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Biomedical subjects

G Tjønnfjord

Publications and source records attributed to G Tjønnfjord.

15 recordsLinked to original sources
PubMed2006

Polyclonal expansion of large granular lymphocytes in common variable immunodeficiency - association with neutropenia.

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency disease, characterized by low levels of circulating immunoglobulins and recurrent bacterial infections, particularly of the respiratory tract. T cell dysfunction is often present, and lymphoproliferative and autoimmune disorders as well as haematological cytopenias are frequently observed. In this study, we report a polyclonal expansion of large granular lymphocytes (LGL) in a substantial proportion of CVID patients, associated with splenomegaly, increased numbers of CD8(+) T cells, inverted CD4 : CD8 T cell ratios and neutropenia. CVID patients who had both increased numbers of LGL and granulocytopenia had elevated levels of soluble Fas ligand (sFasL). Our observations indicate that CVID may be added to the list of inflammatory diseases associated with increased numbers of LGL. Furthermore, our findings suggest common pathogenic mechanisms of granulocytopenia in CVID and lymphoproliferative disease of granular lymphocytes.

Adult↗
PubMed2003

Fewer relapses and increased chronic GVHD in patients transplanted with blood stem cells: a 5-year follow-up in a single centre study.

A total of 61 consecutive adult patients with haematological malignancies with an HLA-identical or one antigen-mismatched haploidentical family donor were randomised to allogeneic transplantation with blood stem cells (BSC) or bone marrow (BM). The median observation time was 5 years. Apart from engraftment parameters and acute graft-versus-host disease (GVHD), transplant-related mortality (TRM), incidence and severity of chronic GVHD, relapse, leukaemia-free survival (LFS) and overall survival (OS) were recorded. In the BSC and BM group, respectively, TRM was 8/30 and 4/30 (P=0.405), the incidence of chronic GVHD was 15/26 and 11/30 (P=0.138), extensive chronic GVHD was 10/26 and 4/30 (P=0.034), and relapse one and 10 patients (P=0.007). In log-rank test restricted to the cases allografted from HLA-identical donors, the difference remained significant with regard to relapse incidence (P=0.039), but not extensive chronic GVHD (P=0.072). No difference in LFS and OS was observed. In conclusion, our study strongly indicates an enhanced graft-versus-leukaemia effect in BSC recipients, which is not expressed in increased survival. The increased chronic GVHD in these patients may contribute, but the relation is complex and not yet understood.

Adolescent↗
PubMed2002

Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed.

PURPOSE: We conducted a retrospective analysis to evaluate the safety and efficacy of Campath-1H, an anti-CD52 humanized monoclonal antibody, in previously treated T-prolymphocytic leukemia (T-PLL) patients in a compassionate-use program. PATIENTS AND METHODS: Seventy-six patients with T-PLL (including four chemotherapy-naive patients) received 3, 10, and 30 mg of Campath-1H on sequential days, followed by 30 mg three times weekly, as 2-hour intravenous infusions, for 4 to 12 weeks. RESULTS: Median patient age was 60 years (range, 35 to 84). Spleen liver, lymph node, and skin involvement were present in 64%, 40%, 54%, and 18% of patients, respectively. All tested patients had CD2, CD7, CD4, and/or CD8 positivity, whereas CD5 and CD3 were positive in 98% and 96% of tested patients, respectively. The objective response rate was 51% (95% confidence interval [CI], 40% to 63%), with a 39.5% complete response (CR) rate (95% CI, 28% to 51%). The median duration of CR was 8.7 months (range, 0.13+ to 44.4), and median time to progression was 4.5 months (range, 0.1 to 45.4) compared with 2.3 months (range, 0.2 to 28.1) after first-line chemotherapy. The median overall survival was 7.5 months (14.8 months for CR patients). The most common Campath-1H-related adverse events were acute reactions during or immediately after infusions. Fifteen infectious episodes occurred during treatment in 10 patients (13%), leading to treatment discontinuation in three. Eight patients experienced possibly related, late-onset infections. Severe thrombocytopenia and/or neutropenia occurred in six patients (8%), leading to treatment discontinuation in four. Two treatment-related deaths occurred. CONCLUSION: Campath-1H is an active drug in T-PLL patients for whom first-line therapy has failed. It has a favorable risk/benefit ratio and should be prospectively investigated in chemotherapy-naive patients.

Adult↗
PubMed2002

Donation of stem cells from blood or bone marrow: results of a randomised study of safety and complaints.

Biological consequences and physical complaints were compared for donors randomly assigned either to blood stem cell (BSC) or bone marrow (BM) donation. In the period 1994-1999, 61 consecutive donors were included. The BSC donors were given G-CSF 10 microg/kg s.c., daily during 5 days before the first leukapheresis. Nineteen donors had one leukapheresis, 10 required two and one donor needed three leukaphereses in order to reach the target cell number of 2 x 10(6) CD34(+) cells/kg bw of the recipient. A median platelet nadir of 102 x 10(9)/l was reached shortly after the last leukapheresis. Three weeks post harvest, 17 of 30 BSC donors had a mild leukopenia. Six had a leukopenia lasting more than a year before returning to normal values. Both groups were monitored prospectively through a standardised questionnaire completed by the donors. BSC donation was significantly less burdensome than BM donation and was preferred by the donors. The short-term risks of BSC mobilisation and harvest seem negligible. The potential long-term effects of G-CSF are unresolved and the donors must be followed closely.

Adolescent↗
PubMed2000

A randomised study of allogeneic transplantation with stem cells from blood or bone marrow.

Sixty-one consecutive adult patients with leukaemia, primary myelofibrosis or myelodysplastic syndrome with an HLA-identical or one antigen mismatched family donor were randomised to allogeneic transplantation with PBPC or BM. Progenitor cells were mobilised into the blood by giving the donors 10 microg/kg/day G-CSF subcutaneously for 5-7 days. G-CSF was not given to patients after transplantation. The time to neutrophil counts >0.5 x 109/l was 17 days (95% CI 15.2-18.8 days) in the PBPC group compared to 23 (95% CI 20.3-25.7 days) in the BM group (P = 0.0005). The time to platelet counts >20 x 109/l was 13 days (95% CI 11.7-14.3 days) in the PBPC group and 21 days (95% CI 18.7-23.3 days) in the BM group (P = 0.0005). Acute GVHD of grades II-IV developed in six patients transplanted with PBPC and three patients transplanted with BM. The numbers of patients with chronic GVHD were 15 and 8, respectively. Transplant-related mortality and leukaemia-free survival showed no significant differences. Transplantation with PBPC appears preferable for the recipient due to faster neutrophil and platelet recovery. However, the final conclusion can not be drawn before long-term results on chronic GVHD and relapse incidence in longer randomised trials are available.

Adolescent↗
PubMed2000

New strategies in the treatment of acute myelogenous leukemia: mobilization and transplantation of autologous peripheral blood stem cells in adult patients.

During the last decade high-dose Ara-C (HIDAC; single doses of 3 g/m(2)) and autologous stem cell transplantation have been increasingly used as postremission therapy in adult acute myelogenous leukemia (AML). Controlled clinical trials have demonstrated a long-term disease-free survival of 40%-50% for patients treated with at least two courses of HIDAC. Other studies have demonstrated that postremission autologous bone marrow transplantation results in a disease-free survival equal to or better than conventional chemotherapy. However, autotransplantation with mobilized peripheral blood stem cells (PBSC) would now be preferred instead of autologous bone marrow, due to the shorter hematopoietic reconstitution period. The results reviewed in the present article suggest that HIDAC and autologous PBSC transplantation can be combined in the postremission treatment of adult AML, and this combination therapy may also reduce minimal residual disease and the risk of posttransplant relapse. From the available studies it cannot be concluded whether graft purging further reduces the relapse risk. However, the possible advantage of combination therapy with repeated courses of HIDAC and autologous PBSC transplantation needs to be demonstrated in prospective clinical trials before it can be recommended as a part of the routine treatment in AML.

Adult↗
PubMed1996

Direct growth suppression of myeloid bone marrow progenitor cells but not cord blood progenitors by human cytomegalovirus in vitro.

Recently, considerable interest has arisen as to use cord blood (CB) as a source of hematopoietic stem cells for allogenic transplantation when bone marrow (BM) from a familial HLA-matched donor is not available. Because human cytomegalovirus (HCMV) has been shown to inhibit the proliferation of BM progenitors in vitro, it was important to examine whether similar effect could be observed in HCMV-infected CB cells. Therefore, the effect of HCMV challenge on the proliferation of myeloid progenitors from BM and CB was compared using both mononuclear cells (MNC) and purified CD34+ cells. A clinical isolate of HCMV inhibited the colony formation of myeloid BM progenitors responsive to granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, macrophage-CSF, interleukin-3 (IL-3) and the combination of IL-3 and stem cell factor (SCF). In contrast, colony growth of CB progenitors was not affected. In addition, HCMV inhibited directly the growth of purified BM CD34+ cells responsive to IL-3 and SCF in single cell assay by 40%, wheras the growth of CD34+ progenitors obtained from CB was not suppressed. The HCMV lower matrix structural protein pp65 and HCMV DNA were detected in both CB and BM CD34+ cells after in vitro challenge. However, neither immediate early (IE)-mRNA nor IE proteins were observed in infected cells. Cell cyclus examination of BM and CB CD34+ cells revealed that 25.7% of BM progenitors were in S + G2/ M phase wheras only 10.7% of the CB progenitors. Thus, a clinical isolate of HCMV directly inhibited the proliferation of myeloid BM progenitors in vitro wheras CB progenitors were not affected. This difference in the susceptibility of CB and BM cells to HCMV may partly be caused by the slow cycling rate of naive CB progenitors compared to BM progenitors at the time of infection.

Adult↗
PubMed1995

Neutropenic fever following cladribine therapy for symptomatic hairy-cell leukemia: predictive factors and effects of granulocyte-macrophage colony-stimulating factor.

BACKGROUND: Neutropenic fever is the commonest complication of cladribine therapy for hairy-cell leukemia (HCL), leading to a 3% mortality rate. Our aim was to identify predictive factors and evaluate the effects of concomitant granulocyte-macrophage colony-stimulating factor (GM-CSF). PATIENTS AND METHODS: We studied 102 patients with active HCL given cladribine for 7 days. Pretreatment parameters predicting neutropenic fever were analysed. Twelve patients at high risk for febrile complications also received 400 micrograms GM-CSF per day on days 1 through 21. RESULTS: Pretreatment anemia, hypocholesterolemia, bone marrow differential with a high percentage of hairy cells and a low percentage of myelopoietic cells, low albumin, and high C-reactive protein predicted neutropenic fever. The addition of GM-CSF did not improve the kinetics of recovery for neutrophils, hemoglobin or platelets, as compared to matched control patients. However, GM-CSF significantly reduced cladribine-induced lymphopenia, but not the incidence of neutropenic fever. CONCLUSION: Factors predicting febrile neutropenia were identified. GM-CSF protected from cladribine lymphotoxicity but did not improve neutropenia or febrile episodes.

Cladribine↗
PubMed1995

Low-dose cladribine for symptomatic hairy cell leukaemia.

Cladribine is an effective therapy for hairy cell leukaemia (HCL), but the standard regime is frequently complicated by neutropenic fever and prolonged T-cell depression. We studied 102 patients with active HCL following treatment with various doses of cladribine given for 7 d. Two patients received 1 mg cladribine/m2/d without toxicity or effect. Eight subsequent patients received 2 mg cladribine/m2/d, and normalized cytopenia as quickly as 94 control patients receiving a standard dose (3.4 mg/m2 or 0.085 mg/kg), with significantly less lymphopenia and a similar complete remission rate.

Adult↗
PubMed1995

Subcutaneous injections of 2-chlorodeoxyadenosine for symptomatic hairy cell leukemia.

PURPOSE: To evaluate the clinical efficacy and safety of 2-chlorodeoxyadenosine (CdA) when administered by subcutaneous injection to patients with symptomatic hairy cell leukemia (HCL), and to evaluate predictive factors for response. PATIENTS AND METHODS: Seventy-three patients were given CdA as a subcutaneous injection once daily for 7 days. Complete remission (CR) required normalized blood counts and the absence of B-ly 7-positive bone marrow cells by flow cytometry. CdA concentrations in plasma following the first injection were analyzed by high-pressure liquid chromatography. RESULTS: Fifty-nine patients (81%) achieved a durable CR after one (n = 55) or two courses, and 10 had a partial remission (PR). With a median follow-up duration of 20 months, no patient had a clinical relapse. Neutropenic fever that required intravenous antibiotics occurred in 28 patients (38%). No toxicity at injection sites was observed. Incomplete response was predicted by an elevated lymphocyte count and serum beta 2-microglobulin level, and by a high percentage of hairy cells in the bone marrow. Plasma CdA levels were similar to those achieved from intravenous administration. CONCLUSION: Subcutaneous injection of CdA is safe and as effective as continuous infusion without problems associated with the mode of administration. Our schedule simplifies CdA treatment and can be generally recommended.

Adult↗
PubMed1994

Estimated 8-year survival of more than 40% in a population-based study of 79 adult patients with acute lymphoblastic leukaemia.

We report 11 years experience with a modified version of a chemotherapy programme in use at the MRC Leukaemia Unit from 1982 to 1984, supplemented by allogeneic bone marrow transplantation in first relapse or second or later remission from 1985. 79 consecutive patients aged 15-60 years with newly diagnosed acute lymphoblastic leukaemia (ALL) were given induction chemotherapy. This included a standard DAT course (daunorubicin, cytarabine and thioguanine) applied as in acute myelogenous leukaemia approximately midway in the induction programme. A 3-year rotating maintenance programme consisted of combinations of cytotoxic drugs used in the induction therapy. CNS prophylaxis did not include CNS irradiation. Allogeneic BMT was not performed in first remission. The overall complete remission (CR) rate was 82% (65/79). 26 patients relapsed (seven first in the CNS). Seven patients underwent allogeneic BMT of whom six are alive and well with a mean observation time of 32 months (range 4-99 months) after transplantation. Three patients died in first CR. Estimated 5- and 8-year overall survival was 51% (95% confidence interval (CI) 39-63) and 47% (CI 33-61). For patients who reached CR, the corresponding figures were 63% (CI 50-76) and 57% (CI 41-73). Estimated disease-free survival in the remitters was 54% (CI 40-68) at 5 years and 44% (CI 28-60) at 8 years. Patient age below 25 years and white cell count below 15 x 10(9)/l at presentation were both found to improve the chance of overall survival.

Adolescent↗
PubMed1992

Survival in 91 adults with acute myelogenous leukaemia treated with 1-6 intensive courses of chemotherapy.

Ninety-one patients with acute myelogenous leukaemia (AML) aged 17-59 years were treated with a chemotherapy programme which could be completed within 30 weeks for patients who achieved complete remission (CR). Four courses included daunorubicin, cytarabine and thioguanine, while two courses included amsacrine, etoposide and cytarabine. Sixty-five patients obtained CR (71%), more often in patients below (82%) than above (60%) 40 years of age (P = 0.03). Five patients underwent allogenic bone-marrow transplantation, and one patient received an autologous bone-marrow transplant after relapse. Five patients developed central nervous system leukaemia. The overall actuarial 3- and 5-year survival was 29% and 21%, respectively; for patients who obtained CR the corresponding survival rates were 40% and 30%, respectively. Patients below 40 years of age appeared to fare better (5-year survival 26%) than older patients (5-year survival 16%). The estimated disease-free survival rate was 26% at 3 years and 22% at 5 years. The main advantage of this regimen is that results compare favourably with those obtained with other regimens were achieved, without exposing patients to long periods of maintenance therapy.

Actuarial Analysis↗
PubMed1990

[Folic acid deficiency can cause severe anemia and pancytopenia].

Pancytopenia is occasionally a consequence of folate deficiency. The most important differential diagnostic considerations are haematologic malignancies, aplastic anaemia and vitamin B12 deficiency. We discuss the problem as exemplified by three patients. Bone marrow examination and determination of blood concentrations of vitamin B12 and folate will give the correct diagnosis.

Adult↗