Vaginal outflow tract obstruction by graft-versus-host reaction.
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We describe a 25-year-old patient suffering from vaginal outflow obstruction which presented as secondary amenorrhea during hormone replacement therapy. The patient had undergone bone marrow transplantation for acute myelocytic leukemia, which caused ovarian failure. Oral mucositis associated with a chronic GVH reaction also occurred. For 3 years she was treated with HRT and had regular menses which gradually ceased and were associated with dyspareunia and abdominal cramps. Abdominal US examination demonstrated hematocolpus. Sonography guided adhesiolysis of a dense vaginal obstruction allowed free drainage with histologic confirmation of a graft-versus-host reaction. The possibility of vaginal stricture or obstruction should be considered in all patients after BMT who suffer from graft-versus-host disease. (+info)
HLS7, a hemopoietic lineage switch gene homologous to the leukemia-inducing gene MLF1.
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Hemopoietic lineage switching occurs when leukemic cells, apparently committed to one lineage, change and display the phenotype of another pathway. cDNA representational difference analysis was used to identify myeloid-specific genes that may be associated with an erythroid to myeloid lineage switch involving the murine J2E erythroleukemic cell line. One of the genes isolated (HLS7) is homologous to the novel human oncogene myeloid leukemia factor 1 (MLF1) involved in the t(3;5)(q25.1;q34) translocation associated with acute myeloid leukemia. Enforced expression of HLS7 in J2E cells induced a monoblastoid phenotype, thereby recapitulating the spontaneous erythroid to myeloid lineage switch. HLS7 also inhibited erythropoietin- or chemically-induced differentiation of erythroleukemic cell lines and suppressed development of erythropoietin-responsive colonies in semi-solid culture. However, intracellular signaling activated by erythropoietin was not impeded by ectopic expression of HLS7. In contrast, HLS7 promoted maturation of M1 monoblastoid cells and increased myeloid colony formation in vitro. These data show that HLS7 can influence erythroid/myeloid lineage switching and the development of normal hemopoietic cells. (+info)
A phase I trial of humanized monoclonal antibody HuM195 (anti-CD33) with low-dose interleukin 2 in acute myelogenous leukemia.
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HuM195 is a recombinant humanized IgG1 monoclonal antibody reactive with CD33, a Mr 67,000 glycoprotein expressed on early myeloid progenitor cells and myeloid leukemia cells. HuM195 has been shown to rapidly target and saturate acute myeloid leukemia (AML) cells after i.v. infusion into patients and is capable of mediating antibody-dependent cellular cytotoxicity. This activity is enhanced in vitro when natural killer (NK) effector cells are preincubated with low concentrations of interleukin 2 (IL-2). Previous Phase I trials of HuM195 in patients with relapsed AML demonstrated safety and attainment of complete responses, but significant antileukemic activity appears limited to patients with low leukemia tumor burdens. Therefore, in the present trial, we sought to determine whether low-dose IL-2 could safely enhance the numbers of NK cells and therefore the cytotoxic capability of HuM195 via presumptive NK cell antibody-dependent cellular cytotoxicity in vivo against myeloid leukemia cells. Thirteen patients with relapsed or refractory AML and one patient with advanced myelodysplastic syndrome were treated with 0.6x10(6) IU/m2 of s.c. IL-2 daily for 35 days. Starting on day 15, patients received twice weekly i.v. infusions of HuM195 (3.0 mg/m2) for 3 weeks. Immediately after the HuM195 infusion, the patients received IL-2 i.v. infusions over 2 h at one of three escalating dose levels of 0.5x10(6), 1.0x10(6), and 2.0x10(6) IU/m2. Peripheral blood mononuclear cells were quantitated and immunophenotyped by flow cytometry. Safety, tolerability, bone marrow mononuclear cell morphology, and immunophenotype, as well as responses were assessed. Of the 14 patients who entered the study, 10 were able to complete at least one cycle of therapy. Adverse effects to the s.c. IL-2 were relatively mild and included erythema and induration of the skin at the injection site and low-grade fever. Toxicity from the sequential HuM195 and i.v. IL-2 infusions included nausea, rigors, and fever. Toxicity was IL-2 dose related with dose-limiting toxicity seen at the 2.0x10(6) IU/m2 dose level. Three patients had stable disease at the completion of the first cycle and went on to receive a second cycle of treatment. CD3-positive, CD56-positive, and CD33-positive cells were generally found to significantly decrease immediately after each administration of i.v. IL-2 and HuM195. CD56-expressing cells increased in 6 of 10 patients from the beginning to the end of therapy. Among the 10 evaluable patients, 2 patients had significant decreases in the percentage of blasts in the bone marrow (one of which achieved a complete bone marrow remission), 5 patients had stable levels of bone marrow blasts, and 3 had progression of disease on therapy. The combination of IL-2 and HuM195 shows modest biological activity and clinical antileukemic activity but also produced significant toxicity. (+info)
Serum ferritin in acute leukaemia at presentation and during remission.
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In patients with acute myeloblastic leukaemia the mean serum ferritin concentration showed a twenty-five-fold increase compared with normal people, and in children with acute lymphoblastic leukaemia (A.L.L.) there was a thirteen-fold increase. The high concentration of circulating ferritin seemed to be related to increased synthesis by leukaemic cells. The return of serum concentrations to normal in A.L.L. patients after successful chemotherapy suggested that ferritin concentration may be a useful index of active disease and may help in prognosis. (+info)
Histone abnormalities in adult acute leukemias.
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Arginine-rich and lysine-rich histones were extracted from various cytologic types of leukemic blasts and from preparations rich in normal monocytes. On polyacrylamide disc electrophoresis, the patterns of normal monocyte histones closely resembled those found in acute histiomonocytic leukemia (Schilling type). The electrophoretic patterns of histones obtained from leukemic blasts in acute myelomonocytic leukemia (Naegeli type) were similar to those found in both acute myelobastic leukemia and chronic granulocytic leukemia. The results support the concept that acute myelomonocytic leukemia may be closely related to, or a variant of, acute myeloblastic leukemia, and that acute histiomonocytic leukemia is most probably a monocytic rather than a myeloblastic disorder. In addition to accepted morphologic and enzymatic criteria, the present studies suggest that differences in histone patterns might be useful in further distinguishing between histiomonocytic, myeloblastic, and myelomonocytic leukemias. (+info)
Interacting populations affecting proliferation of leukemic cells in culture.
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Peripheral blood cells from three patients with acute leukemic have been studied using a suspension culture method previously described.1 Cytogenetic studies in two of the patients permitted the identification of the proliferating cells in the cultures as being derived from a leukemic population. Cell separation studies using velocity sedimentation supported the concept that growth of the leukemic cells in culture is dependent on an interaction between two populations of leukemic cells. (+info)
Isoleucine metabolism by leukemic and normal human leukocytes in relation to cell maturity and type.
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The metabolism of an essential amino acid, isoleucine, by human leukemic and gradient-separated normal human leukocytes of various types and maturity was studied. Blood leukocytes were isolated and incubated with (U-14C) isoleucine. Separation of metabolic intermediates was accomplished by sequential extraction. The rate of isoleucine incorporation into protein by immature cells from untreated patients with acute leukemia (15.9 plus or minus 2.4 nmoles/hr per 10-8 leukocytes) was considerably higher than the rates of incorporation by mature neutrophils (3.2 plus or minus 0.5 nmoles/hr per 10-8 leukocytes), lymphocytes (7.7 plus or minus 1.2 nmoles/hr per 10-8 leukocytes), and eosinophils (6.2 plus or minus 1.3 nmoles/hr per 10-8 leukocytes). Those cell preparations with more blast cells had higher rates of protein synthesis. In addition, those cells with greater thymidine incorporation had higher rates of protein synthesis. The leukocytes both oxidized isoleucine and incorporated it into cell isoleucine and incorporated it into cell lipid. The rates of these metabolic processes were characteristic for various types and maturity of leukocytes. This study demonstrates a relationship of rate of protein synthesis to leukocyte immaturity. This relationship is maintained in neoplastic leukocytes. It suggests that the requirement of the mitotic process for newly synthesized protein is greater than that for the elaboration of the protein products of the mature leukocyte. (+info)
De novo appearance of the ph-1 chromosome in a previously monosomic bone marrow (45,XX,-6): conversion of a myeloproliferative disorder to acute myelogenous leukemia.
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Bone marrow examination of a patient with a myeloproliferative disorder revealed monosomy for chromosome No. 6 (45,XX,-6). Two months later, during blastic crisis, reinvestigation of the bone marrow showed the presence of the Ph-1 chromosome in the previously aneuploid cell line (45,XX,-6,-22,+Ph-1). This case differs from those previously published in that the Ph-1 chromosome appeared de novo during the development of frank acute myelogenous leukemia. (+info)