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PubMed1984

[Clinical and occult testicular relapses in children with acute lymphoblastic leukemia. Treated with the D.74 and pethema 7/78 protocols].

The incidence of testicular infiltrates in 68 boys with acute lymphoblastic leukemia in first remission (1974-81), was prospectively investigated through careful clinical exams and routine bilateral biopsies at 2-3 years of remission. All boys were under 14 years of age and they were treated with protocols D.74 and pethema 7/78. Seven patients (10.3%) presented an isolated testicular relapse (ITR) during the chemotherapy period. In 13 out of the 43 testicular biopsies (31%) leukemic infiltrates were found and in other 2 findings were controversial. Three boys, two of them whose previous biopsy was negative, had an ITR, 6 to 18 months after stopping therapy. Finally, other 3 had simultaneous relapses in testes and bone-marrow: one during chemotherapy and two after suppression. In total, 23 patients (33.8%) in first remission had overt or occult ITR. Overall incidence of testes leukemia, is calculated to be 40% in all the group. Incidence of early and occult ITR was higher in boys with initial WBC counts over 20 X 10 9/l. Therapy in ITR generally consisted in local radiotherapy (20-25 Gy), a new induction treatment followed by 2 year maintenance treatment; in 3 patients with early ITR, orchidectomy was also performed and six were given a new preventive SNC treatment. Clinical course in the 7 patients with early ITR was unfavourable in 5 with subsequent hematological relapses and death; one had a long-term disease-free survival (78 + months) and the other was a recent case. 10 out of the 13 patients with occult infiltrates followed in remission and four were of treatment with a follow-up over 64 months. The 3 patients with late ITR were in second remission at 8-14 months after a new cessation of therapy. It may be concluded from this study that prognosis in ITR is related to the phase of presentation: It is unfavourable in cases of early ITR but in cases of occult infiltrates detected by routine biopsies and in late ITR the combined therapy is effective in most cases.

Adolescent↗
PubMed1994

Endogenous Fusarium endophthalmitis in a patient with acute lymphocytic leukemia.

Endogenous fungal endophalmitis is an uncommon complication of systemic mycosis. Only a few cases involving Fusarium have been reported, most with unfavorable visual outcomes. We examined a 31-year-old woman with acute lymphocytic leukemia who developed sudden visual loss in her right eye. A dense, white placoid infiltrate was present in the right macula extending into the vitreous. An iris nodule and hypopyon were present in the left eye. A vitreous aspirate of the right eye was positive for Fusarium species. The patient progressively lost vision despite amphotericin B and 5-fluorocytosine therapy. She died from bronchopneumonia, fungemia, and multisystem failure. Histopathologic study disclosed a panophthalmitis with Fusarium organisms invading all the ocular coats in the right eye. Leukemic infiltrates were present in the left iris, anterior chamber, and trabecular meshwork. The ocular destructiveness of Fusarium may be caused by marked mycotic vascular invasion and occlusion with consequent infarction and necrosis of ocular tissues.

Adult↗
PubMed1977

Probable myeloblastic leukemoid reaction with disseminated sarcoidosis.

A 55-year-old woman had progressive weakness, weight loss, night sweats, fever, right-sided facial weakness, and hepatomegaly. Reticulonodular infiltrates were seen on chest x-ray film and a central filling defect was noted on liver scan. Study of the peripheral blood was noted on liver scan. Study of the peripheral blood revealed pancytopenia and myeloblasts. The bone marrow was not markedly hypercellular but contained noncaseating granulomas and myeloblasts. The patient's condition deteriorated and she died on the 22nd hospital day. Autopsy disclosed disseminated sarcoidosis but no evidence of leukemic infiltrates. Although concomitant "smoldering" acute leukemia cannot be ruled out, the findings in this patient can be best explained on the basis of a myeloblastic leukemoid reaction accompanying sarcoidosis.

Biopsy↗
PubMedDate not supplied

Parenchymal brain leukemia. Case report: problems related to the diagnosis and treatment.

A case of intracerebral nodular leukemic mass that developed in a girl eight years after a diagnosis of acute lymphoblastic leukemia (ALL) and 18 months after second discontinuation of therapy for a central nervous system (CNS) relapse is reported. The morphologic picture and the long time that elapsed from the diagnosis raised the suspicion of a cerebral neoplasm; the immediate and dramatic effect of steroid treatment, on the contrary, indicated the presence of a leukemic infiltration and in the meantime, a bone marrow relapse occurred. The patient soon after received high-dose Cytosine Arabinoside (HD ARA C) + Vincristine (VCR) + Levo-Asparaginase (L-ASE) + Prednisone (PDN) without any intrathecal antiblastic drug. We observed a neurological recovery and a complete disappearance of the mass. After consolidation of the remission the patient began an ablative regimen for bone marrow transplantation. The efficacy of HD ARA C in the treatment of the intracerebral nodular leukemic mass is emphasized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1981

Arthritis in acute leukemia. Clinical and histopathological observations.

Eight patients had acute leukemia and arthritis. In five the arthritis had no evident cause other than the leukemia, and three had crystal-induced arthritis. Effusions from both groups of patients were often inflammatory. The average synovial fluid leukocyte count from the five effusions attributed to leukemia was 8,790/cu mm. A synovial needle biopsy specimen from one of these patients showed acute and chronic inflammation but no leukemic infiltration. Bone involvement was suggested by bone pain in only one patient. In no case did arthritis persist in the presence of a hematologic remission. In the three patients with crystal-induced arthritis, the average synovial fluid leukocyte count was 13,000/cu mm. There were crystals of monosodium urate in one and of calcium pyrophosphate dihydrate in two patients. Suspected blast forms were seen in the synovial fluid of only one patient, one of those with pseudogout. Electron microscopic studies of needle biopsy specimens of synovial membrane from leukemic patients with arthritis described herein for the first time showed no blast forms, virus-like particles, or electron-dense deposits in vessel walls to suggest specific mechanisms for the arthritis.

Adult↗
PubMed1985

Open lung biopsy in patients with acute leukemia.

The results of open lung biopsy in 15 patients with acute leukemia, pulmonary infiltrates, neutropenia, and fever were reviewed. The patients averaged 26 hospital days of neutropenia and 20 hospital days of fever before open lung biopsy, and all patients received broad-spectrum antibacterial agents (mean 17 days) before open lung biopsy. Nine (67 percent) received amphotericin B prior to open lung biopsy (mean 22 days). Open lung biopsy yielded a specific clinically helpful diagnosis in six patients, but only two of these patients survived the hospitalization during which open lung biopsy was performed. Open lung biopsy detected fungus in four patients and leukemic infiltrates in two patients. Management was appropriately modified in these patients. In nine patients, a specific diagnosis of the pulmonary infiltrate was not obtained by open lung biopsy. Antimicrobial regimens were not changed substantially for these patients. In six patients, the results of open lung biopsy may have been misleading. Two patients had pulmonary fungal diseases at autopsy, undetected by open lung biopsy eight days and five weeks prior to death. Another patient had invasive aspergillosis and one had cytomegalovirus pneumonitis not detected by open lung biopsy. Two patients had false-positive preliminary histologic reports of pulmonary infection. On the basis of this experience, in this specific population of patients, open lung biopsy was often of little help in directing medical therapy or influencing clinical outcome.

Adolescent↗
PubMed1991

Isolated relapse of acute myelogenous leukemia presenting as a gastric ulcer.

Isolated gastrointestinal (GI) infiltrate is unusual at presentation or relapse of acute myelogenous leukemia (AML). We report a case of acute myelogenous leukemia (FAB-M4) whose isolated relapse presented as a bleeding gastric ulcer. The patient was a 30-year-old male who had been diagnosed to have AML in June 1988. While in third complete remission, he underwent a sibling allogeneic HLA-matched bone marrow transplant. Five months after transplantation, he was readmitted for pneumonia. While in the hospital, he had an episode of upper GI bleeding. The endoscopy revealed a leukemic gastric ulcer, with morphology and immunophenotyping identical to his initial AML. There was no evidence of leukemia in the blood or bone marrow. Although different types of leukemic infiltrates have been recognized at post-mortem examination, our case is unique because AML presenting as an isolated malignant ulcer has not been described previously. We conclude that relapsing AML may present as an isolated gastric ulcer and suggest that any suspicious lesion on upper GI endoscopy should be biopsied after aggressive platelet support.

Adult↗
PubMed1992

The severe combined immunodeficient (SCID) mouse as a model for human myeloid leukemias.

Recent work has demonstrated the ability of lymphoblastic leukemias of pre-B- and T-cell origin to grow in severe combined immunodeficient (SCID) mice with a pattern reminiscent of the human clinical disease. Here, we investigated the possibility of engrafting human myeloid leukemias using both established cell lines and primary patient material. Whereas the two growth factor-independent cell lines K562 and U937 grew aggressively and induced leukemia in these animals, three other myeloid cell lines which require interleukin 3 or granulocyte-macrophage colony-stimulating factor for continuous growth in vitro failed to induce disease. Primary bone marrow and peripheral blood cells from five out of seven patients with different types of myeloid leukemias (undifferentiated, megakaryoblastic, monoblastic and chronic myelogenous leukemia in blast crisis) induced patterns of leukemic infiltration that were distinct for each leukemia subtype. The diagnosis of leukemia in SCID mice was established by microscopic detection of myeloblasts in the bone marrow, peripheral blood and, in some instances, in extramedullary sites, including the central nervous system and gonads. The karyotype and phenotype of the blasts recovered from mouse tissues were identical to those of the original patient cells. Moreover, human specific ALU sequences were amplified from the bone marrow DNA by polymerase chain reaction. Despite their ability to grow in vivo by serial transfers in SCID mice, the leukemic cells recovered from mouse tissues could not be maintained in vitro, even in the presence of recombinant cytokines. Overall, these data indicate that the SCID mouse may represent a useful animal model for human myeloid leukemias and for the development of new pharmacological and molecular approaches to therapy.

Adult↗
PubMed1995

CD 45 gating correlates with bone marrow differential.

In this study we assess a flow cytometric gating method and its correlation with a concurrent manual bone marrow differential in abnormal marrows. Like normal bone marrow cells, leukemic blasts fall into discrete areas when a cytogram of CD 45 expression and Right Angle Light Scatter is plotted in Log scale. We studied 50 specimens with a suspected diagnosis of leukemia. Gates were set on the eight discrete clusters typically found in normal bone marrow. We employed these gates to determine the differential of the abnormal bone marrows. Our results show a high correlation between the flow differential and the manual differential with the following r values: blasts 0.875; promyelocytes 0.914; myeloid precursors 0.879; neutrophils 0.776; lymphocytes 0.707; monocytes 0.913; and erythroid precursors 0.873. In addition some leukemic infiltrates appear to produce a characteristic pattern with the CD 45 vs. RALS cytogram. In this study, there is a total of 6 cases (3 false positives and 3 false negatives) where the flow differential does not render the same diagnosis as the manual differential, and 4 cases in which there is evidence of marked peripheral contamination leading to disagreement between the two methods. This method provides a relatively easy and powerful tool which can be applied to all bone marrow specimens that undergo flow cytometric analysis. It can greatly enhance the identification and lineage assessment of leukemic blasts in the bone marrow. The correlation with a manual differential is high, and this gating method may provide an inexpensive and easy means of obtaining an automated bone marrow differential.

Adolescent↗
PubMed1981

Relapse of acute myeloblastic leukemia lasting for four years. Production by leukemic cells of colony-stimulating activity and non-production of leukemia-associated inhibitor.

A 36-year-old woman with acute myeloblastic leukemia (M2) achieved complete remission in Feb. 1973, after ten weeks of chemotherapy with rubidomycin-cytosine arabinoside. She received weekly immunotherapy with bacillus Calmette-Guerin and allogeneic non-irradiated blast cells and monthly chemotherapy with thioguanine-cytosine arabinoside as maintenance. The bone marrow remained normocellular for 20 months. A first relapse occurred after this period. A second remission was achieved by seven courses of different cytostatic combinations. A second relapse, refractory to all cytostatic combinations tried, occurred in June 1976. She was thereafter in relapse until her death in July 1980. Autopsy showed extensive leukemic infiltration in bone marrow, liver, spleen, pericardium, stomach, and lymph nodes. Cytochemistry, surface markers, the capacity to stimulate lymphocytes, the in vitro growth pattern (colony-forming unit culture) of bone marrow and biochemical analyses did not give any remarkable results. In contrast, the peripheral blood cells produced a normal amount of colony-stimulating activity, which is significantly more than that produced by the blood from other leukemia patients. In liquid culture, the peripheral blood cells from this patient also seemed to live longer and mature more than cells from other leukemia patients. Finally, the peripheral leukemic cells from this patient seemed to produce far less leukemia-associated stem cell inhibitor than cells from other leukemia patients. The normal colony-stimulating activity production by leukemic cells and the absence of leukemia-associated stem cell inhibitor may therefore explain the long survival of this patient in relapse.

Adult↗
PubMed1976

The pathologic characteristics of leukostasis and leukemic nodules occurring in the central nervous system of guinea pigs with L2C/NB leukemia.

Leukostasis and leukemic nodules are found in the central nervous system (CNS) of at least 75% of guinea pigs during the terminal stages of untreated L2C/NB leukemia, a transmissible, acute lymphocytic leukemia. The CNS lesions develop after extensive visceral leukemic infiltration at a time when the white cell count is rising to 10(5)-5 x 10(5) cells/mm3, and the differential examination shows predominantly blasts. Leukostasis precedes formation of the nodule. Both lesions may be found in any part of the central nervous system including the spinal cord, but are most numerous in the diencephalon and rostral brain-stem. Ultrastructural studies demonstrate that parenchymal leukostasis develops chiefly within capillaries, and is associated with endothelial cell degeneration and necrosis. Fibrin deposits are not seen within affected capillaries. The sequence of development, pathologic and hematologic characteristics of leukostasiss and leukemic nodules in human and L2C/NB leukemia are virtually identical. The CNS lesions of untreated L2C/NB leukemia are a precise, convenient model for the study of intracerebral leukostasis and leukemic nodules.

Animals↗
PubMed2001

Leukemic synovitis as a presentation of myelomonocytic blast crisis of chronic myeloid leukemia.

We describe a patient with a 2-month history of right shoulder monoarthritis and fever as the presenting symptoms of a subsequent diagnosis of chronic myeloid leukemia in blast crisis. Imaging studies showed changes consistent with leukemic infiltration of the soft tissues around the right shoulder joint and the proximal humerus. Immunophenotypic and morphologic analysis of the large number of cells obtained from the synovial fluid confirmed the shoulder synovitis to be an extramedullary manifestation of myelomonocytic blast crisis of chronic myeloid leukemia. The patient was not a candidate for aggressive chemotherapy treatment because of her poor overall condition, and she had no compatible donor for allogenic bone marrow transplantation. Her painful arthropathy was refractory to standard pain management but she achieved excellent pain relief with palliative radiation therapy. We conclude that the involvement of extramedullary sites by chronic myeloid leukemia blast cells can predate hematological blast crisis in some of chronic myeloid leukemia cases. Also, painful leukemic synovitis can be managed by low dose radiotherapy in a candidate who is refractory to chemotherapy and other medical therapy.

Adult↗
PubMed2001

Sweet's syndrome in the setting of CD34-positive acute myelogenous leukemia treated with granulocyte colony stimulating factor: evidence for a clonal neutrophilic dermatosis.

BACKGROUND: Sweet's syndrome in the setting of hematologic dyscrasias can be categorized into paraneoplastic-associated SS, drug-induced SS, and SS with leukemia cutis. Apart from those cases demonstrating concomitant leukemic infiltrates, it has been surmised that SS is a reactive phenomenon induced by a specific cytokine milieu. METHODS: The authors present a patient with CD34+ acute myelogenous leukemia (AAML) who developed SS in the setting granulocyte colony stimulating factor (GCSF) therapy. Routine light microscopy and molecular studies were carried on the patient's skin biopsy specimen and post-treatment marrow. An X inactivation assay for clonality was employed. RESULTS: Routine light microscopic examination revealed differentiated myeloid precursors including myelocytes and metamyelocytes within the subcutis; myeloblasts were not identified. In addition, in the overlying skin, features typical of SS were observed. The neutrophils demonstrated dysplastic features including hypolobation compatible with a Pseudo Pelger-Huet anomaly. X inactivation studies showed clonality both within her post-treatment marrow and skin biopsy specimen. CONCLUSIONS: Sweet's syndrome developing in CD34+ AML patients following GCSF therapy likely reflects therapy induced differentiation of sequestered leukemic cells, hence indicative of a clonal neutrophilic dermatosis.

Acute Disease↗
PubMed1989

Immunophenotyping to detect and characterize acute lymphocytic leukemia in testicular biopsies.

This study establishes the utility of immunophenotyping testicular biopsy specimens in patients with acute lymphoid leukemia. The value of immunophenotyping in detecting or excluding leukemic testicular infiltration is demonstrated in six children with acute lymphocytic leukemia. A panel of monoclonal antibodies was employed on snap-frozen testicular biopsies, allowing both detection and immunologic characterization of four neoplastic lymphocytic infiltrates. Two samples were proven both histologically and phenotypically negative for leukemic infiltration. One of the four leukemic cases was clinically silent and might have escaped detection except for phenotyping. One leukemic infiltrate was also suspected to possess a multidrug-resistant phenotype (p-glycoprotein +); the latter possibility was excluded by an absence of reactivity with anti-p-glycoprotein monoclonal antibody. Thus, three clinically useful applications are demonstrated: (1) confirmation of testicular leukemic relapse, gaining assertion in histologically uncertain cases; (2) exclusion of clinically suspected disease relevant to cessation of therapy, and (3) detection/exclusion of drug-resistant phenotypes. Unexpectedly, we found expression of plasma cell-associated antigen in testicular germ cells, which may prove to be diagnostically useful in the future evaluation of germ cell tumors.

Antibodies, Monoclonal↗
PubMed1997

Cutaneous involvement in children with acute lymphoblastic leukemia or lymphoblastic lymphoma. The Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC).

OBJECTIVE: Skin involvement in children with acute monocytic leukemia or CD30-positive anaplastic large-cell lymphoma is well-known. In contrast, very little is known about the malignant cutaneous infiltrates in children with acute lymphoblatic leukemia (ALL) or lymphoblastic lymphoma (LBL). This study was designed to determine the frequency of these specific lesions in childhood ALL or LBL and the characteristics of such patients. DESIGN: We studied the clinical and biological findings of children with cutaneous involvement at initial diagnosis of ALL or LBL enrolled between August 1989 and March 1995 in the multicentric trial 58881 of the Children's Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC). RESULTS: Among the 1359 children enrolled in the multicenter trial EORTC 58881, 24 presented with skin involvement at diagnosis. ALL was diagnosed in 15 patients and LBL in 9. In 15 cases, skin lesions were observed within a median time of 6 weeks (range, a few days to 8 months) before the diagnosis of the hematologic disease. Twenty-one children had at least one skin lesion located on the head. Diffuse cutaneous lesions were observed in 7 infants with high-risk ALL. Seventeen of the 24 children remain in the first complete remission (median follow-up of 3 years; range 2 months to 5 years) and 3 are in the second remission with a follow-up of 14 to 24 months. CONCLUSION: The present study demonstrates that cutaneous involvement can be an early manifestation of ALL or LBL. Cutaneous leukemic infiltrates can be observed in children with standard risk as well as in high-risk ALL. Cutaneous involvement in children with LBL is mainly associated with a B-cell precursor immunophenotype of the lymphomatous cells. The most frequent location of skin lesions in children with ALL or LBL is on the head. Further studies are needed to evaluate the prognosis of children with such involvement at diagnosis.

Age Factors↗
PubMed2003

E mu-BRD2 transgenic mice develop B-cell lymphoma and leukemia.

Transgenic mice with lymphoid-restricted overexpression of the double bromodomain protein bromodomain-containing 2 (Brd2) develop splenic B-cell lymphoma and, upon transplantation, B-cell leukemia with leukemic infiltrates in liver and lung. Brd2 is a nuclear-localized transcription factor kinase that is most closely related to TATA box binding protein-associated factor, 250 kDa (TAF(II)250) and the Drosophila developmental protein female sterile homeotic. Constitutive expression of BRD2 in the lymphoid compartment increases cyclin A transcription, "priming" transgenic B cells for proliferation. Mice stochastically develop an aggressive B-cell lymphoma with the features of B-1 cells, including CD5 and surface IgM expression. The B-cell lymphoma is monoclonal for immunoglobulin gene rearrangement and is phenotypically stable. The lymphoblasts are very large and express a transcriptome that is similar to human non-Hodgkin lymphomas. Both a wild-type BRD2 transgene and a kinase-null point mutant drive lymphomagenesis; therefore we propose that, rather than kinase activity, Brd2-mediated recruitment of E2 promoter binding factors (E2Fs) and a specific histone acetyltransferase to the cyclin A promoter by both types of transgene is a mechanistic basis for neoplasia. This report is the first to describe a transgenic mouse model for constitutive expression of a protein with more than one bromodomain.

Animals↗
PubMed1980

Acute lymphoblastic leukemia. Association with vasopressin-responsive diabetes insipidus.

A rare case of acute lymphoblastic leukemia presenting with vasopressin-responsive diabetes insipidus (DI) is reported. The patient presented with polydypsia and polyuria of 9 L/day. Findings from special investigations of the CNS, including brain scan, computerized tomographic scan, EEG, and lumbar puncture were within normal limits. The patient's condition improved substantially after receiving vasopressin injections and later chlorpropamide. The incidence and underlying mechanism of this rare complication of acute leukemia are reviewed, and the response of DI to chlorpropamide is discussed briefly. In this patient it is presumed that the DI was caused by leukemic infiltration of the supraopticohypophyseal tract, posterior pituitary, or hypothalamus.

Adult↗
PubMed1980

Cranial computerized tomography in childhood leukemia.

The value of computerized tomography (CT) of the head in childhood leukemia is emphasized by a striking example. The response of the leukemic infiltrate to radiation suggests that an earlier (presymptomatic) scan might have led to major improvement in management. A routine CT scan may be warranted in children with a prolonged remission in search of a CNS reservoir for leukemia cells.

Brain Diseases↗