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H Holte

Publications and source records attributed to H Holte.

At least 55 records · Page 3Linked to original sources

Combination chemotherapy with mitoguazon, ifosfamide, MTX, etoposide (MIME) and G-CSF can efficiently mobilize PBPC in patients with Hodgkin's and non-Hodgkin's lymphoma.

Many centers use CY and G-CSF to mobilize PBPC. In this study we explored whether a standard chemotherapy regimen consisting of mitoguazon, ifosfamide, MTX and etoposide (MIME) combined with G-CSF was capable of mobilizing PBPC in lymphoma patients. Twelve patients with Hodgkin's disease (HD) and 38 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 to 20) of chemotherapy prior to mobilization. It was found that the optimal time of PBPC harvest was at days 12 and 13 after initiating the mobilization regimen. The median number of collected CD34+ cells per kg body weight was 7.1 x 10(6) (range 0.5-26.2). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 69% of the patients after one apheresis. When additional cycles of apheresis were done, only 6% failed to harvest this number of CD34+ cells. There was a statistically significant inverse correlation between the number of prior chemotherapy cycles and CD34+ cell yield (P = 0.003). No such association was found between CD34+ cell yield and prior radiotherapy. When MIME/G-CSF was compared with Dexa-BEAM/G-CSF, it was found that MIME/G-CSF tended to be more efficient in mobilizing PBPC in spite of being less myelotoxic. All patients transplanted with MIME/G-CSF mobilized PBPC had fast and sustained engraftment. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF can be successfully used to mobilize PBPC.

Adolescent↗

Hodgkin's disease in a national and hospital population: trends over 20 years.

The aim of the study was to investigate the incidence rate and time trends in a national registry population of Hodgkin's disease (HD) and the effects of selection in a hospital population. A national registry population of all HD patients from Norway and a hospital population of HD patients treated at the Norwegian Radium Hospital (NRH) were studied retrospectively from 1971 to 1993. The incidence of non-Hodgkin's lymphomas (NHL) in Norway increased steadily from 1961 in contrast to a stable incidence pattern for HD before 1980 and a decreasing incidence since 1980. Due to improved diagnostic tools after 1980, an increasing proportion of patients previously diagnosed as lymphocyte depleted and unclassified HD were classified as NHL. As these histologies are dominant in older patients, the incidence of older patients with HD and the total population of HD have decreased since 1980. As a result, the proportion of young adults with a favourable histology has increased. These changes may partly explain the increased patient survival observed both in the national and the hospital population. The hospital population comprised 92% of patients aged 15-39 years, 80% of patients aged 40-59 years and 53% of patients aged > 60 years in the national population. The selection of younger patients in the hospital material may explain a higher survival rate as compared with the national population.

Adolescent↗

Bone-marrow MR imaging before and after autologous marrow transplantation in lymphoma patients without known bone-marrow involvement.

PURPOSE: To study lumbar bone marrow by means of MR imaging before and after bone-marrow transplantation in lymphoma patients. Particular emphasis was paid to heterogeneity and to focal manifestations, i.e. appearances that could simulate tumor. MATERIAL AND METHODS: Twenty-two patients who were disease-free for a minimum of 30 months after transplantation were studied in 107 MR examinations. Two radiologists visually evaluated coronal T1-weighted and short inversion time inversion-recovery (STIR) images. RESULTS: T1-weighted images demonstrated a more heterogeneous marrow after transplantation than before it. Sharply defined focal low signal intensity areas appeared on this sequence in 5 (23%) of the 22 patients at between 21 and 60 weeks after transplantation. The mean age of these 5 patients was 48.4 years (range 42-54 years). The difference in age between these 5 patients and the remaining 17 patients, who had a mean age of 33.4 years (range 14-51 years), was statistically significant (p < 0.01, Student's t-test, 2-sided test). CONCLUSION: Sharply defined focal low signal intensity areas may be seen on T1-weighted images of bone marrow in patients who are in complete remission after transplantation, particularly in those aged over 40-45 years.

Adolescent↗

Systemic pneumococcal disease after staging splenectomy for Hodgkin's disease 1969-1980 without pneumococcal vaccine protection: a follow-up study 1994.

We surveyed, during 1994, all 325 patients who underwent staging laparotomy with splenectomy for Hodgkin's disease in Norway 1969-80, before pneumococcal vaccine was available in this country. The patients were thus not immunized preoperatively. Of 162 patients (49.8%) who died before 1994, 8 (2.4% of the total study) died from pneumococcal septicaemia and 16 (6.2%) from infections totally. Of 163 patients (50.2%) who were alive in 1994, 158 cooperated and filled in a questionnaire: 22 had been hospitalized for serious infections; 2 with pneumococcal septicaemia, and 6 with pneumonia, although lacking a specified microbiological diagnosis. We observed 325 patients representing 4420 patient-years, 3066 patient-years among survivors and 1354 patient-years among the dead. This resulted in an incidence rate of systemic pneumococcal disease of 226 per 100,000 patient-years, which is a relative risk of 20.5 compared to the general Norwegian population during 1994. Septicaemia for these patients most often had an abrupt clinical start even for relapse-free individuals and occurred from 2 to 17 yr after splenectomy (mean 10 yr). The risk of developing an overwhelming pneumococcal septicaemia with high case-fatality in asplenic patients seems to persist for these patients at about the same level even 15-20 yr after splenectomy. Only 12.7% of the survivors had been given pneumococcal vaccine in the autumn of 1993. Despite the fact that medical journals and media in Norway focused upon the problem of pneumococcal disease in asplenic individuals in the autumn of 1993 and spring of 1994, a substantial proportion of these patients (55.3%) still remained unimmunized when interviewed in the autumn of 1994. None of our systemic pneumococcal disease patients was vaccinated. Our data underline the need for prophylactic immunization with effective vaccines against pneumococcal infection in splenectomized Hodgkin's disease patients.

Adolescent↗

[High-dose therapy of cancer with CD34 positive cells as stem cell support].

In this article we report our initial clinical experiences in connection with immunomagnetic isolated CD34-positive cells from peripheral blood progenitor cells. Six patients, five with breast cancer and one with non-Hodgkin's lymphoma, were mobilized by chemotherapy and G-CSF (5ug/kg). CD34-positive cells were isolated by means of immunomagnetic beads (Dynalbeads) and Isolex 300 Cell Separator (Baxter, USA). Mean purity of isolated CD34-positive cells was 97% (94.7-99.7) and mean yield was 54% (35-68). Three patients were treated with high dose therapy followed by reinfusion of CD34-positive cells as stem cell support. Recovery of neutrophils (> 0.5 x 10(9) leucocytes/liter) occurred at day 8, 11 and 13 and of platelets (> 20 x 10(9) platelets/litre) at day 9,14 and 32. It is concluded that immunomagnetic isolated CD34-positive cells give high purity and yield. Although use of CD34-positive cells reduces the content of contaminating tumour cells in the graft, breast cancer cells were still detectable in two out of five CD34-positive cell products.

Antigens, CD34↗

[High-dose therapy with autologous stem cell support in malignant lymphoma and breast cancer. Experiences with hematopoietic stem cells isolate from blood].

Since 1994, 17 breast cancer patients and 16 lymphoma patients have been treated at the Norwegian Radium Hospital with high-dose therapy supported by autologous peripheral progenitor cells. All the patients were given granulocyte colony stimulating factor in the recovery phase after cytotoxic treatment in order to mobilize and harvest peripheral progenitor cells. Aphareses were successful in all patients and the mean number of CD34 cells reinfused per kilo body weight was 7.05 x 10(6) for the lymphoma patients and 11.1 x 10(6) for the breast cancer patients. The mean time to recover > or = 0.5 x 10(9)/l granulocytes and > or = 20 x 10(9)/l platelets after reinfusion of stem cells was 10 days and 11.7 days respectively for the lymphoma patients, while the breast cancer patients engrafted at day 8.6 and day 9.3. No severe treatment-related complications were observed.

Adult↗

[High dose therapy with autologous stem cell support in malignant disorders. Excerpt from the statement by the advisory group of the State Health Services].

New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorders for which high dose therapy with stem cell support should be explored versus conventional treatment in randomised prospective trials.

Cost-Benefit Analysis↗

[Treatment with growth factors and cytokines in hematologic diseases].

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.

Cytokines↗

Fat replacement of Hodgkin disease of bone marrow after chemotherapy: report of three cases.

Three cases are presented with fat replacement of Hodgkin disease of bone marrow after chemotherapy. Magnetic resonance imaging on admission demonstrated low-signal intensity of lesions on T1-weighted images and high-signal intensity on short inversion time inversion-recovery images. Seven lesions were observed, five of which were located in the spine and two in the pelvis. All lesions showed reversal of signal intensities after completion of chemotherapy. T1-weighted fat saturation images confirmed the fatty nature of the lesions after treatment. All patients had a nodular sclerosis, Hodgkin disease, type 2. One can speculate as to whether the conversion to fat actually represents a particularly successful result of chemotherapy.

Adipose Tissue↗

Purging of tumor cells from leukapheresis products: experimental and clinical aspects.

Peripheral blood progenitor cell autografts are being used increasingly in conjunction with high-dose therapy of cancer patients, in the belief that these products have a low probability of containing tumor cells. However, recent findings demonstrate that tumor cell involvement is frequent in leukapheresis products. Although the clinical value of purging has not been clinically established by prospective randomized trials, several studies indicate that contaminating tumor cells in autografts contribute to relapse of the disease in the recipients. We describe our experimental and clinical experience in purging tumor cells from leukapheresis products. Based on our work with purging of lymphoma cells from bone marrow by the use of anti-B cell and anti-T cell antibodies and immunobeads, a purging procedure to deplete leukapheresis products of lymphoma cells has been developed. Moreover, we present data showing that breast cancer cells can be efficiently removed from leukapheresis products using antibreast cancer antibodies, either in combination with immunobeads or as immunotoxins. Our experience with enrichment of CD34 cells employing immunobeads in leukaphresis products from patients with breast cancer and lymphomas shows high purity and yield of CD34 cells. In spite of this, contaminating tumor cells can be observed, strongly suggesting that a combination of CD34 cell enrichment and a purging procedure might be warranted.

Antibodies, Monoclonal↗

Immunomagnetic purging of lymphoma cells from autografts.

This report describes experiences at the Norwegian Radium Hospital in immunomagnetic purging of lymphoma from autologous stem cell grafts by negative and positive selection. Clinical data from 83 patients who received purged marrow grafts and 3 patients who received purged, mobilized leukapheresis products are presented. Early data indicate that immunomagnetic enrichment of CD34+ cells from leukapheresis products does not routinely achieve effective purging, as 1%-2% residual lymphoma cells could still be detected in the selected grafts.

Hematopoietic Stem Cell Transplantation↗

Clinical stage I and II Hodgkin's disease: long-term results of therapy without laparotomy. Experience at one institution.

BACKGROUND: We concluded a program in which we administered radiotherapy only to clinical stages I and II Hodgkin's disease patients at standard risk, with the addition of 4 cycles of combination chemotherapy before radiotherapy for high-risk patients. PATIENTS AND METHODS: From 1980 to 1991, 313 patients with clinical stages I or II Hodgkin's disease underwent treatment in our hospital. Fifty percent of the patients in groups previously identified as being at high risk for relapse received 4 cycles of combination chemotherapy before radiotherapy. The remaining half of the patients received radiotherapy only. RESULTS: Low- and high-risk patients aged 15-59 years had, respectively, complete remission (CR) rates of 97% and 94%, 5-year survivals of 95% and 91%, and 5-year freedom from relapse (FFR) rates of 78% and 89%. Older low- and high-risk groups had CR rates of 97% and 93%, 5-year survivals of 60% and 56% and 5-year FFR of 77% and 93%, respectively. CONCLUSION: Here we present our favorable results after treating standard-risk patients with clinical stages I and II Hodgkin's disease with radiotherapy only. With the addition of chemotherapy, the rate of relapse in the high-risk patients was reduced below that of the standard-risk patients. Overall survival was the same for the high- and standard-risk patients.

Adolescent↗

Prognostic variables and results of salvage treatment in Hodgkin's disease.

Treatment results and prognostic variables were studied in 549 adult patients with Hodgkin's disease after first-line and salvage treatment. After first-line treatment, 479 out of 549 patients (87%) achieved complete remission (CR). During a mean observation time of 74 months, 99 patients (21%) relapsed. Sixty-nine patients (70% of relapsed patients) achieved a second CR. Variables predicting poor response (< CR) and shortened survival after first-line treatment were advanced disease, B-symptoms and age >60 years. In relapsing patients, age >60 years, relapse within 12 months and non-CR after relapse treatment predicted a poor prognosis, and none of these patients were alive after 10 years. Localized disease at diagnosis and relapse, and relapse later than 24 months predicted a good prognosis with 10-year survival after relapse of 68% and 57%, respectively. Patients with a second relapse had 5-year survival of 28% and 10-year survival of 14%. Based on the prognostic variables at first-line treatment and at relapse, selection of patients to more intensive treatment is discussed.

Adolescent↗

ChlVPP is as effective as alternating ChlVPP/ABOD in advanced stage Hodgkin's disease.

The purpose of the study was to evaluate and compare the efficacy and tolerability of two cytostatic regimens-chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) vs. ChlVPP alternating with doxorubicin, bleomycin, vincristine and dacarbazine (ABOD). One hundred eligible patients with stage IIIA-IVB Hodgkin's disease were randomized to either ChlVPP or ChlVPP alternating with ABOD. The complete response rate (CR) was 80% in both treatment groups. After a median follow-up time of 59 months, 42 (84%) of the patients in the ChlVPP-treated group were in CR compared with 39 (78%) treated with ChlVPP/ABOD. The estimated five-year overall and relapse-free survival rates were 87% and 74%, respectively, for the ChlVPP-treated patients and 76% and 73% for the ChlVPP/ABOD-treated patients. The ChlVPP regimen showed a slightly better subjective tolerance than the ChlVPP/ABOD regimen. The given dose intensity was very close to optimal, and equal for the two regimens.

Adult↗

Activation of coagulation and deep vein thrombosis after bone marrow harvesting and insertion of a Hickman-catheter in ABMT patients with malignant lymphoma.

Evidence of activation of coagulation was sought in serial plasma samples from 25 ABMT candidates with malignant lymphoma admitted for bone marrow harvesting: 10 females and 15 males, median age 41 years (range 27-58 years). Nineteen patients had non-Hodgkin's lymphoma (NHL) and six had Hodgkin's disease. Of those with NHL, 14 had high-grade and five low- grade disease. The plasma levels of markers of activation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, fibrinopeptide A and fibrinmonomers) increased significantly (P < 0.001) in association with harvesting. Except for fibrinopeptide A, the indicators of activation were still significantly elevated 24 h after marrow aspiration. Beta-thromboglobulin, a marker of the platelet release reaction, also increased significantly (P < 0.01). Four out of nine patients in whom a long-term central venous catheter was inserted just after marrow aspiration, developed catheter-related deep vein thrombosis, verified venographically, shortly after harvesting. These results suggest that patient with malignant lymphoma undergoing marrow harvesting develop a hypercoagulable state, and that insertion of a central intravenous catheter immediately after marrow harvesting should be avoided to prevent the development of symptomatic deep vein thrombosis.

Adult↗

Leukemic blasts with markers of four cell lineages in Down's syndrome ("megakaryoblastic leukemia").

Among 16 patients with Down's syndrome (DS) and acute leukemia admitted to our department during a ten year period, 6 were diagnosed as acute megakaryoblastic leukemia (AMkL). The diagnosis was based on clinical and hematologic criteria, confirmed in three patients with the use of monoclonal antibodies (MoAb) specific for megakaryocytic antigens. In these three, and in a fourth patient, the leukemic blasts were positive for other myeloid, lymphoid and erythroid markers in MoAb testing. We suggest that AMkL in DS is a mixed lineage leukemia with blasts presenting a variety of cell surface antigens, indicating origin from an early progenitor cell with the capability of megakaryocytic differentiation. Of the 6 patients with AMkL, 4 treated with standard AML protocols are in complete continuing remission (CCR) with observation periods from 57+ to 148+ months.

Adolescent↗