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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More detailed identification and understanding of the heterogeneity of leukemias using a broad panel of markers seems to be essential for the successful design of more sophisticated and effective treatments. Based on the FAB system, immunological phenotypes using a panel of monoclonal antibodies, and rearrangements of immunoglobulin and T-cell receptor genes, acute leukemia can be divided into six subtypes such as B-lineage, T-lineage, AML, NK-lineage, AUL and mixed lineage leukemia. The definition of B-lineage and T-lineage cells, a new classification for mixed lineage leukemia, incidence of dual rearrangements and their clinical significance are discussed.
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PMID:[Phenotypic and genotypic analysis of acute leukemia--current status of lineage specific classification]. 151 51

Of 6,099 children treated for malignancy, 16 (ages 3.5 to 18 years) developed acute appendicitis between 1962 and 1989. Fourteen had leukemia (ALL 10, AML 4). One each had rhabdomyosarcoma and Ewing's sarcoma. Active malignancy at diagnosis was noted in 10, 4 of whom had severe neutropenia (absolute neutrophil count less than 500/mm3). Of all the leukemics (2,794/6,099), abdominal pain during induction was a frequent complaint. The incidence of appendicitis, however, was low (0.5%). Nine of the 16 patients presented classically, facilitating prompt diagnosis and treatment. Six diagnoses were delayed. Three of these patients presented atypically with vague, nonlocalized pain, abdominal distention, lack of abdominal guarding, fever, dehydration, diarrhea, and unusual symptoms such as upper gastrointestinal bleeding. In each of these 6 patients the appendix was ruptured. Delays led to complications and deaths. Three patients required perioperative transfusions to treat excessive bleeding and two patients with ruptured appendicitis developed wound abscesses. Two patients died; in one, ruptured appendix was diagnosed only at autopsy. The other patient died of uncontrolled sepsis. Typhlitis occurring during induction chemotherapy may present similarly and is the main differential diagnosis. Typhlitis will usually improve with medical treatment alone. Nausea and vomiting (13/16), right lower quadrant pain (13/16), guarding (14/16), tachycardia (12/16), fever (10/16), and rebound tenderness (10/16) were the most frequent signs and symptoms of appendicitis. Persistent localized abdominal pain and guarding, lack of improvement with medical treatment, clinical deterioration, and the development of a mass were our indications for laparotomy. Despite major improvements in therapy, there is still a 37.5% error rate in our ability to accurately diagnose appendicitis in pediatric cancer patients.
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PMID:Acute appendicitis in children with leukemia and other malignancies: still a diagnostic dilemma. 152 62

We report the biological characteristics of leukaemic blasts from two cases of acute leukaemia with an interstitial deletion of the long arm of chromosome 9 (9q-). Case 1 (FAB: M1) showed del(9)(q12q22) as the sole karyotypic anomaly, and case 2 (FAB: M1) presented del(9) (q12q22) in association with trisomy 10. In both cases, leukaemic blasts presented unique cytological features, such as prominent vacuoles on Giemsa staining, or strong localization of myeloperoxidase resembling 'pseudo-Chediak-Higashi' granules. Immunophenotyping of blasts revealed the biphenotypic expression of T-lymphoid/myeloid antigens (CD2, CD7/CD33) in addition to CD34. Neither T-cell receptor beta (TCRB), T-cell receptor gamma (TCRG) nor Ig heavy chain (IGH) genes were clonally rearranged. Furthermore, there was neither rearrangement nor expression of ABL, which is located at 9q34, indicating that the deletion involved bands centrometric to 9q34 did not induce the activation of ABL. DNA synthesis of the blasts was stimulated (stimulation index greater than 2.0) in the presence of interleukin (IL)-3, IL-4, granulocyte colony-stimulating factor or erythropoietin (Epo). IL-3 and IL-4 could also support the in vitro growth of leukaemic blast colonies, and the IL-3- or IL-4-dependent blast colony growth was synergistically enhanced by the addition of IL-6 or Epo. These observations imply that T-lymphoid/myeloid or pluripotent stem cells may be closely involved in the development of 9q- AML.
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PMID:Interstitial 9q deletion in T-lymphoid/myeloid biphenotypic leukaemia. 155 Jul 72

For the purpose of establishing a method for reasonable clinical use of anthracyclines in leukemia chemotherapy, we examined the pharmacokinetics and the mode of action with five anthracyclines such as daunorubicin (DNR), doxorubicin (DOX), aclarubicin (ACR), THP adriamycin (THP), idarubicin (IDA). In the patients with AML, blood ACR or IDA level increased and then disappeared very rapidly after iv bolus injection. In contrast, their metabolites (M1 or IDAol) increased for up to 2 or 4 hrs and remained much longer than ACR or IDA. The concentration of ACR, IDA or their metabolites were found to be much higher in the leukocyte fraction than in erythrocyte fraction or plasma. In HL60 cell suspension, anthracyclines were rapidly accumulated into the cells, and the uptake of IDA or THP were higher than the other agents. In HL60 cells, anthracyclines accumulated in the nuclear fraction but ACR was accumulated markedly in the cytosol fraction. From the result of DNA binding assay, binding at excess to calf thymus DNA of ACR was suggested to be approximately 2 times higher than that of other agents. DNA strand brakes in HL60 cells treated with anthracyclines were shown by pulse field gel electrophoresis, and IDA was found to have stronger activity to cause the DNA strand breaks. In conclusion, it seemed that anthracyclines showed similar action mechanisms, but in some respects quantitative differences were existed among them. Anthracyclines should be given to patients based on their pharmacological characteristics to obtain higher remission rate and suppress resistant cells.
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PMID:[Pharmacokinetics and action mechanism of anthracyclines]. 155 93

Aggressive chemotherapy of myelodysplastic syndromes is rarely feasible because these disorders predominantly occur in elderly patients who often have concurrent illnesses. Alternative treatment modalities must therefore be evaluated. This review summarizes the results that have been obtained with low-dose chemotherapy, especially with low-dose cytosine arabinoside (Ara-C). Overall response rates to treatment with low-dose Ara-C are about 40%, with some 20% of patients achieving a complete remission. Transition of MDS to AML does not reduce the probability of response. The therapeutic outcome cannot be reliably predicted by clinical or experimental parameters. Hematological toxicity is substantial, with approximately 10-25% treatment-related deaths. Duration of response is short and rarely exceeds one year. In terms of overall survival, low dose Ara-C does not appear to be superior to supportive care only. Other cytotoxic agents have not been studied in detail, but data available do not suggest an appreciable advantage over Ara-C. Before denying low-dose chemotherapy a helpful role in MDS, randomized studies should concentrate on those patients who can be expected to derive the greatest benefit. Because of their short survival, patients with RAEBt or those transformed to overt leukemia are such candidates.
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PMID:The role of low-dose chemotherapy in myelodysplastic syndromes. 156 Jun 70

The expression of c-myb mRNA and protein was analyzed in fresh leukemic cells by Northern-blot analyses and by immunofluorescent staining using monoclonal c-myb specific antibodies. Staining of the cells was evaluated by flow cytometry. The results demonstrate c-myb mRNA expression predominantly in acute lymphocytic leukemia (ALL, 4/4 cases), acute myeloic leukemia (AML, 17/17) and chronic myeloic leukemia (CML, 12/12) but rarely in chronic lymphocytic leukemia (CLL, 1/17). Immunofluorescent analyses revealed expression of c-myb protein in the nucleus of ALL (5/7) and AML (9/9) with a good correlation of c-myb-positive cells and with the number of proliferating (Ki67-positive) blast cells.
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PMID:Heterogeneous expression of c-myb protein in human leukemia detected by simultaneous two color flow cytometric analysis. 156 Jun 75

An exponential function is proposed to describe cell growth, which incorporates the parameter signifying the population's proliferative index (f). This growth function could describe with precision the increase of peripheral blasts registered in one case of untreated CML at blast crisis, in which it revealed a pattern of growth characterized by f maintained constant at 0.5. The specific rate of blast growth remained unchanged throughout CML blast crisis. Based on the proposed growth expression and the calculation of progenitor cell presence in blood, a similar pattern of growth, in which f = 0.5, became apparent for AML progenitors in two cases of relapsing AML. The presence of leukemic progenitors in blood was quantified by adopting an indirect approach. The estimated fs compared closely with 3H-thymidine indexes previously obtained (literature data) for leukemic blasts and their progenitors. It is considered that the pattern of proliferation that maintains f = 0.5 may characterize the mode of cell growth that pertains in stages of advancing leukemia. Transfer of cells from quiescence to the state of proliferative activity is assumed as controlled, viewed in the line of a model of cell growth that requires f = 0.5 and constant specific rate of growth.
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PMID:Malignant cell growth in advancing leukemia. 156 70

The hyperthermia as well as radiation responses of multidrug resistant (CEM/VLB100 with classical MDR and CEM/VM-1 with atypical MDR), methotrexate resistant (CEM/MTX) subclones of CCRF-CEM T-lineage ALL cell line were compared with those of a drug sensitive (CEM-1-3) subclone from the same parent cell line. Also analyzed were the hyperthermia as well as radiation responses of multidrug resistant (HL60/AR) and drug sensitive subclones of the HL60 AML cell line. Notably, the drug resistant subclones of CEM and HL60 were as sensitive to hyperthermia as were the drug sensitive subclones. Importantly, no thermotolerant plateau was observed in the hyperthermia survival curves of the drug resistant subclones, indicating that drug/multidrug resistance is not associated with a greater likelihood of thermal tolerance development during hyperthermia. Similarly, the drug resistant CEM and HL60 subclones were not more radiation resistant than the drug sensitive subclones. Thus, the classical or atypical forms of multidrug resistance or methotrexate resistance of the analyzed leukemic cell lines were not associated with radiation resistance. Furthermore, the radiation survival curves of the drug resistant subclones lacked a distinct initial shoulder and their n values were not greater than those of the drug sensitive subclones, suggesting that multidrug resistance is not associated with an increased ability to repair or accumulate sublethal radiation damage. Our findings provide evidence that there is no apparent association between drug/multidrug resistance and heat or radiation sensitivity of CEM T-lineage ALL or HL60 AML leukemia cells. The results of this study indicate that acquired resistance to methotrexate, vinblastine, vincristine, etoposide, actinomycin-D, adriamycin, or daunomycin, or pleiotropic multidrug resistance do not necessarily confer radiation resistance for human leukemic cells.
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PMID:Radiation and heat sensitivity of human T-lineage acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) clones displaying multiple drug resistance (MDR). 157 9

In 1990, 4,234 BMT were performed in Europe; 2,097 autologous BMT (388 AML) and 2,137 allogeneic BMT (494 AML). Although an established therapy with leukemia free survival (LFS) at five years of 41% +/- 5% (EBMT results) its value compared to alternative therapies remains controversial. During the year 1985, the EBMT conducted a prospective evaluation study. In 12 centres 168 patients with AML were registered at the time of HLA-typing. Basic patient data and treatment intention were recorded. 79 patients were HLA-typed at diagnosis. 68 patients in 1st CR and 21 at other stages. Follow-up of these patients was obtained as of January 1, 1991. Three-year LFS is 44% for patients with an HLA-identical donor and 21% for those without (p = 0.02). Of the 68 patients HLA-typed in first CR, 40 had an HLA-identical donor and 28 no donor. Three-year LFS is 42% and 35%. resp. (n.s.). The difference in results between patients typed at diagnosis and first CR patients illustrates the problem of selection. We conclude that patient registration early in the disease can give insight into the process of selection. Allogeneic BMT incorporated prospectively at diagnosis into therapy offers a survival advantage for patients in this age category compared to alternative therapies.
Leukemia 1992
PMID:Bone marrow transplantation for acute myeloid leukemia: the EBMT experience. A prospective analysis from HLA-typing. The EMBT Leukemia Working Party. 157 8

These ECOG trials have demonstrated that progressive increments in the intensity of post-remission therapy result in improving long-term, disease-free survival in adults with AML. The median duration of disease-free survival and long-term outcome from different post-remission therapies are summarized in Table 4. [table: see text] Despite the suggestive evidence of the ordered increment in value of intensive consolidation therapy, allogeneic and autologous bone marrow transplantation, it remains to be proved that the differences observed in our preceding studies are statistically significant and clinically meaningful. These remaining questions led to the current ECOG study, EST 3489, a randomized intergroup study conducted with members of the Southwest Oncology Group. The study includes all patients with de novo AML up to age 55; the schema is shown in Figure 3. Induction therapy consists of idarubicin plus cytarabine instead of DAT. A modified short course of this induction therapy is repeated after CR. Patients who have a histocompatible sibling are offered allogeneic bone marrow transplantation. The remaining patients are randomized to receive either autologous bone marrow transplantation or a single course of high-dose cytarabine. Autologous bone marrow transplantation utilizes the previously described high-dose busulfan and cyclophosphamide regimen plus 4-HC purging of the bone marrow. The dosage of cytarabine in the intensive consolidation arm is 3 gm/M2/day IV on days 1-6. The results of this study should determine the relative merits of these different approaches to post-remission therapy. [table: see text] As mentioned earlier, demonstration of improved CR rates is limited by the morbidity and mortality from the myelosuppression that results from induction therapy. This is especially marked for older patients with AML. In patients, ages 55-70 years old, the ECOG is conducting a randomized trial (EST 1490) of conventional induction therapy +/- GM-CSF to determine if accelerated neutrophil recovery can reduce the mortality of induction therapy and thereby increase the remission rate. It may be that the application of GM-CSF and other colony-stimulating factors can increase the CR rate for all patients, increasing the number of patients potentially eligible for cure by post-remission therapy.
Leukemia 1992
PMID:Escalating the intensity of post-remission therapy improves the outcome in acute myeloid leukemia: the ECOG experience. The Eastern Cooperative Oncology Group. 157 10


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