25 results on '"Forrest, Donna L"'
Search Results
2. Bone Marrow Necrosis in Adult Acute Leukemia and Non-Hodgkin's Lymphoma.
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Forrest, Donna L.
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BONE marrow diseases , *HODGKIN'S disease , *ACUTE leukemia - Abstract
Discusses results of findings of bone marrow necrosis (BMN) in adult acute leukemia and non-Hodgkin's lymphoma. Disease characteristics of BMN; Patient characteristics; Cell karyotype; Patient response to treatment regimen.
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- 2000
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3. Constitutional rearrangements of 7q22 in hematologic malignancies: a new case report
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Forrest, Donna L. and Lee, Christine L.Y.
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CHROMOSOME abnormalities , *MYELOPROLIFERATIVE neoplasms - Abstract
Abnormalities of chromosome 7 are a frequent finding in myelocytic malignancies and are associated with a poor prognosis. Based on chromosome banding analysis, two critical regions have been identified: one in band 7q22 and the second in region 7q32∼q35. The chromosomal breakpoint in band 7q22 appears to be heterogeneous and may involve tumor suppressor gene(s). Constitutional rearrangements of 7q22 have rarely been reported in myeloid malignancies. To our knowledge, this is the first report in the literature of a myeloproliferative disorder with a constitutional t(1;7)(q42;q22). [Copyright &y& Elsevier]
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- 2002
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4. Correlation between trough imatinib plasma concentration and clinical response in chronic myeloid leukemia
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Forrest, Donna L., Trainor, Shannon, Brinkman, Ryan R., Barnett, Michael J., Hogge, Donna E., Nevill, Thomas J., Shepherd, John D., Nantel, Stephen H., Toze, Cynthia L., Sutherland, Heather J., Song, Kevin W., Lavoie, Julye C., Power, Maryse M., Abou-Mourad, Yasser, and Smith, Clayton A.
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- 2009
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5. Incidence and socioeconomic factors in older adults with acute myeloid leukaemia: Real‐world outcomes from a population‐based cohort.
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Stubbins, Ryan J., Stamenkovic, Maria, Roy, Claudie, Rodrigo, Judith, Chung, Shanee, Kuchenbauer, Florian C., Hay, Kevin A., White, Jennifer, Abou Mourad, Yasser, Power, Maryse M., Narayanan, Sujaatha, Forrest, Donna L., Toze, Cynthia L., Sutherland, Heather J., Nantel, Stephen H., Nevill, Thomas J., Karsan, Aly, Song, Kevin W., and Sanford, David S.
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ACUTE myeloid leukemia , *OLDER people , *SOCIOECONOMIC factors , *INDUCTION chemotherapy - Abstract
Objectives: Acute myeloid leukaemia (AML) is a disease of older adults, who are vulnerable to socio‐economic factors. We determined AML incidence in older adults and the impact of socio‐economic factors on outcomes. Methods: We included 3024 AML patients (1996–2016) identified from a population‐based registry. Results: AML incidence in patients ≥60 years increased from 11.01 (2001–2005) to 12.76 (2011–2016) per 100 000 population. Among 879 patients ≥60 years in recent eras (2010–2016), rural residents (<100 000 population) were less likely to be assessed by a leukaemia specialist (39% rural, 47% urban, p =.032); no difference was seen for lower (43%, quintile 1–3) vs. higher (47%, quintile 4–5) incomes (p =.235). Similar numbers received induction chemotherapy between residence (16% rural, 18% urban, p =.578) and incomes (17% lower, 17% high, p = 1.0). Differences between incomes were seen for hypomethylating agent treatment (14% low, 20% high, p =.041); this was not seen for residence (13% rural, 18% urban, p =.092). Among non‐adverse karyotype patients ≥70 years, 2‐year overall survival was worse for rural (5% rural, 12% urban, p =.006) and lower income (6% low, 15% high, p =.017) patients. Conclusions: AML incidence in older adults is increasing, and outcomes are worse for older rural and low‐income residents; these patients face treatment barriers. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Canadian chronic myeloid leukemia outcomes post-transplant in the tyrosine kinase inhibitor era.
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Savoie, Mary Lynn, Bence-Bruckler, Isabelle, Huebsch, Lothar B., Lalancette, Marc, Hillis, Chris, Walker, Irwin, Lipton, Jeffrey H., Forrest, Donna L., and Kim, Dennis (Dong Hwan)
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TREATMENT of chronic myeloid leukemia , *DRUG resistance in cancer cells , *CANCER relapse , *STEM cell transplantation - Abstract
Highlights • A 1.3 log reduction in BCR-ABL levels within 3 months post HCT is prognostic in TKI resistance or intolerance. • HCT remains a potential cure for patients with CML resistant or intolerant of TKI therapy. • Advanced phase disease remains a poor prognostic factor post HCT even in the TKI era. Abstract The majority of patients with TKI failure respond to HCT. However, the relapse risk remains high. This study has evaluated transplant outcomes in 223 CML patients with TKI failure due to resistance (n = 132) or intolerance (n = 29), as well as those that were TKI naïve/responding with advanced disease (n = 35) or with chronic phase (CP, n = 27). We studied outcomes according to post-transplant BCR-ABL transcript level within 3 months. With respect to transplant outcomes according to the post-transplant BCR/ ABLtranscript level within 3 months, the group failing to achieve a 1.3 log reduction (n = 14, 12.4%) showed the highest relapse rate of 78.6% at 5 years, compared to 26.2% and 24.1% in the groups achieving 1.3–4.0 log reduction (n = 45, 39.8%), and ≥4.1 log reduction (n = 54, 47.8%) respectively (p < 0.001). Multivariate analysis confirmed that the group failing to achieve a 1.3 log reduction had a 2.3-fold higher risk of death and 6.6 times higher risk of relapse. Poor overall survival after HCT was associated with advanced disease at diagnosis, but not disease status prior to HCT. Of 61 patients who relapsed after HCT, 47 were treated with post-transplant TKI therapy; those receiving TKI after loss of MR2 or MMR showed higher rates of response and survival compared to those receiving TKI after hematologic relapse (p < 0.001). QPCR log reduction level within 3 months post transplantation is prognostic in this population. [ABSTRACT FROM AUTHOR]
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- 2018
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7. Excellent real‐world outcomes of adults with Burkitt lymphoma treated with CODOX‐M/IVAC plus or minus rituximab.
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Zhu, Katie Y., Song, Kevin W., Connors, Joseph M., Leitch, Heather, Barnett, Michael J., Ramadan, Khaled, Slack, Graham W., Abou Mourad, Yasser, Forrest, Donna L., Hogge, Donna E., Nantel, Stephen H., Narayanan, Sujaatha, Nevill, Thomas J., Power, Maryse M., Sanford, David S., Sutherland, Heather J., Tucker, Tracy, Toze, Cynthia L., Sehn, Laurie H., and Broady, Raewyn
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BURKITT'S lymphoma , *CANCER chemotherapy , *STEM cell transplantation , *EPSTEIN-Barr virus diseases , *CANCER treatment - Abstract
Summary: Treatment of Burkitt lymphoma (BL) with intensive, multi‐agent chemotherapy with aggressive central nervous system (CNS) prophylaxis results in high cure rates, although no regimen is standard of care. We examined population‐based survival outcomes of adults with BL treated with a modified combination of cyclophosphamide, vincristine, doxorubicin, prednisone and systemic high‐dose methotrexate (MTX) (CODOX‐M) with IVAC (ifosfamide, mesna, etoposide, cytarabine and intrathecal MTX) (CODOX‐M/IVAC) ± rituximab over a 15‐year period in British Columbia. For the 81 patients identified (including 8 with CNS involvement and 18 with human immunodeficiency virus‐associated BL), 5‐year progression‐free survival (PFS) and overall survival (OS) were 75% [95% confidence interval (CI): 63–83%] and 77% (95% CI: 66–85%), respectively, with no treatment‐related deaths. Those who completed the regimen per protocol (n = 38) had significantly improved 5‐year PFS 86% (P = 0·04) and OS 92% (P = 0·008), as did those under 60 years with 5‐year PFS 82% (P = 0·005) and OS 86% (P = 0·002), which remained significant in multivariate analysis [PFS: hazard ratio (HR) 3·36, P = 0·018; OS HR 4·03, P = 0·012]. Incorporation of high‐dose systemic methotrexate also significantly affected multivariate survival outcomes (OS HR 0·28, P = 0·025). Stem cell transplant in first remission had no effect on OS or PFS. This large, real‐world analysis of BL patients treated with CODOX‐M/IVAC ± rituximab demonstrates excellent survival outcomes comparable to clinical trials. These results help to serve as a benchmark when comparing curative therapies for BL patients as novel regimens are incorporated into clinical practice. [ABSTRACT FROM AUTHOR]
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- 2018
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8. 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.
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Nair, Anish P., Barnett, Michael J., Broady, Raewyn C., Hogge, Donna E., Song, Kevin W., Toze, Cynthia L., Nantel, Stephen H., Power, Maryse M., Sutherland, Heather J., Nevill, Thomas J., Abou Mourad, Yasser, Narayanan, Sujaatha, Gerrie, Alina S., and Forrest, Donna L.
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HEMATOPOIETIC stem cells , *STEM cell transplantation , *SALVAGE therapy , *CHRONIC myeloid leukemia , *PROTEIN-tyrosine kinases , *PATIENTS - 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. [ABSTRACT FROM AUTHOR]
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- 2015
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9. The core autophagy protein ATG4B is a potential biomarker and therapeutic target in CML stem/progenitor cells.
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Rothe, Katharina, Hanyang Lin, Lin, Kevin B. L., Amy Leung, Hui Mi Wang, Malekesmaeili, Mehrnoush, Brinkman, Ryan R., Forrest, Donna L., Gorski, Sharon M., and Xiaoyan Jiang
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IMATINIB , *PROGENITOR cells , *AUTOPHAGY , *PROTEIN expression , *BIOMARKERS - Abstract
Previous studies demonstrated that imatinib mesyiate (lM) induces autophagy in chronic myeloid leukemia (CML) and that this process is critical to cell survival upon therapy. However, it is not known if the autophagic process differs at basal levels between CML patients and healthy individuals and if pretreatment CML cells harbor unique autophagy characteristics that could predict patients' clinical outcomes. We now demonstrate that several key autophagy genes are differentially expressed in CD34+ hematopoietic stem/progenitor cells, with the highest transcript levels detected for ATG4B, and that the transcript and protein expression levels of ATG4 family members, ATG5 and BECLIN-1 are significantly increased in CD34+ cells from chronicphase CML patients (P < .05). Importantly, ATG4B is differentially expressed in pretreatment CML stem/progenitor ceiis from subsequent IM responders vs IM non-responders (P < .05). Knockdown of ATG4B suppresses autophagy, impairs the survival of CML stem/progenitor cells and sensitizes them to IM treatment. Moreover, deregulated expression of ATG4B in CD34+ CML ceiis inversely correlates with transcript levels of miR-34a, and ATG4B is shown to be a direct target of miR-34a. This study identifies ATG4B as a potential biomarker for predicting therapeutic response in treatment-naïve CML stem/progenitor cells and uncovers ATG4B as a possible drug target in these cells. [ABSTRACT FROM AUTHOR]
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- 2014
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10. Targeting Primitive Chronic Myeloid Leukemia Cells by Effective Inhibition of a New AHI-1-BCR-ABL-JAK2 Complex.
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Min Chen, Gallipoli, Paolo, DeGeer, Donna, Sloma, Ivan, Forrest, Donna L., Chan, Matthew, Lai, Damian, Jorgensen, Heather, Ringrose, Ashley, Hui Mi Wang, Lambie, Karen, Nakamoto, Helen, Kyi Min Saw, Turhan, Ali, Arlinghaus, Ralph, Paul, James, Stobo, Jon, Barnett, Michael J., Eaves, Allen, and Eaves, Connie J.
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TREATMENT of chronic myeloid leukemia , *CANCER cells , *TARGETED drug delivery , *PROTEIN-protein interactions , *ENZYME inhibitors , *PROGENITOR cells - Abstract
Background: Imatinib mesylate (IM) induces clinical remission of chronic myeloid leukemia (CML).The Abelson helper integra-tion site 1 (AHI-1 ) oncoprotein interacts with BCR-ABL and Janus kinase 2 (JAK2) to mediate IM response of primi-tive CML cells, but the effect of the interaction complex on the response to ABL and JAK2 inhibitors is unknown. Methods: The AHI-1-BCR-ABL-JAK2 interaction complex was analyzed by mutational analysis and coimmunoprecipitation. Roles of the complex in regulation of response or resistance to ABL and JAK2 inhibitors were investigated in BCR-ABL* cells and primary CML stem/progenitor cells and in immunodeficient NSG mice. All statistical tests were two-sided. Results:The WD40-repeat domain of AHI-1 interacts with BCR-ABL, whereas the N-terminal region interacts with JAK2; loss of these interactions statistically significantly increased the IM sensitivity of CML cells. Disrupting this com-plex with a combination of IM and an orally bioavailable selective JAK2 inhibitor (TG101209 [TG]) statistically significantly induced death of AHI-1-overexpressing and IM-resistant cells in vitro and enhanced survival of leu-kemic mice, compared with single agents (combination vsTG alone: 63 vs 53 days, ratio = 0.84, 95% confidence interval [CI] = 0.6 to 1.1, P= .004; vs IM: 57 days, ratio = 0.9, 95% CI = 0.61 to 1.2, P= .003). Combination treatment also statistically significantly enhanced apoptosis of CD34+ leukemic stem/progenitor cells and eliminated their long-term leukemia-initiating activity in NSG mice. Importantly, this approach was effective against treatment-naive CML stem cells from patients who subsequently proved to be resistant to IM therapy. Conclusions: Simultaneously targeting BCR-ABL and JAK2 activities in CML stem/progenitor cells may improve outcomes in patients destined to develop IM resistance. [ABSTRACT FROM AUTHOR]
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- 2013
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11. Allogeneic haematopoietic stem cell transplantation for chronic lymphocytic leukaemia: outcome in a 20-year cohort.
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Toze, Cynthia L., Dalal, Chinmay B., Nevill, Thomas J., Gillan, Tanya L., Abou Mourad, Yasser R., Barnett, Michael J., Broady, Raewyn C., Forrest, Donna L., Hogge, Donna E., Nantel, Stephen H., Power, Maryse M., Song, Kevin W., Sutherland, Heather J., Smith, Clayton A., Narayanan, Sujaatha, Young, Sean S., Connors, Joseph M., and Shepherd, John D.
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GRAFT versus host disease , *STEM cell transplantation , *HEALTH outcome assessment , *BONE marrow transplantation , *DISEASE relapse , *MORTALITY - 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. [ABSTRACT FROM AUTHOR]
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- 2012
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12. 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.
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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]
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- 2012
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13. Novel agents improve survival of transplant patients with multiple myeloma including those with high-risk disease defined by early relapse (<12 months).
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Venner, Christopher P., Connors, Joseph M., Sutherland, Heather J., Shepherd, John D., Hamata, Linda, Mourad, Yasser Abou, Barnett, Michael J., Broady, Raewyn, Forrest, Donna L., Hogge, Donna E., Nantel, Stephen H., Narayanan, Sujaatha, Nevill, Thomas J., Nitta, Janet, Power, Maryse M., Toze, Cynthia L., Smith, Clayton A., and Song, Kevin W.
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MULTIPLE myeloma , *STEM cell transplantation , *THALIDOMIDE , *MEDICAL protocols , *DRUG therapy , *COMBINATION drug therapy , *PATIENTS - 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. [ABSTRACT FROM AUTHOR]
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- 2011
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14. Response to Tyrosine Kinase Inhibitor Therapy in Patients with Chronic Myelogenous Leukemia Relapsing in Chronic and Advanced Phase Following Allogeneic Hematopoietic Stem Cell Transplantation
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Wright, Matthew P., Shepherd, John D., Barnett, Michael J., Nantel, Stephen H., Sutherland, Heather J., Toze, Cynthia L., Hogge, Donna E., Nevill, Thomas J., Song, Kevin W., Abou Mourad, Yasser R., Narayanan, Sujaatha, Power, Maryse M., Smith, Clayton A., and Forrest, Donna L.
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COMPLICATIONS from organ transplantation , *HEMATOPOIETIC stem cells , *HOMOGRAFTS , *MYELOID leukemia , *STEM cell transplantation , *PROTEIN-tyrosine kinase inhibitors , *CANCER relapse - 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 &y& Elsevier]
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- 2010
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15. IPSS Poor-Risk Karyotype as a Predictor of Outcome for Patients with Myelodysplastic Syndrome following Myeloablative Stem Cell Transplantation
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Nevill, Thomas J., Shepherd, John D., Sutherland, Heather J., Abou Mourad, Yasser R., Lavoie, Julye C., Barnett, Michael J., Nantel, Stephen H., Toze, Cynthia L., Hogge, Donna E., Forrest, Donna L., Song, Kevin W., Power, Maryse M., Nitta, Janet Y., Dai, Yunfeng, and Smith, Clayton A.
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DISEASE remission , *DYSPLASIA , *STEM cells , *CELLULAR therapy , *CONFIDENCE intervals - Abstract
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. [Copyright &y& Elsevier]
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- 2009
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16. Fusion of PRKG2 and SPTBN1 to the platelet-derived growth factor receptor beta gene (PDGFRB) in imatinib-responsive atypical myeloproliferative disorders
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Gallagher, Genevieve, Horsman, Douglas E., Tsang, Peter, and Forrest, Donna L.
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PROTEIN-tyrosine kinases , *FLUORESCENCE microscopy , *IN situ hybridization , *BLOOD proteins - Abstract
Abstract: Chromosomal translocations involving the platelet-derived growth factor receptor beta gene (PDGFRB) have been reported in a subset of patients with atypical myeloproliferative disorders (MPDs). The fusion of the PDGFRB gene, which encodes a tyrosine kinase receptor, with different partner genes results in its constitutive activation. We present the cases of two patients with atypical MPD carrying t(4;5)(q21;q33) and t(2;5)(p21;q33), respectively. Fluorescence in situ hybridization demonstrated that PDGFRB was involved in both translocations. Further characterization of the 4q21 breakpoint using a bacterial artificial chromosome probe revealed PRKG2 as the likely gene partner to PDGFRB. Characterization of the 2p21 breakpoint identified a novel gene partner to PDGFRB, the SPTBN1 gene. Both patients achieved a complete molecular remission after introduction of imatinib mesylate therapy. [Copyright &y& Elsevier]
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- 2008
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17. Long-Term Outcome of Myeloablative Allogeneic Stem Cell Transplantation for Multiple Myeloma
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Kuruvilla, John, Shepherd, John D., Sutherland, Heather J., Nevill, Thomas J., Nitta, Janet, Le, Aulan, Forrest, Donna L., Hogge, Donna E., Lavoie, Julye C., Nantel, Stephen H., Toze, Cynthia L., Smith, Clayton A., Barnett, Micheal J., and Song, Kevín W.
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STEM cells , *CELL transplantation , *MULTIPLE myeloma , *RADIOTHERAPY - Abstract
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 ≤55 years underwent SCT for myeloma. Seventy-two patients underwent myeloablative alloSCT (58 related; 14 unrelated), whereas 86 patients underwent ASCT. Most patients received single-agent high dose dexamethasone or VAD (vincristine, adriamycin, dexamethasone) therapy pre-SCT. Conditioning regimens were melphalan-based for all ASCT patients, whereas the alloSCT patients received melphalan-based (70%), total-body irradiation (TBI)-based (18%), or other (13%). Patients who underwent alloSCT were younger, had a higher Durie-Salmon stage disease, and a shorter median time from diagnosis to transplant. Myeloma subtypes were similar between groups. Other pre-SCT (BMT) characteristics were similar except that ASCT patients had a higher proportion of cases that received palliative radiotherapy pre-SCT. Disease response pre-SCT was similar. At last follow-up, 61 of 158 patients are alive with a median follow-up of 88.4 months (range: 35.5-208.5). The overall survival (OS) of the alloSCT cohort was 48.1% at 5 years and 39.9% at 10 years compared to 46.2% at 5 years and 30.8% at 10 years for the ASCT cohort (P = .94). The event-free survival of the alloSCT cohort was 33.3% at 5 years and 31.4% at 10 years compared to 32.9% and 15.2%for the ASCT cohort (P = .64). Treatment-related mortality (TRM) at 1 year was 22% for the alloSCT cohort and 14% in the ASCT cohort (P = .21). Cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 72% and the cumulative incidence of chronic GVHD (cGVHD) was 68% at 2 years. Neither aGVHD nor cGVHD had an influence on OS or event-free survival, although 5 of 14 patients who have received donor lymphocyte infusions (DLI) have had disease response. The risk of relapse was reduced in those who developed aGVHD (P = .02) but not cGVHD (P = .23). In conclusion, although there are patient who are alive without disease >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. [Copyright &y& Elsevier]
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- 2007
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18. Philadelphia-negative clonal hematopoiesis following imatinib therapy in patients with chronic myeloid leukemia: a report of nine cases and analysis of predictive factors
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Lin, Yulia, Bruyère, Hélène, Horsman, Douglas E., Pantzar, Tapio, Barnett, Michael J., Hogge, Donna E., Nevill, Thomas J., Nantel, Stephen H., Sutherland, Heather J., Toze, Cynthia L., Shepherd, John D., Lavoie, Julye C., Song, Kevin W., Smith, Clayton A., and Forrest, Donna L.
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HYDROGEN-ion concentration , *CANCER patients , *CHROMOSOMES , *DIAGNOSIS - Abstract
Abstract: There are increasing reports of Philadelphia-negative (Ph-negative) clonal hematopoiesis developing among patients with chronic myeloid leukemia (CML) treated with imatinib mesylate (IM). To establish the incidence and significance of these chromosomal abnormalities, we analyzed data on 141 consecutive patients with CML treated with IM at the British Columbia Cancer Agency and Vancouver General Hospital from 1999 to 2004. The cumulative incidence of developing a Ph-negative clone three years from the start of IM was 8.7% at a median of 13.3 months. The Ph-negative clonal abnormalities included monosomy 7 and/or trisomy 8 (seven patients), monosomy for chromosomes X and 22 (one patient), and a (12;16) translocation (one patient). Two of the patients presented with the same chromosomal abnormality in both Ph-negative and Ph-positive cells. None of the Ph-negative clonal abnormalities was associated with myelodysplasia. In a multivariate analysis, an interval from diagnosis to initiation of IM of 1 year or less was associated with an increased risk of developing a Ph-negative clone (relative risk = 20.2; P = 0.025). There was no difference, however, in event-free survival between patients who did and did not develop Ph-negative clones. Therefore, while the development of Ph-negative clonal hematopoiesis in patients with CML treated with IM is uncommon, it appears to be more frequent than that previously seen with IFN, but it does not seem to confer a worse prognosis. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
19. Haematopoietic stem cell transplantation as primary therapy of sporadic adult Burkitt lymphoma.
- Author
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Song, Kevin W., Barnett, Michael J., Gascoyne, Randy D., Horsman, Douglas E., Forrest, Donna L., Hogge, Donna E., Lavoie, Julyle C., Nantel, Stephen H., Nevill, Thomas J., Shepherd, John D., Smith, Clayton A., Sutherland, Heather J., Voss, Nicholas J., Toze, Cynthia L., and Connors, Joseph M.
- Subjects
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BURKITT'S lymphoma , *STEM cell transplantation , *DRUG therapy , *HEMATOPOIETIC stem cells , *HEMATOPOIETIC stem cell transplantation , *LYMPHOBLASTIC leukemia - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
20. Early Stem Cell Transplantation for Refractory Acute Leukemia after Salvage Therapy with High-Dose Etoposide and Cyclophosphamide
- Author
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Johny, Asha, Song, Kevin W., Nantel, Stephen H., Lavoie, Julye C., Toze, Cynthia L., Hogge, Donna E., Forrest, Donna L., Sutherland, Heather J., Le, Alan, Nitta, Janet Y., Barnett, Michael J., Smith, Clayton A., Shepherd, John D., and Nevill, Thomas J.
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STEM cell transplantation , *ACUTE leukemia , *CELLULAR therapy , *ETOPOSIDE - Abstract
Abstract: Primary refractory acute leukemia (AL) has a poor prognosis, although some patients can be salvaged with allogeneic stem cell transplantation (SCT). Induction of complete remission (CR) with conventional chemotherapy before SCT may improve outcome in this patient population. Between March 1991 and October 2003, 59 adults with primary refractory AL were treated with continuous-infusion etoposide (VP) 2.4 to 3.0 g/m2 followed by cyclophosphamide (Cy) 6.0-7.2 g/m2 intravenously over 3 to 4 days with the intention of proceeding to SCT in CR1. Forty-two patients had acute myelogenous leukemia (AML), 13 patients had acute lymphoblastic leukemia (ALL), and 4 patients had acute biphenotypic leukemia. The most frequent nonhematologic toxicities were oral mucosal, gastrointestinal, and hepatic toxicities (44%, 20%, and 15% of patients, respectively). Thirty-two (57%) of 56 evaluable patients entered CR1 with a median time to platelet and neutrophil recovery of 22 and 26 days, respectively. CR1 rates were similar in AML (54%) and ALL/acute biphenotypic leukemia (67%; P = .52), and analysis of baseline characteristics did not reveal any predictors of response to VP/Cy. Twenty-nine of 32 CR1 patients subsequently underwent SCT (24 allogeneic and 5 autologous). Estimated 5-year event-free survival (EFS) and overall survival for the entire cohort are 23% and 26%, respectively. In the allogeneic SCT group, 5-year EFS was 52% for AML patients and 14% for ALL patients (P = .04), and only male sex was predictive of a favorable outcome (P = .03). VP/Cy is able to induce CR1 in most patients with primary refractory AL with an acceptable toxicity profile. Subsequent allogeneic SCT can lead to long-term EFS in a significant proportion of patients. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
21. Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma.
- Author
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Doocey, Richard T., Toze, Cynthia L., Connors, Joseph M., Nevill, Thomas J., Gascoyne, Randy D., Barnett, Michael J., Forrest, Donna L., Hogge, Donna E., Lavoie, Julye C., Nantel, Stephen H., Shepherd, John D., Sutherland, Heather J., Voss, Nicholas J., Smith, Clayton A., and Song, Kevin W.
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HODGKIN'S disease , *GRAFT versus host disease , *BONE marrow transplant complications , *STEM cell transplantation , *DISEASE relapse , *HEMATOLOGY - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
22. Long-term disease-free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation.
- Author
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Toze, Cynthia L., Barnett, Michael J., Connors, Joseph M., Gascoyne, Randy D., Voss, Nicholas J., Nantel, Stephen H., Nevill, Thomas J., Shepherd, John D., Sutherland, Heather J., Lavoie, Julye C., Forrest, Donna L., Song, Kevin W., and Hogge, Donna E.
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LYMPHOMAS , *STANDARD deviations , *BONE marrow , *IMMUNE system , *STEM cells , *ADENOLYMPHOMA - Abstract
Myeloablative allogeneic bone marrow transplantation (BMT) may be curative in patients with follicular non-Hodgkin's lymphoma, however, the impact of this therapy on long-term survival, disease progression and functional status is less clear. Twenty-nine patients (median age 42 years, range: 20–53) with advanced stage follicular lymphoma proceeded to allogeneic BMT a median of 25 (range: 8–154) months postdiagnosis, between 1985 and 2001, and have been followed for a minimum of 2 years. Eleven of 29 (38%) had refractory disease (n = 5 induction failure,n = 6 resistant relapse). Most (27 of 29, 93%) received total body irradiation-based conditioning; stem cell source was marrow from a related donor (n = 20) or unrelated donor (n = 9). Seventeen of 29 patients (59%) were alive a median of 5 years (range: 2–11) post-BMT with a median Karnofsky Performance Score of 100%. Death occurred because of transplant complications in seven patients (cumulative incidence of non-relapse mortality 24%), and progressive lymphoma in five patients (cumulative incidence of refractory/recurrent lymphoma 23%). The 5-year probability of overall and event-free survival was 58% and 53% respectively. Allogeneic BMT has resulted in long-term disease-free survival for approximately 50% of this cohort of patients with advanced follicular lymphoma and most of them now enjoy robust health. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
23. Renal pathology at autopsy in patients who died after hematopoietic stem cell transplantation
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El Seisi, Somaya, Gupta, Rekha, Clase, Catherine M., Forrest, Donna L., Milandinovic, Mirko, and Couban, Stephen
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KIDNEY diseases , *HEMATOPOIETIC stem cell transplantation , *PATHOLOGY - Abstract
Acute and chronic renal dysfunction are common after hematopoietic stem cell transplantation (HSCT). Although the pathology of chronic HSCT nephropathy is well described, the histologic changes that accompany acute renal dysfunction after HSCT are less well known because renal biopsies are rarely undertaken in the peritransplantation period. Archival renal tissue from consecutive HSCT recipients who died and underwent autopsy at a single center during an 8-year period was studied. Abnormalities of renal pathology were described, and associations of histologic abnormalities with clinical events were systemically studied. Abnormalities of renal histology were common among the 26 patients in this study. The 3 most common histologic abnormalities were glomerular sclerosis (19/26; 73%), tubular epithelial atypia (19/26; 73%), and tubular calcification (18/26; 69%). Tubulitis (16/24; 67%) and interstitial fibrosis (16/26; 62%) were also frequently observed. Clinical veno-occlusive disease was not associated with histologic evidence of thrombotic microangiopathy in the kidney at autopsy. Also, clinical graft-versus-host disease was not associated with renal tubulitis. Unexpectedly, the proportion of patients with tubular atrophy (54%) or interstitial fibrosis (62%) was high, considering the young age of the patients at transplantation and their normal pretransplantation creatinine clearance. Well-recognized histologic abnormalities are common in the kidneys of patients who die after HSCT. Although we did not demonstrate associations of these histologic changes with clinical variables before death, larger studies with prospectively collected renal tissue are warranted. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
24. Serotonin Syndrome after Concomitant Treatment with Linezolid and Meperidine.
- Author
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Das, Prabodh K., Warkentin, Dawn I., Hewko, Robert, and Forrest, Donna L.
- Subjects
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SEROTONIN , *NEUROTRANSMITTERS , *SEROTONIN uptake inhibitors , *NEUROTRANSMITTER uptake inhibitors , *ANTIBIOTICS , *ACUTE leukemia , *CANCER , *DRUGS , *OLDER men - Abstract
Serotonin syndrome has been reported with administration of linezolid and serotonin reuptake inhibitors. Meperidine blocks the neuronal reuptake of serotonin. Serotonin syndrome after concomitant linezolid and meperidine therapy has not been described. We describe serotonin syndrome after concomitant use of linezolid and meperidine in a 27-year-old man with acute leukemia. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
25. Disseminated mucormycosis presenting as transplant-associated thrombotic microangiopathy
- Author
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Peterson, Erica A., Gerrie, Alina S., Power, Maryse M., Poulin, Micheal P., Dalal, Bakul I., and Forrest, Donna L.
- Published
- 2011
- Full Text
- View/download PDF
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