20 results on '"Nevill, Thomas"'
Search Results
2. Majocchi's granuloma in a patient with GATA2 haploinsufficiency undergoing hematopoietic stem cell transplantation.
- Author
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Roy C, Belga S, Lavergne V, and Nevill TJ
- Subjects
- GATA2 Transcription Factor genetics, Humans, Trichophyton, GATA2 Deficiency genetics, Hematopoietic Stem Cell Transplantation adverse effects, Tinea
- Published
- 2022
- Full Text
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3. Mortality from Multiple Myeloma Within One Year Following Autologous Stem Cell Transplantation: Defining an Ultra-high Risk Population.
- Author
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Cherniawsky HM, AlAhwal H, Mourad YA, Forrest D, Gerrie A, Kuchenbauer F, Nantel SH, Narayanan S, Nevill T, Power M, Sanford D, Toze C, White J, Escano L, Sutherland H, and Song K
- Subjects
- Adult, Aged, Disease-Free Survival, Female, Humans, Male, Middle Aged, Multiple Myeloma therapy, Neoplasm Recurrence, Local therapy, Progression-Free Survival, Retrospective Studies, Risk Assessment statistics & numerical data, Risk Factors, Time Factors, Transplantation, Autologous statistics & numerical data, Hematopoietic Stem Cell Transplantation statistics & numerical data, Multiple Myeloma mortality, Neoplasm Recurrence, Local mortality
- Abstract
Despite improvements in therapy, approximately 5% of patients who undergo autologous stem cell transplantation (ASCT) experience early mortality (EM), death within 1 year of transplant (EM post-ASCT). Such patients tend to have few comorbidities suggesting their EM is owing to aggressive underlying disease. We sought to characterize this ultra-high risk population through a retrospective review of patients with newly diagnosed multiple myeloma (MM) treated with first-line ASCT. Patients who died within 1 year of ASCT were matched for age, sex, and year of transplant in a 1:2 fashion with a control group. Of 962 transplants performed between January 1, 2007, and May 1, 2019, 41 patients (4.3%) died within 1 year of ASCT from MM-related causes. In a multivariate analysis, anemia, hypercalcemia, high-risk cytogenetics, and elevated lactate dehydrogenase were associated with EM post-ASCT. Forty patients (97.6%) received at least 1 novel agent. Most patients with EM post-ASCT received second-line chemotherapy (80.5%), although survival from initiation of second-line chemotherapy was only 2.1 months. The primary reason for not receiving second-line therapy was rapid relapse. Clinical parameters reflecting disease burden, as well as high-risk cytogenetics, are associated with EM post-ASCT. These patients have a dismal overall survival despite significant advances in treatment of patients with relapsed or refractory myeloma. Further study of these ultra-high risk patients is required to improve disease management and may give further insights into the biology of relapse and resistance in myeloma., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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4. Outpatient Autologous Stem Cell Transplants for Multiple Myeloma: Analysis of Safety and Outcomes in a Tertiary Care Center.
- Author
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Kodad SG, Sutherland H, Limvorapitak W, Abou Mourad Y, Barnett MJ, Forrest D, Gerrie A, Hogge DE, Nantel SH, Narayanan S, Nevill T, Power M, Sanford D, Toze C, White J, Broady R, and Song K
- Subjects
- Adult, Aged, Biomarkers, Female, Humans, Male, Middle Aged, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Neoplasm Staging, Outpatients, Retrospective Studies, Tertiary Care Centers, Transplantation, Autologous, Treatment Outcome, Ambulatory Care methods, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy
- Abstract
Background: Autologous stem cell transplant (ASCT) is the preferred consolidation strategy to treat eligible patients with multiple myeloma (MM) and related plasma cell dyscrasias. Given the increasing volume of patients and longer wait time, outpatient ASCT for MM is the standard of care at the Vancouver General Hospital., Patients and Methods: Patients with MM, POEMS syndrome, and amyloidosis undergoing ASCT were included in this analysis. We analyzed patient characteristics, the number of patients requiring admission, duration of admission, 30-day and 100-day mortality, and overall survival., Results: Between January 2007 and June 2016, 724 patients underwent 752 ASCTs. Of these, 702 were first ASCTs, 44 were second, and 6 were third. The median age was 60 years (interquartile range [IQR], 54-65 years). Reasons for ASCTs were MM (96.9%) amyloidosis (2.4%), and POEMS syndrome (0.7%). There were 431 (59.5%) males in this group. The median time from diagnosis to transplant was 5 months. Conditioning was melphalan 200 mg/m
2 for 89.6% of the patients. Admission to the inpatient ward was required by 245 (32.6%) patients within the first 30 days. The median time to admission was 9 days post-transplant (IQR, 5-13 days). The median duration of admission was 6 days (IQR, 3-9 days). The day 100 all-cause mortality rate was 0.9%, and transplant-related mortality was 0.4%., Conclusion: Outpatient ASCT is a safe and feasible treatment strategy with low transplant-related mortality. Overall resource utilization is significantly lower than inpatient ASCT: however, this requires a multidisciplinary approach with close follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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5. Improving Revised International Prognostic Scoring System Pre-Allogeneic Stem Cell Transplantation Does Not Translate Into Better Post-Transplantation Outcomes for Patients with Myelodysplastic Syndromes: A Single-Center Experience.
- Author
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Alzahrani M, Power M, Abou Mourad Y, Barnett M, Broady R, Forrest D, Gerrie A, Hogge D, Nantel S, Sanford D, Song K, Sutherland H, Toze C, Nevill T, and Narayanan S
- Subjects
- Adolescent, Adult, Aged, Blast Crisis pathology, Cell Count, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Middle Aged, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes pathology, Myelodysplastic Syndromes therapy, Predictive Value of Tests, Recurrence, Retrospective Studies, Risk Factors, Survival Analysis, Transplantation Conditioning methods, Transplantation, Homologous methods, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes diagnosis, Prognosis
- Abstract
The natural history of patients with myelodysplastic syndromes (MDS) is variable. The Revised International Prognostic Score (IPSS-R) is commonly used in practice to predict outcomes in patients with MDS at both diagnosis and before hematopoietic stem cell transplantation (HSCT). However, the effect of change in the IPSS-R before allogeneic HSCT with chemotherapy or hypomethylating agents on post-transplantation outcomes is currently unknown. We assessed whether improvement in IPSS-R prognostic score pre-HSCT would result in improvement in clinical outcomes post-HSCT. Secondary goals included studying the effect of prognostic factors on post-transplantation survival. All patients with MDS who underwent allogeneic HSCT at the Leukemia/BMT Program of British Columbia between February 1997 and April 2013 were included. Pertinent information was reviewed from the program database. IPSS-R was calculated based on data from the time of MDS diagnosis and before HSCT. Outcomes of patients who had improved IPSS-R pre-HSCT were compared with those with stable or worse IPSS-R. Overall survival (OS) and event-free survival (EFS) were estimated using the Kaplan-Meier method, with P values determined using the log-rank test. Hazard ratios were calculated using multivariable Cox proportional hazards regression models to study the effects of the prognostic variables on OS and EFS. A total of 138 consecutive patients were included. IPSS-R improved in 62 of these patients (45%), worsened in 23 (17%), remained stable in 41 (30%), and was unknown in 12 (9%). OS was not statistically different across the improved, worsened, and stable groups (30% versus 22% versus 40%, respectively; P = .63). The cumulative incidences of relapse and nonrelapse mortality at 5 years were 28.4% (95% confidence interval [CI], 21.1 to 36.1) and 31.6% (95% CI, 23.8 to 39.7), respectively. The rate of relapse was 23% in patients with <5% blasts at the time of HSCT, 69% in those with 5% to 20% blasts, and 66% in those with >20% blasts (P = .0004). In the entire cohort OS was 34% and EFS was 33%. There was no significant difference in outcomes between patients who received myeloablative conditioning and those who received nonmyeloablative conditioning before HSCT (OS, 34% and 39%, respectively; P = .63 and EFS, 34% and 32%, respectively; P = .86). OS was not statistically different among patients with improved, worsened, or stable IPSS-R. On multivariate analysis, only 3 factors were associated with OS: cytogenetic risk group at diagnosis, blast count at transplantation, and the presence or absence of chronic graft-versus-host disease. Improving IPSS-R before HSCT does not translate into better survival outcomes. Blast count pretransplantation was highly predictive of post-transplantation outcomes., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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6. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial.
- Author
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Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, Moore J, Nevill T, Popradi G, Roy J, Schultz KR, Szwajcer D, Toze C, and Foley R
- Subjects
- Adult, Allografts, Animals, Antilymphocyte Serum adverse effects, Chronic Disease, Female, Herpesvirus 4, Human physiology, Humans, Immunologic Factors adverse effects, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Preoperative Care methods, Rabbits, Young Adult, Antilymphocyte Serum therapeutic use, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation methods, Immunologic Factors therapeutic use, Transplantation Conditioning methods, Virus Activation drug effects
- Abstract
Background: Pretreatment with anti-thymocyte globulin (ATG) decreases the occurrence of chronic graft-versus-host disease (CGVHD) after haemopoietic cell transplantation from an unrelated donor, but evidence of patient benefit is absent. We did a study to test whether ATG provides patient benefit, particularly in reducing the need for long-term immunosuppressive treatment after transplantation., Methods: We did a phase 3, multicentre, open-label, randomised controlled trial at ten transplant centres in Canada and one in Australia. Eligible patients were aged 16 to 70 years with any haematological malignancy and a Karnofsky score of at least 60 receiving either myeloablative or non-myeloablative (or reduced intensity) conditioning preparative regimens before haemopoietic cell transplantation from an unrelated donor. We allocated patients first by simple randomisation (1:1), then by a minimisation method, to either pretransplantation rabbit ATG plus standard GVHD prophylaxis (ATG group) or standard GVHD prophylaxis alone (no ATG group). We gave a total dose of ATG of 4·5 mg/kg intravenously over 3 days (0·5 mg/kg 2 days before transplantation, 2·0 mg/kg 1 day before, and 2·0 mg/kg 1 day after). The primary endpoint was freedom from all systemic immunosuppressive drugs without resumption up to 12 months after transplantation. Analysis was based on a modified intention-to-treat method. This trial was registered at ISRCTN, number 29899028., Findings: Between June 9, 2010, and July 8, 2013, we recruited and assigned 203 eligible patients to treatment (101 to ATG and 102 to no ATG). 37 (37%) of 99 patients who received ATG were free from immunosuppressive treatment at 12 months compared with 16 (16%) of 97 who received no ATG (adjusted odds ratio 4·25 [95% CI 1·87-9·67]; p=0·00060. The occurrence of serious adverse events (Common Terminology Criteria grades 4 or 5) did not differ between the treatment groups (34 [34%] of 99 patients in the ATG group vs 41 [42%] of 97 in the no ATG group). Epstein-Barr virus reactivation was substantially more common in patients who received ATG (20 [one of whom died-the only death due to an adverse event]) versus those who did not receive ATG (two [no deaths]). No deaths were attributable to ATG., Interpretation: ATG should be added to myeloblative and non-myeloblative preparative regimens for haemopoietic cell transplantation when using unrelated donors. The benefits of decreases in steroid use are clinically significant. Epstein-Barr virus reactivation is increased, but is manageable by prospective monitoring and the use of rituximab. Future trials could determine whether the doses of ATG used in this trial are optimum, and could also provide additional evidence of a low relapse rate after non-myeloablative regimens., Funding: The Canadian Institutes of Health Research and Sanofi., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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7. Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced Disease or Failing Treatment with Tyrosine Kinase Inhibitors.
- Author
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Nair AP, Barnett MJ, Broady RC, Hogge DE, Song KW, Toze CL, Nantel SH, Power MM, Sutherland HJ, Nevill TJ, Abou Mourad Y, Narayanan S, Gerrie AS, and Forrest DL
- Subjects
- Adult, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Male, Middle Aged, Protein Kinase Inhibitors pharmacology, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Protein Kinase Inhibitors therapeutic use, Salvage Therapy methods, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 (P = .04), and complete molecular response (CMR) to HSCT (P < .0001). Donor (female) to patient (male) gender combination (P = .02) and CMR to HSCT (P < .0001) predicted lower relapse. In multivariate analysis, CMR to HSCT remained an independent predictor of OS (odds ratio [OR], 43), EFS (OR, 56) and relapse (OR, 29). This report indicates that the outlook is excellent for those patients who remain in CP1 at the time of HSCT and achieve a CMR after HSCT. However, only approximately 50% of those in advanced phase at HSCT are long-term survivors. This highlights the ongoing need to try to identify patients earlier, before disease progression, who are destined to fail this treatment to optimize transplantation outcomes., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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8. Outcome of Patients With Non-Hodgkin Lymphomas With Concurrent MYC and BCL2 Rearrangements Treated With CODOX-M/IVAC With Rituximab Followed by Hematopoietic Stem Cell Transplantation.
- Author
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Sun H, Savage KJ, Karsan A, Slack GW, Gascoyne RD, Toze CL, Sehn LH, Abou Mourad Y, Barnett MJ, Broady RC, Connors JM, Forrest DL, Gerrie AS, Hogge DE, Narayanan S, Nevill TJ, Nantel SH, Power MM, Sutherland HJ, Villa D, Shepherd JD, and Song KW
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Cytarabine administration & dosage, Disease-Free Survival, Doxorubicin administration & dosage, Etoposide administration & dosage, Female, Humans, Ifosfamide administration & dosage, Lymphoma, Non-Hodgkin pathology, Male, Methotrexate administration & dosage, Middle Aged, Retrospective Studies, Rituximab administration & dosage, Survival Rate, Treatment Outcome, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Gene Rearrangement, Genes, bcl-2 genetics, Genes, myc genetics, Hematopoietic Stem Cell Transplantation, Lymphoma, Non-Hodgkin genetics, Lymphoma, Non-Hodgkin therapy
- Abstract
Background: Double-hit lymphoma is characterized by the presence of concurrent MYC (myelocytomatosis oncogene) and BCL2 (B-cell lymphoma 2) gene rearrangements. Prognosis is poor with standard chemoimmunotherapy. Since 2003, the British Columbia Cancer Agency has used CODOX-M/IVAC+R (cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine, ifosfamide, and etoposide, combined with rituximab) followed by consolidative hematopoietic cell transplantation as definitive treatment for double-hit lymphoma., Patients and Methods: A retrospective review of the survival outcomes of patients with double-hit lymphoma treated at our institution was conducted. Thirty-two patients diagnosed with non-Hodgkin lymphoma with concurrent MYC and BCL2 translocations from 2003 to 2013 were identified. Cases with MYC or BCL2 amplification and those with overexpression in immunohistochemistry analysis were excluded., Results: Median age at diagnosis was 53.0 years (range, 35.5-70.9 years), 23 (72%) were male, and 30 (94%) had stage III to IV disease. CODOX-M/IVAC+R was administered in 25 (78%) patients and 20 (80%) achieved a partial remission or better, of which 9 (36%) had a complete remission. Nineteen of the 32 (59%) patients underwent upfront hematopoietic cell transplantation. At a median follow-up of living patients of 26.4 months, 14 (44%) were alive in remission, 15 (47%) died, and 3 (9%) were alive in relapse. The 2-year progression-free survival (PFS) and overall survival (OS) of all patients were 41% and 53%, respectively. The sixteen patients treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation had a 2-year PFS of 60% and 2-year OS of 82%., Conclusion: Patients with double-hit lymphoma treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation can achieve durable remissions, although disease progression before transplantation remains a significant problem., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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9. Fate of patients with newly diagnosed acute myeloid leukemia who fail primary induction therapy.
- Author
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Othus M, Appelbaum FR, Petersdorf SH, Kopecky KJ, Slovak M, Nevill T, Brandwein J, Larson RA, Stiff PJ, Walter RB, Tallman MS, Stenke L, and Erba HP
- Subjects
- Adolescent, Adult, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Survival Rate, Hematopoietic Stem Cell Transplantation, Histocompatibility Testing, Induction Chemotherapy, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy
- Abstract
The aim of this study was to describe the fate of patients with newly diagnosed acute myeloid leukemia (AML) who did not achieve an initial remission while being treated on a contemporary cooperative group trial. We analyzed the outcome of patients entered into S0106, a recently reported cooperative group trial for patients with newly diagnosed AML. A total of 589 eligible patients was treated, of whom 150 (25%) did not achieve a remission while on study and were available for further analysis. The 4-year survival rate for the entire cohort of 150 patients was 23%. Among the 64 patients who received an allogeneic hematopoietic cell transplant, the 4-year survival rate was 48% compared with 4% for the 86 patients who did not undergo transplantation. Among those transplanted, we could not detect a difference in outcome according to remission status, donor source, type of preparative regimen, or cytogenetic risk category. More than 20% of patients with newly diagnosed AML who fail induction therapy can still be cured, particularly if they are able to receive an allogeneic hematopoietic cell transplant. These results suggest that early HLA typing and donor identification are important components of the initial therapy of AML., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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10. Allogeneic haematopoietic stem cell transplantation for chronic lymphocytic leukaemia: outcome in a 20-year cohort.
- Author
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Toze CL, Dalal CB, Nevill TJ, Gillan TL, Abou Mourad YR, Barnett MJ, Broady RC, Forrest DL, Hogge DE, Nantel SH, Power MM, Song KW, Sutherland HJ, Smith CA, Narayanan S, Young SS, Connors JM, and Shepherd JD
- Subjects
- Adult, Aged, British Columbia epidemiology, Cohort Studies, Comorbidity, Disease Progression, Female, Graft Survival, Graft vs Host Disease etiology, Humans, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Prognosis, Remission Induction, Transplantation Chimera, Transplantation Conditioning methods, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Leukemia, Lymphocytic, Chronic, B-Cell therapy
- Abstract
The curative potential of allogeneic haematopoietic stem cell transplant (allo HSCT) in chronic lymphocytic leukaemia CLL is established, with a demonstrated role for graft-versus-leukaemia and less certainty for other factors in determining outcome. The first two decades of CLL patients proceeding to allo HSCT at the Leukaemia/Bone Marrow Transplant Program of British Columbia (n = 49 consecutive, 1991-2009) were studied to clarify factors predicting outcome. The donor was related in 29 (59%) and unrelated in 20 (41%). Conditioning was reduced-intensity in 27 (55%) and myeloablative in 22 (45%). Thirty-one of 49 patients survive with median follow-up of 5 years (0·2-15). Cumulative incidence of non-relapse mortality; complete remission (CR); clearance of fluorescence in situ hybridization (FISH) abnormality and progression at 10 years was 36%; 69%; 55% and 22%. Overall survival (OS) was 63% at 2 years; 55% at 5 years and beyond. Factors predicting OS (P value by log rank <0·05) were: comorbidity index <3, FISH rank (Dohner) and 17p deletion, alemtuzumab pre-HSCT, achievement of CR post-HSCT, donor chimerism >90%, clearance of FISH abnormality post-HSCT and absence of high-grade (3-4) graft-versus-host disease. Results from this province-wide, two-decade cohort demonstrated that a substantial proportion of patients with high-risk CLL become long term disease-free survivors., (© 2012 Blackwell Publishing Ltd.)
- Published
- 2012
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11. Novel agents improve survival of transplant patients with multiple myeloma including those with high-risk disease defined by early relapse (<12 months).
- Author
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Venner CP, Connors JM, Sutherland HJ, Shepherd JD, Hamata L, Mourad YA, Barnett MJ, Broady R, Forrest DL, Hogge DE, Nantel SH, Narayanan S, Nevill TJ, Nitta J, Power MM, Toze CL, Smith CA, and Song KW
- Subjects
- Adult, Aged, Boronic Acids administration & dosage, Bortezomib, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Lenalidomide, Male, Middle Aged, Multiple Myeloma pathology, Neoplasm Recurrence, Local pathology, Prognosis, Pyrazines administration & dosage, Risk Factors, Survival Rate, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Transplantation, Autologous, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation, Multiple Myeloma mortality, Multiple Myeloma therapy, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local therapy
- Abstract
The treatment of multiple myeloma (MM) has changed with the advent of thalidomide, bortezomib, and lenalidomide, the so-called novel agents (NAs). Given the complexity of MM therapy in the NA era we pursued a population based study to assess for improvements in survival as well as to characterize the relevance of early relapse (within 12 months) and the International Staging System in this clinical setting. We reviewed our experience with 460 patients with MM treated with autologous stem cell transplant (ASCT) between 1988 and 2008, of whom 306 had relapsed. The cohort was divided into two groups based upon relapse pre-2004 and relapse during/after 2004 (2004+), which correlated to availability of bortezomib and lenalidomide. Improvements in both overall survival (OS) (median 32.0 months vs. 71.8 months; p < 0.001) and post-relapse survival (PRS) (median 15.2 months vs. 42.8 months; p < 0.001) correlated with the NA era. Exposure to NAs conferred a better PRS (median 35.7 months vs. 9.1 months; p < 0.001). Although all patients had improvements in survival, those who relapsed late continued to do better. Lastly, in the NA era, the ISS remains an important prognostic tool in relapse, but only in the late relapsing cohort.
- Published
- 2011
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12. Response to tyrosine kinase inhibitor therapy in patients with chronic myelogenous leukemia relapsing in chronic and advanced phase following allogeneic hematopoietic stem cell transplantation.
- Author
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Wright MP, Shepherd JD, Barnett MJ, Nantel SH, Sutherland HJ, Toze CL, Hogge DE, Nevill TJ, Song KW, Abou Mourad YR, Narayanan S, Power MM, Smith CA, and Forrest DL
- Subjects
- Adult, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myeloid, Accelerated Phase mortality, Leukemia, Myeloid, Accelerated Phase therapy, Leukemia, Myeloid, Chronic-Phase mortality, Leukemia, Myeloid, Chronic-Phase therapy, Male, Middle Aged, Protein-Tyrosine Kinases antagonists & inhibitors, Recurrence, Remission Induction, Retrospective Studies, Survival Rate, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Protein Kinase Inhibitors therapeutic use
- Abstract
Tyrosine kinase inhibitors (TKI) have been used to treat relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant (HSCT), with responses seen predominantly in chronic phase (CP) patients. This study aimed to analyze the response to TKI therapy and overall survival for patients relapsing predominantly in advanced phase. We retrospectively reviewed 22 patients treated with imatinib (n=20) and/or dasatinib (n=6) for relapsed CML after HSCT; 8 patients were in CP, and 14 patients had advanced disease. Seven patients also received donor lymphocyte infusions. Hematologic, cytogenetic, and molecular responses were analyzed. Nineteen patients (86%) achieved complete hematologic response (CHR), 17 patients (77%) achieved complete cytogenetic response (CCR), and 14 patients (64%) achieved complete molecular response (CMR). In advanced phase patients, 11 (79%) achieved CHR, 10 (71%) CCR, and 8 (57%) achieved CMR. Grade 3 or 4 cytopenias occurred in 10 cases. With median follow-up of 31.5 months from relapse, 14 (64%) patients remain alive, 13 in CMR. In multivariate analysis, the achievement of CMR was significantly correlated with OS with an odds ratio of 20.5 (95% confidence interval 2.3-182) P=.007. TKI therapy is capable of inducing durable molecular responses for CML relapsing after HSCT, both in chronic and advanced phases. The achievement of CMR appears to be crucial in providing long-term disease control for these patients., (Copyright 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
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13. IPSS poor-risk karyotype as a predictor of outcome for patients with myelodysplastic syndrome following myeloablative stem cell transplantation.
- Author
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Nevill TJ, Shepherd JD, Sutherland HJ, Abou Mourad YR, Lavoie JC, Barnett MJ, Nantel SH, Toze CL, Hogge DE, Forrest DL, Song KW, Power MM, Nitta JY, Dai Y, and Smith CA
- Subjects
- Adolescent, Adult, Bone Marrow Transplantation mortality, Female, Hematopoietic Stem Cell Transplantation methods, Humans, Karyotyping, Male, Middle Aged, Multivariate Analysis, Myelodysplastic Syndromes genetics, Peripheral Blood Stem Cell Transplantation mortality, Prognosis, Retrospective Studies, Risk Factors, Survival Analysis, Treatment Outcome, Young Adult, Cytogenetic Analysis, Hematopoietic Stem Cell Transplantation mortality, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Predictive Value of Tests, Transplantation Conditioning methods
- Abstract
The optimal therapy for myelodysplastic syndrome (MDS) is allogeneic bone marrow (BM) or blood (BSC) stem cell transplantation (SCT), although outcomes are limited by nonrelapse mortality (NRM) and relapse. A retrospective review was performed of 156 patients who underwent SCT (114 BM, 42 BSC) for MDS or secondary acute myelogenous leukemia (sAML) at our institution. Fifty-five patients remain in continuous complete remission: 35 BM recipients and 20 BSC recipients (median follow-up 139 and 89 months, respectively). Estimated 7-year event-free survival (EFS), NRM, and risk of relapse (ROR) are 33% (95% confidence intervals [CI] 25%-43%), 42% (CI 33%-51%), and 25% (CI 17%-33%) for the BM cohort and 45% (CI 32%-64%, P= .07), 32% (CI 18%-47%, P= .15), and 23% (CI 11%-37%, P= .79) for the BSC cohort. Multivariate analysis showed IPSS poor-risk cytogenetics (P< .001), time from diagnosis to SCT (P< .001), FAB subgroup (P= .001), recipients not in complete remission (CR1) at SCT (P= .005), and the development of acute graft-versus-host disease (aGVHD) (P= .04) were all predictive of an inferior EFS. The FAB subgroup (P= .002), poor-risk karyotype (P= .004), and non-CR1 status also correlated with ROR in multivariate analysis. EFS for poor-risk karyotype patients was superior after receiving BSC compared to BM (39% versus 6%, P< .001). SCT outcomes in MDS/sAML are strongly associated with the IPSS cytogenetic risk group, although the use of BSC in poor-risk karyotype patients may lead to a more favorable long-term EFS.
- Published
- 2009
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14. Long-term outcome of myeloablative allogeneic stem cell transplantation for multiple myeloma.
- Author
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Kuruvilla J, Shepherd JD, Sutherland HJ, Nevill TJ, Nitta J, Le A, Forrest DL, Hogge DE, Lavoie JC, Nantel SH, Toze CL, Smith CA, Barnett MJ, and Song KW
- Subjects
- Adult, Cohort Studies, Disease-Free Survival, Female, Graft vs Host Disease, Graft vs Tumor Effect, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Middle Aged, Retrospective Studies, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy, Transplantation Conditioning methods
- Abstract
Allogeneic stem cell transplantation (alloSCT) has been used in the hopes of harnessing the curative potential of the graft-versus-myeloma effect. This study examines the long-term outcomes of a large cohort of patients with myeloma who were treated with myeloablative alloSCT at a single center. Comparisons are made with those who were treated with autologous stem cell transplantation (ASCT). Between January 1989 and February 2002, 158 patients age
10 years post myeloablative alloSCT, similarly there are long-term survivors post-ASCT. Myeloablative alloSCT should not be considered standard treatment, and should only be considered in the context of a clinical trial. - Published
- 2007
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15. Haematopoietic stem cell transplantation as primary therapy of sporadic adult Burkitt lymphoma.
- Author
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Song KW, Barnett MJ, Gascoyne RD, Horsman DE, Forrest DL, Hogge DE, Lavoie JC, Nantel SH, Nevill TJ, Shepherd JD, Smith CA, Sutherland HJ, Voss NJ, Toze CL, and Connors JM
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow pathology, Burkitt Lymphoma drug therapy, Burkitt Lymphoma pathology, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Prognosis, Treatment Outcome, Burkitt Lymphoma therapy, Hematopoietic Stem Cell Transplantation
- Abstract
High dose chemoradiotherapy and haematopoietic stem cell transplantation (SCT) is used as primary therapy for patients diagnosed with Burkitt lymphoma (BL). Forty-three adults presented with sporadic BL in British Columbia between 1987 and 2003. Twenty patients had bone marrow involvement. Sixteen patients did not proceed to SCT because of chemorefractory disease (n = 9) or other reasons (n = 7). Twenty-seven patients proceeded to SCT and had a 3-year event-free survival of 51%. In conclusion, approximately 50% of patients with chemosensitive BL who undergo SCT can be cured; however, a significant number of patients will not proceed to SCT because of early resistance or recurrence.
- Published
- 2006
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16. High-dose therapy and autologous hematopoietic stem-cell transplantation does not increase the risk of second neoplasms for patients with Hodgkin's lymphoma: a comparison of conventional therapy alone versus conventional therapy followed by autologous hematopoietic stem-cell transplantation.
- Author
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Forrest DL, Hogge DE, Nevill TJ, Nantel SH, Barnett MJ, Shepherd JD, Sutherland HJ, Toze CL, Smith CA, Lavoie JC, Song KW, Voss NJ, Gascoyne RD, and Connors JM
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Child, Child, Preschool, Cohort Studies, Female, Hodgkin Disease complications, Humans, Incidence, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute etiology, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes etiology, Neoplasms, Second Primary epidemiology, Retrospective Studies, Risk Factors, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Hodgkin Disease therapy, Neoplasms, Second Primary etiology
- Abstract
Purpose: To determine the incidence of second malignancies among patients with Hodgkin's lymphoma (HL) treated with autologous hematopoietic stem cell transplantation (AHSCT) compared with patients receiving conventional therapy alone and to identify potential risk factors for their occurrence., Patients and Methods: We analyzed data on 1,732 consecutive patients with HL treated at the British Columbia Cancer Agency from 1976 to 2001, including 202 patients undergoing AHSCT. The median follow-up duration was 9.8 years for the whole cohort, 9.7 years for those patients treated with conventional therapy, and 7.8 years from AHSCT., Results: The cumulative incidence of developing any second malignancy 15 years after therapy for HL was 9% (risk ratio = 3.5; P < .001); however, the incidence did not differ between those patients receiving conventional therapy alone compared with those undergoing AHSCT (10% and 8%, respectively; P = .48). In multivariate analysis, the only factor significantly associated with an increased risk of developing any second neoplasm or solid tumor was age > or = 35 years (P < .0001). An increased risk of therapy-induced acute myeloid leukemia and therapy-induced myelodysplastic syndrome was seen for patients aged > or = 35 years (P = .03) and stage III/IV (P = .04)., Conclusion: Patients with HL are at increased risk of developing a second neoplasm. However, those patients undergoing AHSCT do not seem to be at greater risk compared with those patients receiving conventional therapy alone, at least during the first decade after therapy.
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- 2005
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17. Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma.
- Author
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Doocey RT, Toze CL, Connors JM, Nevill TJ, Gascoyne RD, Barnett MJ, Forrest DL, Hogge DE, Lavoie JC, Nantel SH, Shepherd JD, Sutherland HJ, Voss NJ, Smith CA, and Song KW
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Disease-Free Survival, Female, Follow-Up Studies, Graft vs Host Disease, Humans, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin mortality, Male, Middle Aged, Recurrence, Regression Analysis, Retrospective Studies, Survival Rate, Transplantation Conditioning, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation mortality, Lymphoma, Non-Hodgkin surgery
- Abstract
Forty-four patients with relapsed or refractory aggressive histology non-Hodgkin lymphoma (NHL) (diffuse large B cell, n = 23; peripheral T cell, n = 5; transformed B cell, n = 16) proceeded to allogeneic stem cell transplant (allo-SCT) between 1987 and 2003. Median age at transplant was 40 years (range 19-56 years). At the time of transplant, 35 were chemosensitive and nine were chemorefractory. Thirty-three patients had matched sibling donors and 11 had unrelated donors. Forty-two patients (95%) received radiation-based conditioning regimens. Event-free survival (EFS) and overall survival (OS) at 5 years was 43% [95% confidence interval (CI): 27-58%] and 48% (95% CI: 32-63%) respectively. Treatment-related mortality was 25% at 1 year. Grade III-IV acute graft-versus-host disease (GVHD) was the only significant variable affecting OS and EFS, and had a negative impact. Chronic GVHD did not influence survival. Lymphoma relapse <12 months after initial therapy predicted for increased risk of relapse post-transplant (P = 0.02). Patients with chemorefractory lymphoma were not at increased risk of relapse (P = 0.20) with four of nine patients remaining alive without disease 12-103 months post-transplant. In conclusion, allo-SCT for relapsed or refractory aggressive histology NHL results in long-term EFS and OS of 40-50%. Patients with chemorefractory disease can have a durable remission post-transplant.
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- 2005
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18. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver.
- Author
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Lavoie JC, Connors JM, Phillips GL, Reece DE, Barnett MJ, Forrest DL, Gascoyne RD, Hogge DE, Nantel SH, Shepherd JD, Smith CA, Song KW, Sutherland HJ, Toze CL, Voss NJ, and Nevill TJ
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols toxicity, Canada, Cause of Death, Female, Follow-Up Studies, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation mortality, Hodgkin Disease complications, Hodgkin Disease mortality, Humans, Male, Middle Aged, Neoplasms, Second Primary chemically induced, Neoplasms, Second Primary mortality, Probability, Retrospective Studies, Salvage Therapy, Survival Rate, Transplantation, Autologous, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Hodgkin Disease therapy
- Abstract
Beginning in 1985, patients in British Columbia with Hodgkin lymphoma (HL) that was not controlled by conventional chemotherapy routinely underwent high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT). Long-term complications of HD-ASCT have become apparent as more patients survive without recurrence of HL. Data were obtained retrospectively on the first 100 patients that underwent HD-ASCT for HL in Vancouver, focusing on relapse, treatment-related complications, and the occurrence of late events. Fifty-three patients remain alive (median follow-up, 11.4 years [range, 10.0-17.4 years]) with an overall survival (OAS) of 54% at 15 years. OAS was significantly better in patients in first relapse (67%) than in patients with primary refractory-induction failure (39%) and advanced disease (29%) (P = .002). The major cause of death was progression of HL (32% at 15 years). Treatment-related mortality, including death from second malignancy, was 17% at 15 years. Cumulative risk of a second malignancy was 9% at 15 years. Karnofsky performance status was at least 90% in 47 patients although hypogonadism (20 patients), hypothyroidism (12 patients), unusual infections (10 patients), anxiety or depression (7 patients), and cardiac disease (5 patients) were not uncommon in survivors. HD-ASCT can lead to durable remissions in relapsed or refractory HL with acceptable but definite late toxicity. The occurrence of late events necessitates lifelong medical surveillance.
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- 2005
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19. Hematopoietic stem cell transplantation: a primer for the primary care physician.
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Léger CS and Nevill TJ
- Subjects
- Chronic Disease, Graft vs Host Disease prevention & control, Humans, Survival Rate, Transplantation, Autologous, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Hematopoietic stem cell transplantation has been used for many years to treat various malignant and nonmalignant hematologic conditions. However, the high-dose conditioning regimen can lead to major organ dysfunction, life-threatening infection and bleeding. In the allogeneic setting, graft-versus-host disease may also develop, making post-transplant management complex. Once a transplant recipient is discharged from hospital and returns to his or her local community, the primary care physician can play an important role in care. Recipients of stem cell transplants may be severely immunocompromised for many months after transplantation, especially if they are still taking immunosuppressive drugs. Furthermore, endocrine and metabolic deficiencies can develop, and transplant survivors are at risk of a second malignant disease. This review is intended as a basic overview of allogeneic and autologous stem cell transplantation with a special focus on long-term follow-up issues relevant to primary care providers.
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- 2004
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20. Long-term follow-up of patients with chronic myeloid leukemia in chronic phase developing sudden blast phase on imatinib therapy.
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Tantiworawit, Adisak, Power, Maryse M., Barnett, Michael J., Hogge, Donna E., Nantel, Stephen H., Nevill, Thomas J., Shepherd, John D., Song, Kevin W., Sutherland, Heather J., Toze, Cynthia L., Abou-Mourad, Yasser R., Narayanan, Sujaatha, Broady, Raewyn C., and Forrest, Donna L.
- Subjects
TREATMENT of chronic myeloid leukemia ,IMATINIB ,HEALTH outcome assessment ,LONGITUDINAL method ,HEMATOPOIETIC stem cell transplantation ,PROTEIN-tyrosine kinases - Abstract
Sudden blast phase (SBP) is a rare event that occurs in an unpredictable fashion amongst patients with chronic myeloid leukemia (CML) who otherwise appear to be responding satisfactorily to imatinib (IM) treatment. We investigated the incidence, clinical characteristics, treatment outcome and long-term follow-up of 213 patients with chronic phase CML treated with IM according to the European LeukemiaNet guidelines. Nine patients, eight of whom received IM as first-line therapy, developed SBP (4.2% of the total). They tended to have low or intermediate risk Sokal scores at diagnosis, a predominance of the lymphoid phenotype and a short interval from 'optimal' response to the development of BP. Five of the nine patients with SBP are alive in complete molecular remission; however, all of them underwent allogeneic hematopoietic stem cell transplant. The cumulative incidence of SBP for the patients who received IM as first-line therapy was 5.9% and the 2-year overall survival of the nine patients who developed SBP was 56%. Despite the improved outcome for patients with SBP receiving tyrosine kinase inhibitors (TKIs) and transplant, many of these patients are not salvaged with these therapies. This illustrates the need to develop predictive models to identify patients early whose response to TKI therapy will not be durable and hopefully prevent the transformation to advanced disease. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
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