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)

Fifty three patients (pts) received an allogeneic hematopoietic transplant using peripheral blood progenitor cells (PBPC). Diagnosis were acute myeloid leukemia (AML) in 16 pts, acute lymphoblastic leukemia (ALL) in 15, chronic myeloid leukemia (CML) in first chronic phase in 12, aplastic anemia in 4, myelodysplasia in 3 and Hodgkin's disease, major thalasemia and Hunter's syndrome in one each. Mean age was 20 years-old (2-55), 28 males and 25 females. Conditioning regimens were total body irradiation with 1200 cGy and cyclophosphamide 120 mg/kg in 38 pts, busulfan 16 mg/kg and cyclophosphamide 120 mg/kg in 10 pts, total lymphoid irradiation and cyclophosphamide in 3, 2 pts received other chemotherapy based conditionings. PBPC were infused unmanipulated through a central catheter. Graft versus host disease (GVHD) prophylaxis was cyclosporin and short course methotrexate. Donors were 6/6 HLA compatible siblings in 52 cases and 5/6 match in one case. PBPC mobilization was done with G-CSF at a dose of 10 micrograms/kg/day subcutaneously for four days, pheresis started on day 5. Bone marrow harvest was also done in the first thirty cases. Mean cellularities for CD34, CD3, CD4, CD8, CD56, CD19 (cel x 10(6)/kg) were 4.12; 4.59; 2.57; 1.9; 0.55 and 0.68, respectively. Mean recovery of neutrophils > 500/microL was obtained on day +11 and platelets > 20,000/microL on day +13. Patients were hospitalized for a mean period of 26 days (range 18-39) and days with parenteral antibiotics were 12.2 (5-45). Two pts had venoocclusive disease of the liver. Transplant related mortality was 15%. Acute graft versus host disease (GVHD) was observed in 43.4% of pts, only 5 pts had acute GVHD III or IV. Mean time for aGVHD diagnosis was +23 (8-76). Forty three pts were evaluable for chronic GVHD with a mean follow-up of 18 months (4-39). Chronic GVHD was observed in 26.4% by day +240, only 2 pts developed severe cGVHD. The present experience demonstrates an acceptable incidence for cGVHD; however, taking into account recent reports showing an increase of this complication, it seems reasonable not to perform this procedure for non-malignant diseases in which graft versus malignancy effect is not to be expected.
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PMID:[Allogeneic hematopoietic transplantation with stem cells extracted from peripheral blood]. 1096 6

This randomized, controlled study compared the ability to mobilize and collect an optimal target yield of 5 x 10(6) CD34+ cells/kg using stem cell factor (SCF; 20 microg/kg/day) plus filgrastim (G-CSF; 10 microg/kg/day) vs filgrastim alone (10 microg/kg/day) in 102 patients diagnosed with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), who were prospectively defined as being heavily pretreated. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield was reached, or until a maximum of five leukaphereses had been performed. Compared with the filgrastim-alone group (n = 54), the SCF plus filgrastim group (n = 48) showed an increase in the proportion of patients reaching the target yield within five leukaphereses (44% vs 17%, P = 0.002); reduction in the number of leukaphereses required to reach the target yield (P = 0.003); reduction in the proportion of patients failing to reach a minimum yield of 1 x 10(6) CD34+ cells/kg to proceed to transplant (16% vs 26%, P = NS); increase in the median yield of CD34+ cells per leukapheresis (0.73 x 10(6)/kg vs 0.48 x 10(6)/kg, P = 0.04); and an increase in the median total CD34+ cells collected within five leukaphereses (3.6 x 10(6)/kg vs 2.4 x 10(6)/kg, P = 0.05). All patients receiving SCF were premedicated (antihistamines and albuterol), and treatment was generally well tolerated. Five patients experienced severe mast cell-mediated reactions, none of which were life-threatening. In this study of heavily pretreated lymphoma patients, SCF plus filgrastim was more effective than filgrastim alone for mobilizing PBPC for harvesting and transplantation after high-dose chemotherapy.
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PMID:A randomized phase 2 study of PBPC mobilization by stem cell factor and filgrastim in heavily pretreated patients with Hodgkin's disease or non-Hodgkin's lymphoma. 1101 35

High dose chemotherapy (HDC) with autologous stem cell transplantation (SCT) was applied for the treatment of 13 patients (pts) with Hodgkin's disease (HD) (10 with relapsed form and 3 with conventional chemotherapy resistant form) in the Clinic for Hematology, Military Medical Academy, from May 1997 to October 1999. After the initial treatment for the reduction of tumor, burden stem cells were mobilized by cyclophosphamide 2.5-7.0 g/m2 with G-CSF 5-12 micrograms/kg body mass (BM). The average number of colected mobilized mononuclear cells (MNC) was 2.99 (1.66-5.9) x 10(8)/kg BM by the apheresis large volume from peripheral blood. All patients received BEAM (BCNU, etoposide, Cyto-Ara, and melfalan) conditioning regimen with adequate supportive therapy. Good engraftment (100%) was observed at postransplantation period: number of polymorphonuclear cells was > 0.5 x 10(9)/l, on day 13th (10-21) and number of platelets > 20 x 10(9)/l, on day 17th (11-28). One patient (7.6%) died due to infective complications at day 98th after transplantation, 9 (69.2%) patients achieved complete and 3 (23.1%) patients partial remission of the disease. Out of three patients with partial remission, one relapsed, seven months after autologous SCT, with conventional chemotherapy resistant form and two, after the applied conventional locoregional radiotherapy reached remission. One patient (7.6%) developed secondary malignancy of acute myeloid leukemia form with threelinage displasy 27 months after autologous SCT. HDC with autologous SCT contributes to more successful treatment of early relapsed and standard chemotherapy resistant forms of HD and gives the opportunity for successful quality of living for those patients.
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PMID:[Treatment of Hodgkin's disease with high-dose chemotherapy and autologous stem cell transplantation]. 1121 77

Co-mobilization of CD34(+) cells and tumor has been documented in patients with different types of cancer undergoing peripheral blood stem cell transplantation (PBSCT). Conflicting reports were published regarding the role of various growth factors in tumor cells mobilization, hence we studied the extent of CD34(+) cells and lymphoma cell mobilization in 35 non-Hodgkin's (NHL) patients primed by cyclophosphamide (Cy) in combination with granulocyte colony-stimulating factor (GCSF) (A, 13 patients), granulocyte-macrophage (GM)-CSF (B, 10 patients), or GM-CSF followed by G-CSF (C, 12 patients). CD34(+) cells were quantitated by flow cytometry and lymphoma cells by the TaqMan Real Time PCR for bcl-2 gene rearrangement. Successful collection in 4 days of > or = 2 x 10(6) CD34(+) cells/kg needed for prompt engraftment was obtained in 76%, 60%, and 58% of patients in arms A, B, and C, respectively. Lymphoma cell mobilization was detected in 35% patients tested, 78% of which had follicular lymphoma. Lymphoma cell mobilization was similar in the three arms of the study, however, presence of lymphoma cells was prevalent in patients who failed to mobilize the amount of 0.4 x 10(6) CD34(+) cells/kg in 2 days ("poor mobilizers") and reached 42%, compared to 17% in the "successful mobilizers" group of patients. Lymphoma cell contamination in PBSCs was detected proportionately in the peripheral blood and in the bone marrow. We conclude that bcl-2 gene rearrangement is prevalent in patients with follicular histology, and, in these patients, an inverse relationship was observed between mobilization of CD34(+) cells and lymphoma cells. Our results explain the high relative risk (1.98) for mobilization in patients with follicular histology.
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PMID:Differential mobilization of CD34+ cells and lymphoma cells in non-Hodgkin's lymphoma patients mobilized with different growth factors. 1127 70

A "hard to mobilize" patient was defined as one in whom >or= 1x10(6) CD 34+ cells/kg cannot be obtained after two consecutive large volume aphereses. Forty-four consecutive Hodgkin's and non-Hodgkin's lymphoma patients who underwent autologous peripheral blood stem cell (PBSC) transplant treatment between June 1996 and June 1998 were included in this study. Twenty-one patients (48%) met the definition of "hard to mobilize" (Group I). All the rest of the patients (n=23) were the good mobilizers (Group II). The initial mobilization protocol for most patients was 10 microg/kg of G-CSF alone for both groups. For Group I, 7/21 (33%) patients were unable to achieve a minimal dose of >or= 1x10(6) CD34+ cells/kg even after a second mobilization attempt and/or bone marrow (BM) harvest (n=5). Overall, 11/21 (52%) required an additional mobilization and/or BM harvest. Only 3/21 (14%) patients were able to meet the target cell dose of >or= 2.5x10(6) CD34+ cells/kg (median of 4 apheresis). In contrast, 87% of Group II achieved the target dose with a median of 2 aphereses. Predictors of poor mobilization were greater than two prior treatment regimens (p=0.038) and the WBC count (<25,000/microL) on the first day of apheresis (p=0.053). Nineteen patients in Group I and all Group II completed treatment with a median time to engraftment of ANC>500/microl of 12 and 11 days, and platelet >20x10(3)/microl of 31 and 13 days, respectively. Outcome analysis revealed that 6/19 patients in Group I died of relapse within one year from transplant compared with only 2/23 of Group II who died of relapse (p=0.005, log rank test). There were no treatment related deaths in either group. Independent predictive features for "hard to mobilize" patients are a lack of significant increase in WBC count on the first day of apheresis and the number of prior treatment regimens. Poor mobilization appears to predict a worse outcome after autografting for lymphoma patients.
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PMID:Characterization and outcome of "hard to mobilize"' lymphoma patients undergoing autologous stem cell transplantation. 1134 34

In this study we explored whether a standard chemotherapy regimen consisting of mitoguazone, ifosfamide, methotrexate and etoposide (MIME) combined with 5 micrograms/kg or 10 micrograms/kg G-CSF was capable of mobilizing peripheral blood progenitor cells (PBPC) in lymphoma patients. Thirty-three patients with Hodgkin's disease (HD) and 108 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3-40) of chemotherapy prior to mobilization. Eight of 141 patients failed to mobilize PBPC and bone marrow was harvested. In addition, 10 patients obtained a harvest of < 2.0 x 10(6) CD34+ cells/kg. More than 2.0 x 10(6) CD34+ cells/kg were achieved in all HD patients and in 83% of the NHL patients. Fifty-eight per cent of the patients harvested > or = 5 x 10(6) CD34+ cells/kg. Eleven per cent of the patients developed neutropenic fever during the mobilization and 3% had nadir platelet values below 20 x 10(9)/L. An inverse correlation was observed in high-grade NHL (H-NHL) patients between the number of chemotherapy cycles given before mobilization and yield of CD34+ cells. Such an association was not seen among patients with HD, transformed and low-grade NHL. When G-CSF 10 micrograms/kg was used in combination with MIME, this correlation was no longer seen in patients with H-NHL. There was also association between CD34+ cell yield and prior radiotherapy in patients with HD or transformed NHL or low-grade NHL. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF, can be successfully used to mobilize PBPC. Although no significant effect of increased dose of G-CSF was found, our data suggest that MIME/G-CSF 10 micrograms/kg should preferentially be used to mobilize PBPC in H-NHL patients pre-treated with > or = 12 cycles of chemotherapy, in irradiated HD patients and in all low-grade and transformed lymphomas.
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PMID:Combination chemotherapy containing mitoguazone, ifosfamide, methotrexate, etoposide (MIME) and G-CSF efficiently mobilize peripheral blood progenitor cells in heavily pre-treated relapsed lymphoma patients. 1148 95

Treatment of early relapsing or resistant non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) remains problematic. High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation improves the prognosis for patients in response following standard dose regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and simultaneously mobilize stem cells. We used regimens based on ifosfamide and etoposide because these drugs are not usually used as the front-line treatment. Twenty-seven patients with NHL received MINE chemotherapy (mesna and ifosfamide 1330 mg/m2 and etoposide 65 mg/m2 i.v. days 1-3, and mitoxantrone 8 mg/m2 i.v. day 1). The same schedule, but higher doses were used for PBSC stimulation (mesna, ifosfamide 1700 mg/m2, etoposide 175 mg/m2, mitoxantrone 10 mg/m2). Forty-six patients with HD received VIM chemotherapy (mesna, ifosfamide 1200 mg/m2 i.v. days 1-5, etoposide 90 mg/m2 i.v. days 1, 3, and 5, methotrexate 30 mg/m2 i.v. days 1 and 5). After both VIM and high dose MINE, chemotherapy for mobilization was followed by G-CSF administered at a dose 5-16 micrograms/kg/day depending on the clinicians judgement of the patient's pretreatment. Complete response after VIM and MINE were 39% and 38%, respectively; partial response (PR) rates were 17% and 29%, and stable disease (SD) 25% and 4%, respectively. In both groups, patients with relapsing disease had better responses than did those with primary progressive disease. Both regimens exhibited excellent mobilizing capacity. We performed 213 aphereses with a median 3 per patient starting on either day 13 as a median for VIM, or on day 12 as a median for MINE. In the majority of patients, the collection started in the time interval median +/- 1 day (n = 62, 85%). The median yields were 10.6 x 10(6) CD34+ cells/kg and 53.1 x 10(4) CFU-GM/kg for VIM, and 13.3 x 10(6) CD34+ cells/kg and 54.5 x 10(4) CFU-GM/kg for MINE. We collected at least 2.5 x 10(6) CD34+ cells/kg in all but six patients (8%), and the harvested amount of CD34+ cells was less than 1.0 x 10(6)/kg in only two patients (3%). The toxicity of VIM and MINE was minimal and chemotherapy-induced trombocytopenia did not occur with PBSC collection.
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PMID:Ifosfamide- and etoposide-based chemotherapy as salvage and mobilizing regimens for poor prognosis lymphoma. 1148 96

In an effort to improve results in patients with relapsed or refractory Hodgkin's disease (HD), an intensive regimen combining vinorelbine (25 mg/m2 i.v. days 1 and 5) and high-doses of ifosfamide (3000 mg/m2/d, days 1-4 by continuous infusion) with mesna uroprotection and G-CSF support was designed. Forty-seven patients were treated; 14 had failure to initial induction therapy and 33 had disease relapsed from an initial response. The response rate was 83%, with 21 complete (45%, CR) and 18 partial remissions (38%, PR). Partial response was achieved after a median of two cycles (range 1-3) and CR after a median of six cycles (range 2-10). At the end of ifosfamide and vinorelbine, 10 patients in CR, one in PR, and one with stable disease also received radiotherapy to nodal sites of relapse. Eleven patients who had undergone peripheral blood stem cell (PBSC) harvesting following ifosfamide-vinorelbine proceeded to receive high-dose chemotherapy (HDCT) and PBSC transplantation. The main toxic effect was grade III-IV neutropenia, documented in 65% of cycles with a median duration of 4 days, and non-haematological toxicity was mild. The combination of high-doses of ifosfamide and vinorelbine was well tolerated and an active regimen in treatment of patients with relapsed and refractory HD. It was not only useful as salvage therapy with or without consolidative radiotherapy but it also was a valuable induction regimen before high-dose intensification therapy followed by PBSC reinfusion in patients eligible for this approach.
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PMID:High-dose ifosfamide and vinorelbine as salvage therapy for relapsed or refractory Hodgkin's disease. 1148 3

Better predictive factors for autologous blood stem cell mobilization (BSCM) are needed. The purpose of this study was to determine if an independent association exists between lymphocyte or NK cell counts and BSCM. Data were analyzed on 141 consecutive patients aged 19-69 years (median 45) who received combined chemotherapy plus G-CSF for BSCM, and who had measurements of immune cells prior to BSCM. Of the 141 patients, 41% had breast cancer, 14% Hodgkin's disease, 34% non-Hodgkin's lymphoma, and 11% other diagnoses. BSCM involved dose-intensive cyclophosphamide, etoposide, cisplatin (DICEP) plus G-CSF 300 microg (<70 kg) or 480 microg (>70 kg) for 45% of patients, while the remaining 55% received other chemotherapy plus similar doses of G-CSF. Only a single apheresis was performed for 94% of patients. The following factors were analyzed for predictors of BSCM: age, gender, prior chemotherapy, prior radiotherapy, diagnosis, disease status, marrow involvement, mobilization regimen, Hb, WBC, platelet count, B cell, T cell, and NK cell counts. The peripheral blood CD34+ counts on the first day of apheresis (PBCD34) were 6-1783 x 10(6)/l (median 150). The PBCD34 count correlated strongly with the number of CD34+ cells collected/l blood apheresed and with the number of CD34+ cells collected/kg. By multivariate analysis using continuous variables, relapsed status (P = 0.0003), not using DICEP mobilization (P = 0.0001), female gender (P = 0.0057), low platelet count (P = 0.051), and low CD3- 16+ 56+ count (P = 0.0158) were associated with low PBCD34 counts. Using categorical variables, the only factors that independently predicted a PBCD34 count <150 x 10(6)/l were: >1 prior chemotherapy regimen (odds ratio = 5.12, P = 0.0003), not using DICEP mobilization (odds ratio = 4.94, P = 0.0001), and CD3- 16+ 56+ count <125 x 10(6)/l (odds ratio= 2.58, P = 0.0157). In conclusion, the CD3- 16+ 56+ count may be a useful additional predictor of BSCM and warrants further study.
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PMID:The CD3- 16+ 56+ NK cell count independently predicts autologous blood stem cell mobilization. 1154 41

The mobilizing potential and therapeutic activity of ifosfamide/vinorelbine-containing regimens with G-CSF support were explored in patients with pretreated malignant lymphomas. Ten patients with non-Hodgkin's lymphoma (NHL) received ifosfamide and vinorelbine, and 17 with Hodgkin's disease (HD) received ifosfamide, vinorelbine and gemcitabine (IGEV regimen), as induction chemotherapy before high-dose chemotherapy (HDT) with peripheral blood stem cell (PBSC) support. Most of the patients had been heavily pretreated with various chemotherapy regimens +/- radiotherapy. The target yield was > or =3 x 10(6) CD34+ cells/kg of body weight in order to support the subsequent myeloablative chemotherapy. The optimal PBSC harvest occurred on days 11 and 12, with no difference in CD34+ cell mobilization kinetics between the ifos- famide/vinorelbine and IGEV regimens. The median number of CD34+ cells/kg body weight collected was 10.9 x 10(6) (range 1.76-61.1 x 10(6)). The median total CD34+ cell/microl, CFU-GM and white blood cells (WBC) for all individual collections was 81.5/microl, 10 x 10(4)/kg, and 17 900/microl, respectively. The target yield of CD34+ cells was reached in 24 of 27 patients. Hematological side-effects were acceptable and no treatment-related hospitalizations or toxic deaths occurred. Fifteen patients have so far received high-dose therapy and PBSC reinfusion with rapid engraftment. These results confirm that ifosfamide and vinorelbine-based chemotherapy regimen with G-CSF support can be successfully and safely used to mobilize PBSCs.
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PMID:Mobilizing potential of ifosfamide/vinorelbine-based chemotherapy in pretreated malignant lymphoma. 1175 45


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