Transient myeloproliferative syndrome in a phenotypically normal infant.
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Antigens, Surface↗
Biomedical subjects
J Mirro
Publications and source records attributed to J Mirro.
Acute leukaemia with mixed lymphoid and myeloid phenotype.
Three children with acute leukaemia had blasts that expressed both lymphoid and myeloid markers. The blasts met immunological criteria for acute lymphoblastic leukaemia (ALL)--common ALL antigen+, HLA-DR+, terminal deoxynucleotidyl transferase+--but their cytochemical features, including positive myeloperoxidase and Sudan black B, were those of acute nonlymphoblastic leukaemia (ANLL) as defined by the French-American-British Group. 30% of the blasts from one of two patients tested reacted with a monoclonal antibody specific for nonlymphoid cells (MCS-2). The wide overlap in the percentages of blasts expressing lymphoid or myeloid markers indicates that some leukaemic cells in each child had a mixed phenotype. There were no consistent cytogenetic findings, and the Philadelphia chromosome was not present. Complete remission was induced by treatment effective for either ALL (two patients) or ANLL. These three cases appear to represent a rare leukaemia subtype that we have designated acute leukaemia with mixed lymphoid and myeloid phenotype. Its recognition may be important in treatment, since two patients achieved remission with standard therapy for ALL. These cases demonstrate further the phenotypic heterogeneity that may be seen in leukaemic cell differentiation.
Acute Disease↗
Heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia.
Samples of leukemic cell DNA from 14 children with acute nonlymphocytic leukemia (ANLL) and 4 human myeloid leukemia cell lines were analyzed for rearrangement in the heavy chain region of the immunoglobulin gene. The diagnosis of ANLL was confirmed in all patients by morphological, cytochemical, and immunologic studies. By restriction endonuclease digestion and hybridization with cloned heavy chain immunoglobulin gene probes for the constant (Cmu) and joining (JH) regions, the DNA of 2 patients and 1 cell line (ML-1) was found to contain rearrangements. The DNA from the remaining 12 patients and 3 cell lines was not rearranged (germline configuration). Both patients with apparent immunoglobulin gene rearrangement achieved complete remission on therapy for ANLL. Immunoglobulin gene rearrangement in phenotypically defined ANLL suggests (1) that such changes may not be limited to lymphoid leukemia of B cell lineage, or (2) that, in some patients, the leukemic transforming event may involve stem cells capable of both B cell and myeloid differentiation.
Acute Disease↗
Lineage switch in acute leukemia.
Conversions of leukemic cell lineage (lymphoid or myeloid) have been reported only rarely. Our review of the cytochemical and immunophenotypic features of 89 cases of childhood leukemia in marrow relapse indicated lineage switch (lymphoid to myeloid or the reverse) in six patients (6.7%). Five patients with acute lymphoblastic leukemia (ALL) at diagnosis had converted to acute nonlymphoblastic leukemia (ANLL), and one had converted from ANLL to ALL. Each child received lineage-specific multiagent chemotherapy when initially diagnosed, and all achieved a complete remission. After conversion, four patients readily achieved second remissions with treatment for the phenotype evident at lineage switch. Two patients with ANLL at conversion failed ALL-directed reinduction, while one of the two responded to high-dose cytarabine but died during bone marrow hypoplasia, emphasizing the importance of prompt recognition of lineage switch and selection of an appropriate plan of retreatment. Cytogenetic studies disclosed evidence of clonal selection in one patient and clonal stability in two. These findings indicate an unexpectedly high frequency of lineage switch in patients who relapse in the bone marrow after intensive chemotherapy. Although specific causative factors could not be identified, our observations suggest at least two general mechanisms for lineage switch in acute leukemia. In one, chemotherapy appears to eradicate the dominant clone present at diagnosis, permitting expansion of a secondary clone with a different phenotype. In the second, drug-induced changes in the original clone may either amplify or suppress differentiation programs so that phenotypic shift is possible.
Acute Disease↗
Simultaneous analysis of cell surface antigens and cell morphology using monoclonal antibodies conjugated to fluorescent microspheres.
A new method for simultaneous analysis of cell surface antigens and cell morphology using monoclonal antibodies conjugated to fluorescent microspheres ('immunospheres') is described. Wright's staining was performed on cells after reaction with immunospheres, and a direct correlation of cell surface antigen expression and cell morphology was made. Mild formalin fixation of cells inhibited phagocytosis of microspheres, which is a potential source of confusion in the analysis of cell surface binding. Rapid, accurate analysis of cell surface antigen expression in single cell suspensions of heterogeneous human hematopoietic and lymphoid cell populations was facilitated by this method.
Antibodies, Monoclonal↗
Testicular leukemic relapse: rate of regression and persistent disease after radiation therapy.
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Child↗
My-1, new myeloid-specific antigen identified by a mouse monoclonal antibody.
Antibody-secreting hybridomas were produced by fusion of P3-NS1/1Ag--4-1 mouse plasmacytoma cells with splenocytes from a mouse immunized with HL-60 human promyelocytic leukemia cells. A cloned hybridoma cell line was identified that secreted antibody against a cell surface antigen expressed on all normal human peripheral blood granulocytes, on bone marrow granulocytic precursor cells, and on blast cells from 3 of 15 patients with nonlymphoid leukemia. However, the antibody did not react with normal peripheral blood lymphocytes, monocytes, platelets, or red cells, or with blast cells from 20 patients with acute lymphoblastic leukemia or from 5 patients with lymphoma. This monoclonal antibody identified a granulopoietic differentiation antigen (designated My-1) and may prove useful in the subclassification on nonlymphoid leukemia and in the investigation of hematopoiesis.
Animals↗
Granulopoietic differentiation in AML blasts in culture.
A newly described monoclonal antibody detected an antigen (My-1) that is expressed on the cell surface during normal granulopoietic differentiation. The kinetics of expression of My-1 and NASD chloracetate esterase were studied during the formation in culture of blast colonies and normal granulopoietic colonies. My-1-positive cells increased during blast colony formation in 6 of 9 experiments, while NASD esterase-positive cells decreased. In contrast, in normal granulopoiesis in culture both markers increased coherently. We suggest that components of granulopoietic differentiation programs are expressed abnormally during blast colony formation in culture.
Antigens, Surface↗
The presence within single K-562 cells of erythropoietic and granulopoietic differentiation markers.
The continuous cell line K-562, derived from a patient with CML in blast crisis, was examined for markers of granulopoietic (My-1) and erythropoietic (spectrin) differentiation, using specific antibodies detected by indirect immunofluorescence. Both markers were seen, and in 10%--30% of cells, both were present in the same cells. In contrast, the continuous leukemic line HL-60 and KGI contained My-1 only. Controls consisted of colonies in culture containing both granulopoietic and erythropoietic cells (CFU-GEMM). In these, My-1 was seen only in granulopoietic cells and spectrin in erythropoietic cells. The suggestion is advanced that genes coding for differentiation markers are expressed abnormally in K-562.
Antigens, Surface↗
Hepatic sinusoidal dilatation related to oral contraceptives. A study of two patients showing ultrastructural changes.
Two patients who have been on oral contraceptives for five and six years developed sinusoidal dilatation. Hepatic enlargement, tenderness and pain disappeared after the discontinuance of steroid drugs. Ultrastructural changes included dilatation of endoplasmic reticula with accumulation of granular electron dense material, disruption of mitochondrial membranes and deposits of collagen fibers in the intercellular spaces between hepatocytes and in the spaces of Disse. Possible relationship of this condition to peliosis hepatis and focal nodular hyperplasia are discussed.
Adult↗
Cell-mediated immune responses in sarcoidosis.
In an attempt to understand divergent observations regarding the in vitro lymphocyte responsiveness to antigens and mitogens, the frequency of cutaneous reactivity, and the relationship of these variables to clinical features of sarcoidosis, we examined cell-mediated immune responses in 75 untreated patients. In vitro lymphocyte responses to phytohemagglutinin and concanavalin A were significantly decreased among the group of patients with chronic active disease. In vitro lymphocyte responses to streptococcal antigen paralleled the patient's cutaneous reactivity; however, when compared to healthy persons, patients with sarcoidosis responded significantly less often to streptococcal skin tests. Twelve of 13 persons expected to be tuberculin positive by clinical history were found to be dermally reactive, and 11 these 12 exhibited positive in vitro lymphocyte responses to purified protein derivative. Among the remaining 62 patients, failure to respond to all stimuli in vivo and in vitro occurred in only 10. No evidence was found to support the general view that sarcoidosis is characterized by anergy to specific antigens. The patterns of responses to mitogens were neither characteristic nor unique for sarcoidosis. In patients in whom diminished specific cellular immune reactivity was observed, no correlation was evident with specific clinical features of the disease.
Adult↗
Immune reactivity to tumor antigens in leukemia and lymphoma.
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Antibodies, Neoplasm↗
Prevention of CMV disease in allogeneic BMT recipients by cytomegalovirus antigenemia-guided preemptive ganciclovir therapy.
PURPOSE: Cytomegalovirus (CMV) infection can cause severe disease and mortality in recipients of allogeneic bone marrow transplants (alloBMT) when either the donor or recipient is CMV seropositive (high-risk alloBMT). We investigated the efficacy of preemptive therapy guided by detection of CMV antigenemia. METHODS: In 11 high-risk alloBMT recipients, high-dose ganciclovir (GCV) treatment was initiated at first positive antigenemia and was continued until antigenemia became negative. RESULTS: The treatment strategy prevented CMV disease during the follow-up period of the study in 7 alloBMT recipients with positive CMV antigenemia. Three other patients who were shown to be CMV antigenemia negative but positive for CMV DNA in blood by the polymerase chain reaction (PCR) were not treated and did not develop CMV disease. The eleventh patient was negative for CMV by all tests for the duration of the study and did not develop CMV disease. CONCLUSIONS: We have found antigenemia-guided preemptive GCV therapy to be an effective strategy for the prevention of CMV disease in high-risk alloBMT recipients.
Adolescent↗
Recognition of central nervous system metastases in children with metastatic primary extracranial neuroblastoma.
In children with primary extracranial neuroblastoma (NB), intrinsic central nervous system (CNS) metastases (brain parenchyma or leptomeninges) are thought to occur rarely. This study was done to evaluate our anecdotal experience, which suggested that CNS involvement is becoming more frequent. Reports of computed tomographic (CT) and magnetic resonance (MR) imaging scans, biopsies, cerebrospinal fluid (CSF) cytologies, and autopsies were reviewed for children with stage IV NB diagnosed in 1978-1993 and followed at the Children's Hospital of Pittsburgh. Of 43 children over the age of 1 year, CNS metastases were documented in 7 (16.2%). Six patients developed signs or symptoms best explained by the presence of CNS tumor and had radiographic and/or histologic evidence of parenchymal disease (cortical masses on CT and MR, n = 3; suprasellar mass on CT, n = 1; diffuse leptomeningeal carcinomatosis by MR and/or autopsy, n = 2). CSF cytologies were positive in the one patient so tested. An additional asymptomatic patient had extensive CNS involvement at autopsy. In two of these children, the CNS was the first or only site of recurrent disease. It is concluded that intrinsic CNS disease is not uncommon in children with NB over the age of 1 year and there has been a trend toward its increasing recognition in recent years. Whether this is a function of wider use of diagnostic tools or a true change in natural history over time with increased intensity of chemotherapy is not clear. A study that prospectively monitors children with advanced neuroblastoma, radiographically and with CSF cytologies (prior to treatment and at 6-monthly intervals), is under way and should help to better define the natural history in the context of current therapies.
Brain Neoplasms↗
Cyclophosphamide/etoposide: effective reinduction therapy for children with acute nonlymphocytic leukemia in relapse.
Reinduction therapy consisting of cyclophosphamide (250 mg/m2 orally daily for 4 days) followed by etoposide (250 mg/m2 iv daily for 3 days) was administered to 14 children with refractory or recurrent acute nonlymphocytic leukemia. Five complete remissions were achieved in eight patients who had relapsed in the bone marrow 1-27 months after cessation of initial therapy, which included anthracyclines, cytarabine, etoposide, and 5-azacitidine. Reinduction attempts were unsuccessful in patients who had failed to achieve an initial remission and in those whose relapses occurred while receiving therapy. Toxicity, including myelosuppression and mucositis, was within acceptable limits. This drug combination deserves further assessment in therapeutic protocols for patients with acute nonlymphocytic leukemia.
Acute Disease↗