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)

We have previously described a sensitive and specific CD34 enumeration assay and report here a prospective analysis of 25 myeloma patients undergoing PBSC mobilization using this assay to determine the optimal days for collection of CD34+ and CD34+Thy-1+ cells after chemotherapy and growth factor mobilization. Correlations between frequency of peripheral blood CD34+ cells, circulating white blood cell (WBC) count, apheresis CD34+ cell count, nucleated cell count (NCC), and numbers of apheresis colony-forming units granulocyte/macrophage (CFU-GM) were determined. To assess levels of the more primitive subsets of CD34+ cells in the PBSC collections, coexpression of the Thy-1 antigen (CDw90) on CD34+ cells was also assessed. Marked heterogeneity was noted between patients with apheresis samples containing a median NCC of 4.2 x 10(8)/kg (range 1.3-8.1), median CFU-GM 17 x 10(4)/kg (range 0.15-32 x 10(4)/kg), and median CD34+ cell count of 1.39 x 10(6)/kg (range 0.02-6.6). The frequency of CD34+ cells in PBSC collections coexpressing Thy-1 was also heterogenous (6.2-50% of CD34+ cells), median 21.6%, mean 24.7 +/- 2%. The apheresis CD34+ cell count correlated with the peripheral blood CD34+ cell percentage (r = 0.71, p < 0.0001) but only weakly with the peripheral WBC. Apheresis CD34+Thy-1+ cell numbers correlated strongly with the circulating CD34+ cell numbers (r = 0.80), but no correlation was noted between these candidate stem cells and the peripheral WBC. In contrast, apheresis CFU-GM levels correlated most strongly with the peripheral WBC count (r = 0.61, p < 0.0001). The apheresis CD34+ cell count correlated with apheresis CFU-GM (r = 0.75, p < 0.0001) but not with the apheresis NCC. Apheresis CD34+Thy-1+ counts significantly correlated only with the apheresis CD34+ cell count and not with the apheresis CFU-GM or NCC. A higher percentage of circulating and apheresis CD34+ cells expressing Thy-1 were found on day 1 of collection, and the percentage of CD34+ cells expressing Thy-1 decreased on each subsequent day of measurement: median of 22% day 1 vs. 16.6% day 4, p = 0.04. This study therefore confirms that accurate quantitation of circulating CD34+ cells best predicts the optimal day for apheresis collection of CD34+ and CD34+Thy-1+ cells and is superior to the WBC count in this regard. Furthermore, the candidate stem cell (CD34+Thy-1+) subset is most prevalent during the earliest phases of CD34+ cell mobilization.
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PMID:Optimizing the CD34+ and CD34+Thy-1+ stem cell content of peripheral blood collections. 854 56

Haemopoietic recovery is more rapid after peripheral blood stem cell (PBSC) transplantation than after autologous bone marrow transplantation, and the aim of this study was to assess the role of the large number of lymphocytes and monocytes (accessory cells) in a PBSC leukapheresis product in this rapid regeneration. Haematological recovery was therefore assessed in 10 PBSC recipients with lymphoma or myeloma in whom monocytes and T cells were depleted by a median of 2.3 and 3.3 logs by CD34+ cell selection using the CEPRATE SC stem cell concentration system and compared with recovery in 59 recipients who received whole PBSC. After allowing for the number of progenitor cells reinfused, there was no significant delay in engraftment induced by accessory cell depletion. Plasma levels of granulocyte-colony stimulating factor (G-CSF), granulocyte/monocyte-colony stimulating factor (GM-CSF), interleukin-6 (IL-6), stem cell factor (SCF) and macrophage-inhibition factor-alpha (MIP-1-alpha) during the transplant procedure were similar whether or not accessory cells were given. The G-CSF and IL-6 levels rose between days 5 and 14 post transplantation to approximately 1 ng/ml and 50 pg/ml respectively. This study indicates that accessory cells reinfused with PBSC collections are not responsible for the subsequent cytokine profile or rapid haematological recovery.
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PMID:Accessory cells do not contribute to G-CSF or IL-6 production nor to rapid haematological recovery following peripheral blood stem cell transplantation. 855 91

Twenty-one previously untreated multiple myeloma (MM) patients and 10 previously treated patients with refractory or relapsed disease received two or three cycles of intermediate-dose melphalan (70 mg/m2) (IDM), administered intravenously every 6 weeks. Seven previously untreated patients received three and all other patients received two courses of IDM. The objective of the study was to reduce the toxicity of high-dose melphalan (140 mg/m2) (HDM) while maintaining its cytotoxic efficacy and secondly to ensure the possibility of collecting sufficient numbers of peripheral blood stem cells (PBSC) for transplantation. 18 (85%) previously untreated patients responded, of whom four achieved CR (18%). In addition five out of 10 previously treated patients with refractory or relapsed disease responded although bone marrow toxicity in this category was a major drawback. Toxicity was moderate, consisting of alopecia and moderate bone marrow suppression: the granulocyte count dropped below 0.5 x 10(9)/l and platelets below 25 x 10(9)/l for a median of 8 and 6 d, respectively. No serious infections occurred and the majority of patients attended the out-patient clinic. In 12/14 previously untreated patients sufficient peripheral blood CD34+ cells for harvest were present in the repopulation phase after the first IDM. In nine patients peripheral blood stem cells were collected and eight patients have undergone successful transplantation. Repeated IDM followed by filgrastim is highly effective in untreated MM and may be safely administered to reduce tumour load prior to PBSC collection. Autologous stem cells harvested after repeated IDM have a full long-term repopulating capacity.
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PMID:Intermediate-dose melphalan (IDM) combined with G-CSF (filgrastim) is an effective and safe induction therapy for autologous stem cell transplantation in multiple myeloma. 856 9

We have evaluated CD34+ cell positive selection from granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in 26 patients with either multiple myeloma (MM, n = 18) or follicular non-Hodgkin's lymphoma (NHL, n = 8). 26 PBPC were collected with two leukaphereses: 16 contained sufficient numbers of CD34+ cells and were elected. The absolute number of CD34+ cells in the leukapheresis products was found to be significantly related to the duration of underlying disease and exposure to prior treatment. CD34+ cell positive selection allowed recovery of a median of 35% of CD34+ cells, the selected fraction containing a median number of 1.43 x 10(6)/kg CD34+ cells/kg (range 0.48-41.5). 10 patients were transplanted and received a median dose of 1.51 x 10(6) CD34+ cells (range 0.48-4.2). The median time to granulocyte ( > 0.5 x 10(9)/l) and platelet ( > 20 x 10(9)/l) engraftment was 12 and 13 d respectively (ranges 10-13 and 0-95). Lymphoma cells were found by a sensitive polymerase chain reaction technique in four out of five CD34+ cell fractions tested.
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PMID:G-CSF alone mobilizes sufficient peripheral blood CD34+ cells for positive selection in newly diagnosed patients with myeloma. 860 84

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

More effective and safer regimens are needed for patients who have advanced multiple myeloma resistant to or relapsing despite prior treatment with alkylating agents and VAD. We treated 58 such patients using the combination of twice daily cyclophosphamide (total dose 1.8 g/m2) and VAD (hyperCVAD). Treatment was given to outpatients followed by G-CSF at 5 microgram/kg/d until granulocyte recovery. Twenty-three patients responded (40%), with a median duration of granulocyte depression to less than 500/microliter of 4 days and a mortality rate of 2%. The median survival time for all patients was 15 months, and the median remission time of responding patients was 8 months. Patients who had low LDH, low B2M, or primary resistant disease lived significantly longer than patients without these features. The combination of fractionated cyclophosphamide and VAD provided an effective and safe rescue treatment for many patients who had advanced myeloma resistant to standard therapies.
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PMID:HyperCVAD for VAD-resistant multiple myeloma. 863 45

The Norwegian Society of Haematology has worked out guidelines for the use of granulocyte-colony stimulating factor and granulocyte-monocyte colony stimulating factor and interferon alpha in clinical haematological practice. We recommend not using growth factors as a routine to prevent or to treat fever in patients with granulocytopenia induced by cytostatics, or patients with myelodysplastic syndromes. At present such treatment should be restricted to clinical trials. The same conclusion was reached in regard to use of erythropoietin in the case of myelodysplastic syndromes. Harvesting of stem cells from peripheral blood is a well documented indication for administration of growth factors. Interferon alpha as maintenance treatment for cases of multiple myeloma and low grade malignant lymphoma delays progression of the disease but does not improve chance of survival. There is no documentation of improved quality of life. Use of interferon alpha is not justified as a routine treatment for multiple myeloma. In chronic myelogenous leukemia, interferon alpha seems to be equal to or better than hydroxyurea, and may be considered for patients who cannot undergo allogeneic bone marrow transplantation.
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PMID:[Treatment with growth factors and cytokines in hematologic diseases]. 880 16

Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.
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PMID:Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia. 870 95

Peripheral blood is increasingly used instead of bone marrow as a source of hemopoietic precursor cells for transplantation. The optimal technique still needs to be defined. Selection of CD34+ cells in transplant material may be of benefit in allogeneic and autologous peripheral blood precursor cell transplantation (PBPCT), since it allows elimination of unwanted CD34-negative cells, such as T-cells and contaminating tumor cells. We have evaluated the feasibility of CD34 selection in PB transplants and studied hemopoietic reconstitution after autologous transplantation of CD34 selected precursor cells. Between August 1994 and June 1995 CD34 selection was performed on 12 transplants for 9 patients with malignant disease (non-Hodgkin lymphoma [n = 5]; Ewing sarcoma [n = 1]; chronic lymphocytic leukemia [n = 1]; breast cancer [n = 1]; multiple myeloma [n = 1]). PBPC were collected with a Fenwall CS 3000 harvester after stimulation with G-CSF. For selection of CD34+ cells the Ceprate LC34 system (CellPro) was used. A median CD34 purity of 73% (range 40-94%) was achieved. The median number of CD34 positive cells per transplant was 4.8 x 10(6)/kg body weight (range 0.7-15.8). The median number of colony forming cells per transplant was 31 x 10(4)/kg body weight (range 1.5-131.3). For autologous PBPCT the minimal number of CD34 positive cells required in the transplantate was arbitrarily set at 1.0 x 10(6)/kg body weight. This number was achieved in 10 of the 12 transplants. The median loss of CD34+ cells during selection was 1.5 x 10(6)/kg body weight (range 0.2-6.4). In 2 patients the total number was reduced to below the critical value of 1.0 x 10(6)/kg. 7 of the 9 patients received the CD34 selected transplant after intensive chemotherapy and irradiation. The median follow-up time after PBPCT was 196 days (range 62-278). All 7 patients are now alive and with normal hemopoietic function. A granulocyte count above 0.5 x 10(9)/l and a platelet count above 20 x 10(9)/l was achieved on day 14 (median), and on day 19 after PBPCT. We conclude that CD34 selection is technically feasible and that CD34 selected cells can be used for PBPCT. The procedure is time consuming and expensive; it requires complex organization at laboratory level, and the benefit of CD34 selection with regard to T-cell depletion and tumor purging still needs to be proven. However, CD34+ selection is likely to open new perspectives in transplantation medicine.
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PMID:[Autologous transplantation of hematopoietic precursor cells following CD34 selection]. 872 Jul 23

Three major molecules have been recognized as IgE-binding structures on hematopoietic cells: the heterotrimeric high-affinity receptor for IgE (Fc epsilon RI), the low-affinity receptor for IgE (Fc epsilon RII/CD23) and the Mac-2/IgE-binding protein (epsilon BP). The latter has been shown to be expressed on polymorphonuclear neutrophils (PMN), where it regulates IgE-dependent activation. Experiments were undertaken to determine whether the IgE-binding capacity of PMN is mediated exclusively by this molecule. No detectable binding of human myeloma IgE to unstimulated PMN from normal volunteers could be evidenced. In contrast, PMN stimulated with granulocyte macrophage colony stimulating factor (GM-CSF) (500 U/ml) for 24 h displayed positive IgE binding. This binding was significantly inhibited in the presence of mAb directed against Mac-2/epsilon BP and also in the presence of anti-CD23 mAb, but not of anti-Fc epsilon RI mAb or isotype-matched controls. By flow cytometry, CD23 expression was detected on GM-CSF-primed PMN by several anti-CD23 mAb, including EBVCS-5, BB10 or Mab135, which recognize different epitopes. CD23 was also evidenced by immunocytochemistry in GM-CSF-primed PMN. By in situ hybridization, GM-CSF-treated PMN exhibited a hybridization signal for CD23 mRNA and the presence of the CD23b isoform-specific mRNA was detected by RT-PCR. These findings indicate that PMN can synthesize CD23 molecules under GM-CSF induction. This strong CD23 expression might be of physiopathological relevance in IgE-dependent activation during allergic processes.
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PMID:Granulocyte macrophage colony stimulating factor induces Fc epsilon RII/CD23 expression on normal human polymorphonuclear neutrophils. 872 38


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