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Total body hyperthermia in combination with etoposide and melphalan in a child with acute myelomonocytic leukemia.

In vitro and clinical studies have shown antineoplastic effects of hyperthermia alone and in combination with other treatment modalities. Synergistic cytotoxic effects of chemotherapy and hyperthermia have been demonstrated on leukemic cell clones in vitro. It seems that hyperthermia is effective in overcoming chemotherapy resistance. Several groups treated solid tumors by using total body hyperthermia (TBHT). However, only a few studies have been reported investigating the clinical effects of TBHT in myeloproliferative disorders. We report the case of a 7-year-old boy with myelomonocytic leukemia treated with TBHT (2 hours, 42 degrees C) combined with etoposide (600 mg/m2), melphalan (30 mg/m2) and hyperglycemia (200-300 mg/dl). Within 24 hours after TBHT, the leukemic cells decreased after TBHT from 53,000/microliters to zero. Skin leukemic infiltrates, resistant to conventional treatment, also responded well. Although our patient relapsed 34 days after TBHT, these results indicate that TBHT in combination with cytotoxic treatment may be a useful treatment modality in refractory leukemia.

Antineoplastic Combined Chemotherapy Protocols↗

A new translocation t(1;4;11) in congenital acute nonlymphocytic leukemia (acute myeloblastic leukemia).

A new translocation t(1;11;4)(1pter----1p32::11q23----11q13::4p16--- -4qter) was found in the peripheral blood of a patient with congenital acute myeloblastic leukemia (AML). It was concluded that this translocation may represent a new mutation, which caused the leukemia with very high leukocytosis, hepatosplenomegaly, leukemic infiltration of the majority of the organs, and a very poor prognosis.

Chromosomes, Human, Pair 1↗

Interaction of cyclosporin A with antineoplastic agents.

A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.

Adult↗

Ocular involvement in hamsters transplanted with a human leukemic T-cell line.

A leukemic T-cell line (TALL-1) was serially transplanted for 5 passages into newborn hamsters treated with antilymphocyte serum. This cell line was derived from a leukemic patient with clinical evidence of ocular involvement. I.p. implantation of 1--3 X 10(7) cells resulted in disseminated growth of tumors in all 15 recipients after 23--41 days and 8 of them showed leukemic infiltration of the uveal tract of one or both eyes.

Adult↗

MRI of the knee region in leukemic children. Part I. Initial pattern in patients with untreated disease.

The results of MRI studies performed on the medullary cavity in the knee region of 15 children with leukemia and 5 healthy children are reported. By the age of a few years the signal intensities and the relaxation times of bone marrow begin to resemble fat. Early leukemic infiltration can therefore be more easily recognised in the knee region than in the spine using simple T1 weighted Spin-Echo images. We observed an abnormal signal pattern in all our patients which fell into three groups: (a) diffuse uniform (b) diffuse non-uniform and (c) patchy. We have not been able to correlate these into age, sex or the risk factor determined by clinical or laboratory methods. The diffuse patterns seem to dominate in cases of ALL, the patchy forms in AML. No correlation could be found between the blast levels established by the iliac crest biopsy and the results of MRI.

Adolescent↗

Tubular (acinar) transformation of the choroid plexus epithelium.

The choroid plexus in the normal state shows a beautiful papillary (or villous) architecture supported by the intricately ramifying, thin fibrovascular stroma. This configuration is retained in benign and malignant neoplasms derived therefrom. The choroid plexus was involved in the pathological process of leukemic cell infiltration in one case reported here and in chronic cryptococcal leptomeningitis in the other case. The epithelial cells of the choroid plexus of the lateral ventricle were arranged extensively in a tubular (acinar) configuration, in association with remarkable stromal fibrosis caused by an infiltration of leukemic or inflammatory cells. In addition, choroid plexus epithelial cells in the first case contained a moderate amount of intracytoplasmic glycogen. These two cases indicate that the non-neoplastic choroid plexus epithelium can undergo transformation into a tubular (acinar) structure as a response or adaptation to the fibrotic processes of the stroma. This finding should be differentiated from metastatic adenocarcinoma. This finding also provides some suggestions as to the pathogenesis of "tubular (acinar) adenoma," a rare variant of benign choroid plexus neoplasm.

Arachnoid↗

Interdigitating reticulum cells in lymph nodes of Sézary syndrome. Freeze-fracture and ultrathin-section morphology.

Lymph nodes with extensive leukemic infiltration from three patients with the Sézary syndrome were examined in ultrathin sections and in freeze-fracture replicas. Sézary cells (SC) and interdigitating reticulum cells (IDC) were the predominant cell types in the lymph nodes. Both were closely connected with each other by apparently interdigitating cytoplasmic processes. The projections between these cells were, in the main, processes from the IDC. In freeze-fracture replicas these cellular processes did not appear as interdigitations but were more bubble-like, and for this reason these cells are imprecisely described by the term "interdigitating." The SC were seen to possess only short cytoplasmic processes. The frequent polar grouping of cell organelles in SC in the region of the contact zone with IDC and the high organelle content of IDC ('activated IDC') could be the morphologic expression of intense interaction between IDC and SC. IDC displayed three features in freeze-fracture which are not specific to the Sézary syndrome, but should be applicable to IDC in general: (1) they exhibited an approximately equal density of intramembrane particles in both the E-face and the P-face, (2) some of the intramembrane particles in the P-face were assembled in clusters and (3) the surface showed bubble-like formations of the cytoplasmic processes. On the basis of these properties it was possible to distinguish IDC from macrophages and lymphocytes in freeze-fracture replicas.

Antigen-Presenting Cells↗

Central diabetes insipidus due to acute monocytic leukemia: case report and review of the literature.

We describe a 69-year-old man who presented with a four-month history of polyuria and polydipsia. Plasma vasopressin levels were undetectable, and a dehydration test was abnormal. Based on these findings, a diagnosis of central diabetes insipidus has been established. Hematologic studies showed acute monocytic leukemia. A relationship between the hematologic and endocrine disturbance has been hypothesized, and histological examination at autopsy showed leukemic infiltration of the pituitary stalk. This patient represents the third case in the world literature of central diabetes insipidus associated with acute monocytic leukemia.

Diabetes Insipidus↗

Spontaneous remission of acute myeloid leukemia after infection and blood transfusion associated with hypergammaglobulinaemia.

Spontaneous remissions of acute myeloid leukemia (AML) have been documented in association with infection as well as blood transfusions. Activation of the immune system including an increased number of NK cells and cytokine release have been implicated in the mechanism of this phenomenon. We have observed spontaneous remissions in two patients with AML (one with a t(8;21)-positive M2, one with M5b), both occurring after infection and blood transfusions. The bone marrow showed a reduction of blast cells from 65% to 2% or 40% to 1%, respectively. Remission was accompanied by a marked polyclonal hypergammaglobulinemia in both cases (IgG values of 6420 and 2160 mg/dl, IgA of 802 and 811 mg/dl, respectively). A concomitant increase in bone marrow plasma cells was observed in both patients. Reduction of AML1/ETO PCR positivity from one-step to two-step PCR (approximately 100-fold) was documented in the patient with a t(8;21), while a regression of lymph node and skin leukemic infiltrations occurred in the patient with M5b. One patient relapsed after 4 months, at a time when his serum immunoglobulin levels had markedly decreased. The other patient is in continuous remission after 14 months. These cases suggest a potential role for a humoral immune response in the mechanism of spontaneous remission.

Acute Disease↗

Small bowel obstruction in acute myelogenous leukemia: stenosis or paralysis?

We describe a patient with acute myelogenous leukemia who suffered a small bowel obstruction on the second day of chemotherapy. The patient had to be operated immediately, and the terminal ileum and a part of the colon was removed. The resected specimen showed leukemic infiltration (chloroma) of the bowel with marked atrophy of the muscular layer. However, there was no complete stenosis. For this reason we believe that the reason for the acute abdominal symptoms on the second day of chemotherapy could be paralysis of the bowel due to muscular atrophy.

Abdominal Pain↗

[Extramedullary initial manifestations of acute myeloid leukemia (AML)].

Extramedullary myeloblastic tumors, so-called myelosarcomas (granulocytic sarcomas, chloromas) have been reported only sporadically in the pertinent literature which reflects their rather infrequent occurrence. These lesions may accompany the initial manifestation or signal relapse of acute myeloid leukemia (AML) or coincide with blastic transformation of a chronic myeloproliferative disorder. However, even more rarely, primary myelosarcomas may precede AML by months or years or may be associated with myelodysplastic syndromes (MDS) that never progress to manifest leukemia. In a retrospective evaluation a clinicopathological study on these latter two variants of isolated extramedullary manifestations of AML was performed to elucidate certain aspects of site involvement and histopathology by application of enzyme and immunohistochemistry. For this reason, we selected 6 patients presenting with a myelosarcoma in combination with MDS and 12 patients revealing only uncharacteristic reactive changes of the bone marrow. Of these patients 8 developed AML following an observation time of up to 2 years. Focal leukemic infiltrates were most often localized in the skin ( n=4), oral mucosa ( n=4), lymph nodes ( n=3), gastrointestinal tract ( n=3) or pleura and retroperitoneum ( n=3 each). Myelosarcomas were usually regarded by the clinicians as putative malignant lymphomas unless further evaluation, especially involving chloroacetate esterase reactions as well as immunostaining with a panel of antibodies reactive with lysozyme, myeloperoxidase, CD68, CD43, CD56, CD117 and CD34 proved their true nature. Although at that time bone marrow findings were inconclusive, a straightforward diagnosis was reached by considering the possibility of a (primary) myelosarcoma in these patients.

Adolescent↗

Effect of aging and dietary restriction on hepatocyte proliferation and death in male F344 rats.

The proliferation and death of hepatocytes in rats fed ad libitum and rats on dietary restriction were evaluated in 3 to 24-month-old rats by employing immunocytochemistry for proliferating cell nuclear antigen (PCNA) and terminal dUTP nick end labeling (TUNEL). These techniques were also used to examine hepatic tissue infiltrated with leukemic cells in 24-month-old rats fed ad libitum. PCNA-strongly positive hepatocytes, PCNA-positive hepatocytes, and TUNEL-positive hepatocytes were reported previously to be equivalent to hepatocytes in the S phase, hepatocytes in the cell cycle, and dying hepatocytes, respectively. The proportion of PCNA-strongly positive hepatocytes and PCNA-positive hepatocytes declined with age. Dietary restriction diminished PCNA-strongly positive hepatocytes significantly but not PCNA-positive hepatocytes in young rats, but the proportion of PCNA-strongly positive hepatocytes was significantly higher following dietary restriction than that in rats fed ad libitum in advanced age. Growth stimulation by leukemic cell infiltration resulted in a recovery of the age-related decline of PCNA-strongly positive hepatocytes. Aging was associated with a progressive increase in the proportion of TUNEL-positive hepatocytes, with a smaller effect following dietary restriction than in rats fed ad libitum after 6 months of age. Our results indicate that age and dietary restriction induce proliferative inhibition. The inhibition depends on PCNA expression; this suggests that suppression of cell proliferation and cell death are enhanced in hepatocytes of senile rats.

Aging↗

Acute lymphoblastic leukemia of the skin and subcutaneous tissues; the first manifestation of disease in a 6-month-old infant: a case report with literature review.

Leukemic infiltrate involving the skin and subcutaneous tissue was the first manifestation of disease in a 6-month-old female infant. Knowledge of age-related distribution patterns of the red (cellular) and yellow (fatty) marrow is crucial for the interpretation of magnetic resonance imaging (MRI) studies. Diffusely decreased signal intensity throughout the bone marrow on the T1-weighted images specifically involving the epiphyseal ossification centers in infants 6 months after their appearance should be suggestive of a marrow infiltrative/replacement process. Correlation with the peripheral blood smear and bone marrow aspirate are necessary for the diagnosis of leukemia.

Bone Marrow↗

Association of monocytic leukemia in patients with extreme leukocytosis.

Fifteen of 73 newly diagnosed patients with acute myeloid leukemia (AML), admitted to Mount Sinai Hospital between July 1977 and October 1979, presented with leukocyte counts greater than 100,000/microliter. Eleven of these 15 patients with hyperleukocytosis had myelomonocytic (AMML-M4) or monocytic (AMOL-M5) leukemia compared to 15 of 58 patients with lower white cell counts (p < 0.001). Identification of type of leukemia, using the FAB classification, was based on morphology and special stains, including myeloperoxidase, Sudan black B, periodic acid-Schiff and nonspecific esterase with and without inhibition by fluoride. The proportion of patients with splenomegaly is higher in those with hyperleukocytosis (73 percent) than in those with lower white blood cell counts (p < 0.001) regardless of cell type. Leukemic infiltration of the skin, gums and central nervous system was seen exclusively in patients with AMML and AMOL. The serum lysozyme levels were significantly higher for all patients with AMML and AMOL regardless of the white blood cell count. The mean serum lysozyme for M-4, M-5 patients was 59.7 microgram/ml compared to 18.9 microgram/ml in patients with other cell types (p < 0.0001). Patients with a white blood cell count less than or equal to 100,000/microliter had a complete remission rate of 69 percent compared to 47 percent for patients with higher white blood cell counts.

Humans↗

Right heart obstruction due to intracavitary prolymphocytic leukemia.

A 52-year-old woman with prolymphocytic leukemia in whom right heart failure developed from leukemic infiltration of the heart with right ventricular outflow tract obstruction is described. Two-dimensional echocardiography helped guide successful treatment of this complication with radiation and chemotherapy.

Echocardiography↗

Ocular involvement in congenital leukemia.

Congenital leukemia, a rare disease with distinct features, was diagnosed in a 5-week-old girl. The infant was tachypneic and tachycardic, with intercostal retractions, distended abdomen, and multiple hematomas. Despite aggressive treatment, the child died. Histologic examination of tissue obtained at autopsy disclosed leukemic infiltrates in the ocular muscles, conjunctiva, uveal tract, and optic nerve.

Anterior Eye Segment↗

Ovarian masses in children: a review of 91 cases of malignant and benign masses.

Ovarian masses in children are uncommon. We reviewed all cases of ovarian masses presenting to this hospital from 1979 to 1990. Ninety-one patients fulfilled the criteria and had medical records available. All patients were less than 18 years old. Four were diagnosed antenatally. Thirty-four tumors presented prior to 8 years of age and 1 (2.9%) was malignant. Fifty-eight tumors presented after 8 years of age and 18 (33%) were malignant. Seventy-two patients had benign disease and 19 had malignant tumors. Of those with benign disease 22 had simple or epithelial cysts, 25 had teratomas, 13 had torsion with cyst formation, 3 had granulosa cell tumors, and 9 had other less common lesions. Analysis of symptoms could not distinguish between benign and malignant lesions; however, age was less (P < .03) and tumor size smaller (P < .001) in patients with benign lesions. Benign lesions presented at a mean age of 8.8 years. Fifty-four patients had an ultrasound, all were diagnostic: simple mass (14), complex mass (8), or cyst (32). Mean size of the masses was 9.5 x 7.7 cm. Fourteen patients had a contralateral ovarian cyst. The malignant lesions included 14 germ cell tumors (4 endodermal sinus, 4 teratoma, 2 choriocarcinoma, 2 dysgerminoma, 1 embryonal, and 1 mixed), 4 epithelial tumors (1 mucinous cystadenocarcinoma, papillary cystadenocarcinoma, papillary serous cystadenocarcinoma, and endometrioid adenocarcinoma), and one patient with leukemic infiltration (ALL). Germ cell tumors presented at a mean age of 11.8 years. Eight of these patients had an ultrasound and all showed a mass (7) or cyst (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗