Endobronchial granulocytic sarcoma causing acute respiratory failure in acute myelogenous leukemia

Infiltration by leukemic cells may occur in many organs. When localized masses caused by myeloid leukemic infiltration occur, they are called granulocytic sarcomas. Such tumors may be mistaken for primary carcinomas. In this report, we describe a 63-yr-old man with acute myelogenous leukemia who developed progressive atelectasis of the left lower lobe of the lung. Bronchoscopy revealed a fungating endobronchial tumor completely obstructing the left lower lobe bronchus and partially occluding the left upper lobe bronchus. Biopsies from this lesion showed an endobronchial granulocytic sarcoma. Despite chemotherapy, the patient developed progressive hypoxemia and died.     

Accelerated myeloblast destruction and abnormal lysosome disruption in cultured bone marrow: association with indolent acute myelogenous leukemia.

Despite no chemotherapy and a marrow morphologically typical of frank relapse, an acute myelogenous leukemia (AML) patient survived for nearly 1 yr. During this time she remained asymptomatic and maintained nearly normal levels of platelets and hemoglobin. Cytochemical and electron microscopic studies of her bone marrow in liquid culture revealed on several occasions a unique maturational sequence in that leukemic cells differentiated to form morphologically abnormal primary granules which appeared to rupture and cause cytolysis of these cells. In these cultures, blasts rapidly disappeared and were replaced by more mature granulocytes, in contrast to observations in cultures derived from five other patients with AML in relapse which showed persistently elevated blast counts with no evidence of maturation in vitro. These findings support the concept that in AML cell maturation is regularly impaired and in some cases also aberrant. In addition, the abnormal granule formation with autolysis of the leukemic cells observed in one patient may explain both the early cell death in vitro and this patient's relatively indolent clinical course. Similar in vitro studies may help predict atypical clinical courses in patients with AML and facilitate design of appropriate chemotherapy.     

Reversible congestive heart failure related to profound hypocalcemia secondary to hypoparathyroidism

A 71-year-old man presented with acute pulmonary edema related to new onset of severe left ventricular dysfunction (ejection fraction, 30%). His symptoms did not improve with emergency therapy with diuretics and dobutamine. He was noted to be severely hypocalcemic (5.5 mg/dL) and subsequently showed dramatic improvement in symptoms and ejection fraction (58%) with correction of hypocalcemia with intravenous calcium and calcitriol replacement. Hypocalcemia was related to surgically induced hypoparathyroidism. The patient had been instructed to decrease calcium supplements and to discontinue calcitriol 3 months previously due to hypercalcemia. Additional factors that may have contributed to hypocalcemia included vitamin D deficiency, alendronate therapy for osteoporosis, and chronic kidney disease. We concluded that the patient's congestive heart failure was precipitated by severe hypocalcemia and resolved with correction of hypocalcemia. Hypocalcemia is a rare cause of reversible congestive heart failure that should be in the differential diagnosis in any patient presenting with heart failure and not responding to traditional therapy.     

Abnormalities in granule formation in acute myelogenous leukemia.

Granule formation was investigated in differentiating neutrophils of a patient with acute myelogenous leukemia (AML) by means of the combined techniques of electron microscopy and peroxidase cytochemistry. Two important pathologic features were observed: first, an abnormal concentration and packaging of peroxidase into Auer rods in leukemic promyelocytes, and second, the presence of Auer rods surrounded by single-unit membranes in some mature polymorphonuclear leukocytes (PMN). An additional unexpected finding was the discovery of two distinct populations of PMN circulating concurrently; a minor (less than 5%) normal one that contained both peroxidase-positive azurophilic and peroxidase-negative specific granules and a major abnormal one characterized by the absence of specific granules. None of these abnormalities was observed during the two remissions of this patient's disease. During relapse a "hiatus leukemicus" occurred, which also revealed two populations of cells, a majority population of leukemic blasts, and a minority population of a few normal PMN. These findings documented several developmental abnormalities in the differentiating cells of myelogenous leukemia and also suggested that concurrent normal and abnormal populations of PMN may be a helpful diagnostic feature of a leukemic process.     

Autologous bone marrow transplantation in children with acute leukemia

Eight children with acute leukemia were treated with chemoradiotherapy or high-dose chemotherapy followed by infusion of autologous marrow unpurged or purged mainly with monoclonal antibodies. Four were treated in their first remission, three in their second remission, and one in the fourth remission. Patients were isolated in laminar air flow rooms with sterile conditioning. Infused mononuclear cells ranged from 1.0 to 3.8 x 10(7)/kg. Hematologic engraftment was obtained in five patients. The other three patients, who were treated with monoclonal antibody or drug, received unpurged back up marrow because of delayed bone marrow reconstitution. Two recovered, but one died before engraftment. Hematologic recovery was delayed after autologous bone marrow transplantation. The median time to achieve 1,000 leukocytes/microliters, 500 neutrophils/microliters, and last platelet transfusion was 36 days (12-90), 36 days (12-90), and 70 days (39-214), respectively. Moreover, further increases beyond these levels remained unusually slow, especially in platelets. Two of eight patients relapsed at 5 and 15 months and the other patient died of interstitial pneumonitis. Actuarial disease free survival was 62.5%. There was a trend toward improved disease free survival for patients transplanted in the first remission (100%).     

The hypocalcemia of acute pancreatitis.

Variables of calcium metabolism were measured in 11 patients with clearly documented acute pancreatitis. Total and ionized clacium levels were either low or in the low-normal range as were phosphorus and total magnesium levels. Parathyroid hormone levels were high, and there was a significant inverse correlation with ionized calcium. Gastrin levels were normal, calcitonin values were uniformly below the detection limit of the assay, and pancreatic glucagon levels were elevated. The hypocalcemia of acute pancreatitis was probably not caused by abnormalities of glucagon, calcitonin, or gastrin secretion. Furthermore, parathyroid hormone secretion was apparently not impaired. Hypomagnesemia possibly played a minor role. This study suggests that the hypocalcemia of acute pancreatitis is secondary to extraskeletal calcium sequestration or an as yet unidentified defect of bone metabolism, or both.     

Low turnover bone disease in Egyptian children with acute leukemia

The aim of this work was to study bone turnover markers, calcium homeostasis and bone mineral density (BMD) in children with acute leukemia at diagnosis, after induction chemotherapy, and during maintenance therapy to delineate abnormalities present. After evaluation of L2-L4 BMD using dual-energy X-ray absorptiometry in patients with acute myeloid and lymphoid leukemia at presentation and after treatment, the results were compared to 352 healthy age- and sex-matched Egyptian controls. Calcium homeostasis parameters and bone turnover biochemical markers (serum osteocalcin and urinary deoxypyridinoline) were also assayed and the results were compared to 12 healthy age- and sex-matched controls. Osteopenia was observed at diagnosis and during treatment in patients with acute leukemia. At diagnosis osteopenia was observed in 27 patients (62.8%): 10 (23.3%) had non severe osteopenia and 17 (39.5%) had severe osteopenia. This low BMD persisted in those who were followed up. Parathyroid hormone (PTH) (pg/ml) levels demonstrated non significant differences between children with acute leukemia at different stages of therapy and controls, while, 25 (OH) D3 (ng/ml) was significantly lower in acute leukemia patients at different stages of therapy compared to controls (p<0.001). Osteocalcin (ng/ml) is significantly lower in patients at different stages of the disease compared to controls (p<0.001) but there was no significant difference between patients at different stages of therapy. Deoxy-pyridoline cross links showed non-significant difference between the different types of acute leukemia and with controls. Osteopenia is a significant problem in children with acute leukemia at presentation and after chemotherapy. Osteopenia in acute leukemia appears to be of the low turnover type (decreased osteoblastic activity and decreased bone mineralization).     

Studies on pseudo-Chediak-Higashi granules formation in acute promyelocytic leukemia]

Leukemic cells from acute promyelocytic leukemia containing pseudo-Chediak-Higashi (P-CH) granules in a 38-year-woman were studied with ultrastructural and cytochemical techniques to evaluate the origin and nature of the granules. Wright-Giemsa stain revealed giant granules to be azurophilic. Cytochemical stain revealed p-CH granules ot the basic of their peroxidase and glycoprotein content. Electron microscopy revealed numerous giant granules formed by fusion of azurophilic granules these morphological, different type granules were classified into four types, 1) circular granule with homogeneous matrix, 2) circular granule with heterogeneous change by autolysis, 3) Auer body-like granule with crystalline arrangement, 4) vacuolar formation. The results demonstrate that the Auer body-like granule of P-CH granules in leukemic cells is a morphologically variant type of the classical Auer body observed in common acute myeloid leukemia.