Auer Rods Research Articles

British Society for Haematology guidelines for the diagnosis and evaluation of prognosis of Adult Myelodysplastic Syndromes.

British Society for Haematology guidelines for the diagnosis and evaluation of prognosis of Adult Myelodysplastic Syndromes.

Cup-like blasts in acute myeloid leukaemia with NPM1 and IDH2 mutations.

An 86-year-old woman presented with fever and pneumonia. Her laboratory investigations showed leucocytosis (15 × 10⁹/L) with 92% blasts, anaemia (haemoglobin 5.5 g/dl), thrombocytopenia (platelet 31 × 10⁹/L), and elevation of fibrinogen degradation products (FDPs > 120 μg/ml). The patient refused bone marrow examination. Hypogranular blasts without Auer rods containing nuclear invagination, the so-called “cup-like” or “fish-mouth” appearance, accounted for approximately 17% of the blasts in peripheral blood. Blasts were strongly positive for myeloperoxidase and showed normal female karyotype (46,XX) [Figure 1]. The immunophenotypic features of the blast included expression of CD13(dim), CD33 and CD56 and absence of CD34 and HLA-DR expression, which mimicked those of acute promyelocytic leukaemia (APL) [Figure 2]. Targeted next-generation sequencing using the Oncomine Myeloid Research Assay (Thermo Fisher Scientific, MA, USA) revealed pathogenic variants with allele frequencies greater than 1% in nucleophosmin 1 (NPM1; p.Trp288CysfsTer12), isocitrate dehydrogenase 2 (IDH2; p.Arg140Gln) and Fms-like tyrosine kinase 3 (FLT3; p.Asn676Lys), of which the variant allele frequencies (VAF) were 47.94%, 51.3%, and 3.55%, respectively. The patient was eventually diagnosed with acute myeloid leukaemia (AML) with mutated NPM1. AML with cup-like blasts (CLB-AML) is defined as the presence of more than 10% of blasts with nuclear invaginations that span at least 25% of the nuclear diameter, which are commonly associated with AML M1/2 (myeloid) and M4/5 (myelomonocytic/monocytic) in the FAB classification. NPM-1 and FLT3-ITD mutations have been detected in more than 60% of CLB-AML cases with normal karyotype. NPM1-mutatd AML showing APL-like immunophenotype, negative for both CD34 and HLA-DR, often harbours co-mutations in IDH1/2 or TET2 [1]. Furthermore, high D-dimer/FDP levels, CLB, and APL-like immunophenotype are frequently observed in AML with mutated NPM1 harbouring FLT3 or IDH1/2 co-mutations [2]. Our case is consistent with these clinical, morphological, and molecular features. VAF of FLT3 mutation is less than 5% and much lower compared to that of NPM1 and IDH2, which means that FLT3 mutation may not affect the cup-like morphology and clinical presentation in our case. NPM1-mutated AML carrying concurrent FLT3-ITD mutation especially with high (≥0.5) allelic ratio is well known to be associated with poor prognosis. Molecular analysis is very important in CLB-AML with APL-like phenotype in terms of predicting prognosis and determining the optimal treatment strategy including allogeneic stem cell transplantation or molecular targeted therapies such as FLT3 or IDH1/2 inhibitors. We thank Dr. Makoto Ikejiri, Dr. Kaname Nakatani, and Dr. Keiki Nagaharu at Mie University Hospital for NGS analysis. We thank Gabrielle White Wolf, PhD, from Edanz Group (http://en-author-services.edanz.com/ac) for editing a draft of this manuscript. Y. Sugimoto has received honoraria from Novartis, funding from Takara Bio, and research support from Astellas, Kyowa Kirin, and Ono, and is an accepted researcher from Shojunkai Takeuchi Hospital. All other authors do not have any conflicts of interest to declare.

Multiple Auer rods in a mixed-phenotype acute leukemia

Multiple Auer rods in a mixed-phenotype acute leukemia

A Rare Case of Pancytopenia Post Heart Transplant

Introduction Hematologic malignancy following solid organ transplant is uncommon and no cases have been reported in heart transplant recipients. We present a case of acute promyelocytic leukemia (APL) after orthotopic heart transplant. Case Report 57 year-old, with dilated cardiomyopathy secondary to sarcoidosis and no history of malignancy underwent successful orthotopic heart transplant. He had one episode of cell mediated rejection which was treated with pulse dose steroids. He was on tacrolimus, cellcept and prednisone for maintenance immunosuppression. Ten months post-transplant, routine laboratory test revealed pancytopenia which was attributed to medication side effects. His cellcept and valcyte were discontinued. He received Filgrastim. Cytomegalovirus, Epstein-Barr virus, and Parvovirus B-19 infections were ruled out. He had recurrent episodes of decline in his absolute neutrophil counts and was referred to hematology. A bone marrow aspirate and smear showed left shift granulocytic maturation arrest in a promyelocytic/myelocytic stage and cells suggestive of Auer rod. FISH cytogenetics, with 23% positive for PML-RARA fusion gene, confirmed the diagnosis of APL. He was initiated on therapy with All-trans retinoic acid (ATRA). Treatment with arsenic trioxide was deferred due to concerns for cardiotoxicity. His treatment course was also remarkable for differentiation syndrome which responded to hydroxyurea and dexamethasone. Overall, he had good response to ATRA and repeat BMB showed normocellular marrow with trilineage hematopoiesis with no evidence of APL. Summary Clinicians should maintain a high degree of suspicion when patients with a history of OHT develop unexplained pancytopenia. A small case series revealed the population most commonly affected with post-transplant APL were males, with a median age of 50 years at diagnosis and within a median interval of two years post solid organ transplant. Our patient was able to achieve remission without the standard chemotherapeutic agents used to treat APL associated with cardiotoxicity such as arsenic trioxide and anthracycline. To our knowledge, this case is the first reported of post orthotopic heart transplant acute promyelocytic leukemia.

A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlyingPLZF/RARA gene rearrangements

AbstractAcute promyelocytic leukemia (APL) is typified by the t(15;17) translocation, which leads to the formation of thePML/RARA fusion gene and predicts a beneficial response to retinoids. However, approximately 10% of all APL cases lack the classic t(15;17). This group includes (1) cases with cryptic PML/RARA gene rearrangements and t(5;17) that leads to the NPM/RARA fusion gene, which are retinoid-responsive, and (2) cases with t(11;17)(q23;q21) that are associated with the PLZF/RARA fusion gene, which are retinoid-resistant. A key issue is how to rapidly distinguish subtypes of APL that demand distinct treatment approaches. To address this issue, a European workshop was held in Monza, Italy, during June 1997, and a morphologic, immunophenotypic, cytogenetic, and molecular review was undertaken in 60 cases of APL lacking t(15;17). This process led to the development of a novel morphologic classification system that takes into account the major nuclear and cytoplasmic features of APL. There were no major differences observed in morphology or immunophenotype between cases with the classic t(15;17) and those with the cryptic PML/RARAgene rearrangements. Auer rods were absent in the t(5;17) case expressing NPM/RARA. Interestingly, this classification system distinguished 9 cases with t(11;17)(q23;q21) and, in addition, successfully identified 2 cases lacking t(11;17), which were subsequently shown to have underlying PLZF/RARA fusions. The PLZF/RARAcases were characterized by a predominance of blasts with regular nuclei, an increased number of Pelger-like cells, and by expression of CD56 in 4 of 6 cases tested. Use of this classification system, combined with an analysis for CD56 expression, should allow early recognition of APL cases requiring tailored molecular investigations.

Chronic Myelomonocytic Leukemia in Qatar, Single Institute Experience

Background Chronic myelomonocytic leukemia (CMML) is a rare de novo clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). The diagnosis is challenging and carrying risk for leukemic transformation. The median age at CMML diagnosis is ~71-73 years, with a male preponderance. According to the 2016 World Health Organization (WHO) classification of myeloid neoplasms, CMML is characterized by the presence of sustained (>3 months) peripheral blood (PB) monocytosis (≥1 × 109/L; monocytes ≥10% of white blood cell count) along with dysplastic features in the bone marrow (BM). < 20% blasts/blasts equivalent in the PB and BM. It has recommended categorization of CMML into "proliferative" (MPN-CMML) and "dysplastic" (MDS-CMML) sub-types; based on a total leukocytic count (TLC) (of ≥13 × 109/L for MPN-CMML). Also, based on PB and BM blast %, CMML can be sub-classified into three categories; (a) CMML-0 (<2% PB blasts including promonocytes and <5% BM blasts), (b) CMML-1 (2-4% PB blasts including promonocytes and 5%-9% BM blasts), and (c) CMML-2 (>5% PB blasts including promonocytes and 10%-19% BM blasts and/or when any Auer rods are present. Objective: To retrospectively analyze the cases of CMML diagnosed in the Hematology Department, National Center for Cancer Care and Research (NCCCR), Doha, Qatar from January 2013 to July 2020 with the assessment of risk and prognosis. Materials and methods: The results from flow cytometry, cytology, PB, and BM morphology, cytogenetics and molecular genetics were re-estimated. The CMML-specific prognostic scoring system (CPSS) was used for the risk stratification. Results:12 patients diagnosed as CMML were detected and included in the study, 10 males and 2 females, with a median age of 64 years. 3 Arabs and 9 non-Arabs. 10 patients were transfusion dependent. 6 patients had splenomegaly and 2 of them had massive splenomegaly (>20 cm in craniocaudal length). According to the TLC, 8 were myeloproliferative (CMML/MP) and 4 were myelodysplastic CMML. 4 of our patients were below 40 years (classified as young adults as per WHO) and all were of the proliferative type. The flow cytometry of PB and/or BM was done to 11 patients. The monocytic cells were characterized by co-expressing CD14 and CD64 and showed aberrant expression of CD56 on 5 patients. According to the morphology of the BM, one case was described as MDS/MPN or MPN, and the rest of the cases were diagnosed as MDS/MPN. According to WHO 2016 diagnostic criteria of CMML: one case was diagnosed as CMML0, one case was diagnosed as CMML1, 9 cases were diagnosed as CMML2 and one case was diagnosed as MPN/MDS -CMML2 or as MPN. The cytogenetic risk was high in 4 patients, intermediate in one patient, and low in 7 patients. According to CPSS, one patient was an intermediate risk I, 4 was intermediate-risk II, and 7 were high risk. Molecular analysis and NGS were done for 4 patients that were most recently diagnosed. One case showed NRAS in 30%, one case showed KRAS in 57%, one case showed DNMT3A and NPM1 each 42% and one case showed WT1 (36%), FLT3 (33%) and NPM1 (15%). Regarding management and supportive care, 10 out of 12 patients required transfusion support. 4 patients (3 Proliferative and one Dysplastic) were not eligible for active management and received only symptomatic treatment. 5 patients of the proliferative type were started on hydroxyurea. The other 3 patients were of dysplastic subtype who received hypomethylating agent +/- allogenic bone marrow transplant. 6 patients traveled back to their home country and lost follow up, 5 expired, and one patient still alive. Conclusion: CMML is a unique and rare hematopoietic neoplasm with complex biology and pathology. It is an aggressive rare disease that carries a dismal prognosis, with poor survival and a high risk of transformation. The therapeutic options are limited. In our clinic, for the 7 years period, CMML was confirmed only in 12 patients. The great majority of them were old males of the non-Arab nationality, transfusion-dependent, presented with TLC (> 13x10^3/ul Proliferative) of CMML2 subtype and high CPSS risk score. 33% of our patients were young adults (less than 40 years old) and were of the proliferative type. The combination of clinical, morphological, immunophenotyping, cytogenetic and molecular information is required to improve the accuracy of CMML prognostication. Disclosures No relevant conflicts of interest to declare.

Acute myeloid leukemia with mutated NPM1 mimics acute promyelocytic leukemia presentation.

To investigate clinicopathological and molecular features of NPM1-mutated acute myeloid leukemia that presented with infrequent acute promyelocytic leukemia (APL)-like phenotype and clinical presentation. Cases with both de novo or secondary Acute Myeloid Leukemia (AML) were retrieved. Data from flow cytometry immunophenotyping, cytogenetics, molecular studies, and clinical presentation were analyzed. Cases presented with abnormal coagulation parameters and low platelets count; four of them showed a DIC index compatible with overt DIC. Two cases showed Auer rods. In all cases, immunophenotypes mimicked APL: blasts expressed CD33, CD13, and cytoplasmic MPO but did not express CD34, HLA-DR, or CD11b. Notably, CD4 expression was observed in all cases. Neither t(15;17) nor PML/RARα gene rearrangement was detected. NPM1 gene mutation was identified in all cases. In four cases, TET2 or IDH2 co-mutations were identified. Our findings provide additional evidence of association between NPM1-mutated AML with TET2 or IDH2 co-mutations and the APL-like immunophenotype. This AML subset was found to exist in both de novo and secondary AML. High WBC count and blasts with low to moderate side scatter and significant expression of CD4 are observed features that could assist in the differential diagnosis with APL. The occurrence of significant elevated D-dimer levels, or even overt DIC observed at diagnosis in these cases could be relevant for this AML subtype.

27-Year-Old Woman With Fever, Headache, and Anemia

27-Year-Old Woman With Fever, Headache, and Anemia

Acute Promeylocytic Leukemia Presenting as Fatal Intracranial Bleeding in a Rural Setting

Acute promyelocytic leukemia (APL) is a biologically and clinically distinct variant of acute myeloid leukemia (AML), and accounts for 5 to 20 percent of all AML cases. It is a highly curable hematological malignancy with targeted therapy. Patients usually present with symptoms of the complications, typically bleeding. Intracranial bleeding with APL is rarely seen at the presentation, but more common in relapsed cases. APL is a medical emergency with a high rate of early mortality, usually due to catastrophic bleeding if it is not treated timely. It is vital to start treatment once the diagnosis is suspected without waiting for definite diagnosis. We presented a 35-year-old foreign worker who presented with headache and blurring of vision for 5 days, associated with fever and multiple episodes of vomiting on the day of admission. Subsequently he developed status epilepticus and disseminated bleeding. He had raised leukocyte, low platelet, prolonged international normalized ratio and prolonged prothrombin time. His computed tomography (CT) brain revealed intracranial hemorrhage. He was intubated and was transfused one cycle of disseminated intravascular coagulation regime. He was referred to intensive care unit and neurosurgical team. Unfortunately, the patient passed away within 5 hours of hospitalization. His urgent peripheral blood film subsequently came back after he passed away and showed increased white blood cell with more than 90% of abnormal promyelocytes, Auer rods and Faggot cells, suggestive of APL. This case highlights the importance of high index of suspicion; the timely and urgent treatment, which is crucial and might prevent the catastrophic event.

Morphological characteristics, cytogenetic profile, and outcome of RUNX1-RUNX1T1-positive acute myeloid leukemia: Experience of an Indian tertiary care center.

A prototype of good prognosis, t(8;21)-positive AML, has diverse clinical and genetic features which affect its outcome. This study aimed at evaluating the clinico-pathological spectrum of t(8;21)-positive AML and ascertaining prognostic factors influencing its outcome in the Indian subcontinent. A retrospective analysis of 75 cases of t(8;21)-positive AML diagnosed over a period of six years (2013-2018) was carried out. Detailed clinical and laboratory data of the patients were collected from the electronic medical records and reviewed. Median age was 19.5years (range 5-75years) with a M:F of 1.7. Myeloid sarcoma was observed in 9.3% cases. There were 85% FAB AML-M2, 8% AML-M1, and 7% AML-M4 subtypes. Prominent morphological characteristics included dyspoiesis in maturing myeloid cells (83%), long thin tapered Auer rods (58%), cytoplasmic vacuoles (58%), eosinophilia (50%), and mast cells (22%). Auer rods in maturing granulocytes (4% cases) were highly suggestive of the translocation. Additional cytogenetic abnormalities were present in 53% cases. Seventy-one percent (25/35) achieved CR. The overall survival (OS) was 40%, with a median follow-up of 27months (range 4-57months). None of the hematological or cytogenetic factors correlated with OS, except for the presence of myeloid sarcoma which had a trend toward poor survival (P=.07). Outcome of t(8;21) AML is not influenced by any of the clinico-pathological parameters, except for a myeloid sarcoma, which may herald a poor prognosis. Recognition of this distinct subtype of AML would facilitate further molecular screening for risk stratification in resource-constrained settings.

Generation of a New Prognostic Index for Chronic Myelomonocytic Leukemia (CMML) Based on Peripheral Blood Assessment

Introduction The majority of prognostic indexes in CMML include information extracted from bone marrow (BM) evaluation. The blast count in BM in CMML includes the blast and promonocyte percentage. In the extent of our knowledge there are no data evaluating whether both cells have an equivalent prognostic weight for predicting survival. Recent data indicate that an accurate diagnosis of CMML could be established by assessing the monocyte population distribution by flow cytometry and by evaluating its molecular profile by targeted next-generation sequencing in PB. Our aim was to analyze which variables from our series had an independent prognostic value in order to assess if their addition to the most common prognostic scores for CMML, CPSS and Mayo prognostic model (Mayo), contributed to increase their predictive capacity; or if they allowed us to create a new one. Methods One hundred and fifty patients diagnosed with CMML from 1975 to 2019 from a single institution were evaluated. All patients met 2017 WHO criteria. Complete information was available for the following: BM blast percentage, BM promonocyte percentage, PB blast percentage, circulating immature myeloid cells (IMC), presence of Auer rods and complete blood count. The median overall survival (OS) was 35 months (CI 95%: 30-40). We performed univariate and multivariate survival analyses to establish the prognostic weight of each one. Both C-index and Somers'D (Dxy) were used to compare the prognostic accuracy of the different models. Results Patients characteristics are depicted in Table 1. The prognostic impact of the following items was reviewed: BM blasts; BM promonocytes; the sum of BM blasts and promonocytes; proliferative CMML (CMML-P); monocyte count ≥ 5 x 109/L; transfusional dependency; Hb < 100 g/L; platelets < 100 x 109/L; IMC; PB blasts; abnormal karyotype; spanish cytogenetic risk classification; sex, and dysmegacaryopoiesis, dysgranylopoiesis and dyserythropoiesis according to WHO criteria. In the univariate analysis for the OS only the following demonstrated an adverse impact: sex (women 50.7m vs men 33.4m, P=0.023), PB blasts (39m vs 11m, P<0.001), BM blasts ≥ 10% (35.7m vs 21.6m, P=0.033), Hb < 100 g/L (40.9m vs 21.7m, P=0.001), platelets < 100 x 109/L (40.9m vs 31.6m, P=0.004), abnormal karyotype (39.4m vs 31.6, P=0.01), spanish cytogenetic risk classification (37.5m vs 5.4m vs 9.2m, P=0.001), monocyte count ≥ 5 x 109/L (31.6m vs 35.7m, P=0.02), and leucocyte count ≥ 13 x 109/L (24.1m vs 39.8m, P=0.005). As shown, we did not observed an adverse impact on OS when assessing the percentage of promonocytes as continuous variable or categorized at 5% or 10% cut-offs. Only PB blasts, Hb < 100 g/L and platelets < 100 x 109/L maintained their adverse impact in a multivariate cox regression analysis including all the variables that showed an impact in the univariate analysis. These variables maintained their independent prognostic impact when adjusted for sex and age. The Hazard Ratios (HR) were: 2.9, 1.9, 1.7 for PB blasts, Hb and platelets The CPSS and Mayo prognostic model accurately stratified the prognosis in our series, having the last one a higher predictive capacity for the OS (C-index: 0.62 vs 0.65; Dxy: 0.24 vs 0.3). The prognostic accuracy of the CPSS improved when the platelets were added (CPSS-P) (C-index 0.63; Dxy: 0.26). Given the prognostic weight of the three values described, we developed a score based on these: platelets < 100 x 109/L, 0.5 points; Hb < 100g/L, 1 point, and PB blasts, 2 points. The MAR score (Figure 1) segmented the series in three risk categories with significant differences in OS: low (0 points), median OS 54m; intermediate (0.5-1 points), median OS 33m; and high (1.5-3.5 points), median OS 15m. The MAR score showed a better value for C-index (0.66) and Dxy (0.32) than the rest of scores assessed. Conclusions The variables with an independent adverse prognostic value for OS in our series were: Hb < 100 g/L, platelets 100 x 109/L and the presence of blasts in PB. The MAR score, a model based on them showed the best predictive capacity for OS in our series. Disclosures No relevant conflicts of interest to declare.

Mature neutrophils with Auer rod bundles in CBFB-MYH11-positive acute myeloid leukemia.

Mature neutrophils with Auer rod bundles in CBFB-MYH11-positive acute myeloid leukemia.

1731 Leukemic Infiltration Leading to Esophagitis: A Rare Initial Presentation of AML

INTRODUCTION: Acute Myeloid Leukemia (AML) is a group of blood cancers that arise from clonal proliferation of malignant hematopoietic precursor cells in bone marrow. We report a case of AML that presented as esophagitis secondary to leukemic infiltration of the esophagus. CASE DESCRIPTION/METHODS: A 60 year male who presented with 1 month history of worsening retrosternal pain, worsened with eating & drinking, leading to a 9 kg weight loss. Patient was taking increasing doses of NSAIDS to treat this pain unsuccessfully. Patient’s past medical history included hypertension, hyperlipidemia & Bell's palsy. Patient’s EKG & 3 troponins were normal. He had no melena, hematochezia but stool guaiac tested positive. Initial CBC showed a WBC 20.5 k/mm3, Hgb 7.7 g/dL, & Platelets 28 k/mm3 with peripheral smear revealing 86% blasts with rare Auer rods. Patient was diagnosed with AML with NSAID associated gastritis & was started on IV Proton pump inhibitor therapy. Patient underwent a bone marrow biopsy that showed 95% blasts and 5% erythroid. On flow cytometry 95% were myeloblasts. Fluorescence in-situ hybridizationtesting showed MLL mutation with 11q23 rearrangement. While awaiting induction 7 + 3 chemotherapy, patient underwent EGD due to continued odynophagia. It showed multiple discreet large non-bleeding ulcers in the proximal & middle third of the esophagus. CMV esophagitis was suspected & the patient received empiric ganciclovir for 3 days. The final biopsy showed no CMV and colonisation without invasion by Actinomycetes, but it also showed atypical mononucleated cells consistent with leukemic infiltrates in the ulcer bed. Patient received induction chemo 7 + 3 but had partial response based on day 14 bone marrow & was successfully reinducted. He is currently awaiting a bone marrow transplant on consolidation chemotherapy. He is symptom free of esophagitis. DISCUSSION: In AML, large numbers of immature myeloid cells are seen in the bone marrow & in peripheral blood resulting in a crowding out effect of other cell lines. Presentation is usually symptoms of anemia, bleeding from thrombocytopenia or immune deficiency. In previous autopsy series, gastrointestinal involvement of leukemia have been noted, with involvement of the esophagus being less common. There have been reports of leukemic infiltration of the esophagus developing during treatment for AML, but our case is a rare initial presentation with esophagitis from leukemic infiltration which led to the diagnosis and treatment of AML.

Auer rod-like inclusions in the cytoplasm of B-cell lymphoma cells with bone marrow infiltration

Auer rod-like inclusions are rarely seen in B-cell neoplasms patients. Here, we present a case of B-cell lymphoma with Auer rod-like inclusions in lymphoma cells. By light and transmission electron microscopy, these structures closely resembled Auer rods which were found in acute myeloid leukemia. The Auer rod-like inclusions were negative for cytochemical staining of MPO, α-naphthyl acetate esterase, and periodic acid-Schiff. Immunostaining and flow cytometric analysis confirmed monoclonal Kappa-positive malignant lymphocytes. Interestingly, the Auer rod-like inclusions exhibited diverse ultrastructural features, which ranged from fusiform, to needle-shape, to round, to crystalline cuboid, to long rod, to short rod and others; some were membrane structures, some membrane-free dense structures, and some lamellar structures. The patient was diagnosed with B-cell lymphoma with bone marrow infiltration.

Auer Rods, Faggots and Phi Bodies and the Role in the DIC (Disseminated Intravascular Coagulopathy) of Acute Promyelocytic Leukaemia!) = AML M2 Microgranular Variety!

Auer rods are elongated, azurophilic plasmic inclusions in leukaemic blasts belonging to the myeloid series. Their presence confirms the diagnosis of acute myeloid leukaemia..

Neurochemical Modulation Frequency Band of Hippocampal Theta Rhythm

Auer rods are elongated, azurophilic plasmic inclusions in leukaemic blasts belonging to the myeloid series. Their presence confirms the diagnosis of acute myeloid leukaemia..

Early T‐cell precursor acute lymphoblastic leukemia with Auer rods—A case report

Early T‐cell precursor acute lymphoblastic leukemia with Auer rods—A case report

PB1757 MORPHOLOGICAL CHARACTERISTICS, CYTOGENETIC PROFILEAND TREATMENT OUTCOME OF AML1‐ETO POSITIVE ACUTE MYELOID LEUKEMIA; INDIAN PERSPECTIVE.

Background:Acute myeloid leukemia (AML) is characterized by the proliferation of leukemic myeloid blasts bearing granules and/or Auer rods. Besides acute promyelocytic leukemia, the myeloid blasts in other subtypes of AML have a non‐descript morphology.Aims:The aim of this analysis was to determine the morphological features of t (8;21) positive AML and define a score for predicting positivity for this fusion protein in AML.Methods:A retrospective analysis of all the cases of AML diagnosed over a period of five years (2013‐2017) at our centre was performed. The clinical and laboratory data of the patients was collected from the patient medical records. The bone marrow aspirate smears were reviewed to define the specific features of t (8;21) positive AML; dyspoiesis in maturing granulocytes, long thin Auer rods, eosinophilia, cytoplasmic vacuoles and presence of Auer rods in maturing myeloid cells.Results:A total of 68 cases of t (8;21) positive AML were diagnosed during the study period, with a median age of 19.5 years (range 5‐75 years) with a M:F of 1.7:1. Only twenty percent (14/68) patients belonged to the paediatric age‐group (≤14 years). Granulocytic sarcoma was observed in 10.2% patients at presentation. Morphologically, in accordance to the FAB classification there were 56 AML‐M2, 5 AML‐M1 and 7 AML‐M4 subtypes. Thirteen cases (n = 68) exhibited less than 20% blast in the bone marrow. Characteristic morphological features included presence of dyspoiesis (71%), slender long Auer rods (48%), eosinophilia (19%) cytoplasmic vacuoles in the golgi zone of blasts and maturing myeloid cells (48%). Mast cells, and Auer rods in maturing granulocytic series of cells were seen in a very small fraction of patients, 11% and 3% respectively. 29/68 patients opting for treatment were managed as per the 3+7 protocol. Seventy percent (21/30) achieved CR; there were 5 induction and 8 post induction deaths. With a median follow‐up of 27 months, (range 4‐51 months), the overall survival is 40%. Eleven patients relapsed with a median interval of 7 months, twelve patients‐maintained CR.Summary/Conclusion:Since this sub‐group of AML is believed to be a harbinger of good prognosis, recognition of the distinct morphological features of AML1‐ETO AML is essential; it will facilitate a screening for this genetic abnormality. There was no prognostic correlation with any laboratory parameter, however, presence of granulocytic sarcoma in these patients portends a poor prognosis.

CHRONIC MYELOGENEOUS LEUKEMIA TRANSFORMATION INTO ACUTE LYMPHOBLASTIC LEUKEMIA

Introduction : Chronic myelogeneous leukemia (CML) is a myeloproliferative neoplasm that can progress into various conditions. Transformation of CML into acute lymphoblastic leukemia (ALL) is a rare case. Case : A 22-year-old male with history of CML since 2014 and positive BCR-ABL p210 in 2017 came with complaint of weakness. Physical examination showed hepatosplenomegaly. CBC results Hb 7.1 g/dL, WBC 290,620/μL, platelet 434,000/μL. Blood smear evaluation (BSE) suggested CML blastic crisis dd AML-M5. Patient's condition got worse. CBC result showed WBC 96,770/μL and platelet 7,000/μL in 2 weeks later. BSE was dominated by mononuclear cells with scanty blue cytoplasm, no granules, no auer rods, loose chromatine and indistinct nucleoli, suggesting lymphoblasts with a proportion of 60%. Bone marrow aspiration (BMA) and immunophenotyping was done to confirm BSE. The BMA result was dominated by lymphoblast, consistent with ALL. The immunophenotyping result was CD10+, CD34+(0,99%), CD79a+, HLA-DR+, and CD20+. Molecular examination showed positive RUNX1 and NRAS while negative FLT3, NPM1 and del(5q). Discussion : BCR-ABL gene can be found both in CML and ALL. CML transformation into ALL had been reported to be related with deletion of a transcription gene. Diagnosis of ALL can be established by BMA and immunophenotyping. CD34+ expression of lymphoblast in ALL can be varied, but in this case was minimal. Conclusion : Patient with history of CML showed an ALL picture based on BSE, BMA and immunophenotyping suggesting CML transformation into ALL although CD34+ expression was minimal.

Unusual Sites of Auer Rod in AML with t(8;21)

Unusual Sites of Auer Rod in AML with t(8;21)