Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential value of sulphonated aluminium phthalocyanine (AISPc) as a purging agent for bone marrow autografts in acute myeloblastic leukaemia (AML) has been studied using in vitro clonogenic assays for normal (GM-CFC) and leukaemic (AML-CFC) progenitor cells. In nine out of 13 cases, the leukaemic blasts were found to be highly sensitive to AISPc. In six of the sensitive cases clonogenic assays revealed that only 2 +/- 1% of AML progenitor cells survived AISPc treatment under conditions which permitted a GM-CFC recovery of 60 +/- 11%. AISPc photosensitization was also shown to selectively eliminate the leukaemic cell line K562 from an in vitro model of minimal residual disease. Thus photosensitization using AISPc may be an effective method of purging marrow autografts in some cases of AML. Evaluation of the sensitivity of AML clonogenic cells at diagnosis may identify those patients in whom AISPc photo-purging may be of benefit at the time of an autologous bone marrow transplant.
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PMID:Differential phthalocyanine photosensitization of acute myeloblastic leukaemia progenitor cells: a potential purging technique for autologous bone marrow transplantation. 328 71

Intensive chemoradiotherapy with autologous bone marrow rescue has been widely explored as treatment for acute myeloblastic and acute lymphoblastic leukaemia. Encouraging preliminary results have been reported but in no situation has this modality of therapy been proved to be superior to conventional chemotherapy. Attempts to remove minimal residual disease from the harvested marrow have been made by both immunological and pharmacological means, but the value of such procedures has not been tested rigorously. Determination of the precise role of autologous bone marrow transplantation in the treatment of acute leukaemia must await the outcome of randomised controlled trials and will take several years.
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PMID:Autologous bone marrow transplantation in acute leukaemia. 333 71

Thirty-three leukaemic patients in CR were treated by high-dose therapy followed by ABMT: 18 of them had acute non-lymphoblastic leukaemia (ANLL) in first remission (CR1) with a mean age of 23.7 years (3-44). All but one of them were conditioned with a polychemotherapy regimen including 6-thioguanine, Ara-C, CCNU, and cyclophosphamide. The marrow cells were purged by chemical means in 16 cases. Five transplant-related deaths were observed: three cardiac failures, one interstitial pneumonitis and one aspergillus pneumonia. At the time of analysis (October 1984), four patients had relapsed and eight were still in unmaintained CR1 (44+, 46+, 30+, and five between 2.5+ and 8+ months post transplant). Fifteen patients had acute lymphoblastic leukaemia: four were autografted in CR1 and 11 children were grafted in CR2; the conditioning regimen was fractionated total body irradiation followed by cyclophosphamide for all but one patient who was conditioned with BACT (Burkitt leukaemia); the marrow was purged by a chemical agent in 11 patients and by monoclonal antibodies and C' in four: four out of 15 patients relapsed (two grafted in CR1 and two grafted in CR2); 10 patients are still in unmaintained CR: two adults grafted in CR1 (26+; 12+ months) and eight children with a mean follow-up of 13.4 months post graft (2 + -45+ months). The clinical study leads to the following conclusions: in adult patients the marrow should be harvested during CR1 and at the time of minimal residual disease. The quality of previous chemotherapy and conditioning regimen prior to ABMT play a prominent role in the in vivo eradication of the leukaemic cells. The real impact of marrow purging is still unknown and a larger series of homogeneous patients, conditioned with the same protocols and the same transplant timing, is required before any conclusions can be drawn.
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PMID:Autologous bone marrow transplantation (ABMT) for acute leukaemia in complete remission: a pilot study of 33 cases. 352 57

It is well known that even after maximal surgical and/or cytostatic treatment, and even in patients with an apparently complete remission, what is known as minimal residual disease often remains. Adjuvant chemotherapy given for periods longer than six months after the induction of complete remission does not appear, in comparative trials with a five-year follow-up, to improve the final prognosis either in leukaemia or in solid tumours. It is suggested here that the reason may be that minimal residual tumours may consist of cells in the G-O phase. Breast cancer before the menopause may be an exception, since oestrogens present before, but not during, menopause are promotors. This could explain why premenopausal breast cancer seems to be the only tumour transitorily sensitive to adjuvant chemotherapy. Immunotherapy given during complete remission seems to result in longer remission duration and/or overall survival and/or survival after relapse in some but not in all properly conducted trials. It is well known that large tumour masses are not influenced by immunotherapy. In contrast, it is known that cells in G-O, refractory to chemotherapy, may be sensitive to immunotherapy.
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PMID:Clinical trials of the treatment of minimal residual tumours. 352 78

Aneuploidy as an indication of abnormal cellular DNA content has recently been confirmed to be a reliable marker of malignant cells in human solid tumors and hematologic malignancies. Flow cytometry (FCM), measuring cellular DNA content in thousands of cells within seconds, is able to safely detect the "rare event cell," the rare aneuploid cell in a diploid cell population. This very fast and sensitive technique was combined with a newly developed cell separation technique. Cell separation prior to FCM enabled us to detect malignant cells at concentrations of 0.05% in blood, bone marrow, and lymph node cell suspensions of patients with leukemia. An illustration of this method is presented in conjunction with first clinical applications demonstrating that patients with minimal residual disease in clinically complete remission had significantly shorter survival times than patients in whom no minimal residual disease was detected with this new method.
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PMID:Aneuploidy as a marker of minimal residual disease in leukemia. 406 49

Twenty-six patients with acute leukaemia and 14 with high-grade lymphoma received cytosine arabinoside (ara-C) at a twice daily dose of 2 g/m2 administered as a 3-h infusion. Thirty-four patients received 12 doses and six electively received four doses only. Complete remission was achieved in six of seven patients with acute myelogenous leukaemia (AML), one of two evaluable patients with blast crisis of chronic myeloid leukaemia and three of eight patients with acute lymphoblastic leukaemia (ALL). Three further patients with ALL had only minimal bone marrow infiltration after one cycle, toxicity precluding administration of a second. Three patients with AML who received four doses only showed no evidence of response. Four of 14 patients with lymphoma who received 12 doses, entered complete remission. Five additional patients died with minimal residual disease whilst severely neutropenic. A complete and a partial response were seen in two patients with immunoblastic and centrocytic lymphoma respectively who received four doses. These results confirm the activity of high-dose ara-C in patients with AML and suggest that it may also be a potentially useful agent in ALL and high-grade lymphoma, especially as the incidence of CNS toxicity is lower than that reported at higher doses.
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PMID:High-dose cytosine arabinoside: response to therapy in acute leukaemia and non-Hodgkin's lymphoma. 669 29

Indirect Immunofluorescence (IF) for terminal deoxynucleotidyl transferase (TdT) was used in conjunction with the biochemical assay of TdT enzymatic activity to study human leukaemias before and during therapy. In addition, non-leukaemic marrows were analysed to compare the enzyme expression on normal cells. An excellent correlation was observed between the IF and biochemical methods when specimens contained greater than 5% TdT+ cells (by IF); below this level the biochemical assay was less reliable, while the sensitive IF test could detect isolated TdT+ cells among greater than 10 000 TdT negative cells. The IF method also had the advantage of allowing further immunological characterization of TdT+ cells, by simultaneous labelling of membrane antigens with appropriate antisera. TdT+ cells expressing Ia-like antigens (but lacking other antigens associated with B- and T- lymphoid differentiation) were frequently found in low numbers in remission marrows from acute lymphoblastic leukaemia (ALL) patients. However, similar cells were also observed in remission acute myeloid leukaemia, as well as in non-leukaemic regenerating marrows, and marrow from normal donors. The presence of these normal TdT+ precursor cells therefore precluded the use of either IF or biochemical TdT tests for estimating the degree of residual disease or predicting early relapse in patients with non-T, non-B ALL. In contrast, the detection of TdT+ cells with T lymphoid antigens (HuTLA+) but lacking Ia antigens, in thymic (T-cell)-ALL, but not in normal marrow, allowed the use of this combination of markers to detect minimal residual disease in T-ALL.
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PMID:Immunofluorescent and biochemical studies of terminal deoxynucleotidyl transferase in treated acute leukaemia. 700 2

Instability of antigen receptor gene rearrangements during progression of acute lymphoblastic leukemia (ALL) has important implications for polymerase chain reaction (PCR)-based techniques using these genes for the detection of minimal residual disease (MRD). Antigen receptor gene instability may lead to false negative results in bone marrow samples taken during remission. Utilizing the PCR and consensus primers for rearranged immunoglobulin heavy chain (IgH) and T cell receptor gamma (TCR gamma) gene sequences, we analyzed the bone marrow samples at diagnosis and first relapse for 37 children with ALL. The incidence of clonal evolution at the IgH locus was 9/33 (27%) and at the TCR gamma locus 1/15 (7%). In four of the nine patients with clonal evolution at the IgH locus, the sequence at relapse retained the diversity and joining region (D-N-J) sequences from diagnosis. Patients with clonal evolution were characterized by a higher incidence of more than one IgH PCR band at diagnosis and by late relapse (> 18 months from diagnosis). These results suggest that, where possible, patients with more than one IgH PCR rearrangement at diagnosis should be monitored using another antigen receptor gene, such as TCR gamma, since evolution for this gene was found to be a rare event. By combining this approach with a strategy directed at the more stable D-N-J region of the IgH gene, MRD false negativity would have occurred in less than 10% of patients in the present study.
Leukemia 1995 Nov
PMID:Characterization of clonal immunoglobulin heavy chain and I cell receptor gamma gene rearrangements during progression of childhood acute lymphoblastic leukemia. 747 73

In the past, studies on CD34+ cells have been based on the use of monoclonal antibodies conjugated with different fluorochromes that show different fluorescence intensity and yield variable results. Moreover, most of these studies have neither specifically focused on adult human BM samples nor have they used combinations to explore specifically the phenotype of myeloid committed CD34+ cells. The aim of the present study has been to characterize the normal human CD34+ precursor cells from adult BM in order to identify missing or extremely rare phenotypes that can be used for detecting minimal residual disease (MRD) in patients with AML. For this purpose we have utilized the fluorochrome conjugates that provide the most sensitive signals for identifying low antigenic expression, and the technique has been adapted to the characterization of cells present at very low frequencies. Normal human BM samples from 13 adult healthy volunteers have been analyzed using triple stainings at flow cytometry. The mean percentage of CD34+ cells detected was 0.72 +/- 0.33%; these cells displayed an heterogeneous light-scatter distribution. Most CD34+ cells coexpressed CD38 (96.7 +/- 5.7%), HLADR (81.6 +/- 14.0%), CD33 (84.7 +/- 18.3%), CD13 (84.6 +/- 16.2%) and CD71 antigens (65.5 +/- 9.1%). In addition, almost half of CD34+ cells were CD117+ (60 +/- 26.8%). Only a small proportion of CD34+ cells coexpressed CD4 (15.5 +/- 11.7%, CD36 (31.7 +/- 6.2%), CD61 (16.3 +/- 12.9%), CD41 (6.5 +/- 5.5%) or the lymphoid associated markers CD10 (18.6 +/- 11.8%) and CD19 (12.3 +/- 13.2%). Reactivity for the CD15 antigen was observed in a small population of CD34+HLADR+ cells (11.6 +/- 11.2%) although its intensity of expression was lower than that of the more mature granulocytic cells. No CD34+ cells displayed CD14, CD65, CD20, strong CD22, CD3 and CD56 antigens. Accordingly, most adult bone marrow CD34+ cells appeared to be committed to the myeloid lineage (CD13+/CD33+) and displayed an intermediate-to-large FSC/SSC while the lymphoid-committed CD34+ cells (CD19+, CD10+) were in a minority with low FSC/SSC values. By triple marker stainings several phenotypes of CD34+ precursor cells were found to be either undetectable or present at very low frequencies (< 1 x 10(-3)) in the normal human adult bone marrow. These data may be of great value for defining leukemia 'associated' phenotypes used to detect minimal residual disease in adult acute leukemia patients.
Leukemia 1995 Nov
PMID:Phenotypic analysis of CD34 subpopulations in normal human bone marrow and its application for the detection of minimal residual disease. 747 81

This report reviews the diagnostic significance of immune markers, their relationship to patient outcome, and the therapeutic uses of monoclonal antibodies (MoAbs) in acute leukemia. Immunophenotyping allows for rapid and reproducible diagnosis in the majority of cases of acute leukemia. It is of particular importance in recognizing the major immunologic subclasses of acute lymphoblastic leukemia (ALL), and in identifying subtypes of acute myeloblastic leukemia (AML) which cannot be differentiated by morphology and cytochemistry alone, such as FAB M0 or M7. Immune marker analysis has been used to detect minimal residual disease in patients' bone marrow and CSF after treatment. However, the presence of leukemia-associated phenotypes on small numbers of normal cells may reduce the sensitivity of detection in some cases. The prognostic value of immune markers in AML is limited. In ALL, the prognostic significance of the different immunophenotypic subtypes has been lessened by modern treatment protocols. The relationship of mixed-lineage or biphenotypic antigen expression to patient outcome in both AML and ALL is unclear. Therapeutic applications of MoAbs in acute leukemia include immunologic techniques for purging malignant cells from autografts prior to transplantation, T-lymphocyte depletion from allografts as a strategy to reduce graft-versus-host disease, and the use of flow cytometry to monitor the timing and extent of leukapheresis in peripheral stem cell transplantation. MoAbs have also enabled the recent development of transplantation protocols using positively-selected CD34+ stem cells.
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PMID:Monoclonal antibodies in the management of acute leukemia. 748 80


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