D816V mutation in the C-KIT gene must always be performed in patients with suspected systemic mastocytosis. The determination of this mutation contributes to the diagnosis and treatment selection. The finding of D816V mutation in the C-KIT gene in patients with AML and concomitant genetic modifications RUNX-RUNX1T1 (typical translocation t(8; 21) (q22, q22)) or CBFB-MYH11, which is the result of inversion on chromosome 16–(inv (16) (p13, q22)), however, indicates a faster, more aggressive course of the disease and predicts a worse outcome. The finding of the mutation in other patients with AML may indicate the presence of concomitant AML and SM, which was not found in our patients.

Clinical implications of acute myeloid leukemia presenting as myeloid sarcoma

In this retrospective study, we aim to analyze the characteristics, treatments, and overall survival of all patients presenting with isolated myeloid sarcoma (MS) or MS with concomitant acute myeloid leukemia (AML) compared with all patients with AML, treated during the same period. We identified patients with AML with or without MS at diagnosis, presenting to our medical center between the years 1990 and 2005. There was no statistically significant difference between the groups regarding gender, age, cytogenetic risk groups, rate of complete remission, number of cycles of chemotherapy needed to achieve complete remission, and rate of first relapse. The time to death in the MS group was not significantly different (p = 0.60) from the AML group, and radiotherapy did not affect the median time to death. Transplantation prolonged survival in both groups (p = 0.018 and p < 0.0001, respectively). Patients with MS at diagnosis might benefit from upfront aggressive treatment with hematopoietic stem cell transplantation.

Clinical Implications of Acute Myeloid Leukemia Presenting as Granulocytic Sarcoma

AbstractAbstract 2155 Introduction:Granulocytic sarcoma (GS), also known as chloroma, is described as an extramedullary tumor composed of immature myeloid cells. It has been reported to develop in 2–8% of patients with acute myeloid leukemia (AML) and can occur prior to, concomitantly with, or following the diagnosis of AML. Rarely patients present with GS as an isolated mass without evidence of AML (Byrd JC, J Clin Oncol. 1997). Due to the rarity of this disorder, large series of patients are seldom reported and the prognosis and optimal treatment of patients presenting with GS are not clear. Objectives:In this retrospective study we analyzed the presenting characteristics, treatments and overall survival of all patients presenting with isolated granulocytic sarcoma (GS) or GS with concomitant acute myeloid leukemia (AML) at presentation and compared them to all AML patients, treated at our institution during the same period. Methods:We identified cases who were diagnosed as having GS (with or without bone marrow involvement by AML) and cases of AML (without evidence GS at diagnosis) using ICD-9 codes in the hospitalization data base of the Hadassah Medical Center between 1990 and 2005. We excluded patients with GS at the time of relapse. All GS cases were biopsy-proven. Results:The study population consisted of 19 GS and 235 AML non-GS patients. The median age of these patients was 41 and 48 years, respectively. There was no statistically significant difference between the groups regarding gender, age, cytogenetic risk groups, rate of complete remission (CR), number of cycles of chemotherapy needed to achieve CR and rate of first relapse. Hematopoietic stem cell transplant (HSCT) (either autologous or allogeneic) was performed in 10 of 19 patients (52.6%) in the GS group and in 66 of 235 (28.1%) in the AML group (p=0.025). The overall survival in the GS group (median 16 months) was not significantly different (p= 0.60) from the AML group. The median time to death in subjects who had radiotherapy (6/19) was identical (median 21 months, p=0.79) to that of subjects who did not receive radiotherapy. Transplantation was associated with prolonged survival in both GS and AML groups (p=0.018 and p<0.0001 respectively). At the end of the follow up, 4 patients in the GS group who underwent HSCT were alive, compared to none in the group who did not undergo HSCT. Karyotype was found to be a prognostic factor in both the GS and AML groups (p=0.0034 and p<0.0001 respectively). In a multivariate analysis there was no statistically significant difference in the risk of death between subjects in the AML and the GS group; hazard ratio (HR) = 0.83, 95% CI (0.456-1.516), p=0.55, after controlling for age, karyotype and transplantation. As expected, in the model, age less than 47.5 years (HR=0.646 (p=0.0022)) and favorable and intermediate karyotype (HR=0.13 (p<0.0001) and HR=0.44 (p<0.0001) respectively, compared to unfavorable) were associated with a lower risk of death. Subjects who did not undergo transplantation had an increased risk of death compared with subjects who underwent the procedure (HR=1.88, p=0.0023) (Fig. 1). Conclusions:To the best of our knowledge this is the first retrospective series of GS patients with concomitant AML at diagnosis compared to all other AML patients in one medical center. The addition of radiotherapy as a treatment modality for GS patients did not appear to change survival. Patients with GS at diagnosis might benefit from upfront aggressive treatment with HSCT. Due to the rarity of this disorder and the remaining open questions, a prospective multi-center study is necessary to address these issues. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Concurrent acute myeloid leukemia with inv(16)(p13.1q22) and chronic lymphocytic leukemia: Molecular evidence of two separate diseases

Acute myeloid leukemia (AML) occurring concurrently with or after untreated chronic lymphocytic leukemia (CLL) is rare. We report a case of a 59-year-old man who was evaluated for anemia, thrombocytopenia, and leukocytosis with circulating blasts. On the basis of the morphology and immunophenotyping results, a preliminary diagnosis of chronic myelomonocytic leukemia with concurrent CLL was considered. Subsequently, cytogenetic analysis of the leukemic blood specimen revealed inv(16)(p13.1q22) with secondary trisomy 22 in a sideline clone. Fluorescence in situ hybridization confirmed the CBFbeta rearrangement associated with inv(16) in myeloblasts and myelomonocytic cells, but not in CLL cells. Therefore, a final diagnosis of AML with inv(16) with concurrent CLL was made. After standard chemotherapy for AML, the patient achieved complete remission for both his AML and CLL. The unique aspects of this case include concomitant AML and CLL, which do not share clonality, complex cytogenetic abnormalities with trisomy 22 as a secondary abnormality associated with inv(16), and achievement of remission for both AML and CLL by AML chemotherapy regimen. This case also represents one of the rare instances where a diagnosis of AML can be established even when the blast percentage in the marrow and blood is less than 20%.