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)

The incidence of secondary myelodysplastic syndromes and acute leukemia (MDS/AL) was reported for 395 patients autografted for Hodgkin's disease (HD) (n = 96) and non-Hodgkin's lymphoma (NHL) (n = 299) between 1987 and 1998. Eleven patients developed secondary MDS/AL (crude rate at 2.8%) including two lymphoblastic AL cases. The mean time of occurrence was at 32 months after autologous stem cell transplantation (ASCT) and 71 months after diagnosis. The estimated actuarial incidence at 10 years was at 6.3% (+/-4%). Karyotyping revealed complex chromosomal aberrations in only one patient, and two translocations [t(8;21) and t(8;16)]. No features of topoisomerase II inhibitor-related leukemia were found. Only one patient had received ASCT in first remission. The remaining 10 patients had received multiple courses of chemotherapy before stem cell collection and four had relapsed after ASCT and before the occurrence of secondary MDS/AL. Five of 11 patients had received localized radiotherapy and five others received TBI in their conditioning regimen. Ten patients died despite chemotherapy and/or supportive care and only one patient is alive and well after genoidentical allogeneic transplantation. We suggest a cumulative leukemogenic role of pre-ASCT radiation and chemotherapy in the occurrence of these secondary MDS/AL more than the high-dose therapy itself.
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PMID:Myelodysplasias and leukemias after autologous stem cell transplantation for lymphoid malignancies. 1096 73

Secondary malignancies, particularly myelodysplasia (MDS), are serious events following high dose therapy with autologous stem cell support. We observed a higher frequency of secondary malignancies in patients with Hodgkin's disease (HD) than in patients with non-Hodgkin's lymphoma (NHL) undergoing high dose therapy with the same non-TBI conditioning regimen. Three hundred patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) were treated with cyclophosphamide, carmustine and etoposide and autologous stem cell support from 1986 through 1994. Median follow up of survivors is 3.9 years. Five-year survival is 51% for HD and 48% for NHL. Eleven patients developed second malignancies (9/150 treated for HD vs. 2/150 treated for NHL) a median of 2.4 years from transplantation and 5.2 years from initial diagnosis. Six patients had myelodysplasia or acute leukemia (MDS/AML) and 5 had lymphomas or solid tumors. Actuarial risk of MDS/AML at five years for patients transplanted for non-Hodgkin's lymphoma is 3% (95% CI 0.6-9.6%). HD patients had significantly different pretreatment characteristics than patients with NHL. A Cox model showed that greater number of prior relapses and prior radiation therapy were significant risk factors for the development of MDS/AML. These data suggest that CBV is associated with a lower risk of secondary MDS/AML than TBI containing regimens and that much of the risk is associated with the pre-transplantation therapy. The use of autotransplantation early in the course of therapy for relapsed lymphoma might prevent some cases of MDS/AML.
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PMID:Incidence of post transplant myelodysplasia/acute leukemia in non-Hodgkin's lymphoma patients compared with Hodgkin's disease patients undergoing autologous transplantation following cyclophosphamide, carmustine, and etoposide (CBV). 1142 23

Between May 1994 and May 2000, we autotransplanted 48 consecutive patients, 21 females and 27 males aged over 60 years (range: 60-78, median: 63). Sixteen patients had multiple myeloma (MM), 14 high-grade non-Hodgkin's lymphoma (HGNHL), six low-grade non-Hodgkin's lymphoma (LGNHL), nine acute myeloid leukemia (AML), one chronic lymphocytic leukemia (CLL), one Hodgkin's disease (HD) and one breast cancer; the performance status (WHO) was 0-1. Seventeen patients were in 1st CR (35.4%) and one in 2nd CR (2.1%), 25 in PR (52.1%), while five patients had been transplanted with progressive disease (10.4%); seven patients with MM received a double transplant. Patients received high-dose therapy including melphalan alone (13) or associated with other drugs (26), busulfan-cyclophosphamide (three), BEAM (11) and TBI (two). All patients took a median of 11 (range: 8-25) days to reach neutrophils >500/microl, 13 (range: 9-83) days to reach platelets > 20,000/microl and 17 (range: 11-83) days to reach platelets > 50,000/microl. Hematological toxicity, hospital stay and supportive care did not differ from those of a cohort of younger patients. At present, 31 patients are alive (14 in CR, five in PR, five in PD and seven in relapse) and 16 died from PD at a median follow-up of 37 months (1-67). Only one patient died from transplant-related toxicity. Quality of life, evaluated using a QLQ-C30 questionnaire in 25 patients at day +90, was good. In our experience PBPC mobilization and transplantation is feasible in patients aged > or = 60 years and the toxicity of this procedure is acceptable, with an early transplant-related mortality of 1.8%; therefore patients with hematological malignancies potentially curable with high-dose therapy (HDT) should also be candidates for HDT.
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PMID:Very low toxicity and good quality of life in 48 elderly patients autotransplanted for hematological malignancies: a single center experience. 1155 Oct 30

We evaluated prognostic factors and treatment outcome of patients with relapsed/refractory Hodgkin's disease (HD) receiving autologous stem cell transplantation (ASCT). In total, 92 patients received total body irradiation, cyclophosphamide and etoposide (TBI/CY/E) (n=42) or busulfan, melphalan and thiotepa (Bu/Mel/T) (n=50) supported with ASCT. A total of 33 (66%) patients receiving the Bu/Mel/T regimen had a prior history of dose-limiting irradiation. Mucositis, hepatic and pulmonary toxicities were the main causes of morbidity and mortality, irrespective of the conditioning regimen. The transplant-related mortality was 15%. With a median follow-up of 6 years (range 2.5-11), the cumulative probabilities of survival, event-free survival (EFS) and relapse at 6 years were 55, 51 and 32%. The 6-year Kaplan-Meier (KM) probabilities of EFS for patients with less advanced disease (patients in first chemotherapy-responsive relapse or second remission (n=42)) and more advanced disease (all other patients (n=50)) were 60 and 44%. No differences in toxicities and efficacy between the conditioning regimens were found. ASCT is an effective treatment for patients with refractory/relapsed HD. Female patients and patients with less advanced disease at transplant had a better outcome. Patients with prior irradiation benefited from the Bu/Mel/T regimen.
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PMID:Autologous stem cell transplantation for Hodgkin's disease: busulfan, melphalan and thiotepa compared to a radiation-based regimen. 1285 99

Nonmyeloablative allogeneic peripheral blood progenitor cell transplantation with low-dose total body irradiation (TBI; 200 cGy) plus fludarabine followed by cyclosporine and mycophenolate mofetil results in modest graft rejection rates. Acute and chronic graft-versus-host diseases (GVHD) are also seen and may not differ substantially from those that occur after fully ablative transplantation. Adding antithymocyte globulin (ATG) to pretransplant conditioning produces substantial immunosuppression. Because of its persistence in the circulation, ATG can achieve in vivo T-cell depletion. Twenty-five patients who were not eligible for conventional fully ablative allogeneic stem cell transplantation by virtue of age or comorbidities underwent nonmyeloablative allogeneic transplantation with ATG 15 mg/kg/d days -4 to -1, TBI 200 cGy on a single fraction on day -5, and fludarabine 30 mg/m(2)/d on days -4 to -2. Oral mycophenolate mofetil 15 mg/kg every 12 hours and cyclosporine 6 mg/kg every 12 hours were started on day -5. Grafts were unmanipulated peripheral blood progenitor cells mobilized with filgrastim 10 microg/kg/d and collected on day 5. The median age of the recipients was 57 years (range, 30-67 years); diagnoses were non-Hodgkin lymphoma (n = 11), acute myeloid leukemia (n = 6), multiple myeloma (n = 3), acute lymphoblastic leukemia (n = 2), severe aplastic anemia (n = 1), paroxysmal nocturnal hemoglobinuria (n = 1), and myelodysplastic syndrome (n = 1). The median CD34(+) and CD3(+) contents of the grafts were 7.6 x 10(6)/kg and 1.6 x 10(8)/kg, respectively. Five patients received voluntary unrelated donor grafts. Three patients, 2 with voluntary unrelated donor grafts and 1 with a sib donor, received a 1 antigen-mismatched graft. The rest were fully matched. Twenty-two of 25 patients were evaluable for chimerism. Sixteen had >/=95% donor chimerism. Four patients displayed 80% to 90% donor chimerism, 1 displayed 78%, and 1 displayed 64%. Eleven patients relapsed with their original disease. One patient rejected the graft at 180 days. The median hospital stay was 27 days. Complications included GVHD in 6 patients (3 patients had grade I or II GVHD of skin and liver, and 3 patients had grade III or IV GVHD of liver and gut). Two of the patients with GVHD had mismatched grafts. Transplant-related toxicity was seen in 4 patients and infection in 5 patients. The median length of follow-up was 162 days (range, 17-854 days). Complete remissions were seen in 10 patients. Four patients remained in complete response (CR) at 280 to 595 days. One patient relapsed with non-Hodgkin lymphoma after a CR of 728 days. Of the 25 patients, 16 died (6 of relapsed disease, 4 of GVHD, 3 of infection, and 3 of transplant-related toxicity) and 9 are alive (6 with CR-2 of them after donor leukocyte infusion-and 3 with relapsed disease). The addition of ATG to low-dose TBI and fludarabine nonmyeloablative conditioning was well tolerated and resulted in >80% donor engraftment in this small cohort. As in other series of truly nonmyeloablative transplantation, a high rate of relapse was observed. Donor engraftment may be facilitated by the addition of ATG to low-dose TBI and fludarabine conditioning.
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PMID:Low-dose total body irradiation, fludarabine, and antithymocyte globulin conditioning for nonmyeloablative allogeneic transplantation. 1286 59

A 23-year-old female patient was diagnosed as having Hodgkin lymphoma (mixed cellularity type, clinical stage III B) in September 2000. She underwent ABVD chemotherapy and irradiation of a mediastinal lesion, resulting in complete remission. However, the disease reoccurred three month after the completion of initial treatment. She was admitted to our hospital for allogeneic stem cell transplantation. Thoractic vertebra, lumbar vertebra and iliac bone lesions were detected by FDG-PET, and a diagnosis of bone marrow infiltration was made. She received re-induction chemotherapy but did not achieve complete remission. A residual lesion in her bone marrow was detected by FDG-PET. She underwent unrelated allogeneic bone marrow transplantation in May 2002. Preconditioning was VP-16, CY and TBI. Engraftment of white blood cells was on day 15. Skin GVHD was detected at the same time and she was treated with steroid hormones, resulting in improvement. No residual mass could be detected by FDG-PET on day 60. However, she suffered from fever on day 80. Aggravation of the disease was revealed and she died from progression of the disease on day 120. FDG-PET is useful for the monitoring disease status and for determining the optimal timing of various treatments.
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PMID:[Evaluation of bone marrow involvement by FDG-PET for refractory Hodgkin lymphoma treated by unrelated allogeneic bone marrow transplantation]. 1293 62

In patients with refractory lymphoma, we tested the hypothesis that high-dose chemotherapy (BEAM) without stem cell support followed by a reduced intensity (RIC) allogeneic transplant with fludarabine and 2 Gy TBI 28 days later results in tumor debulking and establishment of a graft vs lymphoma effect, with acceptable toxicity. In a pilot protocol we treated 10 patients, 22-62 (median 47) years of age with high-risk or refractory Hodgkin's or non-Hodgkin's lymphoma. Donors were HLA identical siblings (eight) or unrelated volunteers. None died during the neutropenic phase after BEAM which lasted up to the RIC HSCT. The duration of neutropenia was 31-43 (median 36) days. All patients engrafted and nine achieved CR. All developed acute GvHD (median grade III) and all patients at risk developed chronic GvHD. Three patients died of GvHD. One relapsed and six patients are in continuous CR 10-32 (median 15) months after HSCT. This approach appears feasible and results in a high response rate. Neutropenia duration is of concern. It remains to be tested whether separation of debulking chemotherapy and induction of allogeneic effects confers an advantage.
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PMID:High-dose chemotherapy using BEAM for tumor debulking without stem cell support followed by early allogeneic reduced intensity conditioning transplantation to induce a graft-versus-lymphoma effect in patients with high risk or refractory lymphoma. 1506 93

Follicular non-Hodgkin's lymphomas usually present in advanced stage and although frequently are chemotherapy-sensitive remain incurable using conventional approaches. Treatment options are evolving rapidly and now include targeted therapies such as monoclonal antibodies. Recent studies, including the EBMTR-sponsored 'CUP Trial' (conventional Chemotherapy, Unpurged autograft, Purged autograft), demonstrate that for patients under age 60 years with recurrent chemotherapy-sensitive disease, autologous stem cell transplantation (ASCT) provides a survival benefit over conventional therapy. Allogeneic stem cell transplantation (alloSCT) has become a more effective option. Although incorporation of TBI into the preparative regimen may increase treatment-related mortality (TRM), relapses appear to be reduced compared to a chemotherapy-alone regimen. Reduced-intensity alloSCT procedures are now being performed at an increasing rate, in part due to a lower risk for TRM. Until more data are available, however, reduced-intensity alloSCT should be considered only in cases where myeloablative conditioning is contra-indicated. There are no clear means for choosing ASCT vs alloSCT, a decision influenced by the amount of residual tumor, disease-responsiveness, degree of marrow involvement and extent of prior chemotherapy. ASCT or alloSCT in first remission remains an investigational procedure. Future considerations include incorporation of novel preparative regimens, in vitro purging techniques, antilymphoma vaccines, post transplant immunotherapy and ex vivo-manipulated donor lymphocyte infusions.
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PMID:Stem cell transplantation in follicular lymphoma: progress at last? 1548 83

Follicular non-Hodgkin's lymphomas (NHL) usually present in advanced stage and although frequently are chemotherapy-sensitive remain incurable using conventional approaches. Treatment options are evolving rapidly and now include targeted therapies such as monoclonal antibodies. Recent studies, including the EBMTR-sponsored "CUP Trial" (conventional Chemotherapy, Unpurged autograft, Purged autograft), demonstrate that for patients under age 60 years with recurrent chemotherapy-sensitive disease, autologous stem cell transplantation (ASCT) provides a survival benefit over conventional therapy. Allogeneic stem cell transplantation (alloSCT) has become a more effective option. Although incorporation of TBI into the preparative regimen may increase treatment-related mortality (TRM), relapses appear to be reduced compared to a chemotherapy-alone regimen. Reduced-intensity alloSCT procedures now are being performed at an increasing rate, in part due to a lower risk for TRM. Until more data are available, however, reduced-intensity alloSCT should be considered only in cases where myeloablative conditioning is contra-indicated. There are no clear means for choosing ASCT versus alloSCT, a decision influenced by amount of residual tumor, disease-responsiveness, degree of marrow involvement and extent of prior chemotherapy. ASCT or alloSCT in first remission remains an investigational procedure. Future considerations include incorporation of novel preparative regimens, in vitro purging techinques, anti-lymphoma vaccines, post-transplant immunotherapy and ex vivo-manipulated donor lymphocyte infusions.
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PMID:Autologous and allogeneic stem cell transplantation in follicular lymphoma. 1573 73

We analysed the outcome and hospitalization requirements of the first 100 patients (Hodgkin's disease (HD), N=13; multiple myeloma (MM), N=14; CLL, N=12; non-Hodgkin's lymphoma (NHL), N=17; myelodysplastic syndrome (MDS), N=18; AML, N=24 and CML, N=2) treated in Denmark with haematopoietic cell transplantation after non-myeloablative conditioning with TBI 2 Gy+/-fludarabine. The cumulative incidence of acute GVHD grade II-IV and extensive chronic GVHD was 67 and 49%. After a median follow-up of 534 days, the overall survival, PFS, relapse-related mortality and treatment-related mortality were 59, 50, 25 and 17%, respectively. Patients with CLL, NHL, AML and MDS with <5% blasts at any time had a favourable outcome with a PFS of 61-71%. Patients with MM, HD and MDS and a history of > or =5% blasts had a less favourable outcome with a PFS of 19-38% (P=0.001). The cumulative incidence of discontinuation of immunosuppression was 37%. During the first and second year post transplant, patients experienced a mean of 41 and 13 outpatient clinic visits, and 53 and 16 days of hospitalization. Sixteen patients were admitted to the intensive care unit, of whom eight are still alive. In conclusion, transplantation outcomes were encouraging, but complications requiring admission and outpatient clinic visits occur frequently post transplant.
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PMID:Haematopoietic cell transplantation with non-myeloablative conditioning in Denmark: disease-specific outcome, complications and hospitalization requirements of the first 100 transplants. 1824 14


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