Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For sufficient collection of hemopoietic stem cells from peripheral blood for autologous peripheral blood stem cell transplantation (PBSCT), four patients with B-cell-type non-Hodgkin lymphoma (B-NHL) were examined for the appearance of circulating hemopoietic progenitors in blood (PSC) during the hemopoietic recovery phase following marrow ablative therapy in combination with or without administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Each patient received only chemotherapy in the first course, and rhG-CSF (1 microgram/kg/day) was administered for 14 consecutive days from the last day of the second chemotherapy. In the second chemotherapy course with rhG-CSF administration, white blood cell (WBC) counts demonstrated two peaks, and the appearance of granulocyte-macrophage precursor cells (CFU-GM) in blood at the maximum level was coincident with the second peak of WBC elevation. Erythroid precursor cells (BFU-E) were also detectable in blood after chemotherapy but the peak level was not enhanced by the use of rhG-CSF. To determine whether the minimal residual disease (MRD) cells were contaminated in PSC corrected from blood, kappa-lambda imaging (KLI) analysis was performed to detect the malignant B-cell population (mBp) before and after chemotherapy. No mBp was found in two of four patients in blood, although three of them were involved with mBp in bone marrow. The presence of mBp was detected in two patients both before and after chemotherapy, even though these cells were hardly detected morphologically, suggesting the necessity of judging for the incidence of contamination of MRD cells when collecting PSCs.
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PMID:Detecting of the minimal residual disease contaminated in peripheral blood stem cell transplantation in the B-cell malignant lymphoma patients. 810 28

The use of clonospecific probes has recently been employed for the detection of minimal residual disease in B- and T-cell acute lymphoblastic leukemias. However, these methods are predicated upon the successful amplification of the V-D-J rearrangement in the genome of the tumor cells by the polymerase chain reaction (PCR). In order to determine whether the type of B-cell lymphoid malignancy influenced the rate of success of amplifying the region of the immunoglobulin heavy chain gene rearrangement in these lesions, we studied 41 morphologically and immunologically well characterized B-cell neoplasms. DNA was extracted from frozen tissue of the lymphomas and leukemias, and subjected to PCR amplification using a 5' immunoglobulin heavy chain gene variable region consensus Framework 3 region (FR3) primer, and a 3' consensus primer for the immunoglobulin heavy chain joining region. One or two distinct bands, representing the rearranged immunoglobulin heavy chain gene, were detected in six of six small non-cleaved cell lymphomas, five of five small lymphocytic lymphomas, four of six acute lymphoblastic leukemias, four of six follicular lymphomas, three of six diffuse mixed small and large cell lymphomas, one of six diffuse large cell lymphomas, and one of six immunoblastic large cell lymphomas; all control cases of lymphocyte predominant Hodgkin's disease (5/5) and reactive follicular hyperplasia (5/5) were negative. We therefore conclude that the type of B-cell neoplasm influences the ability to detect immunoglobulin gene rearrangements by PCR with currently used consensus primers.
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PMID:Variable rate of detection of immunoglobulin heavy chain V-D-J rearrangement by PCR: a systematic study of 41 B-cell non-Hodgkin's lymphomas and leukemias. 149 28

The polymerase chain reaction (PCR) is a novel technique for the in vitro amplification of specific short DNA fragments, which permits a selective and up to 10(7) fold enrichment of the target sequence. The method is increasingly being used for the molecular genetic analysis of hereditary, infectious and neoplastic disorders. The use of PCR for the detection of minimal residual disease in particular types of leukaemia or lymphoma, such as chronic myelogenous leukaemia expressing specific BCR/ABL-RNA and follicular non-Hodgkin lymphoma with the chromosomal translocation t(14;18) are reviewed. In acute lymphoblastic leukaemia clone-specific sequences from rearranged antigen receptor genes may be molecular markers suitable for amplification. Although PCR holds great promise for "molecular" staging and follow-up, several technical problems have to be kept in mind, and the clinical relevance of PCR-based evidence of minimal residual disease in haematological malignancies requires further investigation.
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PMID:The polymerase chain reaction: a new tool for the detection of minimal residual disease in haematological malignancies. 182 49

Autologous bone marrow transplantation (ABMT) has developed considerably in the past 15 years and is now a routine procedure for the consolidation of acute leukemias, non-Hodgkin's lymphomas and Hodgkin's disease. In addition, ABMT has been tested in multiple myeloma (MM) and even considered in highly selected cases of chronic myelocytic leukemia (CML). Interest has resulted from the discovery of new purging procedures such as long-term cultures with or without serum-free media containing various lymphokines, the evaluation of cryoinjury on malignant cells, the increased detection of minimal residual disease using PCR, and the acceleration of hemopoietic recovery post-ABMT through the use of peripheral blood stem cells and/or lymphokines. Results presented include data from the international (ABMTR) and European (EBMT) registries, and our own unit in Paris. With respect to acute leukemias, (a) the EBMT listed 1,688 patients. The overall results were as follows: for patients autografted in complete remission (CR) 1, the leukemia-free survival and relapse rate at 7 years were 48 +/- 2% and 41 +/- 3% for AML and 44 +/- 5% and 45 +/- 5% in acute lymphoblastic leukemia (ALL), respectively. In CR2, the figures were 34 +/- 4% and 54 +/- 5% for AML and 32 +/- 3% and 62 +/- 4% for ALL, respectively. Patients not relapsing at 1 year post-ABMT had a probability of being cured at 7 years of 86 and 71% if autografted in CR1 and CR2 for AML and 81 and 59% for ALL, respectively. Multivariate analysis of relapse rates in several subpopulations confirmed the efficacy of marrow purging in AML CR1: in patients transplanted prior to January 1988 (minimum follow-up of 2 years), the relapse rate with purged marrow was 35 +/- 5% vs. 47 +/- 3% (p less than 0.005). (b) In Paris, St-Antoine, using TBI and marrow purged with mafosfamide at levels individually adjusted (Blood 1986;67:1367), the probability of remission and DFS were 84 and 62% in AML CR1 63 and 59% in ALL CR1, respectively. There was a statistically significant relationship between the relapse rate and the residual amount of CFUGM progenitors in the marrow after purging. The cutoff point was 0.3%, with a relapse rate of 54% in those receiving marrow containing the higher residual CFUGM fractions and only 29% in those receiving less. With respect to non-Hodgkin's lymphomas, the EBMT listed 698 patients. In intermediate or high grade lymphomas, the DFS at 6 years was 30% and 18% in sensitive and resistant relapses, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Autologous bone marrow transplantation in hematological malignancies. 204 65

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.
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PMID:High-dose, potentially myeloablative chemotherapy and autologous bone marrow transplantation for patients with advanced Hodgkin's disease. 264 73

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

Serum lactate dehydrogenase (LDH) activity is increased in many tumor-bearing patients and can be used as a prognostic marker. We studied serum LDH concentration in 94 consecutive patients with non-Hodgkin's lymphoma who were histologically classified according to the Kiel Classification and were grouped according to the Non-Hodgkin's Lymphoma Pathologic Classification Project Working Formulation. 74 patients were studied at diagnosis, and 20 of them (27%) had an LDH level higher than 250 U/l. High LDH levels were more frequent in cases of true histiocytic, high-grade, and intermediate-grade malignancy lymphoma (4 of 7, 7 of 14, and 7 of 20, respectively) than in cases of low-grade lymphoma (2 of 33). A close relationship of LDH to several prognosis-related disease features was found, including general symptoms, bulky disease, big mediastinal tumor, huge hepatosplenomegaly, bone marrow involvement, and a leukemic syndrome. LDH was higher than normal in a high proportion of cases who were studied in relapse (13 of 20, 65%). These data suggest that in non-Hodgkin's lymphomas the LDH serum concentration is not independent of other disease features, so that the prognostic value of LDH is probably lower than expected from previous studies. Serum LDH activity decreased to normal in all cases of complete remission, but also in cases of partial remission, suggesting that measuring enzyme activity is of a limited usefulness for detecting and monitoring minimal residual disease. For that purpose, LDH isoenzyme studies would be more appropriate.
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PMID:Serum LDH concentration in non-Hodgkin's lymphomas. Relationship to histologic type, tumor mass, and presentation features. 643 91

Lymphomas include a vast number of pathologic conditions in which the search for new active drugs follows different routes. Hodgkin's disease and high-grade non-Hodgkin's lymphoma are very sensitive to chemotherapy, responding well to existing regimens; the inability to cure seems to be caused by acquired drug resistance. Newer strategies using classic chemotherapeutic agents and the use of modulators of resistance are the main focus of research in these malignancies. For indolent lymphomas, the inability to cure may be caused by the difficulty in eradicating completely an apparently sensitive disease. The search for new drugs in this field has focused on chemotherapeutic agents with new mechanisms of action, among which the purine analogues are the most important novelty, and on biologic therapy. There is evidence of activity of drug targeting, using monoclonal antibodies, immunotoxins, and radioimmunotherapy. Their role in the treatment of these malignancies will probably be different from that of traditional drugs, perhaps in the context of eradication of minimal residual disease after effective conventional therapy.
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PMID:New active drugs in the treatment of lymphomas. 782 50

We report a reliable approach for sequencing lymphoma-specific CDRIII regions. CDRIII regions present in DNA prepared from routinely fixed and paraffin-embedded diagnostic lymph node material were amplified by the use of consensus VH and JH primers via PCR. PCR products were subcloned directly, without purification or modification of PCR fragments. Only small amounts of miniprep plasmid DNA of recombinant clones were required for cycle sequencing, resulting in autoradiograms of high quality. The easy and reproducible method which we describe has enabled us to determine the lymphoma-specific CDRIII region in 7/11 high-grade non-Hodgkin's lymphomas as well as in 3/3 cases of ALL and 1/1 case of a centroblastic/centrocytic lymphoma. The obtained sequence data can serve to generate lymphoma-specific oligonucleotides, which then can be used as PCR primers or hybridization probes for the detection of minimal residual disease in individual patients.
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PMID:A reliable approach for sequencing clone-specific CDRIII regions in B-cell lymphoma. 817 24

The identification of minimal residual disease (MRD) in non-Hodgkin's malignant lymphoma is of immediate clinical relevance. Although several polymerase chain reaction (PCR)-based strategies are currently available, they all share serious technical or theoretic limitations with respect to their ability to detect the broad spectrum of mature B-cell neoplasia. We report a new strategy based on anchored PCR that does not rely on a particular chromosomal translocation or VH consensus sequence. It can yield the complete DNA sequence of the immunoglobulin heavy chain variable region (VHDJH). The assay is capable of detecting one neoplastic cell among 10(3)-10(4) normal cells with high specificity and has the potential to greatly expand the variety of B-cell malignant neoplasms that can be studied.
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PMID:Sensitive detection of clonal antigen receptor gene rearrangements in non-Hodgkin's malignant lymphoma with an anchored polymerase chain reaction-based strategy. 824 92


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