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)

Twenty three patients with Hodgkin's disease were treated with BCNU (carmustine), etoposide, and cyclophosphamide at doses of 450-600 mg/m2, 1500-2000 mg/m2, and 120 mg/kg respectively. Bone marrow refrigerated at 4 degrees C for 2-5 days or cryopreserved at -80 degrees C was used to reconstitute bone marrow function. The median age was 28 (range 16-48), and the median Karnofsky performance status was 70. Nineteen patients had progressive disease while on chemotherapy. The median number of prior regimens was three (1-7), and the median number of prior chemotherapy drugs was 10 (range 4-12). Ten patients had received at least two of the drugs used in this study and four had had all three. Indicator lesions included lung (10), peripheral lymph nodes (9), retroperitoneal nodes (8), liver (3), and chest wall masses (2). Ten patients achieved a complete remission (43.5%; 95% confidence limits 23-64%), and five patients had a partial remission (21.7%; 95% confidence limits 5-39%). The median duration of complete remission was 6 months (range 2-13+ months). Responses were shorter in duration for patients with primary refractory disease. Liver function abnormalities were noted in nine (39%) cases. Post transplant, the recovery time was 18 days (range 11-43) for WBC and 24 days (11-77) for platelets. Two patients died of septic episodes while neutropenic. The median number of RBC units used was seven (range 1-45). Ten patients had evidence of pulmonary dysfunction. In seven patients there was symptomatic improvement with steroid therapy, but three patients who were not treated with steroids died as a result of interstitial pneumonia. Future programs should consider bone marrow transplantation in patients with Hodgkin's disease earlier in the course of disease, at the time of minimal residual disease, and employ newer, potentially less toxic drugs.
Leukemia 1989 Jan
PMID:High-dose, potentially myeloablative chemotherapy and autologous bone marrow transplantation for patients with advanced Hodgkin's disease. 264 73

In an animal bone marrow transplant (BMT) model that mimics the human clinical condition, we evaluated the effectiveness of monoclonal antibody (MoAb) therapy in eliminating minimal residual disease (MRD) in a leukemic host. Leukemic rats were prepared with marrow ablative but noncurative doses of busulfan (BU) and cyclophosphamide (CY). Two days after syngeneic BMT, rats were treated with MoAb. Although all control rats died of leukemia relapse, 58% of those treated with MoAb were cured without any demonstrable effect on the rate of peripheral blood leukocyte recovery. Furthermore, the level of complement, an important effector in suppressing leukemia proliferation in the normal rat, was not adversely affected by BU/CY, BMT and MoAb. Thus, we demonstrated in an animal model that MoAb therapy may be a useful, nontoxic adjunct to high-dose chemotherapy and BMT in eliminating MRD.
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PMID:Systemic monoclonal antibody therapy for eliminating minimal residual leukemia in a rat bone marrow transplant model. 264 81

Instrumentation for rare-event analysis should be capable of reliably detecting infrequent cells (less than 1:10,000) while both excluding false-positive signals and including true positive cells found in multicell clumps. We have developed a digital image microscopy (DIM) system in which a cytospin of 2 million cells is scanned with an intensified video camera (ISIT) using an IBM PC AT microcomputer-controlled microscope stage. PASCAL software controls the stage and analyzes video input, storing the location of positive cells to magnetic disk. The user can then "replay" each positive cell under computer control for either visual confirmation or analysis using other fluorescent probes. The computer requires 24 min to scan a cytoprep of 2 million cells, while playback for visual confirmation by the user averages 5 min. Using Hoechst-33342 premarked cells seeded into bone marrow as a model system, we found that the DIM system reliably detects one target cell per million marrow cells. With appropriate immunological markers, this system will aid in evaluating bone marrow purged of tumor cells prior to transplantation and should also be useful for detection of minimal residual disease in blood or bone marrow from patients with leukemia or solid tumors.
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PMID:A digital image microscopy system for rare-event detection using fluorescent probes. 265 39

GM-CSF was used to overcome fatal myelosuppression after cytotoxic chemotherapy. Two different application modalities were compared: a continuous 24 h infusion was more effective compared to a 30 min short term infusion. Using the former modality at a dose of 10 micrograms/kg/d for five days very impressive responses were observed. No major side effects did occur. The first 13 patients treated in this way included 8 AML cases. Only one of these latter patients had a leukemia relapse. However, in this patient the immediate GM-CSF response was clearly separated from the relapse occurring later in the observation period. Thus, the preliminary results of the present paper suggest that GM-CSF besides of being very efficient in accelerating granulocyte recovery does not stimulate the growth of AML blasts in vivo in patients with only minimal residual disease.
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PMID:GM-CSF treatment in aplasia after cytotoxic therapy. 265 87

Adjuvant chemotherapy. The frequent 6 month complete remission induction chemotherapy is not discussed here. What is under debate at present is the prolonged maintenance or adjuvant chemotherapy, which in comparative trials with 5 year follow-up does not appear to improve survival prognosis in leukemia, myeloma, non-Hodgkin lymphoma or post-menopausal breast cancer. However, it may prolong the duration of the first remission. It is suggested that the sensitivity to chemotherapy might depend on cells being induced into the G2 or M phases by growth growth promotor(s), such as estrogens in breast carcinoma. Their presence before the menopause could explain why this neoplasia in this condition is one of the few tumoral diseases transitorily sensitive to adjuvant chemotherapy. Adjuvant immunotherapy is also under debate. Immunotherapy has been reported to give a significant improvement in remission duration and/or overall survival and/or survival after relapse in several tumors and in several trials. However, for almost every trial reporting a statistically significant effect there is one (or more) which shows no significant effect. Theoretically, immunotherapy has several advantages over chemotherapy. It may be effective in minimal residual disease if tumor cells are in the G0 phase. So-called kinetic refractoriness (see separate chapter in this volume) may not apply to immunotherapy. Finally, tumor cells appear to be more sensitive than normal cells to some cytotoxic mechanisms which form a part of the biological response to tumors.
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PMID:Adjuvant treatment of minimal residual tumors. A comparison of chemotherapy and immunotherapy. 266 16

Human T-cell receptor (TCR) delta-chain diversity mainly originates from high junctional variability, since only a limited number of germline elements is available. This extraordinary diversity at the V.J junction, due to the use of two D delta elements and extensive incorporation of N nucleotides, constitutes a specific clonal marker for cell populations exhibiting rearranged TCR delta genes. To this end we amplified in vitro by polymerase chain reaction (PCR) the TCR delta junctional region of five acute lymphoblastic leukemias (ALL), isolated respective DNA fragments, and used them directly as clonospecific probes. The combination of PCR technology and hybridization to clonospecific probes permitted the detection of leukemia DNA at dilution of 1:100,000 in all five cases. Moreover, we were able to investigate one of the ALL patients 11 months after achieving continuous complete remission. Conventional Southern blot analysis failed to detect rearranged TCR genes at this stage. However, residual leukemic cells could readily be detected by PCR technique. We conclude that the strategy proposed here is a very sensitive tool to detect minimal residual disease in a significant proportion of human lymphoid neoplasias.
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PMID:Detection of minimal residual disease in acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor delta chain sequences. 267 18

Two subpopulations of small and large leukemia cells and binucleated cells were present in the bone marrow of a 10-year-old girl with acute lymphoblastic leukemia (ALL). Cytogenetic studies showed some cells with a karyotype of 34,X,-X,-2,-3,-4,-5,-7,-9,-13,-15,-16,-17,-20, and others with a karyotype that was exactly double the chromosome set in the cells with 34 chromosomes. Flow cytometric (FCM) examination of surface common ALL antigen (CALLA) and DNA content of the lymphoblasts led to the identification of the primary hypodiploid DNA stemline (DI = 0.72), which corresponds to the small-sized blasts, and the secondary hyperdiploid DNA stemline (DI = 1.44), which corresponds to the large-sized blasts. Sequential bone marrow examinations with FCM and cytogenetics revealed the persistence of the primary hypodiploid clone during remission and their proliferation with chromosomal evolution at full relapse. These results suggest that more rational inductive therapy should be designed to achieve the favorable outcome of ALL with severe hypodiploidy and that FCM is a useful tool to monitor the minimal residual disease of this subgroup in ALL.
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PMID:Flow cytometric evidence for minimal residual disease and cytological heterogeneities in acute lymphoblastic leukemia with severe hypodiploidy. 275 2

The present study is a retrospective analysis of the outcome in 210 patients diagnosed and treated as having acute lymphoblastic leukaemia (ALL) in Sweden during 1977-84. 131 patients were morphologically rediagnosed as ALL. For the ALL-patients, nine different remission induction regimens were used. Remission frequency was 69%, without statistical difference according to induction treatment. However, the reasons for remission failure differed among therapy groups. The number of responders was significantly higher among patients who received a remission induction therapy with an anthracycline and/or L-asparaginase. Maintenance therapy consisted in most cases of 6-mercaptopurine and methotrexate with reinduction courses for 2-3 years. Median survival time was 13 months and median duration of first remission (MRD) 11 months. For a subgroup of patients (n = 29) treated with the most intense remission induction regimens, including at least 4 cytostatic drugs with both an anthracyclilne and L-asparaginase, the MRD is not yet reached, the shortest follow up time is 43 + months, and the probability of remaining in complete remission is 66%. We conclude that aggressive cytostatic therapy, with induction regimens including both an anthracycline and L-asparaginase, may cure a considerable number of adult ALL-patients.
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PMID:Acute lymphoblastic leukaemia in adults in Sweden 1977-84: a retrospective analysis. Swedish ALL-Group. 279 24

Flow cytometry is a biological analysis technics whose applications may be used for minimal residual disease evaluation. From these applications we retained the DNA content measurement (with DNA index), surface markers analysis, and flow karyotyping. The threshold cell aneuploidy detection depend of the DNA index of leukemia cell population. The establishment of a relation between cell surface markers and malignant character of the cell is difficult to obtain. Study of CALLA antigen in leukemic patients have shown variations of antigenic density with different categories of studied patients. Malignant cells studied at the diagnosis or at the relapse of leukemia have a mean antigenic density higher than normal cells. This fact could be used to evaluate minimal residual disease as shown with recent clinical observations.
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PMID:[Flow cytometry in the detection of residual disease]. 296 35

DNA "fingerprint" (DNA-F) analysis, based on the polymorphism caused by numeric variations in the tandem repeats of minisatellite areas of the human genome, has a potential capacity to reveal even minor genomic changes. In this study we have applied DNA-F to the detection of residual disease in leukemia. In order to identify normal and leukemic cell populations, we used two molecular probes: Jeffrey's minisatellite probes and M13 wild type phage probe, which detect different sets of polymorphic fragments in the human genome. Comparison of varying minisatellite fragments between remission and relapse was performed by Southern blot hybridization in seven patients with acute lymphoblastic leukemia (ALL). The results suggest that Southern hybridization with DNA "fingerprint" probes can prove to be a sensitive method in the detection of minimal residual disease in ALL.
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PMID:Differences in DNA-fingerprints between remission and relapse in childhood acute lymphoblastic leukemia. 277 Mar 33


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