Disseminated amphotericin-resistant fusariosis in acute leukemia patients: report of two cases.

Disseminated fusariosis has emerged as a significant, usually fatal infection in immunocompromised hosts despite antifungal treatment. We describe here two patients with acute leukemia who developed disseminated amphotericin-resistant fusariosis, and review of six studies of cases series in the literature. Two Fusarium solani strains were isolated from blood and skin cultures of one patient, and one strain from the blood culture of the second patient. Both patients died despite antifungal treatment. Strains were identified by sequencing of ITS1 and ITS4 regions. Random amplified polymorphic DNA analysis of the three F. solani isolates showed a low degree of similarity. Screening for Fusarium spp. contaminants within our facility was negative. Using the CLSI M-38-A2 broth dilution method and E tests(®), we found that the MICs were low for voriconazole (0.12 and 0.5 mg/L, respectively), unexpectedly high for amphotericin B (≥8 and ≥32 µg/mL, respectively) and itraconazole (≥16 mg/ml). Patients with leukemia or persistent neutropenia should be assessed for disseminated fungal infections, including biopsy and skin cultures. Antifungal susceptibility tests are important due to the possibility of the strains being amphotericin resistant. Treatments must be aggressive, with high doses of antifungals or combined therapy.

The relationship between cerebrospinal fluid osteopontin level and central nervous system involvement in childhood acute leukemia.

The aim of this study was to evaluate the relationship between cerebrospinal fluid (CSF) osteopontin (OPN) levels and central nervous system (CNS) involvement in children with a diagnosis of acute leukemia. The study sample consisted of 62 patients who had been diagnosed with acute leukemia. The control group consisted of 16 patients that had presented and had no malignant disease, CNS infection or chronic disease. CSF OPN levels were studied with enzyme-linked immunosorbent assay (ELISA) method. The mean CSF OPN level was 32.76±49.22 ng/ml in the patients at the time of diagnosis and 14.93±6.84 ng/ml in the control group (p>0.05). The mean CSF OPN level was 27.68±32.73 ng/ml at the time of diagnosis in the group without CNS involvement and 53.48±89.21 ng/ml in the group with CNS involvement (p>0.05). However, the CSF OPN level at the time of CNS relapse in patients who developed CNS involvement during follow-up (127.4±52 ng/ml) was significantly higher than in the group without CNS involvement at diagnosis and follow-up (mean CSF OPN level: 27.68±32.73 ng/ml) (p<0.001). The analysis of CSF OPN levels at the time of diagnosis-before relapse and at the periods of relapse and remission in patients who had CNS involvement at diagnosis and/or follow-up revealed statistically significant differences between the time points (p<0.001). High CSF OPN levels in childhood acute leukemia patients may be used as evidence for CNS involvement, and any increases found in CSF OPN levels may be a preliminary predictor for CNS involvement.

Successful living donor liver transplantation for severe hepatic GVHD histologically resembling autoimmune hepatitis after bone marrow transplantation from the same sibling donor.

A 30-year-old woman developed severe liver dysfunction 1 year after bone marrow transplantation (BMT) from an HLA-identical sibling donor for B lymphoblastic leukemia (B-ALL) during the tapering of cyclosporin A. The histologic picture resembled autoimmune hepatitis (AIH), although neither autoantibody nor hypergammaglobulinemia was detected. She entered hepatic coma, and underwent living donor liver transplantation from the same donor on day 421 after BMT. She is well 18 months after the procedure, showing normal liver function and hematopoiesis. AIH-like hepatic graft-versus-host disease (GVHD) has not been documented. This patient is the second case of living donor liver transplantation for hepatic GVHD from the same donor.

Candida krusei fungemia in an immunocompromised patient.

Candida krusei is an emerging fungal pathogen found primarily in immunocompromised patients. Intrinsic resistance to fluconazole and decreasing susceptibility to other anti-fungal agents are problematic. When colonization occurs, dissemination may follow rapidly. We present a case of a patient with acute lymphoblastic leukemia who, despite being treated prophylactically with fluconazole, developed disseminated C. krusei.

Controversies of and unique issues in hematopoietic cell transplantation for infant leukemia.

Infants with leukemia who require hematopoietic cell transplantation (HCT) remain 1 of the most significant challenges in pediatric stem cell transplant. Infant leukemia is characterized by a unique biology including a predominance mixed lineage leukemia(MLL) gene rearrangement and juvenile myelomonocytic leukemia. Moreover, the long-term effects of transplantation are particularly prominent in infants who have active endocrine, cardiovascular, pulmonary, neurologic, musculoskeletal, hearing, and vision development, with the added risk of second malignant neoplasms. Currently, there is no solid basis to support allogeneic HCT as first-line therapy for infant acute lymphoblastic leukemia-first remission (ALL-CR1), although indicated for other infant leukemias, including juvenile myelomonocytic leukemia (JMML). The relative long-term toxicity of total body irridiation (TBI) versus non-TBI containing preparative regimens for HCT in infants remains controversial, with the differences, especially on neurocognitive function, unknown.

Successful voriconazole treatment of invasive pulmonary aspergillosis in a patient with acute biphenotypic leukemia.

A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.

Leukemia cutis presenting as localized cutaneous hyperpigmentation.

The usual clinical presentations of leukemia cutis include solitary infiltrated erythematous or violaceous plaques or nodules and multiple localized or generalized papules. On the other hand, cutaneous hyperpigmentation is a frequent finding in patients with malignancies, most of the cases because of chemotherapy or other drugs that the patient is taking. We present a case of cutaneous hyperpigmentation as the presenting sign of leukemia cutis. A 61-year-old male presented with cutaneous hyperpigmentation, which had appeared during the last chemotherapy cycle for treatment for biphenotypic leukemia. Cutaneous lesions consisted of bluish to brownish irregular well-defined discoloration of the skin involving the upper part of the trunk and the temporal regions of the forehead. The patient was asymptomatic and the skin was not infiltrated at all. However, histopathologic study showed nodular infiltrates involving the full-thickness of the dermis and destroying pre-existing adnexa. This infiltrate was composed of atypical basophilic cells with large hyperchromatic nuclei and scant cytoplasm. Immunohistochemical studies showed intense immunoexpression for CD43, CD68, CD45RO and myeloperoxidase within these cells. A diagnosis of biphenotypic leukemia cutis was established. In our review of the literature we have not found any report of cutaneous hyperpigmentation as the presenting manifestation of leukemia cutis.

Fatal Cyberlindnera fabianii fungemia in a patient with mixed phenotype acute leukemia after umbilical cord blood transplantation.

We report a case of Cyberlindnera fabianii fungemia after umbilical cord blood transplantation (CBT). A 69-year-old woman was diagnosed as having mixed phenotype acute leukemia. The patient received CBT for primary refractory disease. After preconditioning chemotherapy, the patient's condition deteriorated, leading to acute respiratory failure from capillary leak syndrome and consequent admittance to the intensive care unit. The patient recovered temporarily following the administration of noninvasive positive pressure ventilation and continuous hemodiafiltration, but died of fungemia with the presence of yeast-like cells 15 days post-CBT. The yeast-like cells were analyzed by sequencing of the D1/D2 domain of the large subunit and the internal transcribed spacer domain, and were identified as C. fabianii. This case shows that molecular genetic-based methods may be effective for detecting undetermined invasive fungal infections in stem cell transplantation settings.

Neonatal mixed lineage acute leukaemia.

We report here an uncommon case of neonatal acute leukaemia that presented concomitant with serological evidence of rubella infection. The clinical course was aggressive and the patient died 5 days after diagnosis from septicaemia. Leukaemic blasts had a mixed lineage immunophenotype co-expressing a constellation of B-lymphoid (CD19, cytCD22, TdT) and myeloid (CD13, CD33, CD14, anti-MPO) markers, as well as multiple adhesion molecules and markers associated with early lympho-myeloid progenitor cells (CD34, CD7, HLA-DR). A previously unrecorded discordant expression of different CD10 and CD34 epitopes was identified using different monoclonal antibodies. The karyotype was 46,XX t(4;11)(q21;q23) and molecular analysis confirmed rearrangement of the trithorax-related oncogene HRX at 11q23. There was a clonal biallelic rearrangement of the immunoglobulin heavy-chain gene. The features of this rare case have implications for possible aetiological events leading to leukaemia.

Renal Presentation in Pediatric Acute Leukemia: Report of 2 Cases.

Renal enlargement at time of diagnosis of acute leukemia is very unusual. We here in report 2 pediatric cases of acute leukemia who had their renal affection as the first presenting symptom with no evidences of blast cells in blood smear and none of classical presentation of acute leukemia. The first case is a 4-year-old girl who presented with pallor and abdominal enlargement. Magnetic resonance imaging showed bilateral symmetrical homogenous enlarged kidneys suggestive of infiltration. Complete blood picture (CBC) revealed white blood count 11 × 109/L, hemoglobin 8.7 g/dL and platelet count 197 × 109/L. Bone marrow aspiration was performed, and diagnosed precursor B-cell ALL was made. The child had an excellent response to modified CCG 1991 standard risk protocol of chemotherapy with sustained remission, but unfortunately relapsed 11 month after the end of therapy. The second child was 13-month old, presented with pallor, vomiting, abdominal enlargement, and oliguria 2 days before admission. Initial CBC showed bicytopenia, elevated blood urea, creatinine, and serum uric acid, while abdominal ultrasonography revealed bilateral renal enlargement. Bone marrow examination was done and showed 92% blast of biphenotypic nature. So, biphynotypic leukemia with bilateral renal enlargement and acute renal failure was subsequently diagnosed. The patients admitted to ICU and received supportive care and prednisolone. Renal function normalized and chemotherapy was started. The child achieved complete remission with marked reduction of kidney size but, unfortunately she died from sepsis in consolidation phase of therapy. This case demonstrates an unusual early renal enlargement in childhood acute leukemia. Renal involvement of acute leukemia should be considered in child presenting with unexplained bilateral renal enlargement with or without renal function abnormalities and bone marrow examination should be included in the workup.

Tocilizumab en niño con leucemia linfoblástica aguda y síndrome de liberación de citoquinas asociado a COVID-19 / Tocilizumab in a child with acute lymphoblastic leukaemia and COVID-19-related cytokine release syndrome

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Transcripto E2A-PBX1 en paciente pediátrico con leucemia aguda híbrida linfoide b/mieloide / E2A-PBX1 transcript in pediatric patient with acute hybrid lymphoid b/myeloid leukemia

Las leucemias agudas representan un grupo heterogéneo de hemopatías malignas que pueden ser de origen linfoide o mieloide en dependencia del clon celular que da lugar al proceso maligno. Sin embargo, existen casos de leucemias agudas con fenotipo mixto donde coexisten características propias de más de un linaje celular y que se conocen hoy como leucemias agudas de fenotipo mixto. Se presenta el caso de un paciente que se diagnosticó como una leucemia aguda híbrida linfoide B/mieloide mediante citometría de flujo. Se encontró la presencia del gen de fusión E2A-PBX1 que se forma como consecuencia de una traslocación entre los cromosomas 1 y 19. El paciente, un niño de 20 meses de nacido, falleció a los 12 días de iniciados los primeros síntomas clínicos. Se conoce que esta anormalidad cromosómica está asociada a un pronóstico desfavorable, principalmente por la grave afectación del sistema nervioso central como en efecto ocurrió. Hasta donde se alcanzó a revisar, no se encontró un reporte similar en la literatura de una leucemia aguda híbrida linfoide B/mieloide positiva al gen defusión E2A-PBX1(AU)

The acute leukemias are an heterogenous group of malignant hemopathies diseases characterized by excessive proliferation of an inmature cellular clon. Depending of the myeloid or lymphoid origin of such clon, the acute leukemia could be classified in myeloid or lymphoid respectivement. However, there are cases of acute leukemias with mixed phenotype where immunologic markers of more than on elineage are present. In the patient of this report was founded a mixed immunophenotype pattern by flow cytometry and the entity was classified as acute hybrid lymphoid B/ mieloid leukemia. Basedon theinicial diagnostic of acutelymphoidleukemia, the molecular studydiscoveredthepresence of E2A-PBX1 fusion gen. That molecular anomaly is formed as consequence of a traslocation between the1 and 19 chromosomes. The patient, a child of 20 months, died 12 days afte rthe first clynic symptoms begining. E2A-PBX1 fusion gen is associated to unfavorable outcome, mainly because the severe damage at the central nervous system as in fact it occurred. Until it was possible review, no any similar report was founded about a case of acute hybrid lymphoidB/myeloid leukemia positive to the E2A-PBX1 fusion gen(AU)

Vena cava superior izquierda persistente: su importancia clínica / Persistent left superior vena cava: Clinical significance

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Neoplasia de células dendríticas blásticas plasmacitoides. Estudio de tres casos / Blastic plasmacytoid dendritic cell neoplasm. A study of three cases

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Fungemia por Trichosporon asahii en un paciente con neoplasia hematológica / Fungemia due to Trichosporon asahii in a patient with hematological malignancy

Antecedentes. La tricosporonosis es una infección oportunista debida a hongos levaduriformes del género Trichosporon. La mayoría de los casos de tricosporonosis invasiva acontecen en individuos inmunodeficientes. Caso clínico. Describimos un caso de infección diseminada por Trichosporon asahii en un paciente hematológico. Se trata de un varón de 52 años diagnosticado de leucemia linfoblástica aguda que desarrolla un cuadro febril durante el tercer ciclo de quimioterapia de inducción. A las 24 h de incubación se observó positividad en los hemocultivos extraídos, visualizándose en la tinción de Gram estructuras alargadas compatibles con elementos fúngicos. La identificación del hongo como Trichosporon asahii se llevó a cabo mediante la asimilación de compuestos de carbono y la amplificación y secuenciación de los dominios D1/D2 y la región espaciadora interna transcrita del ADN ribosómico. El hongo se aisló además de unas lesiones pustulosas que presentaba el paciente en la región pectoral. Tras tratamiento con anfotericina B, el paciente evolucionó favorablemente de las lesiones y del proceso febril. Conclusiones. Trichosporon asahii es un patógeno emergente en pacientes inmunodeprimidos y su presencia no debe ser considerada como colonización, pues existe riesgo de infección invasiva (AU)

Background. Trichosporonosis is an opportunistic infection caused by the genus Trichosporon. The majority of cases of invasive trichosporonosis occurs in immunocompromised individuals. Case report. We describe a case of disseminated infection by Trichosporon asahii in a hematology patient. A 52-year-old man diagnosed with acute lymphoblastic leukemia developed a febrile episode during the third cycle of the induction chemotherapy. The blood cultures were positive after 24 h incubation, showing elongated structures compatible with fungal elements in the Gram stain. The identification of the fungus as Trichosporon asahii was carried out by the assimilation of compounds of carbon and the amplification and sequencing of the D1/D2 domain and the internal transcribed spacer of the ribosomal DNA. The fungus was also isolated from the pustular lesions that the patient had in the chest. After treatment with amphotericin B, the patient progressed satisfactorily. Conclusions. Trichosporon asahii is an emergent pathogen in immunosupressed patients and its presence should not be considered as colonization, as there is risk of invasive infection (AU)