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Gösta Gahrton

Publications and source records attributed to Gösta Gahrton.

13 recordsLinked to original sources
PubMed2006

Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning.

Despite the widespread adoption of reduced-intensity conditioning (RIC) for myeloma, there are few data comparing outcomes with RIC with myeloablative conditioning (MAC). We report the outcomes of patients undergoing allogeneic transplantations for myeloma and reported to the EBMT. A minimum data set was available on 320 RIC and 196 MAC allografts performed between 1998 and 2002. The RIC patients were older (51 vs 45 years) with more progressive disease (28% vs 21%) and more had received a prior transplant (76% vs 11%). In addition, there was a longer time to transplantation and an increased use of peripheral blood and T-cell depletion. For RIC and MAC, respectively, the nonrelapse mortality (NRM) at 2 years was 24% and 37% (P = .002); overall survival, 38.1% and 50.8% (not significant [ns]); and progression-free survival (PFS), 18.9% and 34.5% (P = .001). On multivariate analysis, RIC was associated with a reduction in NRM (HR, 0.5), but this was offset by an increase in relapse risk (HR, 2.0), and the conditioning intensity did not impact on overall survival or retain significance for PFS. These data suggest that there is a continuing need to investigate dose intensity in the conditioning for myeloma allografts.

Adult↗
PubMed2006

Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase.

The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.

Adjuvants, Immunologic↗
PubMed2005

Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation.

Using the European Group for Blood and Marrow Transplantation (EBMT) registry, we retrospectively studied 19 patients with AL (amyloid light-chain) amyloidosis who underwent allogeneic (allo; n = 15) or syngeneic (syn; n = 4) hematopoietic stem cell transplantation (SCT) between 1991 and 2003. For allo-SCT, full-intensity conditioning was used in 7 patients and reduced-intensity conditioning (RIC) in 8 patients. Engraftment was durable in 12 of those 15 patients. The median follow-up time is 19 months. Kaplan-Meier probabilities of overall and progression-free survival were 60% and 53% at 1 year, respectively. Overall, 40% of patients died of transplant-related mortality (TRM). Best hematologic response after SCT was complete remission (CR) and partial remission (PR) in 8 and 2 patients, respectively, leading to an organ response in 8 of these patients. Seven of the 10 patients in remission are long-term survivors. In 5 of 7 evaluable patients in CR, chronic graft-versus-host disease (GvHD) was observed, indicating the contribution of immune effects to disease control. The main clinical problem was cardiac failure in patients with poor performance status due to amyloidosis or in combination with severe infections. These data suggest that allo-SCT might be a promising and potentially curative treatment modality for selected patients with AL amyloidosis.

Adult↗
PubMed2005

Distinctive gene expression pattern in VH3-21 utilizing B-cell chronic lymphocytic leukemia.

The usage of the immunoglobulin (Ig) V(H)3-21 gene is associated with poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) despite V(H) gene mutation status. Many V(H)3-21+ patients also display restricted heavy- and light-chain Ig gene rearrangements, implying a role of antigen selection in disease development. To explore the specific phenotypic/genotypic features among V(H)3-21+ B-CLLs, we compared gene expression patterns in 15 V(H)3-21+ and 24 non-V(H)3-21 patients (11 with unmutated and 13 with mutated V(H) genes) using Affymetrix microarray analysis (approximately 12,500 genes). A distinct expression profile was identified for V(H)3-21+ patients in contrast to the Ig-unmutated and -mutated groups. By applying different algorithms, the data enabled an efficient class discrimination of the V(H)3-21+ subset based on 27 or 57 genes. A set of genes was sorted out which, using different analytical methods, consistently gave a distinction between V(H)3-21+ and non-V(H)3-21 samples. Several of these genes are involved in regulation of DNA replication/cell-cycle control, transcription and protein kinase activity, which may render the V(H)3-21+ cells with a higher proliferative drive. However, no clear evidence of increased B-cell receptor signaling was found in the V(H)3-21+ group. Altogether, our identification of a specific V(H)3-21 profile may provide insights into the pathogenesis of the V(H)3-21+ subgroup.

Aged↗
PubMed2005

Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT.

We report the outcome of 229 patients who received an allograft for myeloma with reduced-intensity conditioning (RIC) regimens from 33 centers within the European Group for Blood and Marrow Transplantation (EBMT). The median age was 52 years and 64% were male. Conditioning regimens were heterogeneous, but most were fludarabine based and T cell depleted with antithymocyte globulin or alemtuzumab. Transplantation-related mortality (TRM) at 1 year was 22%. The 3-year overall survival (OS) and progression-free survival (PFS) were 41% and 21%, respectively. Adverse OS was associated with chemoresistant disease (relative risk [RR], 2.9), more than 1 prior transplantation (RR, 2.0), and male patients with female donors (RR, 1.45). Adverse PFS was associated with chemoresistance (RR, 2.4) and alemtuzumab (RR, 1.8). TRM was increased with female-to-male donation (RR, 2.5) and transplantation more than 1 year from diagnosis (RR, 2.3). Grades II to IV acute graft-versus-host disease (aGvHD) occurred in 31%. Chronic GvHD was associated with better OS and PFS and were 84% and 46% for limited, 58% and 30% for extensive, and 29% and 12% in its absence suggesting that a graft-versus-myeloma effect is important. While RIC is feasible, heavily pretreated patients and patients with progressive disease do not benefit.

Adult↗
PubMed2005

Identification of progression markers in B-CLL by gene expression profiling.

OBJECTIVE: B-cell chronic lymphocytic leukemia is a heterogeneous disease with a pronounced variation in the clinical course. With the purpose of identifying genes that could be related to disease progression, we have performed gene expression profiling on B-CLL patients with an indolent disease and patients with a progressive disease with need for therapy. MATERIALS AND METHODS: we applied the Affymetrix GeneChip technique to 11 B-CLL patients with stable and 10 patients with clinically progressive disease. Supervised and unsupervised clustering methods with different algorithms were used to identify genes that tend to give a distinction between stable and progressive disease. RESULTS: The supervised learning procedures identified groups of genes with a combined power to discriminate samples from progressive and stable disease with 70-90% accuracy. The gene for protein phosphatase 2 regulatory subunit B' (B56) gamma isoform (PPP2R5C) and the gene for retinoblastoma-like 2 (p130) (RBL2) were included among the best discriminators; both genes were downregulated in progressive as compared to stable B-CLL. In a hierarchical clustering analysis based on gene expression pattern three clinical subcategories could be identified: one with a more severe clinical outcome, a second one with good prognosis, and a third one that was intermediate between the other two groups. CONCLUSIONS: Our application of microarray analysis on a clinically well defined material has identified a number of genes with combined expression patterns related to stable or progressive disease in general. Unsupervised clustering suggested the existence of subclasses of samples in the progressive group that may be identifiable through gene expression patterns.

Aged↗
PubMed2005

Progress in hematopoietic stem cell transplantation in multiple myeloma.

PURPOSE OF REVIEW: An attempt is made to value the place of autologous and allogeneic hematopoietic stem cell transplantation in the treatment of multiple myeloma. Recent progress with each treatment modality has significantly changed the outcome for myeloma patients. RECENT FINDINGS: The gold standard for conditioning treatment before autologous transplantation is melphalan 200 mg/m, and the use of peripheral blood stem cells is superior to that of bone marrow. Tandem autologous transplantation is superior to single autologous transplantation, at least for patients who do not respond with complete remission to the first transplant. Allogeneic transplantation using standard high-dose myeloablative conditioning reduces the relapse rate in comparison with autologous transplantation; however, treatment-related mortality is significantly higher. Progress in allogeneic transplantation has been significant, and transplant-related mortality has been reduced. The recent use of nonmyeloablative reduced-intensity conditioning has significantly decreased transplant-related mortality; however, the relapse rate is higher than with standard conditioning, and therefore no significant improvement in overall survival has as yet been seen. Relapse following allogeneic transplantation can be counteracted by donor lymphocyte infusions, but the survival results are so far inconclusive. SUMMARY: Autologous transplantation is still the first choice for most myeloma patients, but it does not seem to be curative. Therefore, allogeneic transplantation should be continued in clinical trials exploring new conditioning methods, the graft-versus-myeloma effect of new cell types, and its combination with new targeted drugs such as bortezomib and lenalidomide.

Hematopoietic Stem Cell Transplantation↗
PubMed2004

Disruption of a novel ectodermal neural cortex 1 antisense gene, ENC-1AS and identification of ENC-1 overexpression in hairy cell leukemia.

Karyotypical alteration of chromosome 5 and in particular band 5q13 is a frequent finding in hairy cell leukemia (HCL). We have previously identified a number of candidate genes localized in close proximity to a constitutional inv(5)(p13.1q13.3) breakpoint in one HCL patient. These included beta-hexosaminodase HEXB, frequently mutated in the lysosomal storage disorder Sandhoff disease. We now report that the 5q13.3 breakpoint disrupts a novel evolutionary conserved alternative isoform of HEXB. This isoform directly overlaps, in a cis-antisense fashion, exon 1 of the gene for ectodermal neuronal cortex 1 ENC-1, and was thus named ENC-1AS. ENC-1 has previously been shown to be overexpressed in several malignancies, and is believed to play a critical regulatory role in malignant transformation of various tumors. Importantly, subsequent analysis of ENC-1 in purified primary HCL tumor cells revealed a striking upregulation of ENC-1 in all 26 patients examined, compared with normal peripheral blood lymphocytes from healthy donors. Upon further analysis of the ENC-1/ENC-1AS locus, we identified a complex 5' regulatory mechanism involving an inverse expression of the ENC-1 sense and the ENC-1AS transcripts in several tissues supporting the hypothesis that expression of ENC-1AS regulates ENC-1 levels. In addition, we have also found tissue-specific methylation of a 1.2 kb segment encompassing the overlapping ENC-1/ENC-1AS 5' exons, adding to the complexity of the regulation of this locus. Altogether, these results suggest that upregulation of ENC-1 contributes to the development of HCL and provides new information on the possible dysregulation of ENC-1 including expression of a novel antisense gene, ENC-1AS.

Base Sequence↗
PubMed2004

Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia: BMT prolongs survival.

INTRODUCTION: Whether busulphan-treated patients develop blastic transformation earlier than hydroxyurea treated has been a controversial issue. In a randomised prospective study, we examined the busulphan versus hydroxyurea influence on time to blast crisis and on survival. When we opened our study in 1984, the clinical benefit of allogeneic bone marrow transplantation (BMT) was not well known; to follow up the long-time outcome of this treatment was therefore of great interest. MATERIALS AND METHODS: Previously untreated CML patients were randomly started on either hydroxyurea (30 mg/kg/day) or busulphan (0.1 mg/kg/day). The end points of the study were overall survival and time to blast crisis. A total of 26 patients subsequently underwent BMT. RESULTS: A total of 179 patients were randomised, 90 of hydroxyurea, and 89 to busulphan treatment. There was no significant difference in survival between hydroxyurea- and busulphan-treated patients (P = 0.46); median survival was 3.5 and 3.2 years, respectively. In all, 85 of the patients were subsequently diagnosed with blast crisis, 41 in the busulphan and 44 in the hydroxyurea group. There was no significant difference between the two groups (P = 0.91). The 26 patients who were allotransplanted survived significantly longer than those who were not transplanted (P = 0.0001). The 5-year-survival rates were 50 and 22% and the 10-year-survival rates were 46 and 2%, respectively. The median survival was 4.7 years for the transplanted and 3.3 years for the nontransplanted patients. CONCLUSION: We did not find any difference between hydroxyurea and busulphan treatment, either in overall survival or in blast crisis-free survival; transplanted patients survived significantly longer than nontransplanted patients.

Adolescent↗
PubMed2002

Goals and activities of the WMDA. World Marrow Donor Association.

The World Marrow Donor Association (WMDA) has the goal to facilitate reliable transfer of bone marrow and other forms of hematopoietic stem cells from one country to another, to promote exchange of information internationally about how to identify suitable donors and to protect the welfare and safety of the donor. It establishes guidelines on standards, ethics and other issues related to the goal of the WMDA. Full voting organisational members are those who deal directly with the donors and the logistics of hematopoietic stem cell transfer internationally for transplantation. Other members are non-voting organisational members and individual corresponding members (general members). They are working on, or interested in hematopoietic stem cell transplantation or science in the field. In order to execute its task, WMDA has several working groups that make proposals to the Board that takes decisions related to WMDA goals.

Hematopoietic Stem Cells↗