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To the editor: Pure erythroid leukemia[1][1] (PEL), or AML-M6b, is a rare form of leukemia characterized by proliferation of >80% undifferentiated or pronormoblastic immature cells committed exclusively to the erythroid lineage.[2][2] Previous reports have described the aggressive nature of

RATIONALE Pure erythroid leukemia is a rare subcategory of acute myeloid leukemia characterized by predominant immature erythroid population. Its occurrence subsequent to acute myelomonocytic leukemia has not been reported before. We reported this rare case to call attention because it may pose a diagnostic challenge. PATIENTS CONCERNS A 54-year-old female patient presented to our hospital in March 2018 with symptoms of easy fatigability. DIAGNOSIS Bone marrow aspiration was hypercellular showing 67.2% blasts mainly including moderate myeloblasts and monoblasts. There was mild dysplasia with some cells having round, oval, or bizarre nuclei which containing 1 to 3 nucleolus. Erythroid lineage was hypoplasia and mature erythrocytes were generally normal. Conventional cytogenetics of bone marrow cells revealed complex karyotype (44, XX, del (5) (q14q34) del (5) (q14q34), del (14) t (11;14) (q10; q10), -16, del (17), -18[10]). INTERVENTIONS The patient was treated with second line chemotherapy but did not respond. QUTCOMES She died of cardiopulmonary failure 19days after starting of therapy. LESSONS This unexpected and relatively uncommon occurrence was associated with a universally rapid and fatal clinical course with survival measured in

Acute erythroid leukemia, also known as acute myeloid leukemia-M6, may be associated with previous chemotherapy or immunosuppressive therapy. For 10 years, a 69-year-old Japanese female patient with pure erythroid leukemia (or acute myeloid leukemia-M6b) was treated for polymyositis with 50–100 mg/day azathioprine. She complained of dyspnea with low-grade fever and was diagnosed as having pure erythroid leukemia. Chromosomal analysis revealed a complex karyotype abnormality, with the deletion of 5q, -6, -7 and addition of 11q13. No morphological myelodysplastic changes were observed in her bone marrow cells. In this study, azathioprine accumulation was considered to be associated with the patient’s leukemogenesis.

Accurate analysis of the erythroid lineage is essential in evaluating bone marrow biopsies and can be particularly challenging in settings of dyserythropoiesis. α-Hemoglobin-stabilizing protein (AHSP) is an erythroid-specific chaperone protein and represents a potential specific marker for erythroid elements. This study defines the immunohistochemical profile of AHSP, as compared with an established erythroid marker CD71, in 101 bone marrow biopsies including normal marrows and cases of acute pure erythroid leukemia, acute erythroid/myeloid leukemia, other types of acute myeloid leukemia, myelodysplastic syndrome, chronic myelogenous leukemia, other types of myeloproliferative neoplasm, chronic myelomonocytic leukemia, acute lymphoblastic leukemia, plasma cell neoplasm, and metastatic carcinoma. In acute pure erythroid leukemia, blasts in 7 of 11 cases showed similar reactivity for CD71 and AHSP, whereas less extensive reactivity was observed for AHSP as compared with CD71 in the remaining 4 cases. In normal marrows and other various disorders, reactivity for AHSP was similar to CD71 and was restricted to the erythroid lineage. Mature erythrocytes were negative for AHSP as were myeloblasts, lymphoblasts, nonerythroid hematopoietic marrow elements, plasma cells, and carcinoma cells. AHSP is an effective marker for detection of normal or abnormal erythroid precursors in bone marrow biopsies and is a useful addition to an immunohistochemical panel for assessment of neoplastic cells of possible erythroid derivation.

Pure erythroid leukemia (PEL) is a rare type of acute myeloid leukemia (AML) with a very aggressive clinical course. Presentation as a myeloid/erythroid sarcoma is exceedingly rare. We describe an infantile PEL presenting as a multifocal myeloid sarcoma, clinically and pathologically mimicking Ewing sarcoma/PNET family of tumors. The patient died 8 weeks after the initial presentation due to widespread disease. Our case shows that PEL needs to be considered in the differential diagnosis of small round blue cell tumors in infancy. A meticulous workup including immunohistochemistry, flow cytometry, molecular, and cytogenetic studies was required to reach the diagnosis.

Objectives GATA binding factor 1 (GATA1) is a transcription factor essential for erythromegakaryocytic differentiation. Given its function in lineage specification, we sought to evaluate the immunohistochemical profile of GATA1 in normal marrow and acute leukemia and assess the use of GATA1 as a specific erythromegakaryocytic immunohistochemical marker. Methods Immunohistochemical studies for GATA1 expression were performed on bone marrow biopsy specimens to define its role in the evaluation of acute leukemia and other hematologic disorders. Results In normal marrows, intense nuclear reactivity is seen in immature erythroid precursors and megakaryocytes. Weak to moderate nuclear positivity is seen in eosinophils and mast cells. In marrows involved by acute leukemia, blasts of pure erythroleukemia and acute megakaryoblastic leukemia exhibit intense nuclear GATA1 positivity, while blasts of acute myeloid leukemia of other categories are negative. GATA1 is also absent in the blasts of acute lymphoblastic leukemia/lymphoma and in the neoplastic cells of metastatic carcinoma and plasma cell neoplasms. Conclusions Intense GATA1 nuclear expression is a sensitive and specific marker for cells of erythroid and megakaryocytic lineages and is an excellent marker for neoplastic cells of pure erythroleukemia and acute megakaryoblastic leukemia.

We reviewed 97 consecutive cases of myeloid neoplasm with erythroid predominance (MN-EP) between 2000 and 2015. Following 2016 WHO classification, MN-EP patients were classified into four groups. Eight pure erythroid leukemia (PEL) (including t-MN and AML-MRC morphologically fulfilled criteria for PEL) patients had dismal outcomes (median OS: 1 month) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis than the other groups. In the univariate analysis, risks of death in MN-EP patients included the morphologic features of PEL, very poor cytogenetic risk by IPSS-R, bone marrow fibrosis, leukocytosis, anemia, hypoalbuminemia, high LDH, and poor PS. In the multivariate analysis, independent predictors of death were morphologic features of PEL (adjusted hazards ratio [HR] 3.48, 95% confidence interval [CI] 1.24–9.74, p = 0.018), very poor cytogenetic risk by IPSS-R (adjusted HR 2.73, 95% CI 1.22–6.10, p = 0.015), hypoalbuminemia (< 3.7 g/dl) (adjusted HR 2.33, 95% CI 1.10–4.91, p = 0.026) and high serum LDH (≥ 250 U/L) (adjusted HR 2.36, 95% CI 1.28–4.36, p = 0.006). Poor or unfavorable risk in different cytogenetic risk systems independently predicted death and UKMRC-R was the best model.

The category of acute erythroid leukemia was significantly revised in the recently published 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms. In the previous 2008 WHO classification, acute erythroid leukemia was categorized into two subtypes: erythroleukemia and pure erythroid leukemia (PEL), whereas in the 2016 WHO update, erythroleukemia was merged into myelodysplastic syndrome, and PEL becomes the only type of acute erythroid leukemia. PEL is a rare and aggressive form of acute leukemia whose biology remains poorly characterized. In this review, we discuss the clinicopathologic features, diagnosis, putative pathogenesis, and molecular biology of PEL, with an overview of novel concepts and future directions in this area.

Objectives: Pure erythroid leukemia (PEL) is an extremely rare entity that may, even more rarely, evolve from a preexisting chronic myeloid neoplasm (CMN); there is minimal literature regarding this latter phenomenon. Methods: We describe 14 patients with PEL that represented progression from a preexisting myelodysplastic syndrome (MDS, n = 8) or myeloproliferative neoplasm (MPN, n = 6), three of which manifested as erythroblastic sarcoma (EBS), a rare entity. These patients had a highly complex karyotype with prominent clonal evolution and a very aggressive clinical course. Results: Patients with PEL from MDS showed a more rapid progression time to PEL and had lower platelet counts compared with PEL from MPN. No other significant differences were found between the two groups. Conclusions: These data represent the largest cohort of patients with PEL and an antecedent CMN, as well as the largest series of EBS reported to date, and underscore the unique morphologic, cytogenetic, immunophenotypic, and clinical features of this uncommon entity.

症例は60歳男性。発熱を主訴に近医を受診し,汎血球減少を認められ当院へ紹介入院となった。入院時WBC 2,600/μl,Myeloblast 4 %,Hb 5.2 g/dl,Plt 1.8×104/μl,LDH 10,026 IU/l。骨髄検査では骨髄芽球4.3%,異形成の強い赤芽球85.2%で,白血病細胞の表面マーカーはGP-Aが陽性であったが,その他の骨髄系,リンパ系のマーカーは全て陰性であった。WHO分類におけるpure erythroid leukemiaと診断し,シタラビンとアントラサイクリン系薬剤による化学療法を行ったが,第44病日に多臓器不全のため死亡した。pure erythroid leukemiaは通常のAMLの治療効果が低く,異なる治療上のアプローチが必要と考えられた。

Acute erythroid leukemia (AEL) is a rare subtype of acute myeloid leukemia (AML), characterized by predominant erythroid proliferation. The 2008 World Health Organization (WHO) classification of AML defined two AEL subtypes: erythroleukaemia (EL), in which erythroid precursors account for 50% or more of all nucleated bone marrow cells and myeloblasts account for 20% or more of the nonerythroid cell population; and pure erythroid leukemia (PEL), in which erythroid precursors account for 80% or more of all nucleated bone marrow cells. We report the case of an elderly female patient with wasting syndrome and pancytopenia without evidence of blasts in peripheral blood. A diagnosis of PEL was established on the basis of bone marrow biopsy findings. The patient died on postadmission day 20, and an autopsy was performed. We reclassified the disease as EL on the basis of the autopsy findings, which included myeloblasts accounting for more than 20% of the nonerythroid cells in the bone marrow, as well as leukemic infiltration and myeloid metaplasia in solid organs, such as the liver, spleen, kidneys, adrenal glands, and abdominal lymph nodes. A rare disease, AEL accounts for less than 5% of all AMLs and is practically a diagnosis of exclusion. Autopsy reports of AEL are extremely rare in the literature. We demonstrate that in the case reported here, leukemia cells tended to infiltrate solid organs with myeloid metaplasia. Our findings also show that a larger neoplastic bone marrow sample is crucial to the correct diagnosis of EL, which is based on morphological and quantitative criteria.

Background The World Health Organization separates acute erythroid leukemia (erythropoiesis in ≥50% of nucleated bone marrow cells; ≥20% myeloblasts of non-erythroid cells) from other entities with increased erythropoiesis – acute myeloid leukemia with myelodysplasia-related changes (≥20% myeloblasts of all nucleated cells) or myelodysplastic syndromes – and subdivides acute erythroid leukemia into erythroleukemia and pure erythroid leukemia subtypes. We aimed to investigate the biological/genetic justification for the different categories of myeloid malignancies with increased erythropoiesis (≥50% of bone marrow cells). Design and Methods We investigated 212 patients (aged 18.5–88.4 years) with acute myeloid leukemia or myelodysplastic syndromes characterized by 50% or more erythropoiesis: 108 had acute myeloid leukemia (77 with acute erythroid leukemia, corresponding to erythroid/myeloid erythroleukemia , 7 with pure erythroid leukemia, 24 with acute myeloid leukemia with myelodysplasia-related changes) and 104 had myelodysplastic syndromes. Morphological and chromosome banding analyses were performed in all cases; subsets of cases were analyzed by polymerase chain reaction and immunophenotyping. Results Unfavorable karyotypes were more frequent in patients with acute myeloid leukemia than in those with myelodysplastic syndromes (42.6% versus 13.5%; P

Pure erythroid leukemia is a rare subtype of acute erythroid leukemia that is characterized by a predominant erythroid population, and erythroblastic sarcoma has not yet been described in the English literature. Here, we report a first case of erythroblastic sarcoma that presented as bilateral ovarian masses in a 3 ½-month-old infant girl with pure erythroid leukemia. Bone marrow aspirate and biopsy showed that the marrow was completely replaced by large-sized blasts consistent with erythroblasts. Immunophenotypically, both the tumor cells from the ovarian mass and bone marrow blasts were positive for CD117, glycophorin A, and hemoglobin A, demonstrating erythroid differentiation. Reverse transcriptase polymerase chain reaction showed that the tumor cells from ovarian mass expressed hemoglobin F and α1 spectrin, confirming their erythroid lineage. Conventional karyotype of the bone marrow aspirates revealed del(6)(q23q25) and trisomy 7 in all 21 cells examined. Fluorescence in situ hybridization of the ovarian mass demonstrated loss of c-myeloblastosis viral oncogene (C-MYB) at 6q23 locus in 41% of the cells, and deletion of chromosome 7 and 7q in 37% and 66% of cells, respectively. Taken together, we showed, for the first time, that pure erythroid leukemia presented as a myeloid sarcoma in the form of ovarian masses.

Pure erythroid leukemia (PEL) is rare, characterized by a neoplastic proliferation of erythroblasts. Given recent incorporation of molecular genetic findings and clinical features in the revised 2008 World Health Organization classification scheme of acute myeloid leukemia, we questioned if PEL still remains as a distinct subtype of acute myeloid leukemia. In this retrospective study, we identified 18 cases of acute leukemia with morphologic and immunophenotypic features of PEL. Following the current World Health Organization classification algorithm, these cases were classified as: 13 acute myeloid leukemia with myelodysplasia-related changes, 3 therapy-related acute myeloid leukemia, and 1 chronic myelogenous leukemia blast crisis, and one unclassifiable due to insufficient clinical information. All 16 cases with cytogenetic data harbored an extremely complex karyotype and the median overall survival of the 18 patients was 3 months (range, 1-7 months). This survival was significantly shorter than that of patients with acute erythroid leukemia, erythroid/myeloid subtype, or acute myeloid leukemia with myelodysplasia-related changes with erythroid predominance (P

Pure erythroid leukemia (PEL) is an extremely rare disorder characterized by neoplastic proliferation of immature erythroblasts. A 66-year-old man, who had received chemoradiotherapy for hypopharyngeal cancer, was admitted because of pancytopenia. Bone marrow was infiltrated with 81% proerythroblasts positive for CD71 and CD235a. An increased number of macrophages with active hemophagocytosis was also present. Chromosome analysis showed hypodiploid complex abnormalities. The patient died of progressive disease despite induction chemotherapy. Erythroblastic infiltration into the liver and hemophagocytosis in the spleen were found at autopsy. Therapy-related PEL with hemophagocytic syndrome and hepatic infiltration of PEL has never been reported.

A young male Crl:CD (SD) rat with erythroid leukemia that presented with emaciation, abdominal distension and a pale visible mucosal membrane was euthanized at 7 weeks of age. At necropsy, enlargement of liver, spleen and pancreatic lymph node was noted. Analysis of blood smear samples revealed many mono- or binucleated erythroblasts that had PAS-positive vacuoles in the cytoplasm. Histopathologically, neoplastic proliferation of atypical cells was observed in the hepatic sinusoids, splenic red pulp, bone marrow, pancreatic lymph node, kidney and lung. Neoplastic cells showed a round to spindle shape, and some neoplastic cells had deeply stained small nuclei and small cytoplasms and resembled erythroblasts. Immunohistochemically, many neoplastic cells were positive for hemoglobin. To our knowledge, this is the first report of erythroid leukemia in a rat of this age. The observed features were similar to those of pure erythroid leukemia in humans.

Acute erythroid leukemia (AEL) is a rare type of acute myeloid leukemia (AML) for which diagnostic criteria have been refined in the 2008 World Health Organization (WHO) classification of AML. The relationship of AEL to myelodysplastic syndromes (MDSs) and to AML with myelodysplasia-related changes (AML-MRC) is not clearly defined. We conducted a retrospective, multi-institutional study of patients with AEL and compared them with patients with MDS or AML-MRC with erythroid hyperplasia (≥ 50% erythroid cells). Among a total of 124 patients with AEL, 32% had a history of MDS or chronic cytopenia, 32% had therapy-related disease, and 35% had de novo disease. Sixty-four percent of patients had unfavorable AML risk-group karyotypes. FLT3 and RAS mutations were infrequent, occurring in 6% and 2%, respectively. The median overall survival (OS) of all AEL patients was 8 months, comparable with that of patients with MDS or AML-MRC with erythroid hyperplasia. The OS was related to cytogenetic risk group, but not blast count or morphologic dysplasia. Our findings suggest that AEL is in the continuum of MDS and AML with erythroid hyperplasia, where karyotype rather than an arbitrary blast cutoff represents the most important prognostic factor.

Acute erythroid leukemia is rare, with isolated reports on presentation as an extramedullary tumor mass (myeloid sarcoma). We describe a case of pure erythroid leukemia presenting as an orbital mass in a 1-year, 9-month-old girl. This is only the second case described in a child. Tissue biopsy of the tumor mass showed medium-sized cells that were glycophorin A positive and negative with conventional myeloid markers. Flow cytometry, bone marrow aspirate, and trephine confirmed the diagnosis of pure erythroid leukemia.

Acute erythroid leukemias encompass 2 main subtypes: acute erythroleukemia (erythroid/myeloid subtype) and pure erythroid leukemia. This article reviews the main clinicopathologic features of the acute erythroid leukemias and the criteria used to diagnose them. In this article, the differential diagnosis between acute erythroid leukemias and their mimics is discussed and helpful morphologic clues and diagnostic tests that help arrive at the correct diagnosis are provided. The appropriate application of diagnostic criteria, including ancillary testing, such as immunophenotyping, cytogenetics, and molecular genetic testing, is essential to categorize bone marrow erythroid proliferations.

This report describes spontaneous occurrence of erythroid leukemia in a 6 week-old male Crlj:B6C3F1 mouse. Macroscopically, severe hepatosplenomegaly was noted, but no abnormalities were observed in other tissues including the thymus and lymph nodes. Hematological examinations of blood and bone marrow smear preparations revealed marked proliferation of erythroid cells at various stages of maturation, but neither obvious atypia nor neoplastic proliferation of granulocytic cells was observed. Microscopically, there was marked infiltration of neoplastic erythroid cells into the hepatic sinusoids, splenic red pulp, and bone marrow, but there was no infiltration into the thymus or lymph nodes. Corresponding to the hematological findings, no distinct proliferation of granulocytic cells was detected microscopically. Immunohistochemical examination revealed that these cells were positive for hemoglobin. The present case of mouse erythroid leukemia closely resembles "pure erythroid leukemia" in humans.

Therapy-related acute myeloid leukemia is an unfortunate sequel to current multimodal intensive chemotherapy. The patient described was diagnosed with pure erythroleukemia, AML-M6b, during therapy for precursor B-cell acute lymphoblastic leukemia. To the best of our knowledge, this is the first report of this unusual association.

[Figure][1] A 65-year-old man was diagnosed with plasma cell myeloma (PCM), status post cyclophosphamide-dexamethasone chemotherapy, autologous stem cell transplant (SCT), and lenalidomide maintenance. Seven years later, he developed therapy-related myelodysplastic syndrome (MDS) with 1%

Acute erythroleukemia (FAB M6) is a rare heterogeneous disease with an increase in red cell precursors and myeloblasts. Three subsets have been described: M6A (myeloblast-rich erythroleukemia); M6B (proerythroblast-rich erythroleukemia); and M6C (myeloblast- and proerythroblast-rich mixed variant). This study was undertaken to define and compare the clinical courses and survival outcomes among M6A, M6B, and M6C variants of erythroleukemia. Sixty-nine cases of M6 leukemia were categorized as consisting of ≥50% erythroid of all nucleated cells and M6A with ≥30% myeloblasts/nonerythroid component; M6B with ≥30% proerythroblasts/erythroid component; and M6C with ≥30% myeloblasts and ≥30% proerythroblasts. The demographics, cell type distribution, and survival (mean ± sd) of these groups were compared. There were 32 M6A, 26 M6B, and 11 M6C patients. No significant difference was seen among the groups in age, sex, or treatment. Compared to M6A, both the M6B (P< 0.0001) and M6C (P< 0.0001) variants showed a statistically significant increase in the percentage of bone marrow erythroid cells, proerythroblasts, and the proerythroblasts/erythroid ratios. Comparing the groups for survival, M6B (3 ± 3.6 months) versus M6A (25 ± 28 months), P< 0.002, and M6C (10 ± 13 months) versus M6A, P< 0.01 had a poorer prognosis. Calculating the proerythroblasts as a component of total bone marrow erythroids provides a complimentary method for delineating the pure red cell erythroleukemia (M6B) and mixed variant (M6C), similar to that for the myeloid/erythroid (M6A) leukemia. Now that it is possible to delineate erythroleukemia subtypes, innovative treatments are indicated to target the malignant erythroid population, which is resistant to myeloid-based therapies. Am. J. Hematol. 65:5–13, 2000. © 2000 Wiley-Liss, Inc.

TO THE EDITOR: Pure erythroid leukemia (PEL) has been defined as a rare, aggressive disease characterized by a neoplastic proliferation of immature cells committed solely to an erythroid lineage with no increase in myeloblasts in the bone marrow (BM) [1, 2, 3]. According to the 2008 World Health Organization (WHO) classification [4], PEL is classified as acute myeloid leukemia (AML), not otherwise specified, only when the case does not fit into any other specific categories. PEL is defined by the presence of immature erythroblasts, which should comprise at least 80% of the BM cells, with no evidence of a significant myeloblastic component [2, 3, 4]. PEL accounts for about 10-20% of all acute erythroid leukemias (AEL) and less than 1% of all AML cases [2], and it has been very rarely reported as a therapy-related AML [5, 6, 7, 8]. Moreover, its occurrence has never been reported after exposure to chemotherapy and radiation for breast cancer.

La leucémie aigue érythroblastique (LAM-M6) est une entité rare, représente 3 à 4% de l'ensemble des leucémies aigues. Il en existe deux types: l’érythroleucémie et la leucémie érythroïde pure. Elle se manifeste le plus souvent par des signes de cytopénie et d'infiltration des tissus extra-hématopoïétiques, elle est plus fréquente chez les adultes que chez les enfants et est de mauvais pronostic. Le but de notre travail est de mettre en évidence les particularités épidémiologiques, diagnostiques et évolutives de cette pathologie rare au sein du CHU HASSAN II de Fès. Nous rapportons le cas de sept patients diagnostiqués leucémie aigue érythroblastique LAM-M6 au laboratoire d'hématologie du CHU Hassan II de Fès entre Janvier 2009 et Aout 2013. Le diagnostic de leucémie aigue érythroblastique a été retenu sur un examen cytologique du frottis sanguin et du médullogramme ainsi que l'examen immunophénotypique. Il s'agit de deux adultes et cinq enfants, la plupart ont présenté une altération de l’état général, des signes de cytopénie et un syndrome tumoral. L’étude cytologique du frottis sanguin et du médullogramme ainsi que les résultats de l'immunophénotypage ont conduit au diagnostic de l’érythroleucémie chez six de nos patients et de leucémie érythroïde pure chez un seul patient. L’évolution a été différente pour ces patients. Le pronostic est grave d'où l'intérêt d'un diagnostic rapide et d'une prise en charge adéquate.

We report two interesting cases of patients with multiple myeloma, who developed a therapy-related myeloid neoplasm in the form of pure erythroid leukemia. In both cases, it was difficult to differentiate the erythroid blasts from plasma blasts by morphology alone. The diagnostic picture was further confounded by the presence of a hyperdiploid karyotype (case 1), which is a frequent cytogenetic abnormality in multiple myeloma but distinctly uncommon in acute myeloid leukemia. These cases highlight the diagnostic challenge encountered with pure erythroid leukemia in the setting of multiple myeloma, and underscore the importance of immunohistochemistry, cytogenetics, and gene rearrangement studies in resolving the diagnostic conundrum. To the best of our knowledge pure erythroid leukemia with a hyperdiploid karyotype arising in a background of pre-existing multiple myeloma, has not previously been reported.

In the updated 2016 revision of WHO classification, pure erythroid leukemia (PEL) is still viewed as a sole entity without any change of definition. However, erythroleukemia (erythroid/myeloid type) (previously defined as myeloid neoplasms with erythroid predominance [EP] and myeloblasts ≥ 20% or < 20% but ≥ 20% of nonerythroid cells) has been removed. The former is now recognized as acute myeloid leukemia, not otherwise specified (AML-NOS), and the latter as no longer acute erythroid leukemia (AEL) but MDS. Such a change in the updated classification provides us the rationale to conduct this cohort study of patients with AML with EP (AML-EP). We report the impact on survival outcomes and the risk factors for mortality in these patients based on the 2016 WHO classification. A total cohort of 97 consecutive cases of acute myeloid leukemia with erythroid predominance (AML-EP) between 2000 and 2015 was enrolled. Following 2016 WHO classification, AML-EP patients were classified into four groups (Figure 1). Nine PEL patients had more dismal outcomes (median OS: 1 month) as compared with non-PEL patients (Figure 2) and showed more bone marrow fibrosis, worse performance status (PS) and higher serum lactate dehydrogenase (LDH) at diagnosis. In the univariate analysis, risks of death were PEL diagnosis, worse cytogenetic risks, bone marrow fibrosis, leukocytosis, anemia, hypoalbuminemia, high (LDH), and poor PS. In the multivariate analysis, independent predictors of death were PEL diagnosis (adjusted hazards ratio [AHR] 3.00, 95% confidence interval [CI] 1.02¡V8.88, p = 0.029), very poor cytogenetic risk by IPSS-R (AHR 2.73, 95% CI 1.22¡V6.11, p = 0.014), hypoalbuminemia (< 3.7 g/dl) (AHR 2.30, 95% CI 1.09¡V4.83, p = 0.028) and high serum LDH (≥ 250 U/L) (AHR 2.31, 95% CI 1.25¡V4.28, p = 0.008). Based on the karyotype, patients were stratified to different cytogenetic risk groups according to the United Kingdom Medical Research Council (UKMRC) criteria for AML, the revised United Medical Research Council (UKMRC-R) criteria for AML, the International Prognostic Scoring System (IPSS) for MDS, the revised International Prognostic Scoring System (IPSS-R) and the presence or absence of monosomal karyotypes. Cytogenetic risks groups determined by UKMRC-R showed the best ability to predict survival outcomes of AML-EP patients (Figure 3). The outcome of PEL was independently much worse than that of non-PEL. Allogeneic HSCT was administered to 10 patients (one PEL, one AML-MRC, three AML-NOS and five MDS cases), whose disease statuses at transplantation were refractory disease for one and complete remission for nine. As compared to supportive care, the mortality among AML-EP patients did not differ from that of the patients receiving allogenic hematopoietic stem cell transplantation, curative chemotherapy or non-curative chemotherapy. In conclusion, after the 2016 WHO classification was published, only PEL were kept as belonging to neoplasms originated from neoplastic erythroid lineage. This retrospective cohort study reports the clinical features, biological data and survival outcomes of patients with AML-EP and identified PEL diagnosis, very poor cytogenetic risk group of IPSS-R, high serum LDH and low serum albumin as independent predictors for death. Cytogenetic risks groups determined by UKMRC-R showed the best ability to predict survival outcomes of AML-EP patients. The outcome of PEL was independently much worse than that of non-PEL. Figure 1 Patient selection Figure 1. Patient selection Figure 2 Survival curves of patients of pure erythroid leukemia and others PEL, pure erythroid leukemia Figure 2. Survival curves of patients of pure erythroid leukemia and others. / PEL, pure erythroid leukemia Figure 3 Impact of the cytogenetic risk group on mortality HR, hazards ratio; CI, confidence interval; AIC, Akaike information criterion; BIC, Bayesian information criterion (the lowest level represents the best prediction ability) *Adjusted for factors with a p < 0.1 in the Cox univariate analysis. Figure 3. Impact of the cytogenetic risk group on mortality. / HR, hazards ratio; CI, confidence interval; AIC, Akaike information criterion; BIC, Bayesian information criterion (the lowest level represents the best prediction ability). / *Adjusted for factors with a p < 0.1 in the Cox univariate analysis. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Congenital pure erythroid leukemia (M6b) is exceedingly rare with only a few reported cases to date. Because of the extreme rarity, almost nothing is known about the pathogenesis, appropriate therapy and prognosis. Diagnosis of erythroid leukemia is usually based on the positivity for Glycophorin A, Glycophorin C or PAS staining. We report a first case of congenital pure erythroid leukemia expressing E-cadherin in the absence of Glycophorin A, Glycophorin C and PAS staining. We analyzed the cytogenetic abnormalities of this extremely rare disease. RESULTS: The patient was the first daughter of healthy and non-consanguineous Japanese parents, born at 40 weeks of gestation by emergency cesarean section in non-reassuring fetal state after uncomplicated pregnancy. Apgar score was 8/9. Characteristic facial appearance was not recognized. At birth, she presented with marked hepatomegaly, purpura and disseminated intravascular coagulation. White blood cell (WBC) count was 63.5x109/L with blastic cells with vacuoles. Although congenital leukemia was suspected, flow cytometric analyses using CD45 blast gating failed to demonstrate leukemic cells. Karyotype was 46, XX. Fluorescence in situ hybridization (FISH) for trisomy 21 and MLL split signal were negative. GATA1 mutation was not detected. WBC count has gradually decreased within 3-4 weeks with supportive care.However, liver failure, hemophagocytic lymphohistiocytosis and schistocytosis developed. Although treatment with dexamethasone and etoposide has started, multiple nodules appeared in the liver 11 weeks after birth. Liver biopsy demonstrated small round cell tumor with high N/C ratio and vacuoles infiltrating the liver. The tumor cells were immunohistochemically positive for CD43, CD71, E-cadherin, beta-catenin, Ki-67 and c-Myc and negative for CD45, CD20, CD10, PAX5, CD3, CD4, CD8, TdT, CD1a, CD34, CD56, cyMPO, c-kit, CD42b, CD61, Glycophorin A, Glycophorin C, tyrosine hydroxylase, PGP9.5, myogenin, glypican3, NKX2.2, CAM5.2 and Periodic Acid Schiff (PAS) staining etc. Flow cytometric analysis revealed CD43+ CD71+ CD36+ CD58+ cells within large CD45 negative cell population. These cells expressed almost no other hematopoietic cell markers used to screen for leukemia. These cells were indistinguishable from normal erythroblast based on surface markers only. However, flow cytometric cell sorting revealed these cells are blasts with vacuoles. Karyotype of tumor cells has changed to 50, XX, +7, +8, add(15)(q22), +19, add(19)(q13.1-13.3)×2, +21. Based on these results, she was diagnosed with pure erythroid leukemia. Low dose Cytosine Arabinoside improved her clinical symptoms. She is alive at 5 months of age. DISCUSSION: E-cadherin is a selective marker of immature erythroblast. In our case, E-cadherin was key in erythroid lineage assignment. To our knowledge, this is the first reported case of infantile pure erythroid leukemia expressing E-cadherin in the absence of Glycophorin A, Glycophorin C and PAS staining. These results suggest that the tumor cells originated from undifferentiated erythroblast. This disease entity should be recognized. Immunohistochemical staining of c-Myc showed strong positivity. The c-Myc gene is located on chromosome 8. FISH for c-Myc split signal was negative. G-banding and FISH revealed trisomy 8. Overexpression of c-Myc may be involved in the pathogenesis of this undifferentiated pure erythroid leukemia. At birth, karyotype was 46, XX and blasts in peripheral blood decreased with supportive care only. However, we observed changes in karyotype of blasts. We assume that second hit was added during clinical course. Whole exome sequencing analysis is in progress to reveal somatic and germline mutations underlying this unrecognized disease. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Pure erythroid leukemia (PEL) is a rare form of acute leukemia characterized by a neoplastic proliferation of immature erythroblasts with an extremely aggressive clinical course. Although there are previous reports describing its association with a complex karyotype and chromosome 5 and 7 abnormalities, there is no knowledge on the mutational landscape of this disease. Also, further evaluation of the optimal treatment strategy for this subset of patients is still required. METHODS: We retrospectively evaluated all patients with pure erythroid leukemia treated at The University of Texas MD Anderson Cancer Center from 1980 to 2016. Cytogenetic analysis was reported following the ISCN 2013 nomenclature. Sequencing data was obtained by use of a 28-gene targeted PCR-based next generation sequencing (NGS) platform. Clinical and demographic data was obtained from clinical records. Response was defined following 2003 IWG criteria. Generalized linear models were used to study the association of overall response (OR), complete response (CR) and risk factors. Kaplan-Meier produce limit method was used to estimate the median overall survival (OS) and leukemia-free survival (LFS). RESULTS: A total of 27 patients had PEL. Patient characteristics are shown in Table 1. Median age at diagnosis was 67 years (range 33-65). Eleven (41%) patients had therapy related disease, 10 (37%) evolved from a prior myelodysplastic syndrome and 1 (4%) from chronic myeloid leukemia. Presence of a complex karyotype was observed in 96% (25/26) patients. A total of 13 (48%) patients with PEL had mutation analysis available. Twelve (92%) had at least one detectable mutation. Median number of mutations was 1 (range 0-3). TP53 mutations were found in 11/12 (92%) patients, and ASXL1, PTPN11 and DNMT3A each found in 1 (8%) patient. Type and frequency of TP53 mutations is shown in Figure 1A. Fifteen (58%) patients with PEL had chromosome 17 abnormalities including monosomy 17, del(17p) and add(17)(p11.2). Five (50%) patients with cytogenetic and mutation data available had both TP53 mutation and chromosome 17 abnormalities. Nine (27%) patients were treated with hypomethylating agent based therapy, 11 (41%) with intensive chemotherapy, 1 (4%) with targeted therapy and 6 (22%) died before receiving any form of therapy. We compared clinical characteristics and outcomes of patients with PEL with that of 162 patients with acute erythroid/myeloid leukemia (AEL) treated at MDACC during the same time period. Patients with PEL tended to be older (p=0.006), have lower platelet count (p=0.009) and lower peripheral blast percentage (p=0.022), higher LDH levels (p CONCLUSION: Pure erythroid leukemia represents 14% of cases of all erythroid leukemia. We establish, in the largest series to date, PEL is characterized by a very complex karyotype. There is also a high prevalence of chromosome 17 abnormalities and mutations in TP53; interestingly, in several patients, there was co-occurrence of both, or double TP53 mutations. Our data demonstrates that severely impaired and completely lost of TP53 function, resulting in genomic instability, is a strong influential factor for PEL pathogenesis in particular, and is consistent with its associated dismal prognosis irrespective of currently available therapies. In view of PEL outcomes and older age at diagnosis, enrollment in clinical trials targeting or circumventing mutant p53, and less intensive approaches is the current optimal strategy for this subset of patients. Table 1 Table 1. Figure 1 Figure 1. Disclosures Ravandi: BMS: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Daver:Sunesis: Consultancy, Research Funding; Ariad: Research Funding; Kiromic: Research Funding; Otsuka: Consultancy, Honoraria; BMS: Research Funding; Pfizer: Consultancy, Research Funding; Karyopharm: Honoraria, Research Funding. DiNardo:Daiichi Sankyo: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Abbvie: Research Funding; Celgene: Research Funding; Agios: Other: advisory board, Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. Kantarjian:Amgen: Research Funding; Bristol-Myers Squibb: Research Funding; ARIAD: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding.

We describe eight cases of erythroleukaemia distinct from FAB-AML M6, which demonstrate minimal erythroid differentiation not associated with a myeloblastic component. Three infants (including a Down's syndrome) and two adults presented with a de novo leukaemia. One case was preceded by an untreated refractory anaemia with excess of blasts and one by polycythaemia vera. One case presented with an inaugural blast crisis of chronic myeloid leukaemia. In four patients the leukaemic cells showed a proerythroblast-like morphology. The four others were initially classified as undifferentiated AL (two cases) or AML M0 (two cases) because of the immature aspect of the cells, their lack of myeloperoxidase activity and the absence of B, T lymphoid and myeloid (My) marker expressions apart from the CD33 antigen. Immunophenotyping in three cases showed an immature erythroblast profile (glycophorins A and B + , spectrin + ). In the five others the erythroid nature was recognized by the expression of ABH blood group system on fresh cells (four cases) and glycophorin A on cells after 3 d in vitro culture with erythropoietin (EPO) + IL3 (two cases). Moreover, an erythroid colony growth of leukaemic origin was observed in three patients. In conclusion, the study of erythroid marker expression is of particular importance when immunophenotyping leukaemic cells with a proerythroblast-like morphology or an undifferentiated aspect and a HLA DR - , CD36 ++ , B - , T - , My - (CD33 ± ) phenotype. We propose the term AML M6 'variant' for this rare type of AML.

Acute erythroleukemia is characterized by a predominant immature erythroid population and accounts for approximately 2–5 % of all cases of acute leukemia. Two subtypes are recognized based on the presence or absence of a significant myeloid component: erythroleukemia and pure erythroid leukemia. Erythroleukemia is predominantly a disease of adults, while pure erythroid leukemia can be seen in any age including children. Here is a case of pure erythroleukemia presenting mainly as late erythroblasts which was diagnosed on bone marrow examination, cytochemistry and was confirmed on immunophenotyping. Possibly this is the only case so for demonstrating deletion of long arm of chromosome 20 in pure erythroleukemia.