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1.
Erythrophagocytosis by neutrophils is a rare phenomenon in myeloid malignancies, and its clinicopathologic significance is not fully understood. We report a unique case of erythrophagocytosis by dysplastic neutrophils in chronic myelomonocytic leukemia (CMML) and subsequent transformation to acute myeloid leukemia (AML). Review of multiple marrow samples, both pretreatment and post-treatment, demonstrated a correlation between percentage of dysplastic neutrophils and degree of erythrophagocytosis. Erythrophagocytosis was observed only in dysplastic forms of neutrophils. Post-transplant marrows with engraftment of donor cells showed no neutrophilic dysplasia or erythrophagocytosis. Possible mechanisms of neutrophilic erythrophagocytosis in myeloid malignancies are discussed. 相似文献
2.
Such E Cervera J Costa D Solé F Vallespí T Luño E Collado R Calasanz MJ Hernández-Rivas JM Cigudosa JC Nomdedeu B Mallo M Carbonell F Bueno J Ardanaz MT Ramos F Tormo M Sancho-Tello R del Cañizo C Gómez V Marco V Xicoy B Bonanad S Pedro C Bernal T Sanz GF 《Haematologica》2011,96(3):375-383
Background
The prognostic value of cytogenetic findings in chronic myelomonocytic leukemia is unclear. Our purpose was to evaluate the independent prognostic impact of cytogenetic abnormalities in a large series of patients with chronic myelomonocytic leukemia included in the database of the Spanish Registry of Myelodysplastic Syndromes.Design and Methods
We studied 414 patients with chronic myelomonocytic leukemia according to WHO criteria and with a successful conventional cytogenetic analysis at diagnosis. Different patient and disease characteristics were examined by univariate and multivariate methods to establish their relationship with overall survival and evolution to acute myeloid leukemia.Results
Patients with abnormal karyotype (110 patients, 27%) had poorer overall survival (P=0.001) and higher risk of acute myeloid leukemia evolution (P=0.010). Based on outcome analysis, three cytogenetic risk categories were identified: low risk (normal karyotype or loss of Y chromosome as a single anomaly), high risk (presence of trisomy 8 or abnormalities of chromosome 7, or complex karyotype), and intermediate risk (all other abnormalities). Overall survival at five years for patients in the low, intermediate, and high risk cytogenetic categories was 35%, 26%, and 4%, respectively (P<0.001). Multivariate analysis confirmed that this new CMML-specific cytogenetic risk stratification was an independent prognostic variable for overall survival (P=0.001). Additionally, patients belonging to the high-risk cytogenetic category also had a higher risk of acute myeloid leukemia evolution on univariate (P=0.001) but not multivariate analysis.Conclusions
Cytogenetic findings have a strong prognostic impact in patients with chronic myelomonocytic leukemia. 相似文献3.
4.
If chronic myelomonocytic leukemia (CMML) transforms into an acute leukemic phase, the blast crisis is invariably myeloid. Occasionally, the other subtypes of myelodysplastic syndrome (MDS) (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation) have been noted to transform into acute lymphoblastic leukemia (ALL). We now report a case of CMML that transformed into ALL and we review the literature of 13 other cases of MDS with ALL transformation. Such cases provide suggestive clinical evidence that MDS can involve a pluripotent stem cell. © 1955 Wiley-Liss, Inc. 相似文献
5.
W J Thomas R B North D G Poplack R B Slease B Duval-Arnould 《American journal of hematology》1981,10(2):181-194
A four-year-old child with recurrent infections and increasing hepatosplenomegaly over a three-year period was evaluated. Increased numbers of myeloid precursors packed the bone marrow and infiltrated the peripheral blood. A diagnosis of chronic myelogenous leukemia (CML) was considered but could not be confirmed by laboratory studies appropriate for the types of CML usually observed in childhood. Examination of the patient's peripheral blood smears revealed many atypical monocytoid cells with unipolar hairy projections. Scanning electron microscopy showed these to be leukemic monoblasts with characteristic broad-based ruffles on the cell surface. A population of myeloid precursors possessing narrow ridge-like profiles was also observed. Progressive infiltration of the spleen caused hypersplenism which necessitated splenectomy. Subsequently, massive liver and bone marrow involvement led to the patient's death. Terminally, the proliferating blast cells were demonstrated to be leukemic monoblasts by analysis of cytochemical staining patterns, surface immunoglobulins, serum lysozyme levels, and monocyte-mediated antibody-dependent cellular cytotoxicity studies. The findings in this case are most compatible with a diagnosis of chronic myelomonocytic leukemia (CMML), a condition not previously described in childhood. Several myeloproliferative disorders with prolonged survival have been reported in children, but special studies were not performed to determine which cell lines were abnormally proliferating. The similarities between these children and our patient with CMML suggest that monocyte studies may be useful in the diagnosis of these unusual disorders, provide insights into their pathogenesis, and aid in the selection of appropriate therapy. 相似文献
6.
Summary This is the first report of a successful bone marrow transplantation for chronic myelomonocytic leukemia. A 41-year-old woman with chronic myelomonocytic leukemia received, as primary treatment, a novel preparatory regimen consisting of high dose fractionated total body irradiation and high dose VP-16 chemotherapy followed by allogeneic marrow transplantation from her histocompatible brother. The patient is now more than two years after marrow transplantation with normal blood counts and a normal bone marrow which is of donor type. For younger patients with this disease who have a histocompatible sibling donor, bone marrow transplantation may represent a valid therapeutic option with curative potential.This investigation was supported by PHS Grants CA 30206 and CA 33572 awarded by the National Cancer Institute, DHHS 相似文献
7.
Birrer A Jusufi F Bernimoulin M Tichelli A Gratwohl A Nissen-Druey C Dirnhofer S Meyer-Monard S Stern M 《European journal of haematology》2008,81(4):267-272
In the absence of a cytogenetic abnormality or overt dysplasia, chronic myelomonocytic leukemia (CMML) may be difficult to be distinguished from reactive monocytosis. We have previously described a typical growth pattern in CMML patients, i.e., 'pseudonormal' colonies resembling granulocytic colonies but consisting entirely of monocytic cells when stained. To study the utility of the colony forming unit cell assay (CFU-C) as a diagnostic tool in patients with monocytosis, we analyzed a cohort of 48 consecutive patients referred to our institution with peripheral blood monocytosis. Thirty-six patients fulfilled the WHO criteria for CMML; 12 were diagnosed with reactive monocytosis. Of the patients with CMML, 28 showed pseudonormal growth with or without leukemic cluster growth, another four showed exclusively leukemic growth. None of the patients with reactive monocytosis showed either leukemic or pseudonormal growth. With a specificity of 100% and a sensitivity of 89%, the CFU-C assay has a unique potential to distinguish CMML from reactive monocytosis. 相似文献
8.
Response to erythropoietic‐stimulating agents in patients with chronic myelomonocytic leukemia
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Blanca Xicoy Ulrich Germing María‐José Jimenez Olga Garcia Regina Garcia Jeniffer Schemenau Carme Pedro Elisa Luño Teresa Bernal Bernardo González Corinna Strupp Maite Ardanaz Andrea Kuendgen María‐Teresa Cedena Judith Neukirchen Marisa Calabuig Salut Brunet Angeles Medina María‐Luz Amigo Fernando Ramos Marta Callejas María Díez‐Campelo Alicia Bailén Rosa Collado Ana Vicente Montserrat Arnan David Valcarcel María Jesús Arilla Lurdes Zamora Luis Benlloch Guillermo Sanz 《European journal of haematology》2016,97(1):33-38
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10.
Goddard SL Chesney AE Reis MD Ghorab Z Brzozowski M Wright FC Wells RA 《American journal of hematology》2007,82(5):405-408
Chronic myelomonocytic leukemia (CMML) is an uncommon disorder characterized by monocytosis of the peripheral blood, absence of the Philadelphia chromosome, fewer than 20% blasts, and one or more lineages showing dysplastic features. Splenomegaly is frequently seen and may be massive. A 56-year-old man with stable CMML and moderate splenomegaly presented to the emergency department with generalized abdominal pain and abrupt drop in hemoglobin. Abdominal imaging revealed splenic rupture and emergency splenectomy was undertaken, with complete recovery. Atraumatic rupture of the spleen has rarely been reported as a complication of CMML or other myelodysplastic disorders. This report should alert physicians to consider this diagnosis in patients with CMML and acute abdominal pain. 相似文献
11.
目的:本研究探讨慢性粒单核细胞型白血病(CMML)的临床特点及影响其预后的相关因素,评估IPSS、WPSS及MDAPS3个积分系统在CMML预后中的应用意义。方法:选取我院2003年5月-2009年7月CMML病例18例,选取同期急性单核细胞白血病(AML-M5)58例作为对照。结果:CMML伴有明显的多系病态造血。干细胞相关抗原CD34、CD117的表达较低,HLA-DR、CD117、CD14抗原表达均低于AML-M5(P<0.05),CD11b抗原表达高于AML-M5(P<0.05)。结论:WPSS积分系统对CMML的预后评估较为理想;CMML时干细胞相关抗原的表达均较低;CD11b高表达可能与CMML的预后不良有关;常规化疗对CMML的治疗效果不佳,造血干细胞移植是目前惟一有可能治愈CMML的方法。 相似文献
12.
Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia 总被引:13,自引:0,他引:13
Invernizzi R Travaglino E Benatti C Malcovati L Della Porta M Cazzola M Ascari E 《European journal of haematology》2006,76(6):494-501
We analyzed the expression of the inhibitor of apoptosis survivin by immunocytochemistry in bone marrow cells from patients with chronic myelomonocytic leukemia (CMML) to evaluate possible abnormalities in comparison with other myelodysplastic (MDS) and myeloproliferative syndromes, and to investigate a possible correlation between survivin expression and altered apoptosis or proliferation, or relevant laboratory and clinical findings. Thirty-four patients with CMML [18 MDS-CMML and 16 myeloproliferative disorder (MPD)-CMML], 90 with MDS, 41 with acute myeloid leukemia (AML), 19 with chronic MPD and 25 control subjects were studied. In normal samples survivin was never detectable. In CMML survivin levels higher than in MDS and AML (P < 0.0001), but similar to those found in MPD were observed. In CMML and MDS apoptosis was significantly higher compared to normal controls and all other subtypes of leukemias (P < 0.0001). Proliferation did not differ significantly in normal controls, MDS and CMML; the lowest levels were observed in AML and MPD (P < 0.0001). In CMML there was no correlation between survivin expression and blast cell percentage, apoptosis or proliferation, FAB or WHO subgroup. Proliferation was higher in MDS-CMML and tended to correlate with overall survival. CMML-2 cases with higher survivin expression showed higher evolution rate and shorter survival. In conclusion, CMML is characterized by high proliferation and apoptosis. Survivin overexpression, by disrupting the balance between cell proliferation/differentiation and apoptosis, may play an important role in its pathophysiology. The detection of survivin-deregulated expression may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments. 相似文献
13.
Olivier Kosmider Véronique Gelsi-Boyer Marion Ciudad Cindy Racoeur Valérie Jooste Norbert Vey Bruno Quesnel Pierre Fenaux Jean-No?l Bastie Odile Beyne-Rauzy Aspasia Stamatoulas Fran?ois Dreyfus Norbert Ifrah Stéphane de Botton William Vainchenker Oliver A. Bernard Daniel Birnbaum Micha?la Fontenay Eric Solary 《Haematologica》2009,94(12):1676-1681
Background
Acquired somatic deletions and loss-of-function mutations in one or several codons of the TET2 (Ten-Eleven Translocation-2) gene were recently identified in hematopoietic cells from patients with myeloid malignancies, including myeloproliferative disorders and myelodys-plastic syndromes. The present study was designed to determine the prevalence of TET2 gene alterations in chronic myelomonocytic leukemias.Design and Methods
Blood and bone marrow cells were collected from 88 patients with chronic phase chronic myelomonocytic leukemia and from 14 with acute transformation of a previously identified disease. Polymerase chain reaction analysis and direct sequencing were used to sequence exons 3 to 11 of the TET2 gene. Annotated single nucleotide polymorphisms were excluded. Survival curves were constructed by the Kaplan-Meier method.Results
We detected TET2 mutations in 44 of 88 (50%) patients with chronic myelomonocytic leukemia, which suggests that TET2 gene mutations are especially frequent in this myeloid disease. A TET2 gene alteration was identified in 18 of the 43 patients studied at diagnosis and was associated with a trend to a lower overall survival rate; confining the analysis to the 29 patients with chronic myelomonocytic leukemia-1, according to the WHO classification, the difference in overall survival between patients with or without TET2 gene mutations became statistically significant.Conclusions
TET2 gene alterations are more frequent in chronic myelomonocytic leukemia than in other subgroups of hematopoietic diseases studied so far and could negatively affect the patients’ outcome. The striking association between TET2 gene alterations and monocytosis, already observed in patients with systemic mastocytosis, could indicate a negative role of TET2 in the control of monocytic lineage determination. 相似文献14.
Jie Peng Zhuang Zuo Bin Fu Yasuhiro Oki Guilin Tang Maitrayee Goswami Priyanka Priyanka Tariq Muzzafar L. Jeffrey Medeiros Rajyalakshmi Luthra Sa A. Wang 《European journal of haematology》2016,96(1):65-71
Nucleophosmin (NPM1) mutations in chronic myelomonocytic leukemia (CMML) are extremely uncommon, and the clinicopathologic features of these neoplasms are poorly characterized. Over a 10‐yr interval, NPM1 mutation analysis was performed in 152 CMML at our institution. NPM1 mutations were identified in 8 (5.3%) patients, five men and three women, with a median age of 72 yr (range, 27–87). In all patients, the bone marrow was hypercellular with multilineage dysplasia, monocytosis, and retained maturation supporting a diagnosis of CMML. NPM1 mutation allele burden was <5% in two patients and >10% in six patients. Four (50%) patients, all with >10% NPM1, progressed AML with a median interval of 11 months (range, 1–21). Compared with 144 CMML without NPM1 mutations, CMML patients with NPM1 mutation presented with more severe anemia (P = 0.053), higher BM monocyte percentage (P = 0.033), and an increased tendency for AML progression (P = 0.088) and an inferior overall survival (P = 0.076). Mutations involving NRAS/KRAS (2/7), TET2(2/5), ASXL1(1/5,) and FLT3(0/8) were not significantly different between these two groups. In summary, CMML with NPM1 mutation shows histopathological features of CMML, but patients appear to have a high probability for AML progression and may require aggressive clinical intervention, especially in patients with a high mutation burden. 相似文献
15.
Takumi Matsumoto Tetsuya Saito 《Modern rheumatology / the Japan Rheumatism Association》2018,28(2):373-375
Chronic myelomonocytic leukemia (CMML), a clonal hematopoietic stem cell disorder with myelodysplastic and myeloproliferative overlap feature, is frequently associated with autoimmune diseases, such as vasculitis, polyarthritis, and neutrophilic dermatosis. We herein report the first case of CMML complicated with spondyloarthritis (SpA). A 64-year-old female patient, admitted to our hospital with buttock pain alternating left and right, was found to have sacroiliitis and spondylitis by contrast magnetic resonance imaging. Peripheral blood test and bone marrow biopsy revealed an increase of monocytes with trilineage dysplasia. We made a diagnosis of CMML. Although arthritic symptoms and imaging findings initially improved by azacitidine, CMML was thereafter transformed into acute myeloid leukemia. She is scheduled to hematopoietic stem cell transplantation. The concomitant onset of sacroiliitis with CMML suggested that her SpA feature was a paraneoplastic phenomenon of CMML. Thus, we must be aware that myelodysplastic syndrome including CMML can manifest as SpA. 相似文献
16.
Boula AM Mantadakis E Xilouri IM Christoforidou AV Foudoulakis AM Samonis G 《American journal of hematology》2005,79(3):216-219
A unique case of a 72-year-old man with chronic myelomonocytic leukemia (CMML) who developed hepatic veno-occlusive disease (VOD) after treatment with a single dose of vincristine and standard doses of cytarabine is described. Unexpected peroneal nerve palsy suggestive of vincristine neurotoxicity occurred concurrently and pointed to vincristine as the most likely cause of the VOD. To the best of our knowledge, association between vincristine and hepatic VOD has not been previously described in chemotherapy-naive patients with CMML. 相似文献
17.
Hirose Y Masaki Y Kawabata H Ogawa N Wano Y Sugai S 《European journal of haematology》2002,69(2):122-125
A 64-yr-old Japanese man presented with mild anemia, leukocytosis, and thrombocytosis in November 1999. A diagnosis of chronic myeloid leukemia was made with a positive Ph chromosome, and interferon alpha treatment was started, 6 million units a day. Two years later, in October 2001, the patient developed leukocytosis, an increased LDH level, and large blasts with basophilic cytoplasm with cytoplasmic projections appeared in the peripheral blood. Bone marrow aspiration revealed increased blasts (59.6%). These blasts were negative on peroxidase stain, positive on acid phosphatase, and weakly positive on alpha naphthyl butyrate esterase stain and periodic acid-Schiff stain. Immunohistochemical staining with monoclonal antibodies revealed that these blasts were strongly positive with anti-CD41 (glycoprotein IIb/IIIa), weakly positive with CD7, CD33, and CD34, and negative with other monoclonal antibodies. A diagnosis of megakaryoblastic transformation from chronic myeloid leukemia was therefore made. Two-color fluorescence in situ hybridization (FISH) for portions of the major-bcr and abl genes from bone marrow cells revealed two fused signals in 90.6% and one fused signal in 5.8% of 106 cells. A cytogenetic study revealed that bone marrow cells were 69, XYY, +6, -7, +8, -9, t(9;22)(q34;q11), +11, +13, -15, -16, dic(17;18)(p11;p11), -18, +19, +21, der(22)t(9;22) in six of nine examined cells. These findings confirmed that these megakaryoblasts originated from megakaryocytes of the chronic myeloid leukemia clone. 相似文献
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19.
Sophie Park Myriam Labopin Ibrahim Yakoub‐Agha Jacques Delaunay Nathalie Dhedin Eric Deconinck Mauricette Michallet Marie Robin Thierry De Revel Marc Bernard Norbert Vey Bruno Lioure Simona Lapusan Reza Tabrizi Jean‐Henri Bourhis Anne Huynh Yves Beguin Gérard Socié François Dreyfus Pierre Fenaux Mohamad Mohty 《European journal of haematology》2013,90(5):355-364
20.
Maria Teresa Voso Massimo Breccia Monia Lunghi Antonella Poloni Pasquale Niscola Carlo Finelli Alessia Bari Pellegrino Musto Renato Zambello Luana Fianchi Giuliana Alimena Giuseppe Leone 《European journal of haematology》2013,90(4):345-348
In patients with myelodysplastic syndromes (MDS), the likelihood of having a sustained response to azacitidine is increased by maximizing treatment duration. This is important as prognosis postrelapse is poor. There is also the concern that early termination of treatment may result in rapid disease progression. We reviewed outcomes in 13 patients who discontinued azacitidine (decitabine in one patient) while still responding to the treatment. Most patients rapidly relapsed; median time to progression was 5.4 months. Reasons for treatment discontinuation included comorbidities, infections, and patient choice. These findings illustrate the risk of prematurely terminating azacitidine therapy in MDS. 相似文献