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

Treatment intensification with autologous bone marrow transplantation (ABMT) was administered to 37 cases of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL) who were in complete or partial remission (CR or PR) after chemotherapy (MOPP/ABVD or F-MACHOP respectively) and to 12 cases of HL and NHL who were in relapse. ABMT treatment was BAVC for NHL and BEAM for HL. Marrow cells were harvested from the marrow and cryopreserved. The number of mononuclear marrow cells that was reinfused ranged between 0.19 and 0.80 x 108/Kg b.w. (median 0.39). All the patients were treated with granulocyte colony stimulating factor (G-CSF, Filgrastim) at a dose of 5 mg/Kg b.w. from day +4 until the absolute neutrophil count exceeded 1 x109/L for 3 consecutive days. Engraftment was observed in all cases, and no transplant-related deaths occurred. The patients with NHL and HL received a median of 12 (range 2-19) and 14.5 (range 9-27) doses of G-CSF respectively. Median time to 20 x 109/L platelet count was 14 to 17 days. Median time to an absolute neutrophil count 0.5x109/L was 13 days. A febrile episode during the period of post-transplant aplasia was documented in 35 patients (71%). Fever was associated with Gram+ bacteraemia in 31% of the cases and with Gram- bacteraemia in 11% of cases. Herpes Simplex infection was documented in two cases. No fungal infections were recorded. Median hospitalisation time from reinfusion ranged between 19.5 days (NHL) and 23 days (HL). Thirty-four of 37 cases (92%) who were transplanted in CR or in PR are currently alive and in continuous CR with a median follow-up time of 37 months after ABMT. Three of 12 cases (25%) who were transplanted in relapse are alive and in CR. Our data point out that ABMT followed by G-CSF is a safe and a very effective procedure for high risk malignant lymphomas, when ABMT is planned and is performed not as a rescue procedure but when it is integrated in the treatment strategy from the very beginning.
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PMID:Treatment intensification of malignant lymphomas with autologous bone marrow transplantation and granulocyte colony stimulating factor. 1035 84

A subgroup of patients with refractory Hodgkin's (HD) or non-Hodgkin's (NHL) lymphoma may be cured with high-dose chemotherapy and peripheral blood progenitor cell rescue. To investigate the relationship of adequate leukapheresis yield and time course of platelet recovery after mobilization chemotherapy, we retrospectively analyzed the leukapheresis yields in seven patients with Hodgkin's disease and fifteen patients with non-Hodgkin's lymphoma undergoing high-dose chemotherapy. Our goal was to develop a rule to determine when to initiate leukapheresis and then to prospectively validate this rule. All patients were mobilized with cyclophosphamide and G-CSF (granulocyte-colony stimulating factor). A total of 144 leukaphereses were completed and analyzed. Based on the CD34 content in the initial harvest product, fifteen patients were defined as poor mobilizers (CD34 < 0.15 x 10(6)/kg) and seven were good mobilizers. The platelet count on the first day of harvesting was significantly associated with the poor mobilizers (P = .03). Age, sex, marrow involvement, disease (HD vs. NHL), prior radiation, time since last chemotherapy, and total number of cycles of prior chemotherapy were not predictive of poor mobilizers. By using a platelet count cut off of 35 x 10(9)/L, we retrospectively analyzed 144 individual leukapheresis products, to test whether CD34 yield was predicted by the peripheral blood platelet count on the day of leukapheresis. This rule had an excellent sensitivity, 91%, and a specificity of 67%. Subsequently, we validated this rule with the next twenty-four patients undergoing leukapheresis of which there were 143 leukaphereses. The prediction rule exhibited a sensitivity of 72% and a specificity of 68% in the validation set. There does appear to be utility in using the platelet count to guide the initiation of leukapheresis after chemotherapy and G-CSF mobilization.
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PMID:Timing of platelet recovery is associated with adequacy of leukapheresis product yield after cyclophosphamide and G-CSF in patients with lymphoma. 1035 61

High-dose chemotherapy (HDCT) followed by autologous blood stem cell transplantation is considered the treatment of choice for patients with relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). However, several authors report failure of standard mobilization regimens in 29% to 56% of these patients making the completion of HDCT impossible and as a result, negatively influencing long-term outcome. Thus, effective new regimens for patients failing initial mobilization are needed. Here we report the results of using etoposide as a mobilizing agent in 16 patients with primary resistant or relapsed malignant lymphoma who had failed prior mobilization of peripheral blood stem cells (PBSC) with cyclophosphamide (4 g/m2) followed by G-CSF. The use of etoposide 500 mg/m2 (days 1-4) + G-CSF resulted in the successful collection of adequate numbers of PBSC with a median harvest of 3.6 x 10(6)/kg (range 2.2-12.6) CD34+ cells in all 16 patients. In 7/16 (44%) patients, the target yield of at least 2.0 x 10(6) CD34+ cells was harvested by a single apheresis and the maximum number of separations for all patients was two. No excessive toxicities appeared, allowing all patients to proceed to myeloablative chemotherapy. In addition, median peak values of circulating CD34+ cells were significantly higher after etoposide as compared to cyclophosphamide (49.2/microl vs 4.7/microl; P = 0.0004). These results indicate that etoposide + G-CSF is a highly effective mobilization regimen in patients who have failed cyclophosphamide mobilization.
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PMID:Successful peripheral blood stem cell mobilization with etoposide (VP-16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization. 1041 7

In order to assess the potential clinical benefit of filgrastim (G-CSF) after peripheral blood stem cell (PBSC) autotransplantation a randomized study was begun in our center in July 1997: 62 patients were involved (30 received filgrastim after PBSC infusion and 32, the control group, received no cytokines). All were adults (median 40 years, range 18-65). Patients with one of three different pathologies were recruited: 28 had advanced breast carcinoma, 23 had lymphomas (12 Hodgkin's disease and 11 non-Hodgkin's lymphoma) and 11 had de novo AML. All of them were transplanted using myeloablative chemotherapy conditioning regimens. G-CSF was administered subcutaneously from day +5 in the treated group at a dose of 5 microg/kg body weight/day. The numbers of CD34+ and mononuclear (MNC) cells infused were similar in each group. Only minor differences regarding the use of G-CSF could be inferred from the analysis of the data. Faster granulocyte engraftment was evident in the treated group (mean of 10 vs 12 days to achieve >0.5 x 109/l granulocytes, P = 0.0008), without differences in incidence and severity of infections, days of fever or duration of antibiotic treatment between groups. There was slightly slower platelet engraftment (mean of 15 days in the group with G-CSF vs 12 days in the other group to achieve >20 x 109/l platelets, P = NS) in this series, but there were no differences in incidence and severity of haemorrhage or platelet transfusion support. Considering the economical costs, the median expenditure per inpatient stay was Eur5961 (range Eur4386-Eur17186) in the G-CSF group compared with Eur5751 (range Eur3676-Eur15640) in the control group (P = 0.47). From our data it could be concluded that for adult patients transplanted with PBSC there is no clear beneficial impact of post-infusion G-CSF administration.
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PMID:A prospective randomized trial of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in adults. 1049 Jul 24

The transplantation of mobilised peripheral blood stem cells is associated with more rapid engraftment than marrow transplantation. We have previously reported that G-IVE (G-CSF, ifosphamide, VP-16, epirubicin) improves the yield of CD34+ cells mobilised in patients with lymphoproliferative disorders compared with cyclophosphamide 3 g/m2 and G-CSF (G/CYCLO). In this study we have extended these observations to a larger series of patients including different lymphoma subtypes. Ninety-seven patients undergoing stem cell mobilisation were studied. Forty-two patients with lymphoproliferative disorders received G-IVE for mobilisation and 55 patients G/CYCLO. The median number of mobilised CD34+cells per leucapheresis was significantly higher for those patients receiving G-IVE: 5.82 x 106/kg (0.19-36) compared with 1.2 x 106/kg (0.04-17), P < 0.001 which resulted in a significantly reduced number of leucapheresis procedures performed in the G-IVE group. When patients were analysed dependent on underlying disease G-IVE mobilised significantly more CD34+cells per leucapheresis for all lymphoma types reaching 8.41 x 10(6)/kg (0.2-32) compared to 1.32 x 10(6)/kg (0. 06-17) for patients with high-grade NHL mobilised with G-IVE and C-GCSF respectively (P = 0.012). For patients with low-grade NHL 3. 12 x 10(6)/kg (0.10-24.39) compared to 1.08 x 10(6)/kg (0.04-9.74) were collected (P = 0.04) and for patients with Hodgkin's disease 3.02 x 10(6)/kg (1.48-36) and 1.04 x 10(6)/kg (0.1-12.3) (P = 0.001). Mobilisation with G-IVE resulted in the achievement of clinically significant CD34+ cell thresholds in a significantly higher proportion of patients compared to cyclophosphamide and G-CSF reaching >2.5 x 10(6)/kg CD34+ cells in 88% vs 62% (P = 0.004), >5 x 10(6)/kg in 67% vs18% (P = 0.001) and >10 x 10(6)/kg in 31% vs 14.5% (P = 0.05). Furthermore, an analysis of engraftment demonstrated that there was a significant reduction in the time to achieve platelet counts of >20 and >50 x 10(9)/l in patients receiving each incremental dose of CD34+ cells. We conclude that G-IVE mobilizes significantly more CD34+cells than G/CYCLO in patients with lymphoproliferative disorders. This effect is consistent in patients with high-grade NHL, low-grade NHL and HD and results in fewer failed stem collections and increased CD34+ cells available for transplantation which results in significantly accelerated platelet engraftment post transplant.
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PMID:Mobilisation of peripheral blood stem cells with IVE and G-CSF improves CD34+ cell yields and engraftment in patients with non-Hodgkin's lymphomas and Hodgkin's disease. 1051 73

Three different methods for determination of CD34+ cells in G-CSF-mobilized peripheral blood were compared. The methods were: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cells enumeration and our own protocol. The procedure we have adopted is essentially a Milan/Mulhouse protocol-derived methodology combined with a multiparametric approach using the PAINT-A-GATE software analysis program. The samples were collected from 70 patients affected by acute leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myeloma and breast cancer who were scheduled to receive autologous PBSC transplantation. PBSC collection was performed following mobilization with subcutaneous G-CSF at 5-10 microg/kg/day. A minimum target of 2 x 10(6)/kg CD34+ cells was considered an acceptable harvest to ensure a safe transplant. On average, three aphereses per patient were performed and a total of 204 apheresis samples were analyzed. Regression analysis of the percentage and absolute number of CD34+ cells, as calculated with each method, achieved an excellent correlation in spite of methodological differences. In fact, both CD34+dim and CD34+CD45- events were included in our gating strategy. In the setting of a triple staining associating CD34, CD38 and CD45, we identified a variable fraction of CD34+CD38+CD45- cells which would be otherwise undetected due to its CD45 negativity. To this end, we used a new technology referred to as laser-scanning cytometry (LSC) which allowed the isolation and morphological identification of CD34+CD45- cells. By comparing CD34+CD45+ and CD34+CD45- cells, we found that they share a common morphology, thus confirming the hypothesis that the latter are to be considered for CD34+ cell calculation. The median number of CD34+ cells/kg, as calculated by the three methods, was: 4.79 x 10(6)/kg (range 1-570) for the Milan/Mulhouse protocol, 3.9 x 10(6)/kg (range 0.8-498) for the ISHAGE one, and 5.17 x 10(6)/kg (range 2-599) for our protocol. The median time to ANC and PLT engraftment was 11 (range 9-24) and 20 (range 10-70) days, respectively. Our protocol achieved the best correlation between CD34+ cells/kg and time to ANC/PLT recovery according to the Spearman's rank test (r = -40 and P < 0. 015 for ANC, r= -46 and P = 0.005 for PLT). We conclude that (1) CD45 does not appear the ideal partner of HPCA-2 for determination of hematopoietic progenitors in mobilized peripheral blood; and (2) for clinical application, a single staining with 8G12 appears simple, reliable and feasible when rigorous procedures for sample preparation and acquisition are followed and an adequate software for multiparametric analysis is available.
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PMID:Enumeration of CD34+ hematopoietic progenitor cells for clinical transplantation: comparison of three different methods. 1055 63

The yield of CD34+ PBPC and colony-forming units-granulocyte-macrophage (CFU-GM) in leukapheresis products and the expression of the adhesion molecules CD11a, CD31, CD49d, CD49e, CD54, CD58, CD62L, c-kit (CD117), Thy-1 (CD90), CD33, CD38, and HLA-DR on CD34+ PBPC were analyzed in patients with cancer of the testis (n = 10), breast cancer (n = 10), Hodgkin's disease (n = 20), high-grade (n = 20) and low-grade (n = 20) non-Hodgkin's lymphoma, and healthy donors (n = 20) undergoing G-CSF (filgrastim)-stimulated PBPC mobilization. For each disease entity, G-CSF was administered in two different doses, 10 microg G-CSF/kg body weight (BW)/day s.c. vs. 24 microg G-CSF/kg BW s.c./day in steady-state condition. Data were compared for each dose group separately. Patients with cancer of the testis and breast cancer mobilized significantly more CD34+ cells than patients with high-grade and low-grade non-Hodgkin's lymphoma and Hodgkin's disease (p<0.05). Correspondingly, expression of CD49d on CD34+ PBPC was significantly lower in the same patients with cancer of the testis compared with high-grade and low-grade non-Hodgkin's lymphoma and Hodgkins' disease and in patients with breast cancer compared with high-grade and low-grade non-Hodgkin's lymphoma, Hodgkins's disease, and healthy donors. Similar results were obtained for CD49e. These data suggest that the expression of the adhesion molecules CD49d and CD49e on G-CSF-mobilized CD34+ cells of patients with solid tumors, non-Hodgkin's lymphoma, Hodgkin's disease, and healthy donors is inversely correlated with the amount of mobilized CD34+ cells.
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PMID:Expression of the adhesion molecules CD49d and CD49e on G-CSF-mobilized CD34+ cells of patients with solid tumors or non-Hodgkin's and Hodgkin's lymphoma and of healthy donors is inversely correlated with the amount of mobilized CD34+ cells. 1079 4

Between August 1991 and December 1998, 400 patients (lymphomas: 197; acute leukemia: 86; multiple myeloma: 70 and solid tumors: 47) were admitted for autologous transplantation. All patients were mobilized with chemotherapy plus G-CSF. The hematological recovery was similar in all disease groups. Patients with acute leukemias and multiple myeloma had a slower platelet recovery. Treatment-related death was 4.5%. The status of the disease at diagnosis was the most significant prognostic factor. With a median follow-up of 23 months the probability of event-free survival at 60 months was 46% for low grade lymphoma, 44% for intermediate and high grade lymphoma, 58% for Hodgkin's disease, 45% for acute myeloblastic leukemia, 38% for solid tumors and 15% for multiple myeloma. The probability of survival at 60 months was 67% for low grade lymphoma, 47% for intermediate and high grade lymphoma, 75% for Hodgkin's disease, 52% for acute myeloblastic leukemia, 54% for solid tumors and 25% for multiple myeloma. It can be concluded that autologous progenitor cell transplantation induces a complete and faster hematological recovery in all groups of patients without any late graft failure. Results are similar to those published in the literature. The treatment-related death was low and acceptable.
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PMID:[Eight years of experience in a single institution in hematopoietic stem cell autologous transplantation in malignant hematological diseases and in solid tumors]. 1083 8

Women over 65 years are underrepresented in Cancer and Leukemia Group B (CALGB) breast cancer trials of adjuvant chemotherapy. There is greater participation in older patients with metastatic breast cancer except when toxic regimens are involved. Studies of stage III and IV Hodgkin's disease have shown that patients over 60 years achieved lower response rates, more leucopenia and thrombocytopenia, the shortest median time to recurrence, and the shortest median survival time. In acute myeloid leukemia a series of trials confirmed the disparity between young patients and those over 60 years whose complete response rate seldom exceeds 50%. In an effort to reduce toxicity rather than enhance the cure rate, CALGB showed that administration of GM-CSF after intensive induction chemotherapy was of no benefit in patients over 60 years. The use of G-CSF in acute lymphoblastic leukemia reduced hematologic toxicity and improved clinical outcome.
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PMID:Age-Related Clinical Trials of CALGB. 1088 3

Mantle cell lymphoma (MCL) is a distinctive clinicopathologic entity and represents 2-8% of all non-Hodgkin's lymphomas. The median survival of patients with MCL is only 3 years, and none of the available conventional chemotherapy regimens appears curative. Encouraging results have been reported with high-dose chemotherapy with autologous stem-cell transplantation (autoSCT). However, a plateau in disease-free survival was not observed in relapsed MCL on the autoSCT trials. Promisingly, alloSCT appears to induce durable remissions via a graft-versus-lymphoma (GVL) effect. Donor lymphocyte infusions (DLIs), by virtue of a GVL effect, have been shown to induce durable remissions in a few cases with refractory MCL that recur after alloSCT. In this article, we review the literature on the evidence of the GVL effects in MCL and describe a patient with relapsed MCL shortly after high-dose chemotherapy with autoSCT. The patient was then successfully treated with Bu/Cy/VP-16 for an alloSCT followed by DLIs in a stepwise fashion. MNCs > 10 x 10(8)/kg were collected by two large-volume leukaphereses from the donor. Harvested stem cells from the 2(nd) day were cryopreserved for the future use as prophylactic DLIs to be given in a stepwise fashion. Cyclosporin and methotrexate were used for GVHD prophylaxis. He had achieved only a partial response by D+64 post transplant. G-CSF-primed cryopreserved DLIs were then infused on D+64 and D+92 to enhance the GVL effect. Grade 3 intestinal GVHD developed 20 days after the 2(nd) DLI and was partially controlled with the combination of cyclosporin, prednisone, and mycophenolate mofetil. Clinical complete remission was observed at D+112, and maintained until the last follow-up day (D+615). Our findings suggest that alloSCT followed by prophylactic DLIs may offer a curative approach to refractory MCL.
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PMID:Successful allogeneic stem-cell transplantation with prophylactic stepwise G-CSF primed-DLIs for relapse after autologous transplantation in mantle cell lymphoma: a case report and literature review on the evidence of GVL effects in MCL. 1093 69


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