Trastornos mieloproliferativos y leucemia en síndrome de Down. Presentación de dos casos clínicos en el período neonatal / Myeloproliferative disorders and leukemia related to Down syndrome. Report of two clinical cases in neonatal period

ElsíndromedeDownpredisponeatrastornosmieloproliferativos. Se estima que del 5 % al 30 % de los neonatos con esta condición desarrollarán mielopoyesis anormal transitoria. El tratamiento no está estandarizado; la exanguinotransfusión y la citarabina podrían ser efectivos. Se describen dos casos de pacientes con síndrome de Down, quienes durante el período neonatal presentaron leucemia mieloide aguda y mielopoyesis anormal transitoria, los tratamientos utilizados y sus desenlaces. Se considera que la sospecha y el diagnóstico temprano de esta entidad son factores determinantes en el pronóstico.

Down syndrome predisposes to haematological disorders. It is estimated that 5-30% of neonates with this condition will develop transient abnormal myelopoiesis. Treatment is not standardized; exchange transfusion and the use of cytarabine could be effective. We present two clinical cases of patients with Down syndrome, who during the neonatal period showed acute myeloid leukemia and transient abnormal myelopoiesis, the treatments used and their outcomes. Suspicion and early diagnosis of this entity are considered determining factors in prognosis.

A t(8;9)(p22;p24)/PCM1-JAK2 Translocation in a Patient With Myeloproliferative Neoplasm and Myeloid Sarcoma: First Report in Korea

No abstract available.

Screening PCR Versus Sanger Sequencing: Detection of CALR Mutations in Patients With Thrombocytosis

BACKGROUND: Mutations in calreticulin (CALR) have been reported to be key markers in the molecular diagnosis of myeloid proliferative neoplasms. In most previous reports, CALR mutations were analyzed by using Sanger sequencing. Here, we report a new, rapid, and convenient system for screening CALR mutations without sequencing. METHODS: Eighty-three bone marrow samples were obtained from 81 patients with thrombocytosis. PCR primers were designed to detect wild-type CALR (product: 357 bp) and CALR with type 1 (product: 302 bp) and type 2 mutations (product: 272 bp) in one reaction. The results were confirmed by Sanger sequencing and compared with results from fragment analysis. RESULTS: The minimum detection limit of the screening PCR was 10 ng for type 1, 1 ng for type 2, and 0.1 ng for cases with both mutations. CALR type 1 and type 2 mutants were detected with screening PCR with a maximal analytical sensitivity of 3.2% and <0.8%, respectively. The screening PCR detected 94.1% (16/17) of mutation cases and showed concordant results with sequencing in the cases of type 1 and type 2 mutations. Sanger sequencing identified one novel mutation (c.1123_1132delinsTGC). Compared with sequencing, the screening PCR showed 94.1% sensitivity, 100.0% specificity, 100.0% positive predictive value, and 98.5% negative predictive value. Compared with fragment analysis, the screening PCR presented 88.9% sensitivity and 100.0% specificity. CONCLUSIONS: This screening PCR is a rapid, sensitive, and cost-effective method for the detection of major CALR mutations.

Myelodysplasia-Related Features of Acute Myeloid Leukemia Evolving From Philadelphia-Negative Myeloproliferative Neoplasms

No abstract available.

Transient myeloproliferative disorder and Down Syndrome. Is there a link?

An extremely premature male neonate presented with an unusual multisystem dysfunction within the first 24 to 48 hours of life. The unfolding of clinical events and investigations revealed a transient myeloproliferative disorder [TMD]. TMD was the main indication for karyotyping of this premature infant without clinical symptoms of Down syndrome. The awareness of TMD in a newborn warrants karyotype analysis to look for trisomy 21 and a close surveillance because of its potential progression to true leukaemia

Management of acquired thrombophilic disorders in 2011: focus on heparin-induced thrombocytopenia, antiphospholipid syndrome, myeloproliferative neoplasms and paroxysmal nocturnal hemoglobinuria

Arterial and venous thrombosis are interrelated disorders at the interplay of platelets and fibrin. Arterial thrombi are platelet-rich and occur at sites vulnerable to atherosclerotic plaque rupture where blood shear rates are high; on the contrary, venous thrombi occur in association with slow blood flow and shear rates. These differences may underlie why anti-platelet agents are more effective in prevention of arterial thrombosis, while anticoagulants are preferred for venous thrombosis. Although some common thrombophilic disorders [e.g., Factor V Leiden, prothrombin gene mutation, etc.] are almost exclusively associated with venous thromboembolism, there are several disorders that are important to consider when caring for patients with both arterial and venous thromboembolism. This article will review the evidence-based management of heparin induced thrombocytopenia with thrombosis, anti-phospholipid antibody syndrome and catastrophic anti-phospho-lipid antibody syndrome, thrombohemorrhagic manifestations of Philadelphia chromosome-negative chronic myeloproliferative neoplasms including polycythemia vera, essential thrombocythemia and primary myelofibrosis, as well as paroxysmal nocturnal hemoglobinuria

Síndromes mieloproliferativos crónicos y embarazo: revisión de casos de pacientes del Departamento de Clínica Hematológica / Chronic myeloproliferative syndromes and pregnancy: a case review of Clinical Hematological Department patients

El manejo convencional de los síndromes mieloproliferativos crónicos (SMP) es un problema cuya frecuencia se ha incrementado. Los datos existentes en la literatura provienen principalmente de series de casos. Esta serie reporta la evolución y el tratamiento de 9 embarazos en 7 pacientes con SMP, 4 con diagnóstico de leucemia mieloide crónica (LMC) y 3 con trombocitemia esencial (TE) asistidos en nuestro Departamento durante los últimos 20 años. La evolución del primer embarazo incluyó: nacido vivo a término 29 por ciento, aborto espontáneo 14 por ciento, nacido vivo pretérmino 29 por ciento y desconocida 14 por ciento. Un embarazo está en curso (14 por ciento). No se registraron muertes fetales. Las complicaciones maternas fueron: sangrado en una paciente con LMC y desprendimiento placentario en otro caso con TE. La segunda gestación resultó en un nacido vivo pretérmino (N=1) y otra está en curso. Todas las pacientes con TE recibieron interferón alta y aspirina durante el embarazo y profilaxis con enoxaparina durante el puerperio. Las pacientes con LMC recibieron: interferón alfa (N=1), hidroxiurea luego del primer trimestre e interferón alfa (N= 1) e imatinib durante el primer trimestre y nilotinib en el tercero la tercer paciente, dando a luz un feto vivo normal. Un mayor número de casos sería necesario para establecer factores pronósticos en este grupo de pacientes.

Chronic myeloproliferative syndromes and pregnancy. A case review of Clinical Hematological Department patients. The management of pregnancy in chronic myeloproliferative disorders (CMPD) is an increasingly frequent problem. Available data in the literature belong to case reports or single centers series. In the current study we report the outcome and treatment of 9 pregnancies among 7 patients with CMPD, 4 with chronic myeloid leukemia (CML) and 3 with essential thrombocythemia (ET) seen in our Department from 1989 to 2009. First pregnancy outcome included full term normal delivery 29 per cent, spontaneous abortion 14 per cent, premature delivery 29 per cent and unknown 14 per cent. No stillbirth was recorded and one pregnancy is currently ongoing. Maternal complications included: bleeding in one CML patient and abruptio placentae in a TE patient. Among second pregnancies, 1 is ongoing and the other resulted in premature delivery. AII TE patients received alpha interferon and aspirin during pregnancy. Prophylaxis with enoxaparin was administered for six weeks postpartum. CML patient were treated as follows: alpha interferon (N=1), hydroxyurea after first trimester plus alpha interferon (N=1). The remaining patient received imatinib and nilotinib giving birth to a normal baby. Further study is necessary to evaluate prognostic factors in these patients.

Congenital transient myeloproliferative disorder progressing to acute myeloid leukemia in Down's syndrome: a case report.

Chromosomal abnormalities like monosomies and trisomies predispose to various malignancies, hematopoietic or non hematopoietic. Patients with Trisomy 21(Down's syndrome) are prone to acute leukemias during childhood, but congenital leukemia in such children is rare (17%) and should be differentiated from a similar condition -Transient Myeloproliferative Disorder (TMD) which does not necessitate any treatment other than follow up. We report a patient of Down's syndrome with TMD in neonatal period which had spontaneous remission at 3 weeks but later died of acute myeloid leukemia at 6 months. The blasts in our case during the TMD episode were Myeloperoxidase(MPO) positive unlike other cases of TMD reported in literature. To the best of our knowledge we have not come across a case of TMD (MPO positive) later progressing to leukemia in Indian literature. Hence we report this case.

Los virus herpes linfotrópicos humanos: epstein-Barr (VEB), 6 y 7 (HHV-6 y HHV-7) en la patogenia de enfermedades mielodisplásicas (SMD) y mieloproliferativas (SMP) / Lymphotropic human herpesviruses: epstein-Barr (EBV), 6 y 7 (HHV-6 and HHV-7) in the pathogenia of myelodysplastic (MDS) and mieloproliferative diseases (MPS)

Con base en alteraciones mielodisplásicas y mieloproliferativas observadas en pacientes con enfermedades linfoproliferativas asociadas a virus herpes linfotrópicos humanos, se realizaron estudios de escrutinio para demostrar eventualmente la reactivación de éstos y su posible implicación en la patogenia y curso de síndrome mielodisplásico (SMD) y de síndrome mieloproliferativo (SMP). Se investigaron 74 biopsias de médula ósea y sueros de pacientes con SMD y 49 biopsias de médula ósea y 36 sueros de pacientes con leucemia mieloide crónica (LMC), a 13 casos de México no se les realizó serología. El diagnóstico y clasificación se hizo según los criterios del Grupo Franco-Americano-Británico (FAB). Se realizaron pruebas séricas de anticuerpos contra antígeno de la cápsula viral (VCA) y antígeno temprano (EA) del VEB con las técnicas de ELISA y de inmunofluorescencia y de HHV-6 y HHV-7 mediante inmunofluorescencia. La inmunohistología se realizó con la técnica de APAAP (fosfatasa alcalina-antifosfatasa alcalina) para expresión antigénica de los 3 virus y por anticuerpos monoclonales. Se determinó proliferación celular con APAAP y con anticuerpo monoclonal contra el antígeno nuclear de proliferación celular (PCNA). Se encontraron títulos de IgG anti-VEB-EA en 62 por ciento de los casos con SMD y en 33 por ciento con LMC, títulos de IgG HHV-6 elevados en 19 por ciento de los casos con SMD y en 9.3 por ciento de LMC y los de HHV-7 elevados en el 37.8 por ciento y 13.9 por ciento, respectivamente. Los títulos de IgM fueron negativos para los tres virus. La expresión de antígeno en la médula ósea fue positiva en el 76 por ciento de SMD a VEB-EA, 48.6 por ciento a HHV-6 p41 y 37.8 por ciento a HHV-7. Los casos de LMC expresaron VEB-EA en el 77 por ciento, HHV-6 en el 54.5 por ciento y HHV-7 en el 21.8 por ciento.

Hemorrhagic and thrombotic complications in patients with myeloproliferative diseases

Objective: To correlate the incidence of hemorrhage and thrombosis to bleeding time (BT) and platelet aggregation in 27 consecutive patients with myeloproliferative diseases (MPD). Design: Retrospective study. Setting: Public tertiary referral center. Patients: Eighteen patients with chronic myelogenous leukemia (CML), 5 with polycytemia vera (PV), 2 with essential thrombocytemia (ET) and 2 with idiopathic myelofibrosis (MF). Duke's BT and epinephrine-induced platelet aggregation were performed on the patients and on 10 healthy individuals. Results: Eleven patients presented symptoms (41 percent): 9 with hemorrhage (33 percent) and 5 with thrombosis (19 percent). There were less symptomatic patients in the CML group (28 percent) than in the other MPD (67 percent), without statistical significance (Fisher, p=0.06). Duke's BT was longer in symptomatic patients (Mann-Whitney, p<0.05). Platelet aggregation was abnormal in 7 patients (26 percent) and 71 percent of them were symptomatic (Fisher, p=0.07) Conclusions: The high incidence of bleeding and thrombosis in patients with MPD was related to prolonged BT, but not to platelet aggregation abnormalities.

Trombosis de la vena porta asociada a trombocitosis esencial: casos clínicos y revisión de la literatura / Thrombosis of the portal vein associated to primary thrombocytosis: clinical cases and literature rewiew

Lately, myeloprolipherative disorders are frequently reported as causes of portal vein thrombosis, probably due to the early detection of latent cases of this condition. We report 2 patients with portal vein thrombosis that presented with abdominal pain, nausea, vomiting and clinical consequences of portal hypertension such as variceal hemorrhage, splenomegaly and ascitis. Diagnosis was made by a CAT scan in one patient and doppler ultrasound in the other. Both patients had a higher platelet counts and an essential thrombocytosis in the bone marrow

Down's syndrome with transient myeloproliferative syndrome.

Two cases of Down's syndrome with high leukocyte count are being reported. Both patients had spontaneous remission without cytotoxic therapy.

Coexistencia de mielofibrosis y colagenopatia / Coexistence of myelofibrosis and collagen disease

Se revisaron 212 protocolos de pacientes con neoplasias y se hallaron 15 casos de síndromes mieloproliferativos. De éstos, se describen dos pacientes que presentaron una colangenopatía mieloproliferativos. De éstos, se describen dos pacients que ptresentaron una colangenopatía asociada, hecho inusual y poco descripto en la literatura. El caso 1 corresponde a un hombre que presenta una artitis reumatoide clásica de 2 años de evolución con esplenomegalia, factor reumatoide, células LE y FAN positivos e hipocomplementemia. Diagnóstico por biopsia: polictemia vera y mielofibrosis. El caso 2 es una mujer de 36 años, que desde hace 4 años presenta severo fenómeno de Raynaud, esplenomegalia y diagnóstico por biopsia de mielofibrosis. Durante la evolución se fueron constatando elementos de diagnsotico que llegaron a configurar una esclerosis sistémica progresiva e hipertensión pulmonar. Además, presentó factor reumatoide y anti-ADN positivos e hipocomplementemia. Las anormalidades hematológicas son comunes en las colagenopatías y pacientes que presentan mielofibrosis tienen una mayor incidencia de autoanticuerpos, complejos inmunes circulantes e hipocomplementemia. Sin embargo, no es frecuente la asociación de mielofibrosis con colagenopatías