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Find video protocols related to scientific articles indexed in Pubmed.
The role of allogeneic stem cell transplantation in Hodgkin's lymphoma.
Curr Treat Options Oncol
PUBLISHED: 04-23-2014
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The treatment of patients with classical Hodgkin's lymphoma relapsing after autologous stem cell transplantation represents a clear unmet need. Overall long-term outcome is not the same in these patients and therapeutic options in this setting are very heterogeneous and include salvage CT and/or RT followed or not by a second stem cell transplantation, palliative care, new drugs, or biological agents. Despite the absence of prospective, randomized, clinical trials, allogeneic stem cell transplantation either from a HLA identical sibling or a matched, unrelated donor represents an attractive option for those young patients with chemosensitive disease after being treated with a salvage protocol. The use of reduced intensity conditioning regimens has been able to drastically decrease nonrelapse mortality, although relapse rate remains a significant issue in this setting. More intense conditioning protocols could eventually decrease the relapse rate after the allogeneic procedure and, as indicated by a recent retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation, nonrelapse mortality does not represent a major problem nowadays for patients with multiply relapsed Hodgkin's lymphoma. Brentuximab vedotin is an antibody-drug conjugate that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. Its use has been approved recently for patients with Hodgkin's lymphoma relapsing after autologous stem cell transplantation. As a single dose, brentuximab vedotin is able to achieve an objective response rate of 75 % with 34 % of the patients achieving a complete remission. Its widespread use will most certainly change the treatment paradigm of this subgroup of patients, either avoiding the allogeneic procedure in some patients or by increasing the group of potential candidates to an allogeneic transplant being used as a "bridge to allo." Additional information on long-term outcome of patients being treated with this drug or the development of prospective clinical trials in this setting will most probably give some light to this question we have nowadays.
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Outcomes of hematopoietic cell transplantation for diffuse large B cell lymphoma transformed from follicular lymphoma.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-11-2014
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There are limited data on the outcomes of autologous or allogeneic hematopoietic cell transplantation (HCT) in diffuse large B cell lymphoma transformed from follicular lymphoma. We analyzed transplantation outcomes in 141 subjects with biopsy-proven diffuse large B-cell lymphoma transformed from follicular lymphoma reported to the Center for International Blood and Marrow Transplant Research between 1990 and 2009. Two groups were identified: autologous HCT (auto-HCT; n = 108) and allogeneic HCT (allo-HCT; n = 33). Fewer auto-HCTs were done for transformed follicular lymphoma in 2003 to 2009, with a shift favoring allo-HCT. Auto-HCT was associated with a 1-year nonrelapse mortality (NRM) of 8% (95% confidence interval [CI], 4% to 14%), 5-year progression-free survival of 35% (95% CI, 26% to 45%), and 5-year overall survival of 50% (95% CI, 40% to 59%). In contrast, allo-HCT was associated with a 1-year NRM of 41% (95% CI, 23% to 58%), 5-year progression-free survival of 18% (95% CI, 6% to 35%), and 5-year overall survival of 22% (95% CI, 8% to 41%). Auto-HCT for transformed follicular lymphoma achieves sustained remission in a high proportion of subjects. The high NRM of allo-HCT offset any benefit that might be associated with this transplantation modality.
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Use of the quality management system "JACIE" and outcome after hematopoietic stem cell transplantation.
Haematologica
PUBLISHED: 01-31-2014
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Competent authorities, healthcare payers and hospitals devote increasing resources to quality management systems but scientific analyses searching for an impact of these systems on clinical outcome remain scarce. Earlier data indicated a stepwise improvement in outcome after allogeneic hematopoietic stem cell transplantation with each phase of the accreditation process for the quality management system "JACIE". We therefore tested the hypothesis that working towards and achieving "JACIE" accreditation would accelerate improvement in outcome over calendar time. Overall mortality of the entire cohort of 107,904 patients who had a transplant (41,623 allogeneic, 39%; 66,281 autologous, 61%) between 1999 and 2006 decreased over the 14-year observation period by a factor of 0.63 per 10 years (hazard ratio: 0.63; 0.58-0.69). Considering "JACIE"-accredited centers as those with programs having achieved accreditation by November 2012, at the latest, this improvement was significantly faster in "JACIE"-accredited centers than in non-accredited centers (approximately 5.3% per year for 49,459 patients versus approximately 3.5% per year for 58,445 patients, respectively; hazard ratio: 0.83; 0.71-0.97). As a result, relapse-free survival (hazard ratio 0.85; 0.75-0.95) and overall survival (hazard ratio 0.86; 0.76-0.98) were significantly higher at 72 months for those patients transplanted in the 162 "JACIE"-accredited centers. No significant effects were observed after autologous transplants (hazard ratio 1.06; 0.99-1.13). Hence, working towards implementation of a quality management system triggers a dynamic process associated with a steeper reduction in mortality over the years and a significantly improved survival after allogeneic stem cell transplantation. Our data support the use of a quality management system for complex medical procedures.
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Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood.
Haematologica
PUBLISHED: 08-09-2013
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We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97%, respectively, p<0.0001) and chronic graft versus host disease (26% vs. 52%, P=0.0005) were less frequent after unrelated cord blood than after matched unrelated donor, whereas no differences were observed in grade II-IV acute graft versus host disease (29% vs. 32%), non-relapse mortality (29% vs. 28%), and relapse or progression (28% vs. 35%) at 36 months. There were also no significant differences in two-year progression-free survival (43% vs. 58%, respectively) and overall survival (36% vs. 51%) at 36 months. In a multivariate analysis, no differences were observed in the outcomes between the two stem cell sources except for a higher risk of neutrophil engraftment (hazard ratio = 2.12, p= p<0.0001) and chronic graft versus host disease (hazard ratio: 2.10, p=0.0002) after matched unrelated donor transplant. In conclusion, final outcomes after transplantation were not different between umbilical cord blood and matched unrelated donor transplant. Umbilical cord blood is a valuable alternative for patients with lymphoid malignancies lacking an HLA-matched donor, being associated with lower risk of chronic graft versus host disease.
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Early thymus and activation-regulated chemokine (TARC) reduction and response following panobinostat treatment in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplant.
Leuk. Lymphoma
PUBLISHED: 08-05-2013
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In a phase 2 trial of panobinostat in 129 patients with relapsed or refractory Hodgkin lymphoma, exploratory analyses of chemokines and cytokines were prospectively performed in 109 patients to determine their association with clinical outcomes. Patients were categorized into two groups (reductions > median and reductions ? median) based on percentage change from baseline of log10 transformed measurements. Thymus and activation-regulated chemokine (TARC) was most strongly associated with clinical outcome. Early reduction of TARC was observed in responding patients, with the greatest reduction at cycle 1, day 15 (C1D15). Of 93 patients with C1D15 samples, there were three complete and 25 partial responses. The group with TARC reductions > median at C1D15 had more responders (18 [39%] vs. 10 [21%]), longer progression-free survival (10.6 vs. 4.9 months), shorter time to response and longer overall survival than the group with reductions ? median. This study is registered at www.ClinicalTrials.gov , NCT00742027.
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Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma: a consensus project of the EBMT-Lymphoma Working Party.
Haematologica
PUBLISHED: 07-02-2013
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The aim of this project was to define indications for hematopoietic stem cell transplantation in follicular lymphoma in Europe. In the absence of evidence-based data, a RAND-modified Delphi procedure was used by an expert panel. After pre-defining statements, these were individually/anonymously scored by each participant using a 9-point scale. Consensus was reached that: 1) high-dose therapy with autologous stem cell rescue is not an appropriate option to consolidate first remission in patients responding to immuno-chemotherapy outside clinical trials; 2) in patients with first chemo-sensitive relapse, high-dose therapy with autologous stem cell rescue is an appropriate option to consolidate remission, especially in patients with a short response after immuno-chemotherapy or with high-risk FLIPI; 3) high-dose therapy with autologous stem cell rescue is also appropriate in second/subsequent chemo-sensitive relapses; 4) allotransplant (preferably a reduced intensity conditioning-allotransplant) should be considered at relapse after high-dose therapy with autologous stem cell rescue. No consensus was reached on the role of high-dose therapy with autologous stem cell rescue in low-risk first relapse, or on when an allotransplant should be preferred over high-dose therapy with autologous stem cell rescue. In the absence of evidence-based data, the consensus method used was a valuable tool to define indications for hematopoietic stem cell transplant in follicular lymphoma.
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Hematopoietic stem cell transplantation in patients with lymphomatoid granulomatosis: a European group for blood and marrow transplantation report.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-18-2013
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Lymphomatoid granulomatosis (LG) is a very rare, Epstein-Barr virus-associated lymphoproliferative disorder of B cells. Prognosis is poor, particularly after relapse and no curative treatment exists. We report the results of high-dose therapy and autologous stem cell transplantation (ASCT) or reduced-intensity conditioning and allogeneic stem cell transplantation (alloSCT) in patients with multiply relapsed LG. A European Group for Blood and Marrow Transplantation survey identified 10 patients who had received 9 ASCT and 4 alloSCT. All patients had active disease at the time of transplantation. With a median follow-up of 5.1 (range, 1.4 to 6.3) years, 6 patients are alive and disease-free. Two ASCT patients died of septicemia early after transplantation, and 1 committed suicide after being in continuous complete remission 19 months after ASCT. Another patient allografted 4 years after ASCT remained disease-free but died of severe graft-versus-host disease 3 months after alloSCT. High-dose therapy followed by ASCT and alloSCT are effective therapeutic options and should be considered in all patients with refractory and multiply relapsed LG.
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Pharmacogenetic analysis in the treatment of Hodgkin lymphoma.
Leuk. Lymphoma
PUBLISHED: 02-01-2013
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About 15-20% of patients with Hodgkin lymphoma (HL) treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy ± radiotherapy still die following relapse or progressive disease. The outcome might be influenced by gene polymorphisms influencing chemotherapy metabolism. We studied 126 patients with HL treated with the ABVD regimen. We analyzed glutathione S-transferases (GSTT1, GSTM1 and GSTP1), cytochromes P450 (CYP3A4 and CYP2D6), UGT1A1 and BLMH gene polymorphisms and their association with clinical and outcome variables. Patients with a GSTM1 genotype associated with extensive or ultrahigh activity had a probability of 93.8% to achieve a complete response, while the remainder of the patients had a probability of 82.3% (p = 0.04). This variable maintained its statistical significance in multivariate analysis (hazard ratio 3.7, 95% confidence interval 1-13, p = 0.05). Patients with an extensive or ultrahigh GSTM1 genotype had better prognostic factors than those with poor or intermediate genotypes (hemoglobin level, p = 0.003; serum albumin, p = 0.05; and International Prognostic Score, p = 0.038). Thus, in the treatment of HL, clinical determinants might be more relevant than the pharmacogenetic parameters analyzed to date.
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Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT.
Blood
PUBLISHED: 01-29-2013
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Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of peripheral T-cell lymphomas with a poor prognosis. Autologous stem cell transplantation (ASCT) was retrospectively evaluated as a consolidation or salvage strategy for EATL. The analysis included 44 patients who received ASCT for EATL between 2000 and 2010. Thirty-one patients (70%) were in first complete or partial remission at the time of the ASCT. With a median follow-up of 46 months, relapse incidence, progression-free survival, and overall survival were 39%, 54%, and 59% at 4 years, respectively, with only one relapse occurring beyond 18 months posttransplant. There was a trend for better survival in patients transplanted in first complete or partial remission at 4 years (66% vs 36%; P = .062). ASCT is feasible in selected patients with EATL and can yield durable disease control in a significant proportion of the patients.
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High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma.
Blood
PUBLISHED: 11-29-2011
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The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated.
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Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkins lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (G
Haematologica
PUBLISHED: 10-11-2011
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Although Hodgkins lymphoma is a highly curable disease with modern chemotherapy protocols, some patients are primary refractory or relapse after first-line chemotherapy or even after high-dose therapy and autologous stem cell transplantation. We investigated the potential role of allogeneic stem cell transplantation in this setting.
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Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance.
Blood
PUBLISHED: 09-06-2011
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Cytogenetic abnormalities (CAs) such as t(4;14), t(14;16) or del(17p), and nonhyperdiploidy are associated with poor prognosis in multiple myeloma. We evaluated the influence of CAs by FISH and DNA ploidy by flow cytometry on response and survival in 232 elderly, newly diagnosed multiple myeloma patients receiving an induction with weekly bortezomib followed by maintenance therapy with bortezomib-based combinations. Response was similar in the high-risk and standard-risk CA groups, both after induction (21% vs 27% complete responses [CRs]) and maintenance (39% vs 45% CR). However, high-risk patients showed shorter progression-free survival (PFS) than standard-risk patients, both from the first (24 vs 33 months; P = .04) and second randomization (17 vs 27 months; P = .01). This also translated into shorter overall survival (OS) for high-risk patients (3-year OS: 55% vs 77%; P = .001). This adverse prognosis applied to either t(4;14) or del(17p). Concerning DNA ploidy, hyperdiploid patients showed longer OS than nonhyperdiploid patients (77% vs 63% at 3 years; P = .04), and this was more evident in patients treated with bortezomib, thalidomide, and prednisone (77% vs 53% at 3 years; P = .02). The present schema does not overcome the negative prognosis of high-risk CAs and nonhyperdiploidy. This trial was registered with www.ClinicalTrials.gov as NCT00443235.
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High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era: an analysis based on data from the European Blood and Marrow Transplantation Registry.
Biol. Blood Marrow Transplant.
PUBLISHED: 07-19-2011
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Autologous stem cell transplantation (ASCT) consolidation remains the treatment of choice for patients with relapsed diffuse large B cell lymphoma. The impact of rituximab combined with chemotherapy in either first- or second-line therapy on the ultimate results of ASCT remains to be determined, however. This study was designed to evaluate the benefit of ASCT in patients achieving a second complete remission after salvage chemotherapy by retrospectively comparing the disease-free survival (DFS) after ASCT for each patient with the duration of the first complete remission (CR1). Between 1990 and 2005, a total of 470 patients who had undergone ASCT and reported to the European Blood and Bone Transplantation Registry with Medical Essential Data Form B information were evaluated. Of these 470 patients, 351 (74%) had not received rituximab before ASCT, and 119 (25%) had received rituximab before ASCT. The median duration of CR1 was 11 months. The median time from diagnosis to ASCT was 24 months. The BEAM protocol was the most frequently used conditioning regimen (67%). After ASCT, the 5-year overall survival was 63% (95% confidence interval, 58%-67%) and 5-year DFS was 48% (95% confidence interval, 43%-53%) for the entire patient population. Statistical analysis showed a significant increase in DFS after ASCT compared with duration of CR1 (median, 51 months versus 11 months; P < .001). This difference was also highly significant for patients with previous exposure to rituximab (median, 10 months versus not reached; P < .001) and for patients who had experienced relapse before 1 year (median, 6 months versus 47 months; P < .001). Our data indicate that ASCT can significantly increase DFS compared with the duration of CR1 in relapsed diffuse large B cell lymphoma and can alter the disease course even in patients with high-risk disease previously treated with rituximab.
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The evolving role of stem cell transplants in lymphomas.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-03-2011
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Autologous stem cell transplantation (ASCT) is an established therapeutic modality in the treatment of lymphomas, especially in the relapse setting. It is also under investigation after first-line therapy, for example, in patients with mantle cell or T cell lymphomas. Each year more than 6000 autotransplants for lymphomas are reported to the European Blood and Marrow Transplantation (EBMT) registry. The number of allogeneic stem cell transplantations (alloSCT) in lymphoma patients has increased over the last decade, with about 1200 transplanted lymphoma patients annually reported to the registry. Optimal timing and indications for alloSCT are not well defined because of absence of randomized trials. Developments in the treatment of lymphomas including immunotherapy have changed the clinical scenarios in regard to ASCT, and many published studies are now outdated. On the other hand, patients relapsing after immunochemotherapy may derive less benefit from ASCT. Consequently, there is an increasing interest in using alloSCT not only in lymphoma patients relapsing after ASCT but also in earlier phases in specific circumstances. Although curative potential is higher with alloSCT compared with ASCT, its wider use has been hindered by excessive nonrelapse mortality (NRM). Along with decreasing NRM figures, popularity of alloSCT may increase in the near future, possibly with the expense of ASCT. Prospective, randomized studies are needed to evaluate feasibility and efficacy of alloSCT in several clinical settings, as most published evidence is based on retrospective registry data or single-center experiences.
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Pulmonary function testing prior to reduced intensity conditioning allogeneic stem cell transplantation in an unselected patient cohort predicts posttransplantation pulmonary complications and outcome.
Am. J. Hematol.
PUBLISHED: 05-21-2011
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Pretransplant pulmonary function tests (PFTs) have been checked mostly in myeloablative allogeneic stem cell transplantation (Allo-SCT). Their value in the setting of reduced intensity conditioning Allo-SCT (Allo-RIC) has been less explored. We retrospectively evaluated the predictive value of PFTs on posttransplant pulmonary complications (PPC) and outcomes in 195 consecutive Allo-RIC patients, based on fludarabine plus busulphan or melphalan. PFT parameters included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio, total lung capacity (TLC), residual volume, and diffusion capacity for carbon monoxide (DLCo) corrected for the hemoglobin levels. Pretransplant PFTs abnormalities were observed in 130 patients (66%). The most frequent abnormalities were abnormal DLCO (n = 83, 44%), followed by FEV1/FVC (n = 75, 38%) and FVC (n = 47, 24%). The abnormalities were severe in 25 (13%) patients, moderate in 65 (33%) and mild in 40 patients (21%). Multivariate analysis showed that TLC was significantly associated with PPC, nonrelapse mortality and overall survival (OS), (HR 4.2, 95% CI. 2-8.5; HR 3.8, 95% CI. 1.7-8.5; HR 2.3, 95% CI. 1.3-4.1, respectively, P = 0.01), while abnormal FVC had a negative impact on PPC and OS (HR 1.8, 95% CI. 0.98-3.6, P = 0.06 and HR 1.7, 95% CI. 1.1-2.6, P = 0.008). This study emphasizes the valuable role of PFTs in identifying patients at risk for PPC, NRM, and lower OS in the Allo-RIC setting.
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Introduction of a quality management system and outcome after hematopoietic stem-cell transplantation.
J. Clin. Oncol.
PUBLISHED: 04-11-2011
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A comprehensive quality management system called JACIE (Joint Accreditation Committee International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation), was introduced to improve quality of care in hematopoietic stem-cell transplantation (HSCT). We therefore tested the hypothesis that the introduction of JACIE improved patient survival.
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Long-term prognostic significance of response in multiple myeloma after stem cell transplantation.
Blood
PUBLISHED: 04-11-2011
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For establishing the true effect of different response categories in patients with multiple myeloma (MM) treated with autologous stem cell transplantation, we evaluated, after a median follow-up of 153 months, 344 patients with MM who received a transplant between 1989 and 1998. Overall survival (OS) at 12 years was 35% in complete response (CR) patients, 22% in near complete response (nCR), 16% in very good partial response (VGPR), and 16% in partial response (PR) groups. Significant differences in OS and progression-free survival were found between CR and nCR groups (P = .01 and P = .002, respectively), between CR and VGPR groups (P = .0001 and P = .003), or between CR and PR groups (P = .003 and P = < 10(-5)); no differences were observed between the nCR and VGPR groups (P = .2 and P = .9) or between these groups and the PR group (P = .1 and P = .8). A landmark study found a plateau phase in OS after 11 years; 35% patients in the CR group and 11% in the nCR+VGPR+PR group are alive at 17 years; 2 cases had relapsed in the nCR+VGPR+PR group. In conclusion, MM achieving CR after autologous stem cell transplantation is a central prognostic factor. The relapse rate is low in patients with > 11 years of follow-up, possibly signifying a cure for patients in CR.
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Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkins lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry.
J. Clin. Oncol.
PUBLISHED: 02-14-2011
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To analyze the outcome, including nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS), of patients with diffuse large B-cell non-Hodgkins lymphoma (DLBCL) relapsed after an autologous stem-cell transplantation (ASCT) and treated with an allogeneic stem-cell transplantation (allo-SCT).
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Dose intensity of chemotherapy in patients with relapsed Hodgkins lymphoma.
J. Clin. Oncol.
PUBLISHED: 10-25-2010
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High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkins lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy.
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Allogeneic stem-cell transplantation in patients with Waldenström macroglobulinemia: report from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J. Clin. Oncol.
PUBLISHED: 10-18-2010
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Allogeneic stem-cell transplantation (alloSCT) is a curative therapeutic option for patients with low-grade lymphoid malignancies. Information regarding alloSCT in Waldenström macroglobulinemia (WM) is limited. This study presents the long-term outcome of a large series of patients with WM treated with alloSCT.
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Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J. Clin. Oncol.
PUBLISHED: 08-09-2010
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To analyze the outcome of allogeneic transplantation for mycosis fungoides and Sézary syndrome (MF/SS) in terms of nonrelapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) and to identify factors associated with the outcome.
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Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study.
Haematologica
PUBLISHED: 07-27-2010
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The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m(2) and melphalan 200 mg/m(2) as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study.
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XPC genetic polymorphisms correlate with the response to imatinib treatment in patients with chronic phase chronic myeloid leukemia.
Am. J. Hematol.
PUBLISHED: 06-25-2010
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Chronic myeloid leukemia (CML) is driven by the BCR-ABL protein, which promotes the proliferation and viability of the leukemic cells. Moreover, BCR-ABL induces genomic instability that can contribute to the emergence of resistant clones to the ABL kinase inhibitors. It is currently unknown whether the inherited individual capability to repair DNA damage could affect the treatment results. To address this, a comprehensive analysis of single nucleotide polymorphisms (SNPs) on the nucleotide excision repair (NER) genes (ERCC2-ERCC8, RPA1-RPA3, LIG1, RAD23B, XPA, XPC) was performed in 92 chronic phase CML patients treated with imatinib upfront. ERCC5 and XPC SNPs correlated with the response to imatinib. Haplotype analysis of XPC showed that the wild-type haplotype (499C-939A) was associated with a better response to imatinib. Moreover, the 5-year failure free survival for CA carriers was significantly better than that of the non-CA carriers (98% vs. 73%; P = 0.02). In the multivariate logistic model with genetic data and clinical covariates, the hemoglobin (Hb) level and the XPC haplotype were independently associated with the treatment response, with patients having a Hb < or =11 g/dl (Odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.5-16.1) or a non-CA XPC haplotype (OR = 4.1, 95% CI = 1.6-10.6) being at higher risk of suboptimal response/treatment failure. Our findings suggest that genetic polymorphisms in the NER pathway may influence the results to imatinib treatment in CML.
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High-dose therapy and autologous stem-cell transplantation in Waldenstrom macroglobulinemia: the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J. Clin. Oncol.
PUBLISHED: 04-05-2010
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The role of autologous stem-cell transplantation (ASCT) in Waldenström macroglobulinemia (WM) is not defined. The aim of this study was to analyze the results of ASCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome.
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Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials.
Haematologica
PUBLISHED: 01-27-2010
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Allogeneic hematopoietic stem cell transplantation is an effective treatment for patients with poor risk lymphoma, at least in part because of the graft-versus-lymphoma effect. Over the past decade, reduced intensity conditioning regimens have been shown to offer results similar to those of conventional high-dose conditioning regimens but with lower toxicity early after transplantation, especially in patients with chemosensitive disease at transplant.
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Matched unrelated donor stem cell transplant in 131 patients with follicular lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
Br. J. Haematol.
PUBLISHED: 09-30-2009
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Matched unrelated donor stem cell transplantation (MUD-SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD-SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced-intensity conditioning (RIC, n = 87) or conventional myeloablative (CONV, n = 44) MUD-SCT between 2000 and 2005 were included. Median time from diagnosis to MUD-SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft: 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD-SCT and had failed a previous autograft more frequently than CONV recipients. Non-relapse mortality (NRM) was 24% and 30% at 100-d and 1-year, respectively. After a median follow-up of 36 months, 17% of the patients developed disease progression, the 3-year progression-free survival (PFS) being 47%. Three-year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUD-SCT results, even in heavily pre-treated populations, in a meaningful PFS and OS.
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The persistence of immunophenotypically normal residual bone marrow plasma cells at diagnosis identifies a good prognostic subgroup of symptomatic multiple myeloma patients.
Blood
PUBLISHED: 09-15-2009
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Multiparameter flow cytometry immunophenotyping allows discrimination between normal (N-) and myelomatous (MM-) plasma cells (PCs) within the bone marrow plasma cell compartment (BMPCs). Here we report on the prognostic relevance of detecting more than 5% residual normal plasma cells from all bone marrow plasma cells (N-PCs/BMPCs) by multiparameter flow cytometry in a series of 594 newly diagnosed symptomatic MM patients, uniformly treated according to the Grupo Español de MM 2000 (GEM2000) protocol. Our results show that symptomatic MM patients with more than 5% N-PCs/BMPCs (n = 80 of 594; 14%) have a favorable baseline clinical prospect, together with a significantly lower frequency of high-risk cytogenetic abnormalities and higher response rates. Moreover, this group of patients had a significantly longer progression-free survival (median, 54 vs 42 months, P = .001) and overall survival (median, not reached vs 89 months, P = .04) than patients with less than or equal to 5% N-PCs/BMPCs. Our findings support the clinical value of detecting residual normal PCs in MM patients at diagnosis because this reveals a good prognostic category that could benefit from specific therapeutic approaches. This trial was registered at www.clinicaltrials.gov as NCT00560053.
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Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis.
Cancer
PUBLISHED: 07-31-2009
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It was investigated whether the European Group for Blood and Marrow Transplantation risk score, previously established for chronic myeloid leukemia, could be used to predict outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological disease in general.
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Allogeneic stem cell transplantation is able to induce long-term remissions in angioimmunoblastic T-cell lymphoma: a retrospective study from the lymphoma working party of the European group for blood and marrow transplantation.
J. Clin. Oncol.
PUBLISHED: 07-20-2009
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To analyze the long-term outcome in terms of nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS) in patients with angioimmunoblastic T-cell lymphoma (AITL) treated with allogeneic stem-cell transplantation (alloSCT).
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Advances in mobilization for the optimization of autologous stem cell transplantation.
Leuk. Lymphoma
PUBLISHED: 07-16-2009
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In autologous stem cell transplantation, mobilized peripheral blood has replaced the bone marrow as the preferred source of hematopoietic stem cells (HSCs). Because HSCs normally exist in the blood in very low numbers, the use of agents to "mobilize" HSCs from the marrow niche to the peripheral blood is essential for successful transplantation. Until recently, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor were the only approved agents by the US Food and Drug Administration for use as peripheral blood stem cell (PBSC)-mobilizing agents in the United States, but G-CSF has become the gold standard. Unfortunately, some patients fail to mobilize sufficient numbers of PBSCs for transplantation in response to G-CSF with or without chemotherapy. Recently, a new agent, plerixafor (AMD3100) added to G-CSF has been approved to enhance PBSC mobilization. This review will discuss the current methodologies to improve hematopoietic stem cell mobilization.
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Comparison of two pretransplant predictive models and a flexible HCT-CI using different cut off points to determine low-, intermediate-, and high-risk groups: the flexible HCT-CI Is the best predictor of NRM and OS in a population of patients undergoing a
Biol. Blood Marrow Transplant.
PUBLISHED: 07-02-2009
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Patient comorbidities are being increasingly analyzed as predictors for outcome after hematopoietic stem cell transplantation (HSCT), especially in allogeneic HSCT (Allo-HSCT). Researchers from Seattle have recently developed several pretransplant scoring systems (hematopoietic cell transplantation comorbidity index [HCT-CI] and the Pretransplantation Assessment of Mortality (PAM) model) from large sets of HSCT recipients with the aim of improving non-transplant models, mainly the Charlson Comorbidity Index (CCI). The validation of these comorbidity indexes in other institutions and in different disease and conditioning-related settings is of interest to determine whether these models are potentially applicable in clinical practice and in research settings. We performed a retrospective study in our institution including 194 consecutive reduced-intensity conditioning (RIC) AlloHSCT (allo-RIC) recipients to compare the predictive value of the PAM score, CCI, the original HCT-CI, and the flexible HCT-CI using a different risk group stratification. The median patient pretransplant scores for the HCT-CI, PAM, and CCI were 3.5, 22, and 0, respectively. The flexible HCT-CI risk-scoring system (restratified as: low risk [LR] 0-3 points, intermediate risk [IR] 4-5 points, and high risk [HR] >5 points) was the best predictor for non-relapse mortality (NRM). The 100-day and 2-year NRM incidence in these risk categories was 4% (95% confidence interval C.I. 2%-11%), 16% (95% C.I. 9%-31%), and 29% (95% C.I. 19%-45%), respectively (P < .001), and 19% (95% C.I. 12%-28%), 33% (95% C.I. 22%-49%), and 40% (95% C.I. 28%-56%), respectively (P=.01). However, we found no predictive value for NRM using neither the original HCT-CI nor the PAM or CCI models. The better predictive capacity for NRM of the flexible HCT-CI than PAM and CCI was confirmed with the c-statistics (c-statistics of 0.672, 0.634, and 0.595, respectively). Regarding the 2-year overall survival (OS), the flexible HCT-CI score categories were also associated with the highest predictive HR. In conclusion, our single-center study suggests that the flexible HCT-CI is a good predictor of 2-year NRM and survival after an allo-RIC.
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Allogeneic hematopoietic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin lymphoma: an analysis of the European Group for Blood and Marrow Transplantation.
Blood
PUBLISHED: 06-04-2009
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Ninety-one children and adolescents 18 years or younger after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed or refractory Hodgkin lymphoma (HL) were analyzed. Fifty-one patients received reduced intensity conditioning (RIC); 40 patients received myeloablative conditioning (MAC). Nonrelapse mortality (NRM) at 1 year was 21% (+/- 4%), with comparable results after RIC or MAC. Probabilities of relapse at 2 and 5 years were 36% (+/- 5%) and 44% (+/- 6%), respectively. RIC was associated with an increased relapse risk compared with MAC; most apparent beginning 9 months after HSCT (P = .01). Progression-free survival (PFS) was 40% (+/- 6%) and 30% (+/- 6%) and overall survival (OS) was 54% (+/- 6%) and 45% (+/- 6%) at 2 and 5 years, respectively. Disease status at HSCT was predictive of PFS in multivariate analysis (P < .001). Beyond 9 months, PFS after RIC was lower compared with MAC (P = .02). Graft-versus-host disease did not affect relapse rate and PFS. In conclusion, children and adolescents with recurring HL show reasonable results with allogeneic HSCT. Especially patients allografted in recent years with good performance status and chemosensitive disease show highly encouraging results (PFS: 60% +/- 27%, OS: 83% +/- 15% at 3 years). Because relapse remains the major cause of treatment failure, additional efforts to improve disease control are necessary.
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Early and late neurological complications after reduced-intensity conditioning allogeneic stem cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-28-2009
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Neurological complications (NC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are common and life-threatening in most cases. They may involve either the central (CNS) or peripheral nervous system (PNS). The aim of this study was to describe incidence and characteristics of NC after reduced-intensity conditioning allo-HSCT (allo-RIC), an unexplored setting. For this purpose, we reviewed 191 consecutive patients who underwent this procedure at our institution between January 1999 and December 2006. The median follow-up for survivors was 48 months (3-98 months). RIC included fludarabine (Flu) 150 mg/m(2) in combination with busulfan (Bu) 8-10mg/kg (n=61), melphalan (Mel) 70-140 mg/m(2) (n=119), cyclophosphamide (Cy) 120 mg/kg (n=7), or low-dose total body irradiation (TBI) 2Gy (n=4). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A (CsA) in combination with methotrexate (MTX; n=134) or mycophenolate mofetil (MMF; n=52). Twenty-seven patients (14%) developed a total of 31 NC (23 CNS and 8 PNS) for a 4-year cumulative incidence of 16% (95% confidence interval [CI] 11-23). CNS complications included nonfocal encephalopathies in 11 patients, meningoencephalitis in 5 patients, and stroke or hemorrhage in 4. PNS complications consisted of 5 cases of mononeuropathies and 3 cases of polyneuropathies. Drug-related toxicity was responsible for 10 of the 31 events (32%) (8 caused by CsA). Interestingly, 14 of the 23 CNS events (61%) and only 1 of the 8 PNS complications (13%) appeared before day +100 (P=.01). Overall, patients presenting NC showed a trend for higher 1-year nonrelapse mortality (NRM) (37% versus 20%, P=.08). In patients with CNS involvement, 1-year NRM was significantly worse (42% versus 20%, P=.02). CNS NC also had a negative impact on 4-year overall survival (OS; 33% versus 45%, P=.05). In conclusion, our study showed that NC are observed after allo-RIC and have diverse features. NC affecting the CNS have earlier onset and worse outcome than those involving the PNS.
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Autologous stem-cell transplantation in patients with HIV-related lymphoma.
J. Clin. Oncol.
PUBLISHED: 03-30-2009
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Peripheral-blood autologous stem-cell transplantation (ASCT) in patients with HIV-related lymphoma (HIV-Ly) has been reported as a safe and useful procedure. Herein we report the European Group for Blood and Marrow Transplantation experience on patients with HIV-Ly undergoing ASCT.
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Comparable survival between HIV+ and HIV- non-Hodgkin and Hodgkin lymphoma patients undergoing autologous peripheral blood stem cell transplantation.
Blood
PUBLISHED: 03-23-2009
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Autologous stem cell transplantation (ASCT) has been successfully used in HIV-related lymphoma (HIV-Ly) patients on highly active antiretroviral therapy. We report the first comparative analysis between HIV-Ly and a matched cohort of HIV(-) lymphoma patients. This retrospective European Group for Blood and Marrow Transplantation study included 53 patients (66% non-Hodgkin and 34% Hodgkin lymphoma) within each cohort. Both groups were comparable except for the higher proportion of males, mixed-cellularity Hodgkin lymphoma and patients receiving granulocyte colony-stimulating factor before engraftment and a smaller proportion receiving total body irradiation-based conditioning within the HIV-Ly cohort. Incidence of relapse, overall survival, and progression-free survival were similar in both cohorts. A higher nonrelapse mortality within the first year after ASCT was observed in the HIV-Ly group (8% vs 2%), predominantly because of early bacterial infections, although this was not statistically significant and did not influence survival. Thus, within the highly active antiretroviral therapy era, HIV patients should be considered for ASCT according to the same criteria adopted for HIV(-) lymphoma patients.
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Study of kidney function impairment after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. A single-center experience.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-13-2009
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Acute renal failure (ARF) is a life-threatening complication after allogeneic stem cell transplantation (Allo-HSCT). Identification of ARF risk factors could be useful to develop preventive strategies for patients at high risk. The goal of this study was to evaluate the incidence and risk factors of ARF after reduced intensity conditioning Allo-HSCT (Allo-RIC). We included 188 consecutive patients who underwent Allo-RIC in our center between January 1999 and December 2006. ARF was defined as a decrease of at least 25% in baseline estimated glomerular filtration rate (GFR) calculated by modification of diet in renal disease (MDRD) equation. Conditioning consisted of fludarabine (Flu) 150 mg/m(2) in combination with busulfan (Bu) 8-10 mg/kg (n = 61), melphalan (Mel) 140 mg/m(2) (n = 115), cyclophosphamide (Cy) 120 mg/kg (n = 7) or low-dose total-body irradiation (TBI) 2 Gy (n = 5). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A (CsA) alone (n = 3) or in addition to methotrexate (MTX; n = 132) or mycophenolate mofetil (MMF; n = 51). The cumulative incidence of ARF at 1 year was 52% (n = 97 patients) after Allo-RIC. Most cases (86%) occurred within the first 3 months, and the main cause was the administration of CsA (71%). The risk factors associated with ARF in multivariate analysis were: administration of MTX (hazard ratio [HR] 1.9, P =.02), more than 3 lines of therapy prior to Allo-RIC (HR 1.8, P = .01), diabetes mellitus (HR 2.1, P < .01), and GVHD grade III-IV (HR 2.1, P = .015). In multivariate analysis, ARF was an independent risk factor for 1-year nonrelapse mortality (NRM) (HR 3, 95% confidence interval [CI]: 1.5-6, P = .002). Patients who experienced ARF had lower 1-year overall survival (OS; 53% versus 74%, P < .05). ARF is a frequent complication in patients after Allo-RIC, and it has a negative impact on outcome. Identification of ARF risk factors could help to avoid exposure to nephrotoxic drugs during the follow-up in patients at high risk.
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Stem cell transplantation can provide durable disease control in blastic plasmacytoid dendritic cell neoplasm: a retrospective study from the European Group for Blood and Marrow Transplantation.
Blood
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Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have a poor prognosis with conventional chemotherapy. In the present study, we retrospectively analyzed the outcome of patients with BPDCN who underwent allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (auto-SCT). A total of 39 patients (allo-SCT, n = 34; auto-SCT, n = 5) were identified in the European Group for Blood and Marrow Transplantation registry. The 34 allo-SCT patients had a median age of 41 years (range, 10-70) and received transplantations from sibling (n = 11) or unrelated donors (n = 23) between 2003 and 2009. MAC was used in 74% of patients. Nineteen allo-SCT patients (56%) received transplantations in first complete remission. The 3-year cumulative incidence of relapse, disease-free survival, and overall survival was 32%, 33%, and 41%, respectively. By univariate comparison, being in first remission at allo-SCT favorably influenced survival, whereas age, donor source, and chronic GVHD had no significant impact. We conclude that high-dose therapy followed by allo-SCT from related or unrelated donors can provide durable remission even in elderly patients with BPDCN. However, it remains to be shown if graft-versus-malignancy effects can contribute significantly to BPDCN control after allo-SCT.
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The role of hematopoietic stem cell transplantation in the treatment of relapsed/refractory Hodgkins lymphoma.
Curr Opin Oncol
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Autologous stem cell transplantation (ASCT) represents the treatment of choice for primary refractory or relapsed Hodgkins lymphoma patients. Nevertheless, the results of ASCT are not universally uniform in all groups of patients. Allogeneic stem cell transplantation (allo-SCT) has increasingly been used to rescue failures after an ASCT. Its use is going to be potentially challenged by the advent of targeted therapy.
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Multiparameter flow cytometry evaluation of plasma cell DNA content and proliferation in 595 transplant-eligible patients with myeloma included in the Spanish GEM2000 and GEM2005<65y trials.
Am. J. Pathol.
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The incorporation of high-dose therapy/autologous stem cell transplantation (HDT/ASCT) and novel agents has significantly improved survival in patients with multiple myeloma (MM), but whether this improvement also benefits patients harboring poor prognostic features, such as nonhyperdiploid MM (NH-MM) and a high proliferation index, remains largely unknown. We analyzed the DNA content and proliferation index of bone marrow plasma cells (PCs) by multiparameter flow cytometry in 595 newly diagnosed transplant-eligible patients with MM included in two consecutive PETHEMA/GEM trials: GEM2000 [VBMCP/VBAD (vincristine, carmustine, melphalan, cyclophosphamide, prednisone/vincristine, bischloroethylnitrosourea, adriamycin, and dexamethasone) followed by HDT/ASCT; n = 319] and GEM2005<65y (randomized induction with VBMCP/VBAD/bortezomib or thalidomide/dexamethasone or bortezomib/thalidomide/dexamethasone followed by HDT/ASCT; n = 276). Of the 595 patients, 295 were classified as NH-MM (49.6%) and 336 (56.5%) as high-proliferative MM (?1% PCs in S-phase). Detection of NH-MM DNA content and ?1% PCs in S-phase were of independent prognostic value for overall survival. Treatment with bortezomib-based regimens abrogated the inferior overall survival of patients with ?1% PCs in S-phase but not of patients with NH-MM. Finally, a comparative analysis of PC proliferation index at diagnosis versus disease progression showed a twofold increase at relapse in 44 of 52 patients (85%) analyzed at both time points. NH-MM and a high proliferation index assessed by multiparameter flow cytometry remain as independent prognostic factors in MM, but the latter may be overcome by incorporating novel agents in the HDT/ASCT setting.
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Autologous and allogeneic stem-cell transplantation for transformed chronic lymphocytic leukemia (Richters syndrome): A retrospective analysis from the chronic lymphocytic leukemia subcommittee of the chronic leukemia working party and lymphoma working pa
J. Clin. Oncol.
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Patients with Richters syndrome (RS) have a poor prognosis with conventional chemotherapy. The aim of this study was to evaluate the outcome after autologous stem-cell transplantation (autoSCT) or allogeneic stem-cell transplantation (alloSCT) in RS.
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Panobinostat in patients with relapsed/refractory Hodgkins lymphoma after autologous stem-cell transplantation: results of a phase II study.
J. Clin. Oncol.
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Hodgkins lymphoma (HL) has no standard of care for patients who are relapsed or refractory to autologous stem-cell transplantation (ASCT). This phase II study examined safety and activity of panobinostat in this population.
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Efficacy, safety and quality-of-life associated with lenalidomide plus dexamethasone for the treatment of relapsed or refractory multiple myeloma: the Spanish experience.
Leuk. Lymphoma
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Here we report the efficacy, safety and health-related quality-of-life (HRQoL) associated with long-term lenalidomide and dexamethasone (Len + Dex) treatment in patients with relapsed or refractory multiple myeloma (RRMM) enrolled in the Spanish cohort of the MM-018 study. In this open-label, multicenter, single-arm expanded access study, 63 patients received Len + Dex until disease progression. The overall response rate was 78%, with 21% of the patients achieving a complete response. The quality of response improved with continuous treatment. The median duration of response was 18.4 months. Median time-to-progression and progression-free survival was 13.3 months for both; median overall survival was not reached. Len + Dex had a manageable safety profile consistent with previously reported phase III studies. HRQoL assessments (n = 42) at baseline and 6 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ MY-20 questionnaires revealed that patients with RRMM treated with long-term lenalidomide reported clinically relevant improvements in certain QoL and symptoms scores regardless of treatment response (ClinicalTrials.gov: NCT00420849).
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