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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoplastic acute leukemia (HAL) is characterized by pancytopenia and by hypocellularity of the bone marrow. The marrow contains equal to or more than 30% myeloblasts. Absence of tissue infiltrates and/or tumor masses is mandatory. Eight patients are described here. They do not fit into the FAB classification for either acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS), except for one patient who subsequently proved to have a chronic myelomonocytic leukemia (CMML). The median age is 65 years. Two patients, including the CMML patient, are alive, 22 and 6 months from diagnosis. Six patients have died. The median survival is 8 months. Normal bone marrow cells cultured either with HAL sera or with HAL peripheral blood mononuclear cells as feeders and exogenous GM-CSF yielded subnormal CFU-GM counts. This might indicate inhibitory activity of HAL serum and defective stimulatory activity of HAL peripheral blood mononuclear cells.
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PMID:Hypoplastic acute leukemia: description of eight cases and search for hematopoietic inhibiting activity. 145 85

The increased risk of neoplasia following cytotoxic therapy for both malignant and nonmalignant disease is well known. Sister chromatid exchange (SCE) frequencies in patients receiving such chemotherapy are often elevated, and the persistence of high levels after treatment may provide an indicator for susceptibility to secondary neoplasia. The cytostatic drug razoxane has been used for the treatment of psoriasis, acute myeloid leukemia (AML), and colorectal carcinoma. Prolonged use of this drug, however, has been associated with the subsequent development of AML and, up to November 1987, 16 cases of acute leukemia following razoxane treatment have been reported. We report the SCE frequencies for 34 patients with colorectal carcinoma who were receiving or had previously been treated with razoxane. Our results show no significant increase in SCE levels in the razoxane group compared with either normal controls or untreated patients.
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PMID:Sister chromatid exchange (SCE) frequency in lymphocytes of patients with colorectal carcinoma treated with razoxane. 145 13

We studied the association between myelodysplastic syndromes (MDS) and malignancies in a cohort of 155 patients with MDS, 21 of whom presented malignant solid tumors. Myelodysplasia was present after the diagnosis of cancer in eight patients (interval between the diagnosis of both conditions 18 months, median survival 49.5 months), simultaneously with diagnosis in 11 (median survival 8 months), and before malignancy in two patients (interval between the diagnosis of both conditions 47 and 7 months). One patient was given chemotherapy for lung cancer, and three patients received radiotherapy for adenocarcinoma of the kidney and cancer of the prostate. At the time of diagnosis of MDS, nine patients already presented metastatic spread. Fourteen patients died, ten as a result of tumor-related complications and four because of transformation to acute nonlymphocytic leukemia. The analysis of the incidence of malignancy in patients with MDS was statistically significant for males, and the relative risk was significant in both sexes. The results of this study show that MDS patients present a higher incidence of malignant tumors than the general population, that MDS may be of real paraneoplastic significance, and that the occurrence of MDS in cancer patients may be considered to be related to the malignancy rather than an independent phenomenon.
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PMID:Myelodysplastic syndromes and malignant solid tumors: analysis of 21 cases. 150 93

By using monoclonal antibodies against lymphoid and myeloid differentiation antigens, surface marker analysis was performed on the tumor cells from 42 patients with acute leukemia and lymphoblastic lymphoma. Nine (21%) of 42 cases were diagnosed biphenotypic leukemia. Two (17%) of the 12 patients with acute myeloid leukemia, four (18%) of 22 with acute lymphocytic leukemia and three (38%) of 8 with lymphoblastic lymphoma expressed both lymphoid and myeloid antigens. Tumor cells from six patients expressed both T-cell and myeloid antigens, and those from three other expressed both B-cell and myeloid antigens. Southern blot analysis was performed on the DNA from four patients with biphenotypic leukemia cells expressing T-cell and myeloid antigens. DNA from one patient showed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene, and that from one other showed clonal rearrangement of both IgH gene and T-cell receptor beta-chain gene. DNA from two other patients showed a germline configuration of both genes. These results indicate that biphenotypic leukemia, especially T-cell and myeloid phenotype, is not so rare in acute leukemia and lymphoblastic lymphoma. The results of immunogenotypic analysis were not consistent with those of immunophenotypic analysis in biphenotypic leukemia.
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PMID:[Immunophenotypic and immunogenotypic analyses of acute leukemia and lymphoblastic lymphoma expressing myeloid and lymphoid antigens]. 150 95

Acute leukemias are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the leukemia and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. The pattern differs between acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) and from subtype to subtype. Some abnormalities are so characteristic as to be virtually pathognomonic for particular types of leukemia. The importance of cytogenetic characterization of leukemias is thus two-fold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality in hematopoietic cells identifies the presence of a neoplastic disease. The aberration profile may reveal whether the patient has ALL or ANLL and which subtype it is. Remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern is an independent prognostic parameter that should be considered when the choice of therapy is made.
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PMID:Cytogenetic analysis in the diagnosis of acute leukemia. 151 24

Acute myeloid leukemia is an attractive disease to treat with radiolabeled antibodies because it is radiosensitive and antibody has ready access to the marrow cavity. In order to evaluate potentially useful radiolabeled antibodies against human acute myeloid leukemia, we have developed a nude mouse xenograft model using the human acute leukemia cell line, HEL. Mice with s.c. xenografts of HEL cells received infusions of radioiodinated anti-CD33 antibody. Examination of the biodistribution of the antibody showed that uptake in the s.c. tumor was maximal [16.9% injected dose (ID)/g at 1 h after infusion] following infusion of 1-10 micrograms of antibody and decreased following infusion of 100 micrograms (6.5% ID/g at 1 h) presumably as a result of saturation of antigen sites. The radiolabel was poorly retained in tumor (4.5-8.2% ID/g at 24 h after infusion). These results were consistent with in vitro studies demonstrating rapid internalization and catabolism of the anti-CD33 antibody. Uptake in tumor could be improved by using either a radiolabel that is retained intracellularly, 111In-DTPA (18.5% ID/g at 24 h), or by targeting a surface antigen that does not internalize upon antibody binding, CD45 (20.5% ID/g at 24 h). These results indicate that this model system will be useful in evaluating the interaction of radiolabeled antibodies with human acute myeloid leukemia cells in an in vivo setting.
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PMID:Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model. 153 Jul 69

Age-related changes in pharmacokinetics and pharmacodynamics of drugs, in functional reserve of target organs, and in tumor biology, may lessen the benefits and enhance the toxicity of cancer chemotherapy. These changes include progressive decline in glomerular filtration rate, enhanced risk and severity of mucositis and peripheral neuropathy, and increased incidence of refractory forms of acute myeloid leukemia. Myelotoxicity is also increased following aggressive combinations of cytotoxic drugs. While hormonal therapy is well tolerated, biological treatment with recombinant alpha interferon at doses higher than 5mU/daily may be associated with acute demential syndromes in persons over 65. Tolerance of treatment may be improved by selecting alternative, safer drugs, antidotes to drug toxicity, and adjusting schedule and route of drug administration. A major advancement in supportive care has been the synthesis of hemopoietic growth factors, which are effective even in patients of advanced age.
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PMID:Pharmacology and organ toxicity of chemotherapy in older patients. 153 39

Plasmacytoid T-cell (PTC) lymphoma is a rare clinicopathologic entity characterized by generalized lymphadenopathy in association with a myeloproliferative disorder. Hepatosplenomegaly and weight loss frequently are present. Nodal T-zone expansion by mononuclear cells with ultrastructural and immunohistochemical features typical of PTC is diagnostic. All of the five previously reported cases of PTC lymphoma coincided with or heralded the onset of a clinically aggressive myeloid leukemia. This strong association and recent immunohistochemical findings in reactive or neoplastic PTC favored a monocyte/macrophage derivation of these cells, and it has been suggested that they be renamed plasmacytoid monocytes (PM). Two additional cases of PTC lymphoma were studied at the institutions of the authors, and the findings supported the concept that PTC belong to the monocytic lineage. The disease presentation was generalized lymphadenopathy with constitutional symptoms. One patient also had hepatosplenomegaly and bilateral renal enlargement concomitantly with myelofibrosis with myeloid metaplasia that progressed within months to acute myelogenous leukemia. Similar rapid evolution of acute monoblastic leukemia occurred in the other patient. Tumor cells within subtotally effaced lymph nodes had positive findings for CD45, CD4, CD7, and LN2 and negative findings for CD3, CD8, and beta F1. Occasional cells had positive findings for CD2. One case demonstrated CD5, HLA-DR, CD71, and CD43 (Leu-22)-positive cells. The myeloid/monocyte-associated antigens CD14 and CD68 were identified in both. The tumor cells lacked the B-cell markers LN1, CD20 (L26), CD19, and CD22 and did not rearrange immunoglobulin heavy chain genes and T-cell receptor beta, gamma, and delta chain genes. The term plasmacytoid T-zone lymphoma or PM proliferation is more appropriate for this rare disease. The close association of the PM proliferation with a myeloproliferative disorder indicates that the two entities are related.
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PMID:Plasmacytoid monocyte proliferation associated with myeloproliferative disorders. 154 Aug 83

In both animal models and human studies in leukemia, residual disease on day 8 following myelosuppressive therapy is in a proliferative phase and therefore may be sensitive to the S-phase specific drug cytarabine. Based on this concept, 17 patients with refractory or relapsed leukemia or lymphoma undergoing either autologous or allogeneic bone marrow transplantation (BMT) were treated on a Phase I protocol using high doses of busulfan (16 mg/kg, days -10, -9, -8, -7) and cyclophosphamide (120 mg/kg, days -6, -5) followed by escalating doses of a 48-h continuous infusion of cytarabine (starting dose 1000 mg/m2/48 h, days -3, -2). Ten patients received autologous transplants (two with Hodgkin's disease, seven with non-Hodgkin's lymphoma, one with chronic myelogenous leukemia (CML) in blast phase). Seven received allogeneic BMT (two with refractory acute myelocytic leukemia (AML), one with refractory acute lymphoblastic leukemia (ALL) undergoing a second BMT, one with Burkitt's-type leukemia, one with ALL in fifth relapse and two with CML in accelerated/blast phase). Two of these patients received a T cell-depleted haploidentical transplant. The maximum tolerated dose of cytarabine was 1500 mg/m2/48 h; a pulmonary syndrome including dyspnea, hypoxemia, and interstitial infiltrates which responded to aggressive diuresis was the dose limiting toxicity. Of the 10 patients who received cytarabine doses of 2000 or 2500 mg/m2/48 h, five patients developed adult respiratory distress syndrome (ARDS) with three patients requiring intubation; two recovered. Of the nine patients with lymphoma, seven responded with complete tumor clearance (CTC) with two patients tumor-free 13 and 15 months post-BMT, one remained refractory and one died too early to evaluate (TETE).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of busulfan, cyclophosphamide, and timed sequential escalating doses of cytarabine followed by bone marrow transplantation. 154 48

Detection of minimal residual disease (MRD) can be useful for adaptation or stratification of treatment in acute leukemia patients and may finally result in individualization of treatment protocols. Although leukemic cells generally have immunophenotypes comparable to their normal counterparts, it is possible to use immunological marker analysis for the detection of MRD based on the assumption that the presence of positive cells outside their normal breeding sites and 'homing areas' is indicative of malignancy. This approach can be used for the detection of MRD in blood and bone marrow of patients with a terminal deoxynucleotidyl transferase (TdT) positive T-cell acute lymphoblastic leukemia (ALL) and patients with a TdT+ acute myeloid leukemia (AML) as well as in cerebrospinal fluid of patients with a TdT+ leukemia. In other types of acute leukemias, immunological marker analysis generally does not allow detection of low frequencies of malignant cells, but in a part of them the polymerase chain reaction (PCR) technique may be valuable. The PCR technique allows the amplification of tumor-specific DNA sequences or mRNA sequences (after reverse transcription into cDNA), if the flanking sequences are well-defined. This PCR-mediated amplification can detect specific sequences which are derived from only a few malignant cells between many normal cells. Well-defined chromosome translocations have been used as tumor-specific markers, such as t(9;22). An advantage of using specific chromosome aberrations as tumor-specific markers is their stability during the disease course. However, only 10-15% of ALL and 25-30% of AML have a specific chromosome translocation and in a large part of them the precise breakpoints are not (yet) known. Recent studies indicate that it is possible to detect MRD in acute leukemias by use of PCR-mediated amplification of the junctional regions of rearranged immunoglobulin (Ig) and T-cell receptor (TcR) genes, using variable (V) and joining (J) gene-specific oligonucleotides as primers. Major pitfalls of this application are the occurrence of multiple rearrangements at diagnosis (oligoclonality) and changes in rearrangement patterns at relapse (clonal evolution), which will lead to false negative results of this MRD-PCR technique. In conclusion, the technique of choice for the detection of MRD is dependent on the immunophenotype of the leukemia, the presence of a well-defined chromosome translocation and the presence of a rearranged Ig and/or TcR gene as well as the chance of immunophenotypic shifts and changes in Ig and TcR gene rearrangement patterns.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Detection of minimal residual disease in acute leukemia by immunological marker analysis and polymerase chain reaction. 154 36


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