Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated killer cells, unrestricted by major histocompatibility (MHC) antigens circulate in the peripheral blood of patients who have undergone autologous and allogeneic bone marrow transplant (BMT) and may contribute to the reduced risk of leukemic relapse observed after these procedures. Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used therapeutically might thereby promote the eradication of minimal residual disease. In order to assess whether these effects on cytotoxicity can be reproduced in vivo, we studied changes in number, phenotype, and MHC unrestricted cytotoxicity of peripheral blood mononuclear cells obtained from patients with hematologic malignancy receiving IL-2 infusions. Patients with acute myeloid leukemia and multiple myeloma were treated after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an initial lymphopenia, followed by a progressive recovery in mononuclear cell numbers and a rebound lymphocytosis after the termination of treatment. This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor) positive cell numbers rose sevenfold. Cells with the ability to kill a natural killer (NK)-resistant, lymphokine activated killer cell (LAK)-sensitive target appeared in the circulation during 16 of 19 infusions and mean LAK activity rose from 5.9% to 15.5% during infusion (E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in the peripheral blood inhibited the growth of myeloid leukemia blasts in agar after overnight co-culture. Depletion experiments showed that LAK activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+ CD16- (T derived) subsets. LAK precursor activity in peripheral blood also significantly increased during IL-2 infusion. Increases in major histocompatibility complex (MHC) unrestricted cytotoxicity can be produced by IL-2 infusions in vivo and may result in improved relapse-free survival following chemotherapy or BMT.
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PMID:Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy. 280 69

Hematologic malignancies, such as acute leukemia and malignant lymphoma. Respond well to cancer chemotherapy. Therefore, it is important to monitor the state of response to chemotherapy as well as to determine the complete disappearance of the tumor and to predict early detection of recurrence in routine clinical work by estimation of tumor marker levels. Although changes in the levels of paraprotein in multiple myeloma have been utilized for monitoring the responsiveness to chemotherapy, since the amounts of paraprotein are directly proportional to the number of myeloma cells, in other hematologic malignancies there are no tumor markers for monitoring the clinical course, for detecting the presence of minimal residual disease, or for predicting disease recurrence. In the future it is expected that developments in biotechnology create a large number of reagents including 'oncogene'-related markers or 'oncogene' products for application to the diagnosis and treatment of cancer patients.
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PMID:[Significance of tumor markers in the treatment of cancer: hematologic malignancy]. 367 91

Fifteen patients with stage II-III multiple myeloma were intended to undergo two sequential cycles of myeloablative chemoradiotherapy with autologous bone marrow or blood stem cell transplantation after response to primary induction chemotherapy. BM grafts were used in 13 of the 15 first transplants whereas PBSC were used for the two remaining first transplants and all second transplants. The preparative regimen was melphalan 200 mg/m2 for the first transplant and melphalan 140 mg/m2 plus total body irradiation (TBI) 10 Gy for the second. Before the first transplant, 12 patients were in PR and three in CR whereas seven were in CR and seven in PR after the first transplantation. Four patients received only one cycle of myeloablative therapy because of incomplete hematopoietic reconstitution after transplantation (three patients) and early death (one patient). Eleven patients proceeded to the second transplant, and six patients were then in CR and five in PR. After the second transplant a further two patients entered CR whereas three remained in PR. Of all 15 patients, 11 remain in continuous complete (eight patients) or partial (3 patients) remission at a mean time of 20 months after the first transplant. Five patients in CR were examined by PCR analysis of the clone-specific immunoglobulin gene rearrangement for detection of minimal residual disease and four of these are PCR-negative up to 33 months after the first transplant. One transplant-related death occurred, and one patient died from progressive disease. This superintensive treatment regimen for younger patients with multiple myeloma has acceptable toxicity, and can induce and sustain long-term complete remissions.
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PMID:Double high-dose chemoradiotherapy with autologous stem cell transplantation can induce molecular remissions in multiple myeloma. 759 60

In order to estimate the clonality of B-cell lymphoproliferative disorders, polymerase chain reaction (PCR) was used to detect the Ig heavy chain gene rearrangement in DNA extracted from formalin-fixed and paraffin-embedded bone marrow biopsies. 16 out of 19 cases (84%) of B-CLL (n = 9), multiple myeloma (n = 7) and B-non-Hodgkin's lymphoma (n = 3) showed sharp monoclonal bands, while polyclonal smears or no PCR-products were observed in non-neoplastic bone marrow or AML specimens. The results showed that the DNA from paraffin-embedded bone marrow biopsies could be used to detect monoclonal IgH rearrangement by PCR method. This forms the basis for the studies of minimal residual disease or B-ML bone marrow infiltrated diseases.
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PMID:[Detection of B-cell clonality in paraffin-embedded bone marrow biopsy specimens by polymerase chain reaction]. 774 82

10 patients were subjected to tandem transplantation for breast cancer (n = 3), ovarian cancer (n = 2) and multiple myeloma (n = 5), at the Second Department of Medicine, Donauspital, Vienna. The breast cancer patients were in stages 2 and 3, respectively, at diagnosis and entered complete remission thereafter. 2 of them developed lymph node metastasis and additional local recurrence, the 3rd patient presented with distant metastasis. The 2 patients with ovarian cancer were in stages Figo III and IV, respectively, at the time of diagnosis, and showed minimal residual disease at second-look-operation. 5 patients with multiple myeloma were in stage 3 pretransplant. Peripheral stem cells were obtained after either high-dose cyclophosphamide or FEC induction and application of cytokines. In 4 patients, tandem transplantation has been completed. 1 patient with multiple myeloma, who had received total body irradiation in combination with chemotherapy for the 2nd transplant, succumbed from idiopathic interstitial pneumonia. No severe clinical complications were observed in all other patients. All patients with solid tumors entered complete remission after the 1st transplantation. 3 of them completed tandem transplantation. Of these, 2 remain in continuous complete remission, the 3rd patient relapsed in lymph nodes day 485. In patients who received only 1 course of high dose chemotherapy with stem cell transplantation, relapses occurred on days 29 and 75, respectively. All patients with multiple myeloma entered only partial remission. We conclude that supralethal chemotherapy with peripheral blood stem cell support is a safe procedure that may at least induce prolonged remissions in solid tumors and hematologic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Tandem transplantation with peripheral autologous hematopoietic blood stem cells in treatment of oncologic and hematologic malignancies. Initial results of the Donauspital, Vienna]. 776 51

Primary plasma cell leukaemia (PPCL) is a rare form of plasma cell neoplasm. Treatments of PPCL have been most disappointing. A patient with PPCL received high-dose melphalan plus total body irradiation and autologous bone marrow transplantation (ABMT). By using third-complementarity-determining region (CDRIII)-specific probes, minimal residual disease (MRD) was detected in remission marrow, collected 1 month before ABMT. MRD was no longer detected by CDRIII-specific probes 6, 19 and 26 months after transplantation. The patient remained in complete remission up to 59 months after ABMT.
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PMID:Long-term disease-free survival after autologous bone marrow transplantation in a primary plasma cell leukaemia: detection of minimal residual disease in the transplant marrow by third-complementarity-determining region-specific probes. 777 34

Gene rearrangement involves a complex process of DNA splicing and deletion that produces a unique genetic code in each B or T lymphocyte. These novel DNA sequences encode immunoglobulin or T-cell receptor proteins that function in recognition of foreign antigens. Recent advances in DNA technology permit laboratory detection of clonal gene rearrangements in lymphoid malignancies including lymphocytic leukemia, lymphoma, and myeloma. Practical applications of gene rearrangement testing include distinguishing reactive from malignant lymphoid proliferations, and assignment of B- or T-cell lineage to a neoplastic process. Active investigation is underway to devise practical strategies for detecting minimal residual disease based on tumor-specific gene rearrangements.
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PMID:Immunoglobulin and T-cell receptor gene rearrangement. 796 Dec 89

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.
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PMID:High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients. 810 34

Allogeneic bone marrow transplantation (BMT) can induce long-term complete remission (CR) in patients with multiple myeloma but it is not yet clear whether the disease can be eradicated. We have used immunoglobulin gene fingerprinting, a PCR-based technique, to evaluate minimal residual disease in 5 patients in unmaintained CR 9-60 months after allogeneic BMT. All 5 patients were PCR-positive within the first year after BMT, suggesting that early PCR positivity is common and not predictive of relapse. Three patients were studied at > 1 year post-transplant; one had become PCR-negative at 1 year, a second at 2 years and the third at 4.5 years post-BMT. The ability of the technique to detect clonal evolution was demonstrated by serial studies in a further patient who relapsed post-BMT. The absence of any detectable disease at the molecular level in 3 patients in long-term CR post-transplant suggests that cure of multiple myeloma may be a realistic goal.
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PMID:Minimal residual disease after bone marrow transplantation for multiple myeloma: evidence for cure in long-term survivors. 813 48

One advantage of the use of peripheral blood stem cells (PBSCs) over autologous bone marrow would be a reduced risk of tumor cell contamination. However, the level of neoplastic cells in the PB of multiple myeloma (MM) patients after mobilization protocols is poorly investigated. In this study, we evaluated PB samples from 27 pretreated MM patients after the administration of high dose cyclophosphamide (7 g/m2 or 4 g/m2) and granulocyte-colony stimulating factor for the detection of myeloma cells as well as hematopoietic progenitors. Plasma cells containing intracytoplasmic lg were counted by microscope immunofluorescence after incubation with appropriate antisera directed against light- and heavy-chain lg. Moreover, flow cytometry studies were performed to determine the presence of malignant B-lineage elements by using monoclonal antibodies against the CD19 antigen and the monotypic light chain. Before initiation of PBSC mobilization, circulating plasma cells were detected in all MM patients in a percentage ranging from 0.1% to 1.8% of the mononuclear cell fraction (mean value, 0.7% +/- 0.4% SD). In these patients, a higher absolute number of PB neoplastic cells was detected after chemotherapy and granulocyte colony-stimulating factor. Kinetic analysis showed a pattern of tumor cell mobilization similar to that of normal hematopoietic progenitors with a maximum peak falling within the optimal time period for the collection of PBSCs. The absolute number of plasma cells showed a 10 to 50-fold increase as compared with the baseline value. Apheresis products contained 0.7% +/- 0.2% SD of myeloma cells (range, 0.2% to 2.7%). Twenty-three MM patients were submitted to PBSC collection. In 10 patients, circulating hematopoietic CD34+ cells were highly enriched by avidin-biotin immunoabsorption, were cryopreserved, and used to reconstitute bone marrow function after myeloablative therapy. The median purity of the enriched CD34+ cell population was 89.5% (range, 51% to 94%), with a 75-fold increase as compared with the pretreatment samples. The median overall recovery of CD34+ cells and colony-forming unit-granulocyte-macrophage was 58% (range, 33% to 95%) and 45% (range, 7% to 100%), respectively. Positive selection of CD34+ cells resulted in 2.5- to 3-log depletion of plasma cells and CD19+ B-lineage cells as determined by immunofluorescence studies, although DNA analysis of CDR III region of IgH gene showed the persistence of minimal residual disease in 5 of 6 patient samples studied. Myeloma patients were reinfused with enriched CD34+ cells after myeloablative therapy consisting of total body irradiation (1,000 cGy) and highdose melphalan (140 mg/m2). They received a median of 4 x 10(6) CD34+ cells/kg and showed a rapid reconstitution of hematopoiesis; the median time to 0.5 x 10(9) neutrophils and to 20 and 50 x 10(9) platelets per liter of PB was 10, 11, and 12 days, respectively. These results, as well as other clinically significant parameters, did not significantly differ from those of patients (n = 13) receiving unmanipulated PBSCs after the same pretransplant conditioning regimen. In summary, our data show the concomitant mobilization of tumor cells and hematopoietic progenitors in the PB of MM patients. Positive selection of CD34+ cells reduces the contamination of myeloma cells from the apheresis products up to 3-log and provides a cell suspension capable of restoring a normal hematopoiesis after a total body irradiation-containing conditioning regimen.
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PMID:Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of multiple myeloma patients: positive selection and transplantation of enriched CD34+ cells to remove circulating tumor cells. 860 57


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