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Myeloid leukemias and lung involvement.

Myeloid leukemias are clonal malignancies characterized by the presence of increased numbers of immature myeloid cells in the marrow and peripheral blood. Pulmonary involvement by myeloid leukemia is relatively uncommon and seen mainly in patients with severe disease. The most common form of pulmonary involvement consists of leukemic infiltration along the lymphatics in the peribronchovascular, septal, and pleural interstitial tissue. Less common manifestations include myeloid sarcoma, leukostasis, leukemic cell lysis pneumopathy, and hyperleukocytic reaction. The radiological manifestations of pulmonary leukemic cell infiltration and leukostasis consist mainly of bilateral thickening of the peribronchovascular interstitium and interlobular septa, a pattern that resembles that of interstitial pulmonary edema. The radiological manifestations of leukemic cell lysis pneumopathy and hyperleukocytic reaction consist of symmetric bilateral areas of consolidation. This manuscript reviews the histological and radiological intrathoracic manifestations of myelogenous leukemias.

Diagnosis, Differential↗

Specific cutaneous infiltrates in chronic myelogenous leukemia.

Specific leukemic infiltration of the skin is possible in all types of leukemia, and occurs most commonly in monocytic leukemias. We report the case of a 76-year-old woman with chronic myelogenous leukemia who showed specific cutaneous lesions one month before she died. In the absence of other signs of accelerated disease or blast crisis, cutaneous lesions should be considered an ominous sign in chronic myelogenous leukemia.

Aged↗

Papular leukemids.

Skin lesions occurring in patients with leukemia may represent specific leukemic infiltrates or may manifest as nonspecific lesions not related to leukemic cell infiltration. Included in the latter are a number of nonspecific papular and nodular lesions generally called "leukemids." We present two patients with lesions we have categorized as papular leukemids.

Aged↗

Phenotypic and ultrastructural profile of M5 leukemia cells in peripheral blood and skin infiltrate.

The leukemic cells circulating in the peripheral blood and invading the skin of a patient with type M5 myelomonocytic leukemia were compared using ultrastructural, cytochemical and immunological criteria. Neoplastic cells exhibited more differentiated morphologic features in the skin than in peripheral blood, resembling tissue macrophages. The cytochemical pattern did not show any appreciable difference, whereas the surface antigenic profile was dissimilar. Most circulating leukemic cells were Leu M1+ and Leu M3+, and the percentage of OKM1+ and OKIa-1+ cells varied in two different blood samples examined. Conversely, OKIa-1 monoclonal antibody stained virtually all the leukemic cells infiltrating the skin in the absence of any appreciable reactivity with the other monoclonal antibodies. The phenotype of the malignant cells in the skin did not vary during the clinical course of the disease. These observations suggest that the cutaneous microenvironment is able to induce leukemic cells to mutate their phenotypic features towards a more mature state, or that only relatively differentiated circulating leukemic cells are able to leave the bloodstream and colonize the skin.

Aged↗

Bilateral optic nerve infiltration in central nervous system leukemia.

PURPOSE: To report the case of a 58-year-old man with sequential bilateral retrolaminar leukemic infiltration of the optic nerves who presented with normal-appearing optic nerves and no optic nerve enhancement. DESIGN: Interventional case report. METHODS: A 58-year-old man with chronic myelogenous leukemia (CML) developed progressive vision loss to no light perception in both eyes over four days. The patient received 14 doses of external beam irradiation and 10 cycles of intrathecal cytarabine. Despite treatment, he developed optic nerve pallor, and visual acuity remained no light perception in both eyes. CONCLUSIONS: In a patient with leukemia, leukemic optic nerve infiltration may occur even with normal-appearing optic nerves and a normal magnetic resonance image. It is important to maintain a high clinical suspicion for optic nerve infiltration so that prompt local irradiation may be initiated.

Antimetabolites, Antineoplastic↗

A bioactively modified fatty acid improves survival and impairs metastasis in preclinical models of acute leukemia.

PURPOSE: Polyunsaturated fatty acids (PUFA) and the sulfur-substituted fatty acid tetradecylthioacetic acid (TTA) inhibit proliferation and induce apoptosis in lymphoma and leukemic cell lines, but it is unknown if they can modify leukemogenesis in the intact organism. EXPERIMENTAL DESIGN: We now examined the effects of PUFA and TTA in rats transplanted with either acute promyelocytic leukemia or acute T-cell leukemia. The rats were randomized to isoenergetic diets containing either lard (control), omega3 (n-3) PUFA, or TTA. RESULTS: Whereas TTA prolonged survival (P < 0.05) in both types of rat leukemia, n-3 PUFA had no significant effect compared with controls. Only TTA inhibited (P < 0.05) leukemic infiltration in the bone marrow and spleen, probably due to apoptosis of the leukemic cells. Plasma metalloproteinase activity, a marker of metastatic activity, was significantly reduced in TTA-fed rats only. CONCLUSIONS: Dietary intake of TTA, but not of n-3 PUFA, in rats with acute leukemia, prolonged their survival. TTA intake was also associated with reduced leukemic cell burden as well as diminished extramedullar dissemination. TTA represents a modified fatty acid that exerts unique effects on malignant hematopoietic cells, and the present study indicates that TTA may have a therapeutic potential in patients with acute leukemias.

Animals↗

The effect of human IL-2-activated natural killer and T cells on graft-versus-host disease and graft-versus-leukemia in SCID mice bearing human leukemic cells.

We have previously reported that xenogeneic lethal acute graft-versus-host disease (GVHD) was induced by transplantation of a mixture of human IL-2 activated natural killer (NK) and T cells into SCID mice conditioned with 4 Gy total-body irradiation (TBI), but not by IL-2-activated pure human T cells or NK cells. TBI and transplantation of the mixture of activated cells were both required to produce the lethal effect. We now report the effect of human IL-2 activated NK, T, or NK+T effector cells on the development of acute and chronic GVHD and GVL in SCID mice bearing human leukemic cells. Ten days after being inoculated i.v. with 2 x 10(7) human U-937 or K-562 leukemic cells, SCID mice, hereafter termed hu-leukemic mice, were radiated with 4 Gy TBI and transplanted i.v. with 5 x 10(7) human IL-2-activated NK, T, or NK+T effector cells. Hu-leukemic control mice received neither TBI nor effector cell transplantation. Acute GVHD-positive control SCID mice were transplanted with 5 x 10(7) H-2-incompatible C57Bl/6 splenocytes following 4 Gy TBI. The mice were observed for signs of GVHD and leukemia for 90 days. Twenty of 20 non-effector cell-transplanted control hu-leukemic mice developed signs related to leukemia and died with leukemic infiltration in the brain, liver, kidney, and lung 50-65 days after inoculation. Flow cytometry (FC) demonstrated 21-89% human leukemic cell infiltration in the bone marrow. Fourteen of 14 hu-leukemic mice transplanted with NK+T effector cells did not develop signs of advanced leukemia but died within 17 days of acute GVHD. FC demonstrated no human leukemic cells in their marrow. Twelve of 15 and 18 of 25 hu-leukemic mice transplanted with either NK or T cells survived 90 days without any evidence of symptomatic leukemia (P < 0.01 compared with non-effector cell-transplanted groups). NK-transplanted hu-leukemic animals experienced mild-to-moderate acute GVHD during the first 10-20 days posttransplantation, but gradually recovered and did not develop chronic GVHD. Hu-leukemic animals transplanted with T effector cells manifested no signs of leukemia or acute GVHD but chronic GVHD skin lesions appeared 80-90 days after transplantation. We conclude that acute GVHD, chronic GVHD, and GVL are associated but separable phenomena.

Animals↗

Cutaneous presentation of juvenile chronic myelogenous leukemia: a diagnostic and therapeutic dilemma.

Annular, erythematous, circinate plaques were the first manifestation of juvenile chronic myelogenous leukemia (JCML) in an otherwise healthy 2.5-year-old boy who had had these lesions since 6 months of age. The lesions showed an atypical hematopoietic infiltrate on biopsy. Biopsy of a bone marrow specimen and peripheral blood smear were normal six months before leukemic transformation. At 3 years of age the boy developed splenomegaly, thrombocytopenia, and petechiae, and a bone marrow aspirate and cell marker studies were regarded as consistent with, if not diagnostic of, JCML. Four previous cases of cutaneous leukemic infiltrate associated with JCML have been published. Our patient had recurring urticarial-like plaques for two years before the initial bone marrow finding of JCML. Given the poor prognosis and progressively evolving course of JCML, it may be appropriate to consider therapy before bone marrow changes, based on the presence of the cutaneous eruption with the appropriate findings on skin biopsy and an elevated fetal hemoglobin.

Child, Preschool↗

Acute lymphocytic leukemia presenting as masquerade syndrome.

An 11-year-old child presented with plastic iridocyclitis and hypopyon. Subsequent paracentesis revealed leukemic infiltrates. A bone marrow biopsy confirmed the diagnosis of acute lymphocytic leukemia. Because of this unusual case of leukemic hypopyon, we advocate anterior chamber paracentesis and pediatrician referral in all cases of refractory uveitis.

Anterior Chamber↗

In vivo phenotypic characteristics of AKR T-cell lymphomas with different leukemic potential: possible role of alpha 4 beta 7 integrin in the progression towards the leukemic phenotype.

The present study was undertaken in order to determine whether the expression of specific surface molecules which mediate immune recognition as well as cell-cell and cell-matrix interactions is associated with the leukemic evolution of T-cell lymphomas. To this end, we have investigated the in vivo phenotypic characteristics and the in vitro natural-killer(NK)-cell susceptibility of a group of MCF-247-induced AKR/J T-cell lymphomas with different leukemic potential. We found that in the AKR/J model, the biological aggressiveness of leukemic cells is not dependent upon an escape from host immune surveillance as a consequence of an in vivo down-regulation of H2-Kk determinants or a resistance to NK lysis. Moreover, NK susceptibility of AKR/J lymphomas does not seem to correlate with the level of H2-antigen expression. No obvious correlation was found between the leukemic phenotype and the amount of MEL-14, LFA-1, ICAM-1, Pgp-1/CD44 and THAM/CD26 antigen expression. An in vivo coordinated up-regulation of alpha 4 and beta 7 integrin chains, with the highest levels of expression detected in secondary sites of leukemic infiltration, was observed in the highly leukemic lymphoma NQ22 and, albeit to a lesser extent, in lymphomas with moderate leukemic potential. Conversely, non-leukemic lymphomas were repeatedly alpha 4- and beta 7-negative. These findings suggest that in the AKR/J system the expression of alpha 4 beta 7 integrin may contribute to leukemic spreading of T-cell lymphomas.

Animals↗

[An autopsy case of malignant histiocytosis-like disorder following hypersensitive reaction to mosquito bite].

An autopsy case of an 18-year-old Japanese girl with a malignant histiocytosis-like disorder that developed during the course of a hypersensitive reaction to mosquito bite is reported. Episodes of hypersensitive reactions to mosquito bite had been repeated since she was 12 years old and at the age of 18 years she died of acute respiratory failure only 11 days after a mosquito bite. On autopsy, the dermal reaction to the last mosquito bite had already calmed down, and 'poorly differentiated histiocytes', which were presumed from their histochemical characteristics, had remarkably infiltrated into multiple organs, appearing like leukemic infiltration. Only a small number of them were noted in the lymph nodes and the bone marrow. The results of histochemical examination of 'poorly differentiated histiocytes' was as follows: (1) Neither markers for granulocytes (peroxidase and naphthyl AS-D Cl esterase) nor markers for lymphocytes and plasma cells (leukocyte common antigen and immunoglobulins) were detected. (2) Some markers for histiocytes (peanut lectin agglutinin and lysozyme) were positive in some of the proliferated cells. (3) A marker for T-zone histiocyte (s-100 protein) was negative. These results suggested that the proliferated cells included cells of the monocyte-macrophage system. These cells morphologically showed no phagocytic activity and were suggested to be immature histiocytes. Jurco et al. reported (poorly differentiated) malignant histiocytosis consisting of immature histiocytes without phagocytic activity, by using histochemical methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Radiation-induced erythroleukemia in the beagle dog. A hematologic summary of five cases.

Eleven cases of myeloproliferative disease occurred in a group of 24 beagle dogs placed in a 60Co gamma-ray field at about 13 months of age and irradiated at an exposure rate of 5 R/22-hour day for duratior of life. Of these 11 dogs, 5 (described in this paper) were diagnosed as having erythroleukemia. The bone marrow showed marked erythroblastic hyperplasia, with maturation arrest of the erythroid elements, and increased numbers of myeloblasts and promyelocytes. The terminal peripheral blood was characterized by marked anemia and thrombocytopenia, with circulating erythrocytic precursors and abnormal erythrocyte morphology. Splenomegaly and hepatomegaly occurred in 4 of the 5 animals. In the spleens and livers of all 5, there was extensive leukemic infiltration and proliferation. The extent of leukemic involvement in other tissues and organs varied in individual dogs.

Animals↗

Patterns of abnormality on bone scans in acute childhood leukemia.

Bone scintigraphy is not performed routinely in the diagnostic work-up of children with leukemia; however, the initial diagnosis of childhood leukemia is often difficult to make and may be delayed. Patients may present with fever and skeletal symptoms and, in such cases, bone scintigraphy may be requested in the early search for a diagnosis. Recognition of the potential scintigraphic abnormalities that result from leukemic infiltration of bone and bone marrow will often facilitate an early diagnosis of leukemia. Bone scans also play a role in detecting osteomyelitis in the immunosuppressed leukemic child with fever and bone pain. This article presents four patients illustrating the salient features of bone scintigraphy in these clinical settings.

Arthritis, Infectious↗

Granuloblastic masses in the breast: report of two cases.

Two patients with granuloblastic masses of the breast, onsetting at diagnosis and as first relapse site of acute myeloid leukemia are reported. The first case had been diagnosed initially as a carcinoma, and the patient underwent bilateral mastectomy. Acute leukemia was only revealed by histology of the surgical specimen. In the second case a second neoplasia, occurring during acute leukemia, was suspected: a fine needle aspirate of the breast mass showed a leukemic infiltrate. Involvement of breast during acute myeloid leukemia is a rare event and, in our experience, of bad prognostic significance. Mammary glands may be a sanctuary for leukemic cells, contributing to unresponsiveness to chemotherapeutic agents.

Acute Disease↗

Leukemic hypopyon in acute myelogenous leukemia.

We encountered a patient with acute myelogenous leukemia (AML) who developed leukemic hypopyon. Leukemia initially spread into the pharynx, gingiva, lymphnode, and bone marrow. He achieved complete remission after chemotherapy but developed blurred vision and hypopyon. Anterior chamber paracentesis disclosed leukemic infiltration of the anterior chamber. Infiltration of the central nervous system also occurred. He received systemic chemotherapy, intrathecal chemotherapy, and local chemotherapy. However, he did not achieve prolonged remission. These findings suggest that these chemotherapy treatments have an inadequate effect for AML with anterior chamber infiltration. This rare complication is associated with extramedullary infiltration of leukemia.

Anterior Chamber↗