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.

Promyelocytic Leukemoid Reaction: Unusual Findings in a Patient with Sepsis

Neutrophilic leukemoid reaction may occur in many situations, including hemolysis, malignancy, infection, and exposure to certain toxins. It usually shows morphological overlap with chronic myeloid leukemia in which promyelocytes are not majorly associated. Here, we present a case of promyelocytic leukemoid reaction in a patient with sepsis. A 28-year-old man was admitted for renal stone removal. After percutaneous nephrolithotomy, his condition deteriorated with fever (37.8℃), tachycardia (130/min), acute renal failure, pleural effusion, and pulmonary edema. Complete blood count indicated a white blood cell count of 73.39×10⁹/L including 82% promyelocytes, hemoglobin 8.9 g/dL, and platelet count of 85×10⁹/L. A bone marrow aspirate showed that promyelocytes accounted for 73.8% of all nucleated cells. Following bone marrow examination, treatment with all-trans retinoic acid (ATRA) was started immediately. Reverse transcription polymerase chain reaction (RT-PCR) study revealed the absence of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) and other RARA (retinoic acid receptor alpha) rearrangements. Once the chromosome analysis of bone marrow cells demonstrated the normal karyotype, ATRA was discontinued.

Neutrophilic Leukemoid Reaction Associated with Malignancy Initially Suspected as Chronic Neutrophilic Leukemia

Although neutrophilia can manifest from various causes, it is important to be able to distinguish chronic neutrophilic leukemia (CNL) from neutrophilic leukemoid reactions (NLR). In this paper, we describe four cases of leukocytosis with neutrophilia, including one case of CNL with a T618I mutation in colony stimulating factor 3 receptor (CSF3R) and three cases of NLR associated with malignancy or sepsis, which were initially suspected as CNL. Of the three NLR cases, one was associated with ovarian cancer, one with monoclonal gammopathy of undetermined significance and one with multiple myeloma with sepsis. This study demonstrated that confirming the clonality of myeloid cells with CSF3R T618I could contribute to making an accurate differential diagnosis between CNL and NLR in patients with solid cancers or plasma cell neoplasms caused by paraneoplastic syndromes and/or infection.

Incidentally Found Chronic Neutrophilic Leukemia in a Patient with Rectal Cancer / 대한내과학회지

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm characterized by sustained neutrophilia, splenomegaly, and hypercellular bone marrow without Philadelphia chromosome. Diagnosis of CNL requires exclusion of identifiable causes of reactive neutrophilia, such as infection and tumors. Our patient presented with general weakness and weight loss. Computed tomography (CT) showed a mass in the distal rectum, which was confirmed to be an adenocarcinoma by colonoscopic biopsy. Positron emission tomography-CT showed multiple liver, bone, and lymph node metastases. Liver and lymph node biopsies revealed neutrophilic infiltration with no evidence of adenocarcinoma. The pathological findings of the bone marrow were compatible with CNL. Cytogenetic analysis revealed a normal karyotype, and molecular analysis was negative for BCR/ABL. Here, we present a 73 year-old man diagnosed with concurrent CNL and rectal cancer.

GATA1 mutations in a cohort of Malaysian children with Down syndrome-associated myeloid disorder

<p><b>INTRODUCTION</b>Children with Down syndrome (DS) are at increased risk of developing distinctive clonal myeloid disorders, including transient abnormal myelopoiesis (TAM) and myeloid leukaemia of DS (ML-DS). TAM connotes a spontaneously resolving congenital myeloproliferative state observed in 10%-20% of DS newborns. Following varying intervals of apparent remission, a proportion of children with TAM progress to develop ML-DS in early childhood. Therefore, TAM and ML-DS represent a biological continuum. Both disorders are characterised by recurring truncating somatic mutations of the GATA1 gene, which are considered key pathogenetic events.</p><p><b>METHODS</b>We herein report, to our knowledge, the first observation on the frequency and nature of GATA1 gene mutations in a cohort of Malaysian children with DS-associated TAM (n = 9) and ML-DS (n = 24) encountered successively over a period of five years at a national referral centre.</p><p><b>RESULTS</b>Of the 29 patients who underwent GATA1 analysis, GATA1 mutations were observed in 15 (51.7%) patients, including 6 (75.0%) out of 8 patients with TAM, and 9 (42.9%) of 21 patients with ML-DS. All identified mutations were located in exon 2 and the majority were sequence-terminating insertions or deletions (66.7%), including several hitherto unreported mutations (12 out of 15).</p><p><b>CONCLUSION</b>The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort.</p>

Eritema nudoso secundario a reacción tipo 2 como manifestación de lepra lepromatosa / Erythema nodosum secondary to type 2 reaction as a manifestation of lepromatous leprosy. A case report

Introducción: El eritema nudoso leproso o leprorreacción de tipo 2 supone una reacción de hipersensibilidad nmunológica humoral de tipo III en la lepra lepromatosa y borderline, la cual se presenta clásicamente como nódulos subcutáneos dolorosos en la piel, además de otras manifestaciones sistémicas. En este reporte de caso se mostrará una forma típica de este tipo de leprorreacción. Presentación del caso: Paciente masculino de 28 anos de edad, con diagnóstico de lepra lepromatosa multibacilar en tratamiento, quien fue remitido al Hospital de San José por presentar cuadro clínico de un mes de evolución de fiebre, malestar general, pérdida de peso y aumento de lesiones nodulares en miembros superiores, con hallazgo adicional de bicitopenia y neutropenia severa. Durante la estancia hospitalaria, es valorado por el Servicio de Dermatología quienes consideran el diagnóstico de eritema nudoso leproso e inician tratamiento; además se evidencia mejoría de la neutropenia con posterior aparición de leucocitosis en aumento y en el frotis de sangre periférica, la presencia de blastos, por lo que se sospecha que el paciente curse con una enfermedad hematolinfoide. Por lo anterior, es valorado por el Servicio de Hematología quienes lo descartan, tratándose entonces de una reacción leucemoide probablemente secundaria a su patología de base. Finalmente, el paciente evoluciona favorablemente y es dado de alta sin complicaciones. Conclusión: La leprorreacción de tipo 2, es una reacción inmune mediada por inmunocomplejos que se presenta típicamente como nódulos subcutáneos dolorosos en la piel, además de presentarse con síntomas constitucionales asociados y daño en otros órganos como hígado, riñón y médula ósea. El conocimiento de las leprorreacciones, el diagnóstico y tratamiento oportunos son fundamentales para prevenir la orbimortalidad en estos pacientes.

Introduction: Erythema nodosum leprosum, or type 2 leprosy reaction, is a type III humoral immunological reaction in the lepromatous and borderline categories of the disease. This classically presents as painful subcutaneous nodules on the skin, and other systemic manifestations. In this case report, a typical form of this type of leprosy reaction will be shown. Case presentation: A 28year-old male patient diagnosed and being treated for multibacillary lepromatous leprosy, was referred to the San Jose Hospital one month after onset. He presented with clinical symptoms such as fever, malaise, weight loss, and increased nodular lesions in the upper limbs, with additional finding of bi-cytopenia and severe neutropenia. He was evaluated by the Dermatology Department during his hospital stay, where he was diagnosed with erythema nodosum leprosum and began treatment for it. A further improvement was observed in the neutropenia, with an increase in leucocytosis. The presence of blasts was found in the peripheral blood smears, which led to the suspicion that the patient had a haemato-lymphoid disease. This was evaluated by the haematology department, but was ruled out. Therefore, this condition corresponded to a leukemoid reaction, probably secondary to the underlying disease. Finally, the patient progressed well and was discharged without complications. Conclusions: Type 2 leprosy reaction is an immune reaction mediated by the immune complex that occurs typically as painful subcutaneous nodules on the skin, in addition to the associated constitutional symptoms and damage to other organs such as liver, kidney and bone marrow. Knowledge of leprosy reactions, and their timely diagnosis and treatment are essential in preventing morbidity and mortality in these patients.

Leukemoid Reaction, a Rare Paraneoplastic Syndrome in Urothelial Cell Carcinoma: Is It an Indicator of a Poor Prognosis?

A leukemoid reaction is usually associated with malignancies of the lung, stomach, and thyroid. In contrast, urothelial cell carcinoma is rarely associated with leukemoid reactions, with few cases reported over the past 30 years. Here, we describe a patient with urothelial cell carcinoma who exhibited a leukemoid reaction. The patient had an elevated white blood cell count and experienced a rapid and aggressive clinical course, terminating in death. For urothelial cell carcinoma patients exhibiting a leukemoid reaction, removal of the inciting tumor is the definitive treatment. However, considering the aggressive nature of these tumors, if the patient is unsuitable for radical surgical management, palliative chemotherapy should be considered.

Caracterización de mutaciones en el gen GATA-1 en pacientes con Síndrome de Down y diagnóstico de mielopoyesis anormal transitoria o leucemia megacarioblástica aguda / Mutation characterization in the GATA-1 gene in patients with Down's Syndrome diagnosed with transient abnormal myelopoiesis or acute megakaryoblastic leukemia

Los pacientes con síndrome de Down tienen un riesgo más elevado de presentar leucemia megacarioblástica aguda (LMCA). Un 10% de los recién nacidos con ese síndrome presentan un cuadro de mielopoyesis anormal transitoria (MAT), indistinguible de la LMCA, que en general remite espontáneamente. En ambos grupos de pacientes se describió una alta incidencia de mutaciones en el gen GATA-1. Se analizaron 14 muestras de ADN de médula ósea (10 MAT/4 LMCA) correspondientes a 13 pacientes con Síndrome de Down mediante PCR y secuenciación, para describir la frecuencia y las características de las mutaciones en el gen GATA-1 en la población estudiada y sus consecuencias a nivel proteico. Se detectaron mutaciones en 10 de 10 MAT y en 3 de 4 LMCA, que a nivel proteico originarían un codón de terminación prematuro (n= 5), alteraciones en el sitio de corte y empalme (splicing) (n= 6) o cambio de secuencia (n= 3). Se confrmó la alta frecuencia de mutaciones en el gen GATA-1 en recién nacidos con Síndrome de Down y MAT o LMCA.

Patients with Down's Syndrome have a higher risk of developing acute megakaryoblastic leukemia (AML). Ten per cent of newborn infants with this syndrome have transient abnormal myelopoiesis (TAM), indistinguishable from AML, which generally remits spontaneously. A high incidence of GATA-1 gene mutations was described in both groups of patients. Fourteen bone marrow DNA samples (10 ATM/4 AML) were analyzed by PCR and sequencing; these samples were obtained from 13 patients with Down's Syndrome to describe the rate and mutation characteristics of the GATA-1 gene in the studied population and its consequences at a protein level. Mutations were detected in 10 out of 10 TAM and in 3 out of 4 AML, which at a protein level would result in an early termination codon (n= 5), alterations in the splicing site (n= 6) or sequence change (n= 3). The high rate of GATA-1 gene mutations was confirmed in newborn infants with Down's Syndrome and MAT or AML.

A case of leukemoid reaction in a patient with sarcomatous hepatocellular carcinoma / 대한간학회지

A leukemoid reaction is defined as reactive leukocytosis exceeding 50,000/mm3, with a significant increase in early neutrophil precursors, and can be a paraneoplastic manifestation of various malignant tumors. A 71-year-old male patient complained of decreased appetite, fatigue, and abdominal fullness. He had a palpable, firm liver, and laboratory investigations suggested leukemoid reaction. Liver dynamic computed tomography revealed a hypervascular mass, and an ultrasound-guided fine-needle aspiration of the mass confirmed hepatocellular carcinoma (HCC) with a sarcomatoid component. The leukocyte count of the patient had increased to 147,800/mm3, and he died 10 days after admission. This is a rare case of leukemoid reaction in a patient with sarcomatous HCC.

Reacciones leucemoides en el recién nacido / Leukemoid reactions in the newborn

Presentamos el caso de una recién nacida prematura y de bajo peso al nacer que desarrolló cuentas leucocitarias elevadas hasta más de 100,000 x mmc, sin otras anormalidades hematológicas y que resolvió espontáneamente. A propósito del caso se revisó las ca usas de reacciones leucemoides en el período neonatal. En primer lugar la causa más conocida: síndrome míeloprollferatlvo transitorio, descrito en trisomía 21. En pacientes sin anomalías cromosómicas el uso de esteroides para inducir la maduración pulmonar , la corioamnlonitls y la prematurez extrema son exploradas como causas de RL. Luego revisamos el desarrollo de dlsplasia broncopulmonar y el síndrome de respuesta inflamatoria slstémlca en relación a RL...(AU)

Perinatal factor and neonatal outcome of very low birth weight infants with leukemoid reaction / 대한주산의학회잡지

PURPOSE:Leukemoid reaction (LR) represents inflammatory reaction in very low birth weight (VLBW) infants, and has been reported to relate with the development of bronchopulmonary dysplasia (BPD). This study was done to assess the relationship between perinatal characteristics and neonatal outcome of leukemoid reaction in VLBW infants. METHODS:Three hundred and seventy two VLBW infants admitted to the NICUs of SNUCH and SNUBH between June 2005 to June 2008 were studied in a retrospective case-controlled manner. Of these VLBW infants, 32 LR (+) infants were compared with 83 LR (-) infants who were matched for gestational age and birth weight with respect to perinatal and neonatal clinical characteristics. LR was defined as a white blood cell (WBC) count of more than 40,000 cells/mm3 or absolute neutrophil count of more than 30.000 cells/mm3 during the first month of life. RESULTS:Of 413 VLBW infants, There was no significant difference between the LR (+) and LR (-) infants in sex, Apgar scores, maternal peripheral WBC count, the use of antenatal steroids and maternal age. Comparing with LR (-) infants, LR (+) infants had a higher positive rate for amniotic fluid culture (67% vs 11%; P< or =0.01), U. ureaplasma in amniotic fluid (52% vs 10%; P=0.01), histologic chorioamnionitis (81% vs 33%; P=0.01) and funisitis (50% vs 7%; P=0.01). The incidences of respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, sepsis, intraventricular hemorrhage and BPD showed no significant difference between LR (+) and LR (-) infants. CONCLUSION:LR during the first month of life in VLBW infants was associated with chorioamnionitis, but not with the incidence of bronchopulmonary dysplasia or other neonatal morbidities. These findings suggest that LR may be a simple reflection of transient accelerated neutrophil production induced by prenatal inflammation without significant neonatal consequences.

Analysis of Prenatal and Postnatal Factors Associated with Complications and Prognosis in Premature Infants with Leukemoid Reaction

PURPOSE: This study determined the prenatal and postnatal factors associated with complications and prognosis in premature infants with leukemoid reaction. METHODS: We retrospectively reviewed the medical records of premature infants with gestational ages 30,000/mm3. The infants who had leukemoid reaction comprised the study group, while the remainder of infants made up the control group. The relationships between maternal and neonatal variables and ANC were studied. RESULTS: Leukemoid reaction was detected in 3.1% of the study infants (8 of 252). Factors more frequently associated with infants with leukemoid reaction were as follows: maternal chorioamnionitis, high levels of maternal and infant C-reactive protein, gestational age <37 weeks, birth weight <2,500 g, low Apgar score, prolonged ventilator support, and a high incidence of bronchopulmonary dysplasia (BPD). However, there were no significant differences with respect to the antenatal usage of steroids, the incidences of patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, and mortality between the two groups. CONCLUSION: Leukemoid reaction in premature infants was associated with chorioamnionitis and high levels of serum C-reactive protein in mothers and infants, and BPD in infants. These findings suggest that leukemoid reaction is secondary to inflammation caused by infection.

Leukocyte adhesion deficiency type 1 presenting as leukemoid reaction.

Leukocyte Adhesion Deficiency (LAD) is characterized by the inability of leukocytes, in particular neutrophilic granulocytes, to emigrate from the blood stream towards sites of inflammation. Infectious foci are nonpurulent and may eventually become necrotic because of abnormal wound healing. LAD-I is characterized by the absence of the beta-2 integrins CD II and CD 18 on leukocytes. We present a male neonate referred with continuation of leukemoid reaction in spite of antibiotic therapy of simultaneous omphalitis. The diagnosis of LAD-I was confirmed by flow cytometry, showing a deficiency of beta-2 integrins on the surface of the leukocytes. After management, the patient was discharged with prophylactic antibiotics.

Hepatocellular carcinoma presenting as neutrophilic leukaemoid reaction--a rare entity.

Leukaemoid reaction is a rare, growth factor-driven, paraneoplastic manifestation of hepatocellular carcinoma. It may masquerade as the neutrophilic chronic myeloid leukaemia or as chronic neutrophilic leukaemia. A 52-year-old male presented with hepatosplenomegaly and severe leucocytosis. He had progressive leucocytosis, neutrophil alkaline phosphatase score elevated, liver function tests altered. FNAC from the mass in the liver revealed features of moderately differentiated hepatocellular carcinoma. The patient deteriorated within two weeks and died thereafter.

Eosinophilic leukemoid reaction associated with carbamazepine hypersensitivity.

Carbamazepine is widely used in the treatment of epilepsy, neuralgic pain, and bipolar affective disorders. Several adverse drug reactions have been described during the course of carbamazepine administration, including exanthemata and hematological reactions. Carbamazepine is one of the common drugs that have been implicated in the etiology of drug hypersensitivity syndrome. A 50-year-old male presented with generalized erythroderma following 10 weeks of ingestion of carbamazepine 200 mg daily for idiopathic epilepsy. His systemic examination was within normal limits. Blood counts revealed marked eosinophilia of 52% (absolute eosinophil count of 10,400 per mm3). Bone marrow aspiration revealed a moderate increase in the eosinophilic series with cells showing normal morphology. The eosinophil counts returned to normal after 2 weeks of oral prednisolone therapy. This case is reported because of its rarity in the Indian medical literature.

A case of pseudomembranous colitis presenting as leukemoid reaction without symptoms in a diabetic patient / 대한내과학회지

Pseudomembranous colitis (PMC) is highly prevalent in patients with broad spectrum antibiotic therapy. It can result in significant morbidity and mortality, especially if it is not diagnosed early. The clinical manifestation of PMC is diverse and symptoms usually are increased order of severity. Although leukocytosis is common, leukemoid reaction is very rare in PMC. We report a case of PMC associated with a leukemoid reaction without typical symptoms in a type 2 diabetic patient who have the multiple diabetic complications.