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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human leukemias are a group of hematologic neoplasms characterized by uncontrolled proliferation of cells concerned with blood cell production. The cause(s) of human leukemia remains unknown. Bone marrow (BM) is believed to be the site of origin of human leukemias, although the specific locus(i) and/or cell(s) from which it arises have not been definitively identified. Generally, human leukemias and related proliferative diseases are thought to be clonal in nature; affecting a single hematopoietic stem cell, which then proliferates and replaces the marrow of normal hematopoietic stem cell systems. The condition is believed to be malignant in nature. Results of our current morphologic studies on well-fixed, ideally-stained thin sections of plastic-embedded bone marrow biopsies (BMB) from a large number of acute (AML, ALL) and chronic (CGL, CLL) leukemia patients suggest that human leukemias may not be clonal diseases. Instead, a large population of other resident cells--'endosteal cells'--appears to become involved in the process and it is possible that all members of this group enter the activity simultaneously. This change (transformation) in the endosteal cell population might be due to an abnormality (qualitative or quantitative) of diffusable, humoral factors (yet to be identified) that are responsible for the growth and proliferation of these hematopoietic precursor cells. In this context, the human leukemias may be considered not as malignant, but rather the result of an aberration of factor(s) that control hematopoiesis. In this respect, the human leukemias, particularly AML, ALL and CML, might be analogous to pernicious anemia (megaloblastic anemia) as it was understood 40-50 years ago.(ABSTRACT TRUNCATED AT 250 WORDS)
Med Hypotheses 1992 Sep
PMID:The origin and spread of human leukemia. 143 86

A total of 56 patients were diagnosed as primary myelodysplastic syndrome (MDS) at Chang Gung Memorial Hospital, Kaohsiung from April 1986 to December 1991. The median age was 65 years with an equal sex ratio. All patients presented with anemia and 52% with pancytopenia. The overall median survival for the entire group was 7 months, in which the chronic myelomonocytic leukemia (CMMoL) was 7 months, and 4 months for each of the refractory anemia with excess of blasts (RAEB) or the refractory anemia with excess of blasts in transformation (RAEB-T), however, the median survival had not been reached at 27 months for refractory anemia (RA) and at 33 months for refractory anemia with ring sideroblasts (RARS). Low-does arabinosyl cytosine (Ara-C) was administered in 9 patients with RAEB and RAEB-T, but no survival benefit was noted. Infection, especially pneumonia, was the most common cause of death. In 61 febrile episodes with clinically suspected sepsis, 10 (17%) were documented to associate with bacteremia. Twelve patients (7 RAEB, 4 RAEB-T, and 1 CMMoL) evolved to acute myelogenous leukemia (AML), the median interval from diagnosis to evolution was 4.8 months. This series indicates that only two groups of FAB subtypes could be clearly separated in terms of morphological findings and clinical outcome; RA and RARS constitute a good prognostic group, whereas RAEB, CMMoL, and RAEB-T constitute a poor prognostic group.
Changgeng Yi Xue Za Zhi 1992 Sep
PMID:Primary myelodysplastic syndrome: an analysis of 56 patients. 146 34

Between 1978 and 1988, 20 children with medulloblastoma (MB) of the brain were treated postoperatively with MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine). All but one received post-operative radiation prior to MOPP. Eight of 20 patients remained in continuous complete remission from MB, two of whom eventually developed myelodysplastic syndrome (MDS). Following resection of MB at age 12 months, one patient was treated with 24 courses of MOPP over 2 years without radiation therapy. She developed pancytopenia, and MDS was diagnosed 19 months after the completion of MOPP. Analysis of unstimulated bone marrow (BM) chromosomes showed structural abnormalities involving chromosomes 7, 10, 17, and 21. Eight months later, MDS evolved into acute myeloid leukemia. The second patient was diagnosed with MB at age 7 years and received postoperative craniospinal radiation followed by 12 courses of MOPP over one year. Five months after completion of MOPP, she developed MDS with monosomy 7 on chromosome analysis of bone marrow cells. Therapy-related MDS may be a complication of MOPP chemotherapy for MB in young children.
J Neurooncol 1992 Sep
PMID:Therapy-related myelodysplastic syndrome in children with medulloblastoma following MOPP chemotherapy. 146 65

We review results of intensive chemotherapy (IC) obtained in myelodysplastic syndromes (MDS). Overall, the complete remission (CR) rates and median CR duration obtained with IC are low in MDS, especially when compared to results obtained in de novo AML treated with the same chemotherapy regimens; very few MDS patients achieve prolonged remissions. Failure to achieve CR, in MDS, results both from a high incidence of resistant disease and toxic deaths, the latter being due to longer periods of aplasia than in de novo AML. However some subgroups of MDS seem to obtain higher CR rates and more prolonged remissions. These include patients younger than 45 to 50 years, those with a large excess of marrow blasts or Auer rods at diagnosis, and patients with a normal karyotype or at least without involvement of chromosomes 5 and/or 7. Results of IC clearly have to be improved in MDS. Higher CR rates may possibly be obtained by intensifying induction regimens, but this will probably require the addition of growth factors, in order to reduce the already very long periods of aplasia seen with IC in MDS. For consolidation therapy, new approaches, and especially autologous bone marrow transplantation, will have to be investigated.
Leuk Lymphoma 1992 Sep
PMID:The role of intensive chemotherapy in myelodysplastic syndromes. 149 70

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.
Am J Hematol 1992 Sep
PMID:Myelodysplastic syndromes and malignant solid tumors: analysis of 21 cases. 150 93

The retinoblastoma (RB) protein levels in blast-enriched mononuclear fractions from the peripheral blood of 33 newly diagnosed patients with acute myelogenous leukemia were studied. Ten patients who had previously been treated were also analyzed, nine of whom had achieved prior complete remission. Low RB protein expression was found in 13 of 43 (30%) of the acute myelogenous leukemia patients as determined by Western blotting and immunochemical analysis. Of particular interest among the 20 newly diagnosed patients treated with the same therapeutic regimen, the median survival was 39 days for those with low RB protein expression compared to 333 days for those with high levels of RB protein expression in their leukemic cells (P less than or equal to 0.02). This preliminary study suggests that decreases of RB protein expression in peripheral blood of myeloid leukemic cells occur frequently and may be associated with shortened survival of acute myelogenous leukemia patients.
Cancer Res 1992 Sep 01
PMID:Clinical implications of decreased retinoblastoma protein expression in acute myelogenous leukemia. 151 26

In this study, we evaluated the individual in vitro sensitivity of fresh acute myeloid leukemia (AML) cells to VP-16, and attempted to correlate VP-16 cytotoxicity with AML cell growth characteristics and drug-induced DNA single-strand breaks (SSB). Primary (PE1) colony inhibition assays allowed us to characterize two distinct groups of AML: group I (patients 1 through 6), which displayed sensitivity to VP-16 similar to that of normal CFU-GM (IC90 of 20.52 +/- 2.44 micrograms/mL v 20.48 +/- 2.23 micrograms/mL after 1 hour drug exposure, respectively); and group II (patients 7 through 11), which was more sensitive to VP-16 (IC90 of 7.26 +/- 2.93 micrograms/mL, P = .004). Subsequently, groups I and II were termed normosensitive and hypersensitive, respectively. This objective VP-16 sensitivity classification, as determined by PE1, remained unaltered when assessed by secondary (PE2) colony inhibition assay (evaluating the self-renewal fraction of AML progenitors), or by cytofluorometric viability assay (evaluating the ultimately differentiated blast cell population). These findings would suggest that individual sensitivity to VP-16 of a particular cell population is maintained throughout CFU-AML differentiation. Finally, we report that sensitivity of AML cells to VP-16 did not correlate either with cell growth characteristics or with SSB generation. Indeed, AML cell sensitivity to VP-16 appeared more closely related to DNA repair kinetics after drug removal, ie, hypersensitivity being essentially characterized by a prolonged retention of SSB during the posttreatment period. Interestingly, the established HL-60 cell line, which presented greater sensitivity to VP-16 cytotoxicity than KG1, HEL, and K562, was also found to exhibit delayed DNA SSB repair kinetics, as compared with the other AML cell lines. These results suggest that hypersensitivity to VP-16 of some AML cells may be related to a deficient DNA-repair mechanism.
Blood 1992 Sep 01
PMID:Sensitivity of fresh acute myeloid leukemia cells to etoposide: relationship with cell growth characteristics and DNA single-strand breaks. 151 45

Testicular relapse (TR) in adult acute myelogenous leukemia (AML) is uncommon, occurring in only 1-2% of patients with bone marrow relapse. TR in the absence of systemic relapse has been reported previously in 2 adults and 12 children, of which 67% were monocytic variants of AML. This article presents the case of a 29-year-old man with AML that relapsed in his testicle without evidence of bone marrow relapse. This patient and the two previously mentioned adults experienced bone marrow relapse within 2 months and died within 7 months of their TR. TR in adult myelogenous leukemia should be considered a harbinger of systemic relapse and suggests a need for aggressive local and systemic therapy.
Cancer 1992 Sep 15
PMID:Testicular relapse in adult acute myelogenous leukemia. 151 5

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.
Cancer 1992 Sep 15
PMID:Cytogenetic analysis in the diagnosis of acute leukemia. 151 24

The curability of acute myelocytic leukemia (AML) in adults relies upon two treatment strategies. The first is induction therapy to effectively reduce the patient's leukemia burden and allow for recovery of normal hematopoiesis. Once this is achieved and the patient enters a complete remission, further potentially curative post-remission therapy can be administered. Induction therapy has not changed significantly over the past two decades, relying primarily on conventional-dose cytarabine and an anthracycline combination. Post-remission therapy, on the other hand, has changed with the introduction of more intensive and aggressive cytoreductive treatment as well as utilization of myeloablative regimens followed by either allogeneic or autologous bone marrow transplantation (BMT). The scope of this review is to evaluate the different curative post-remission treatment approaches for adult patients with AML. Discussions will focus on younger patients (less than 65 years) with responsive disease who enter a complete remission and then have post-remission therapy options available to them. Often, decisions concerning post-remission therapies are based solely on age and the availability of compatible donors; however, since understanding of the biology of leukemia has expanded and treatment strategies have improved, our ability to recommend particular treatment approaches has also evolved. We are now in a position to recommend therapeutic options based on disease and host characteristics.
Leukemia 1992 Sep
PMID:Post-remission therapy of acute myelocytic leukemia in adults: curability breeds controversy. 151 3


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