Papers by Eshetu G . Atenafu
Transplantation and Cellular Therapy, 2021
Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option f... more Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option for patients without a suitable 10/10 HLA matched donor. We share an updated experience at our center of using in vivo dual T-cell depletion with anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) in peripheral blood haploHCT and report the impact of reducing the dose of ATG from 4.5 mg/kg to 2 mg/kg on post-transplantation complications and outcomes. Ninety-five consecutive adults underwent haploHCT at our center between August 2016 and February 2020, all of whom were included in the study. Nine (9.5%) patients received myeloablative conditioning, and 86 (90.5%) patients underwent reduced-intensity haploHCT. All patients received thymoglobulin, PTCy and cyclosporine (CsA) for graft-versus-host disease (GVHD) prophylaxis: Sixty (63.2%) patients received 4.5 mg/kg, and 35 (36.8%) patients received 2 mg/kg of ATG. Clinical information was collected retrospectively and updated in June 2020. The median age was 57 (18-73), and acute myeloid leukemia was the most prevalent diagnosis (58.9%). The day 100 cumulative incidence of grade II-IV and grade III-IV aGVHD, and 1-year moderate/severe cGVHD were 22.3%, 11.1%, and 20.2%, respectively. Those patients who received 2 mg/kg of ATG had higher incidence of grade III-IV aGVHD (23.9% vs 3.5%, P = .006) and comparable moderate/severe cGVHD (1-year 20.6% vs 19.8%, P = .824) than those patients who received 4.5 mg/kg. Overall, the 18-month overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) were 43.8%, 38.4%, and 40.2%, respectively. The reduction of the ATG dose did not have a significant impact in OS (hazard ratio [HR] 1.06, P = .847), RFS (HR 0.984, P = .955), and in NRM (HR 1.38; P = .348). The reduction of the ATG resulted in a negative impact on aGVHD without conferring any benefit in OS, RFS, and NRM. Consequently, the ATG dose used at our institution in combination with PTCy and CsA for haploHCT continues to be 4.5 mg/kg.
Blood, 2017
Background: In the era prior to the availability of novel agents, we have previously reported tha... more Background: In the era prior to the availability of novel agents, we have previously reported that the median progression-free survival (PFS) and overall survival (OS) of high-risk (HR) multiple myeloma (MM) patients (pts) undergoing a single autologous stem cell transplant (ASCT) was only 9.9 and 18.3 months, respectively (Chang H et al., Bone Marrow Transplant, 36 (2005), 793). The current study expands our experience in newly diagnosed HR pts and focuses on the outcomes in pts treated with single or tandem ASCT. Methods: A retrospective chart review of myeloma pts was conducted based on pt information retrieved from the Princess Margaret Myeloma Database. 245 pts with HR MM diagnosed and treated in our centre from Oct 1998 to Dec 2016 were identified. Survival rates were calculated using the Kaplan-Meier product-limit method and the log rank-statistic was used for comparison of survival curves. Results: Pts were considered HR based on the presence of any one of the cytogenetic fe...
BMC Pediatrics, 2021
Objective To establish reference intervals for hemoglobin and mean corpuscular volume (MCV) in an... more Objective To establish reference intervals for hemoglobin and mean corpuscular volume (MCV) in an ethnically diverse community sample of Canadian children 36 months and younger. Methods We collected blood samples from young children at scheduled primary care health supervision visits at 2 weeks, 2, 4, 6, 9, 12, 15, 18, 24, and 36 months of age. Samples were analyzed on the Sysmex XN-9000 Hematology Analyzer. We followed the Clinical and Laboratory Standards Institute guidelines in our analysis. Data were partitioned by sex and also combined. We considered large age partitions (3 and 6 months) as well as monthly partitions. Reference intervals (lower and upper limits) and 90% confidence intervals were calculated. Results Data from 2106 children were included. The age range was 2 weeks to 36 months, 46% were female, 48% were European and 23% were of mixed ethnicity. For hemoglobin, from 2 to 36 months of age, we found a wide reference interval and the 90% confidence intervals indicate...
Journal of Medical Imaging and Radiation Sciences, 2020
Gynecologic Oncology, 2020
International Journal of Gynecological Pathology, 2020
TP53 status is the most important prognostic biomarker in endometrial carcinoma. We asked the que... more TP53 status is the most important prognostic biomarker in endometrial carcinoma. We asked the question whether p53 mutated endometrial endometrioid carcinomas grade 3 (EEC3) or endometrial serous carcinomas (ESC), the latter ubiquitously the harboring TP53 mutation, have different outcomes. TP53 mutation status was assessed by surrogate p53 immunohistochemistry on 326 EEC3 and ESC from 2 major cancer centers in Canada. Mutant-type p53 expression, including overexpression, complete absence, or cytoplasmic expression, was distinguished from the wild-type pattern. Statistical associations with clinico-pathological parameter, other key biomarkers, and survival analyses were performed. P53 mutant-type immunohistochemistry was observed in all 126 ESC and in 47/200 (23.5%) EEC3. ESC and p53 mutated EEC3 had an unfavorable outcome compared with p53 wild-type EEC3 (hazard ratio=2.37, 95% confidence interval=1.48-3.80, P=0.003, hazard ratio=2.19, 95% confidence interval=1.16-4.12, P=0.016, respectively) in multivariable analyses adjusted for age, stage, center, and presence of lymph-vascular invasion. There was no significant difference in survival between ESC and p53 mutated EEC3 in multivariable analysis. Furthermore, p53 mutated EEC3 and ESC almost completely overlapped in univariate survival analysis when mismatch repair (MMR)-deficient cases were excluded, which suggests that EEC3 harboring combined MMR deficiency and TP53 mutations behave more according to the MMR status. Significant differences between p53 mutated MMR-proficient EEC3 and ESC in PTEN and p16 expression status remained. p53 mutated, MMR-proficient EEC3 and ESC have overlapping survival significantly different from p53 wild-type EEC3, which justifies a similar treatment with current non-targeted standard therapy. Although this is so, separate classification should continue due to biological differences that will become important for future targeted therapy.
Supportive Care in Cancer, 2019
Objective We evaluated whether conducting psychosocial screening using a validated measure (the P... more Objective We evaluated whether conducting psychosocial screening using a validated measure (the Psychosocial Assessment Tool, PAT) and providing a summary of PAT results to the patient's treating team improves quality of life (QOL) in newly diagnosed patients with cancer, their caregivers and siblings, in general, and in relation to the initial family psychosocial risk. Methods Families were randomly allocated to an intervention (IG, treating team received PAT summary describing low, medium, or high psychosocial risk) or control group (CG, no summary provided to treating team) in two Canadian pediatric cancer centers. Caregivers (N = 122) of children newly diagnosed with cancer, patients (n = 36), and siblings (n = 25) completed QOL assessments at 2-4 weeks (T1) and 6 months post-diagnosis (T2). Caregivers also completed PAT and proxy QOL for patient and sibling. Results In general, patient-proxy total QOL improved in IG compared to CG over time but only for high psychosocial risk patients (p < .05). Patient proxy cancer-related QOL improved over time regardless of group allocation; caregiver QOL also improved over time (ps < .05). Conclusion This study demonstrated the benefits of psychosocial screening results only on proxy patient QOL outcomes with high psychosocial risk near diagnosis. Evaluating QOL benefits in pediatric oncology patients is critical for establishing the clinical value of psychosocial screening.
European Journal of Haematology, 2019
Manuscript text word count-3090 (excluding references) Number of references-49 Number of tables-2... more Manuscript text word count-3090 (excluding references) Number of references-49 Number of tables-2 Number of figures-3 Number of supplementary figures-4 Conflicts of interest There are no funding sources to declare. The authors declare no relevant conflicts of interest, financial or otherwise. Contributions SP collected the data and wrote the paper, EA analyzed the data, WL, AL, JM, JL, FM, AV, DK and RK provided valuable input into the study design, analysis, and interpretation and reviewed the manuscript.
Blood, 2018
Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative fo... more Introduction: Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for the treatment of various hematological diseases, in part due to the effect of conditioning chemotherapy, and in part due to graft-versus-malignancy effect. However, alloHCT is associated with significant morbidity and mortality. Multiple co-morbidity indices have been published in the literature for the purpose of pre-transplant risk assessment. The purpose of the presented study is to assess a number of these pre-transplant scores on a single-center transplant population and to determine the score with improved risk stratification ability using concordance statistics. Methods: We investigated the impact of the prospectively collected Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) on post-transplant outcomes for 243 recipients of allo-HCT performed between August 2014 and October 2016 at the Princess Margaret Cancer Center (Toronto, Canada), and compared this score to ot...
Blood, 2012
4501 Introduction: CMV (Cytomegalovirus) reactivations are a major cause of morbidity and mortali... more 4501 Introduction: CMV (Cytomegalovirus) reactivations are a major cause of morbidity and mortality in recipients of hematopoietic cell transplantation (HCT). Risk factors for CMV reactivations have not been fully elucidated. We evaluated first and subsequent CMV reactivations. Methods: Three hundred and forty seven patients transplanted consecutively between year 2005 and 2010 at Princess Margaret Hospital were assessed. CMV monitoring was performed by pp65 antigenemia testing. Positive patients (defined as >1 positive cells per 105 peripheral blood leukocytes examined) were treated preemptively with ganciclovir. 206(59%) patients received HCTs from related and 141(41%) from unrelated donors. 152(44%) were female and 195(56%) male. Graft versus host disease (GVHD) prophylaxis included Cyclosporine (CSA)/Mycophenolate mofetil (MMF) (n=100, 28.8%), CSA/Methotrexate (MTX) (n=101, 29.1%), CSA/CAMPATH (n=139, 40%), other (n=7, 2%). Results: With a median follow up of 15 months, 132 p...
Blood, 2016
Introduction: Gemcitabine, dexamethasone and cisplatin (GDP) has become a standard salvage chemot... more Introduction: Gemcitabine, dexamethasone and cisplatin (GDP) has become a standard salvage chemotherapy (SC) regimen for relapsed/refractory (RR) lymphoma prior to autologous stem cell transplantation (ASCT) (Crump JCO 2014). Response to SC is now evaluated using 18-Fluoro-deoxyglucose positron-emission-tomography (FDG-PET) scans based on the recent Lugano classification (Cheson JCO 2014). We evaluated the response of patients (pts) with Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL) to GDP by PET-CT scans and attempted to determine whether PET was predictive of outcome. Methods: We performed a retrospective chart review of consecutive HL and DLBCL (diffuse large B-cell lymphoma) pts who underwent ASCT following GDP SC at our centre between January 2014 and July 2016. All pts previously received anthracycline-based chemotherapy (typically ABVD for HL or R-CHOP for NHL) for primary treatment. Pts underwent FDG-PET scans after 3 cycles of SC and scans were retrospecti...
Blood, 2016
It has been demonstrated that lenalidomide causes selective degradation of IKZF1 (Ikaros) and IKZ... more It has been demonstrated that lenalidomide causes selective degradation of IKZF1 (Ikaros) and IKZF3 (Aiolos) which are two essential transcription factors for proliferation of multiple myeloma cells. Consequently, the drug sets up a molecular sequence of events that lead to programmed cell death in the tumoral cells. This anti-proliferative effect is mediated by down-regulation of c-Myc and interferon regulatory factor 4 (IRF4). However, it is not clear whether IKZF1/IKZF3 protein expression in myeloma cells is predictive of clinical outcome. Thus, we evaluated bone marrow samples of 50 relapsed/refractory multiple myeloma (MM) patients regarding IKZF1/3 protein expression before starting lenalidomide. There were 31 males and 19 females with median age of 59 years (range 41-75). They all had received lenalidomide-based therapy after relapse following autologous stem cell transplantation (ASCT), thalidomide, or bortezomib. The median follow-up was 86.4 months. By immunohistochemistry...
Blood, 2013
5501 Relapse is a major cause of treatment failure of allogeneic hematopoietic cell transplantati... more 5501 Relapse is a major cause of treatment failure of allogeneic hematopoietic cell transplantation (HCT) for Chronic Myeloid Leukemia (CML). DLI (Donor lymphocyte infusion) and TKI (Tyrosine Kinase inhibitors) are the two standard treatment options in this setting but reports comparing their long-term outcomes are scarce. Between 1993 and 2012, 28 patients underwent DLI and 18 patients received TKI for chronic or advanced phase relapse of CML at our institution. Chronic hematologic, cytogenetic and molecular relapses were considered as chronic phase relapses. Accelerated phase and blast crisis relapses were considered as advanced phase relapses. Overall survival (OS), failure free survival (FFS) and cumulative incidence of failure (CIF) were analyzed retrospectively and for these analyses, failure was defined as lack of response, relapse or intolerance requiring change in treatment. This study had Institutional Research Ethics Board approval. Among18 patients treated with TKI, 15 p...
International Journal of Radiation Oncology*Biology*Physics, 2019
Top 10 highest ranked radiomic features were combined, one at a time, with the clinical features,... more Top 10 highest ranked radiomic features were combined, one at a time, with the clinical features, resulting in a very significant (p<0.001) increase in AUC from the addition of the top 9 radiomic features, and no increase from adding the 10 th best radiomic feature. An optimized combination of radiomic and clinical features resulted in a dramatically higher performance (resampled AUC: meanZ0.792, 95% C.I of meanZ0.790-0.793) compared to clinical features alone (0.676, 0.674-0.678). Conclusion: The increase in performance from incorporating radiomic features suggests that quantitative characterization of tumor structure through the use of radiomics adds complementary information to what is typically available in the clinical workflow.
Dental Research Journal, 2019
Background: The study's purpose was to study buccal pouch grafting (BPG) with xenograft, freeze-d... more Background: The study's purpose was to study buccal pouch grafting (BPG) with xenograft, freeze-dried bone allograft (FDBA), or FDBA + decalcified FDBA (DFDBA) on alveolar ridge width preservation and overlying soft tissue thickness at dog premolar extraction sites. Materials and Methods: In this animal study, 4 dogs had their mandibular first premolar (P1) and distal roots of P2, P3, and P4 extracted (after endodontic treatment of the mesial roots) bilaterally. A small buccal pouch was created at each extraction socket and four treatments tested: nothing, xenograft, FDBA, or FDBA + DFDBA. Casts made pretreatment and at 1 and 3 months after treatment allowed measurements of buccolingual alveolar ridge width (BLRW), while overlying buccal soft tissue thicknesses were measured clinically. Data were assessed using analysis of variance to compare changes in soft tissue thickness and BLRW between times and treatments. Tukey-Kramer adjustment for multiple comparisons was applied for doing post hoc, pairwise comparisons. Results were considered significant if P < 0.05. Results: Control sites showed significant (P = 0.0067) decreases in soft tissue thickness over time while there was a trend for increased soft tissue thickness at all grafted sites. There were significant losses in BLRW over time for control (P = 0.0032) and FDBA groups (P = 0.015) with a trend for loss with FDBA + DFDBA. Pairwise comparison using Tukey-Kramer adjustment revealed significant increases in BLRW from T1 to T3 for the xenograft group relative to all the others. Conclusion: BPG using xenograft is effective in maintaining hard and soft tissue stability following tooth extraction.
Analytical Chemistry, 2019
The analysis of circulating tumor cells (CTCs) provides a means to collect information about the ... more The analysis of circulating tumor cells (CTCs) provides a means to collect information about the evolving properties of a tumor during cancer progression and treatment. For patients with metastatic prostate cancer, noninvasive serial measurements of bloodborne cells may provide a means to tailor therapeutic decisions based on an individual patient's response. Here, we used a high-sensitivity profiling approach to monitor CTCs in patients with metastatic castrate-resistant prostate cancer (mCRPC) undergoing treatment with abiraterone and enzalutamide, two drugs used to treat advanced prostate cancer. The capture and profiling approach uses antibody-functionalized magnetic nanoparticles to sort cells according to protein expression levels. CTCs are tagged with magnetic nanoparticles conjugated to an antibody specific for the epithelial cell adhesion molecule (EpCAM) and sorted into four zones of a microfluidic device based on EpCAM expression levels. Our approach was compared to the FDA-cleared CellSearch method, and we demonstrate significantly higher capture efficiency of low-EpCAM cells compared to the commercial method. The nanoparticle-based approach detected CTCs from 86% of patients at baseline, compared to CellSearch which only detected CTCs from 60% of patients. Patients were stratified as prostate specific antigen (PSA) progressive versus responsive based on clinically acceptable definitions, and it was observed that patients with a limited response to therapy had elevated levels of androgen receptor variant 7 (ARV7) and the mesenchymal marker, N-cadherin, expressed on their CTCs. In addition, these CTCs exhibited lower EpCAM expression. The results highlight features of CTCs associated with disease progression on abiraterone or enzalutamide, including mesenchymal phenotypes and increased expression levels of ARV7. The use of a high-sensitivity method to capture and profile CTCs provides more informative data concerning the phenotypic properties of these cells as patients undergo treatment relative to an FDA-cleared method.
Journal of Clinical Oncology, 2015
6583 Background: Hospitalization during chemotherapy is a significant event from both the patient... more 6583 Background: Hospitalization during chemotherapy is a significant event from both the patient and healthcare system perspectives but little is known about how often it occurs and in which settings. We conducted a systematic review to define the frequency of and factors associated with treatment-related hospitalization among cancer patients (pts) undergoing chemotherapy. Methods: A systematic search of Medline and EMBASE databases, from 1946 to September 2013, was undertaken to identify articles reporting rates of hospitalization in pts with cancer undergoing chemotherapy. Observational studies and clinical trials were eligible but results were analysed separately for each group. Summary statistics were used to describe the results and the Chi-square test was used to compare the groups. Results: Sixty articles met inclusion criteria: 44 observational studies comprising 189,342 pts and 16 randomized controlled trials comprising 13,086 pts. The majority of articles (80%) focused on chemotherapy given wit...
Journal of Clinical Oncology, 2015
e18022 Background: Therapy for patients (pts) with high risk and relapsed/refractory AML is unsat... more e18022 Background: Therapy for patients (pts) with high risk and relapsed/refractory AML is unsatisfactory. Since Jan 2011, we have employed FLAG-IDA as first line therapy in pts with high risk AML (i.e. poor risk cytogenetics, antecedent MPN or MDS, or therapy-related AML), or as first salvage in pts with primary refractory/relapsed AML, in an attempt to improve CR rates, OS and to permit more pts to advance to allogeneic stem cell transplantation (alloSCT). Methods: This retrospective review evaluates outcomes of pts with high risk and primary refractory/relapsed AML who were treated with FLAG-IDA between Jan 2011 to Dec 2014 at the Princess Margaret Cancer Centre. Results: 46 pts received FLAG-IDA as first induction [median age 58.5 y (21-76 y)] and 69 pts as salvage [median age 51 y (18-76 y)]. Overall CR rates (CR + CRp) for frontline (n = 43 evaluable) and salvage therapies were 79.1% (88% CR; 11% CRp) and 57.9% (70% CR; 30% CRp), respectively; whereas, CR durations were 3 (0.5-15) mos and 6 (0-58) ...
Melanoma research, 2018
Metastatic uveal melanoma (MUM) has a poor prognosis, with no established standard of care. Delin... more Metastatic uveal melanoma (MUM) has a poor prognosis, with no established standard of care. Delineation of prognostic factors in MUM patients may enable stratified treatment algorithms of stage-specific survival. Overall, 132 MUM patients who presented to a single tertiary institution in Toronto, Canada, over 12 years were identified and data (demographics, clinical status, radiographic images, and laboratory values) were extracted. Associations with systemic first-line treatment outcome 12 weeks after first-line treatment, time to progression (TTP), and overall survival (OS) were explored by univariate and multivariable analysis. Age, presence of liver metastases, and time from primary presentation to metastatic presentation were significant variables affecting first-line treatment outcomes. Age, Eastern Cooperative Oncology Group (ECOG) score, presence of liver metastases, liver metastasis size, neutrophil lymphocyte ratio, absolute neutrophil count, lactate dehydrogenase (LDH), a...
International Journal of Radiation Oncology*Biology*Physics, 2018
findings by determining the three-dimensional (3-D) spatial dose distribution of the mandibular a... more findings by determining the three-dimensional (3-D) spatial dose distribution of the mandibular area of ORN origin. Materials/Methods: Subsequent to institutional review board approval, we identified patients with grade IV ORN requiring major surgery among patients with OPC treated with IMRT between 2002 and 2013. The initial computed tomography (CT) scans documenting the diagnosis of ORN were identified. The mandibular areas affected with ORN were manually segmented for all patients to create 3-D ORN volume of interest (ORN-VOI). Planning CTs and dose grids were subsequently retrieved. ORNdepicting CT scans were then co-registered to planning CT scans using a validated commercial image registration software (Velocity AI 3.0.1, Atlanta, GA). Finally, ORN-VOIs were mapped to planning CT scans, and dose grid then dosimetric parameters were extracted for each VOI. Results: Among 1500 patients reviewed, twenty-five patients (1.7%) with grade IV ORN were identified. Median follow-up was 76 months (range 24-183) and median time to development of ORN was 22 months (range 5-132). Median age at diagnosis was 61 years (range 47-72), and 84% were men. The site of tumor origin was base of tongue, tonsil, and posterior pharyngeal wall in 12, 12, and 1 patient(s), respectively. Median radiation prescription dose was 70 Gy in 33 fractions. Only two patients developed ORN contralateral to the tumor site. The average of minimum dose to ORN-VOIs (i.e. the isodose line that covers 100% of the ORN volume) was 54.3 Gy. The first, second, third, and fourth quartile minimum dose distribution for ORN-VOI ranged from 32.4-46.7, 46.7-54.6, 54.6-64.6, and 64.6-68.5 Gy, respectively. The averages of mean and maximum doses to ORN VOIs were 66.3 Gy (range 54-75) and 72.5 Gy (range 64-78), respectively. Conclusion: The mandibular areas of origin of advanced ORN in OPC patients treated with IMRT received at least 55 Gy in approximately half of the examined cohort. However, lower doses, in the intermediate dose range (32-55 Gy), were also associated with mandibular ORN. Our findings suggest that the intermediate dose beam-path results in long-term bone toxicity for OPC survivors.
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Papers by Eshetu G . Atenafu