Publications by authors named "Jason Tay"

64 Publications

N-Terminal pro-brain natriuretic peptide (NTproBNP) in patients with symptomatic multiple myeloma: report from a single institution.

Ann Hematol 2021 Jul 21. Epub 2021 Jul 21.

Department of Medical Oncology and Hematology, Tom Baker Cancer Center, 1331 29th St, NW, Calgary, AB, T2N 4N2, Canada.

Elevated levels of serum cardiovascular markers including natriuretic peptides (NPs) such as amino terminal pro-brain natriuretic peptide (NTproBNP) have been associated with disease severity and survival in cancer patients and more recently in multiple myeloma (MM). In the present study, we retrospectively reviewed 87 consecutive symptomatic TEMM (transplant-eligible) and 126 TIMM (transplant-ineligible) patients treated at our institution that did undergo NTproBNP testing from 2017 to 2020. Median age at diagnosis was 59.3 years and 75.4 years for the TEMM and TIMM groups, respectively (p = 0.0001). NTproBNP ≥ 300 ng/L was used to assess survival outcomes in the group of symptomatic MM. Patients with AL amyloidosis and symptomatic MM were excluded from the study. Median OS for patients with NTproBNP ≥ 300 ng/L was shorter (45.9 months) as compared to those with NTproBNP of < 300 ng/L (non-reached) (p = 0.0001). In addition, OS was shorter for those with CCI > 2, ISS2-3, and high-risk cytogenetics by FISH and ≥ 70 years of age. Multivariate analysis showed that HR cytogenetics and ISS2-3 were independent predictors for OS in the entire cohort of MM patients. When restricted to TIMM, age ≥ 80 years and NTproBNP ≥ 800 ng/L were predictors for OS in univariate and multivariate analyses. In conclusion, NTproBNP appears to be an independent predictor factor for OS in symptomatic TIMM patients. The use of NTproBNP as a frailty marker remains to be elucidated. However, NTproBNP could potentially be used to guide treatment decisions aimed to minimize cardiovascular and renal toxicity for myeloma therapies that potentially do have cardio-renal implications.
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http://dx.doi.org/10.1007/s00277-021-04591-zDOI Listing
July 2021

Perceptions of healthcare professionals towards palliative care in internal medicine wards: a cross-sectional survey.

BMC Palliat Care 2021 Jun 30;20(1):101. Epub 2021 Jun 30.

Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore.

Background: The extension of palliative care services to meet the needs of patients with chronic non-malignant life-limiting conditions faces misconceptions amongst healthcare professionals. A study of prevailing perceptions of healthcare professionals on this wider palliative care service was thus conducted to identify current obstacles, guide the education of local healthcare professionals and improve service accessibility.

Methods: A cross-sectional study was carried out at the Singapore General Hospital. An anonymised and close-ended online questionnaire was disseminated to 120 physicians and 500 nurses in the Department of Internal Medicine. The online survey tool focused on participant demographics; perceptions of palliative care and its perceived benefits; roles and indications; and attitudes and behaviours towards palliative care referrals.

Results: Forty four physicians and 156 nurses suggested that care of terminally ill patients with chronic non-malignant life-limiting conditions are compromised by concerns over the role of palliative care in non-cancer care and lapses in their prognostication and communication skills. Respondents also raised concerns about their ability to confront sociocultural issues and introduce palliative care services to patients and their families.

Conclusions: Gaps in understanding and the ability of nurses and physicians to communicate end of life issues, introduce palliative care services to patients and their families and confront sociocultural issues suggest the need for a longitudinal training program. With similar concerns likely prevalent in other clinical settings within this island nation, a concerted national education program targeting obstacles surrounding effective palliative care should be considered.
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http://dx.doi.org/10.1186/s12904-021-00787-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247075PMC
June 2021

Treatment response measurements and survival outcomes in a cohort of newly diagnosed AL amyloidosis.

Amyloid 2021 Jun 7:1-7. Epub 2021 Jun 7.

Tom Baker CancerCenter, University of Calgary, Calgary, Canada.

Introduction: The assessment of AL amyloidosis response is based on serum free light chains (sFLC) levels, and serum and urine monoclonal protein investigations. Recently, difference between involved and uninvolved free light chains (dFLC), involved free light chain (iFLC) and complete response (CR) has been reported as independent predictor of survival and a refinement of the hematological response criteria has been proposed by several groups.

Methods: In the current study, all consecutive newly diagnosed symptomatic AL amyloidosis patients were evaluated. The primary objective of the study was to assess hematological and organ response after first line of treatment.

Results: A cohort of 76 cases with upfront treatment was used for this analysis. After a median of 3 months post-therapy, hematological response was seen in 88% of cases including CR in 26.3%, VGPR in 38.2% and PR in 23.7%. Median OS was longer in patients with dFLC < 10 mg/L at 3 months, iFLC <20 mg/L at 1 and 3 months, and those achieving CR. Multivariate analysis showed presence of CR as the most important independent prognostic factors for survival.

Conclusions: Our study suggests that maximal sFLC response and CR are potential endpoints to define clinical outcomes. Large collaborative studies are required to validate and optimize response criteria.
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http://dx.doi.org/10.1080/13506129.2021.1921725DOI Listing
June 2021

Monoclonal Gammopathy of Undetermined Significance Clinic during the Coronavirus Disease-19 Pandemic: Caring for the Vulnerable in an Academic Medical Center.

Rev Invest Clin 2021 06 2;73(4):259-264. Epub 2021 Jun 2.

Department of Medical Oncology and Hematology, Tom Baker Cancer Centre, Calgary; Charbonneau Cancer Research Institute, Calgary, Canada.

Background: Patients with monoclonal gammopathy of undetermined significance (MGUS) have clinical features including older age, presence of medical comorbidities, susceptibility to infections, and thrombotic tendencies which are relevant when assessing their risk during the coronavirus disease (COVID-19) pandemic.

Objective: To study the vulnerability of patients with MGUS during the COVID-19 pandemic, we assessed the local management of MGUS patients and their clinical outcomes.

Methods: Retrospective chart reviews were performed for all patients with MGUS seen at a university medical center clinic (2014-2020).

Results: A total of 228 MGUS patients were included; 211 patients are alive, 7 patients died before the pandemic, and 10 patients died since the pandemic declaration. The mean age and the overall survival (OS) of the patients who died before versus during the pandemic were 83.0 versus 75.2 years, p = 0.4, and OS 40.6 versus 53.2 months, p = 0.3, respectively. One patient died of COVID-19. Nine patients had venous thromboembolisms (VTE), all of which occurred before the pandemic onset.

Conclusions: There were no significant differences found in the mean age or OS of the MGUS patients who died before versus after the pandemic onset. An increase in VTE rates was not seen. Study results are limited by small patient numbers.
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http://dx.doi.org/10.24875/RIC.21000078DOI Listing
June 2021

The impact of COVID-19 in the management of AL amyloidosis and Immunoglobulin Deposition Disease: A single-center experience.

Eur J Haematol 2021 Mar 29;106(3):340-345. Epub 2020 Nov 29.

Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada.

Introduction: Patients with AL amyloidosis and immunoglobulin deposition diseases (IDD) are vulnerable during the COVID-19 pandemic due to the immune compromise from the plasma cell disorder and therapy-related immune defects. We describe a local experience in providing care for patients with AL amyloidosis and IDD.

Method: Patient treatment and disease status since the beginning of the pandemic on March 11, 2020, as declared by WHO, were collected and analyzed.

Results: Ninety-six patients with AL amyloidosis and IDD were included. Four patients with IDD and 22 patients with systemic AL amyloidosis were receiving treatment during the pandemic. Since the pandemic, patients' treatments were discontinued if they achieved VGPR or better postinduction. Seven patients discontinued all treatment after achieving VGPR, and others required treatment modifications. 28 patients have been tested for COVID-19, and all tests have been negative. Three patients died since the pandemic, two from organ complications of systemic AL amyloidosis and one from an unrelated cause.

Conclusion: The management of AL amyloidosis and IDD must be individualized on the clinical characteristics, centers' access to care under the pandemic restrictions, and the epidemiological aspects of the outbreak.
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http://dx.doi.org/10.1111/ejh.13552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753531PMC
March 2021

Age no bar: A CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma.

Cancer 2020 12 23;126(23):5077-5087. Epub 2020 Sep 23.

The University of Texas M.D. Anderson Cancer Center, Houston, Texas.

Background: Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults.

Methods: The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori.

Results: An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m . On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P = .02]) compared with the reference group (those aged 60-69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m , including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%]; P = .003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%]; P = .003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%]; P = .01]), likely representing frailty.

Conclusions: The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.
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http://dx.doi.org/10.1002/cncr.33171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063213PMC
December 2020

Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) for the Treatment of Newly Diagnosed AL Amyloidosis: Impact of Response on Survival Outcomes.

Clin Lymphoma Myeloma Leuk 2020 06 7;20(6):394-399. Epub 2019 Nov 7.

Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address:

Background: CyBorD (cyclophosphamide, bortezomib, and dexamethasone) is an effective regimen for the treatment of patients with newly diagnosed immunoglobulin light chain (AL) amyloidosis. CyBorD can induce rapid hematologic responses (HRs). However, it remains inadequate to enhance outcomes in high-risk groups. In addition, minimal information is available on the impact of minimal residual disease (MRD) in overall survival.

Patients And Methods: All consecutive patients with newly diagnosed AL amyloidosis treated with CyBorD from January 2012 to August 2018 were evaluated. HR and organ response was assessed as per standard guidelines. Further, MRD was evaluated by multiparameter flow cytometry in patients with confirmed complete response (CR).

Results: After a median of 4 cycles, HR was seen in 31 (91.2%) cases, including CR in 9 (26.5%), very good partial response in 9 (26.5%), and partial response in 13 patients (38.2%). Organ response at 6 months was documented in 11 (32.4%) cases. With respect to cardiac response, a > 30% decrease of NT-proBNP was observed in 4 (19%) of 21 evaluable cases (NTproBNP > 650 ng/L) at a median of 6 months. The median progression-free survival was 26.7 months. Patients who achieved CR exhibited a better overall survival compared with those without CR (P = .001). No difference on overall or progression-free survival among cases achieving CR irrespective of their MRD status was observed (P > .05).

Conclusions: In summary, CyBorD showed a ≥ very good partial response rate of 53% with 26.5% achieving CR, which is similar to that seen in previous studies. In addition, MRD negativity assessed by multiparameter flow cytometry in patients with CR resulted in no difference on survival outcomes.
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http://dx.doi.org/10.1016/j.clml.2019.11.005DOI Listing
June 2020

Liberal Versus Restrictive Red Blood Cell Transfusion Thresholds in Hematopoietic Cell Transplantation: A Randomized, Open Label, Phase III, Noninferiority Trial.

J Clin Oncol 2020 05 21;38(13):1463-1473. Epub 2020 Feb 21.

Ottawa Hospital Centre for Transfusion Research, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Purpose: Evidence regarding red blood cell (RBC) transfusion practices and their impact on hematopoietic cell transplantation (HCT) outcomes are poorly understood.

Patients And Methods: We performed a noninferiority randomized controlled trial in four different centers that evaluated patients with hematologic malignancies requiring HCT who were randomly assigned to either a restrictive (hemoglobin [Hb] threshold < 70 g/L) or liberal (Hb threshold < 90 g/L) RBC transfusion strategy between day 0 and day 100. The noninferiority margin corresponds to a 12% absolute difference between groups in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score relative to baseline. The primary outcome was health-related quality of life (HRQOL) measured by FACT-BMT score at day 100. Additional end points were collected: HRQOL by FACT-BMT score at baseline and at days 7, 14, 28, 60, and 100; transplantation-related mortality; length of hospital stay; intensive care unit admissions; acute graft-versus-host disease; Bearman toxicity score; sinusoidal obstruction syndrome; serious infections; WHO Bleeding Scale; transfusion requirements; and reactions to therapy.

Results: A total of 300 patients were randomly assigned to either restrictive-strategy or liberal-strategy treatment groups between 2011 and 2016 at four Canadian adult HCT centers. After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group ( < .0001). The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units [standard deviation, 4.81 units] 5.02 units [standard deviation, 6.13 units]; = .0004). After adjusting for transfusion type and baseline FACT-BMT score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points; 95% CI, -2.5 to 5.6 points), which was noninferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies.

Conclusion: In patients undergoing HCT, the use of a restrictive RBC transfusion strategy threshold of 70 g/L was as effective as a threshold of 90 g/L and resulted in similar HRQOL and HCT outcomes with fewer transfusions.
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http://dx.doi.org/10.1200/JCO.19.01836DOI Listing
May 2020

Anti-myeloma potential of ruxolitinib in co-existing JAK2V617F-positive smouldering myeloma and polycythaemia vera.

Br J Haematol 2020 05 20;189(3):e114-e118. Epub 2020 Feb 20.

Tom Baker Cancer Center, Department of Medical Oncology and Hematology, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1111/bjh.16533DOI Listing
May 2020

High incidence of Pneumocystis jirovecii pneumonia in allogeneic hematopoietic cell transplant recipients in the modern era.

Cytotherapy 2020 01 27;22(1):27-34. Epub 2019 Dec 27.

Alberta Health Services, Calgary, Alberta, Canada; University of Calgary, Calgary, Alberta, Canada.

Background: International guidelines for Pneumocystis jirovecii pneumonia (PJP) prevention recommend prophylaxis for ≥6 months following allogeneic hematopoietic cell transplantation, and longer in patients with graft-versus-host disease (GVHD) or on immunosuppressive therapy (IST). These recommendations are based on cohorts of patients who did not routinely receive anti-thymocyte globulin (ATG) for GVHD prophylaxis.

Methods: We performed a retrospective chart review of 649 patients, all of whom received ATG as part of GVHD prophylaxis.

Results: The cumulative incidence of definite PJP was 3.52% at both 3 and 5 years (median follow up, 1648 days for survivors). PJP occurred in 13 non-GVHD patients between days 207 and 508, due in part to low CD4 T-cell counts (<200 CD4 T cells/µL). PJP occurred in eight GVHD patients between days 389 and 792, due in part to non-adherence to PJP prophylaxis guidelines (discontinuation of PJP prophylaxis at <3 months after discontinuation of IST). Breakthrough PJP infection was not observed in patients receiving prophylaxis with cotrimoxazole, dapsone or atovaquone, whereas three cases were observed with inhaled pentamidine.

Discussion: In conclusion, for non-GVHD patients receiving ATG-containing GVHD prophylaxis, 6 months of PJP prophylaxis is inadequate, particularly if the CD4 T-cell count is <200 cells/µL or if there is a high incidence of PJP in the community. For patients with GVHD receiving ATG-containing GVHD prophylaxis, continuing PJP prophylaxis until ≥3 months post-discontinuation of IST is important. Cotrimoxazole, dapsone and atovaquone are preferred over inhaled pentamidine.
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http://dx.doi.org/10.1016/j.jcyt.2019.11.002DOI Listing
January 2020

Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors: A Report from the Center for International Blood and Marrow Transplant Research.

Biol Blood Marrow Transplant 2020 03 11;26(3):553-561. Epub 2019 Nov 11.

Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland.

Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.
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http://dx.doi.org/10.1016/j.bbmt.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367505PMC
March 2020

Slow lenalidomide desensitization protocol for patients with multiple myeloma: case series from a single center.

Leuk Lymphoma 2019 12 13;60(13):3199-3203. Epub 2019 Jun 13.

Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada.

Lenalidomide is an immunomodulatory agent that belongs to a family of IMiDs used to treat multiple myeloma. Hypersensitivity and skin reactions are adverse effects of lenalidomide that may lead to discontinuation of its use for multiple myeloma making them contraindicated to other IMiD therapies. Desensitization protocols have been developed to desensitize patients to lenalidomide skin reaction and rash. We report a case series of 5 patients undergoing slow lenalidomide desensitization protocol in an outpatient cancer center setting. Four of the five patients were able to be successfully desensitized to lenalidomide. We also demonstrate safety of using slow lenalidomide desensitization while on combination therapy for control of multiple myeloma.
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http://dx.doi.org/10.1080/10428194.2019.1627537DOI Listing
December 2019

Clinical outcomes of polyvalent immunoglobulin use in solid organ transplant recipients: A systematic review and meta-analysis - Part II: Non-kidney transplant.

Clin Transplant 2019 07 24;33(7):e13625. Epub 2019 Jun 24.

Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Immunoglobulin (IG) is commonly used to desensitize and treat antibody-mediated rejection in solid organ transplant (SOT) recipients. The impact of IG on other outcomes such as infection, all-cause mortality, graft rejection, and graft loss is not clear. We conducted a similar systematic review and meta-analysis to our previously reported Part I excluding kidney transplant. A comprehensive literature review found 16 studies involving the following organ types: heart (6), lung (4), liver (4), and multiple organs (2). Meta-analysis could only be performed on mortality outcome in heart and lung studies due to inadequate data on other outcomes. There was a significant reduction in mortality (OR 0.34 [0.17-0.69]; 4 studies, n = 455) in heart transplant with hypogammaglobulinemia receiving IVIG vs no IVIG. Mortality in lung transplant recipients with hypogammaglobulinemia receiving IVIG was comparable to those of no hypogammaglobulinemia (OR 1.05 [0.49, 2.26]; 2 studies, n = 887). In summary, IVIG targeted prophylaxis may decrease mortality in heart transplant recipients as compared to those with hypogammaglobulinemia not receiving IVIG, or improve mortality to the equivalent level with those without hypogammaglobulinemia in lung transplant recipients, but there is a lack of data to support physicians in making decisions around using immunoglobulins in all SOT recipients for infection prophylaxis.
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http://dx.doi.org/10.1111/ctr.13625DOI Listing
July 2019

Clinical outcomes of polyvalent immunoglobulin use in solid organ transplant recipients: A systematic review and meta-analysis.

Clin Transplant 2019 06 23;33(6):e13560. Epub 2019 Apr 23.

Division of General Internal Medicine, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Polyvalent immunoglobulin is commonly used for desensitization and treatment of antibody-mediated rejection in kidney transplantation but its impact on other outcomes is not known. This systematic review investigated the impact of immunoglobulin prophylaxis on infection, rejection, graft loss, and death following kidney transplantation. A comprehensive literature search located 18 studies (n = 8 randomized controlled trials). None examined the effect of immunoglobulin prophylaxis in transplant recipients with hypogammaglobulinemia. Quality of included studies was variable with high to very high risk of bias. In the randomized trials, immunoglobulin use did not reduce cytomegalovirus infection (OR 0.68 [0.39, 1.21]; 6 studies, n = 295), rejection (OR 0.96 [0.50, 1.82]; 4 studies, n = 187), or graft loss (OR 1.03 [0.46, 2.30]; 6 studies, n = 265). In non-randomized studies, immunoglobulin did not reduce cytomegalovirus infection (OR 0.63 [0.20, 1.94]; 6 studies, n = 361) or death (OR 1.32 [0.05, 38.79]; 3 studies, n = 222) but reduce rejection (OR 0.47 [0.24, 0.94]; 4 studies, n = 268) and graft loss (OR 0.15 [0.05, 0.43]; 2 studies, n = 118). Data were scarce and sample size of current evidence was small. Adequately powered randomized trials are needed to determine if immunoglobulin is an effective intervention to reduce infection, rejection, graft loss, or death following kidney transplantation with and without hypogammaglobulinemia.
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http://dx.doi.org/10.1111/ctr.13560DOI Listing
June 2019

Bortezomib Maintenance for the Treatment of Monoclonal Gammopathy of Renal Significance.

Mediterr J Hematol Infect Dis 2019 1;11(1):e2019007. Epub 2019 Jan 1.

Tom Baker Cancer Center, Department of Medical Oncology and Hematology, Calgary, AB, Canada.

Monoclonal gammopathy of renal significance (MGRS) defines renal diseases resulting from the nephrotoxic effects of monoclonal proteins secreted from non-malignant clonal B cells or plasma cells, that do not meet criteria for multiple myeloma, Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia, or lymphomas. Renal disease in MGRS can result from monoclonal immunoglobulin deposition to different parts of the kidney and includes a wide spectrum of glomerular, tubulointerstitial and vascular renal diseases. Recognizing MGRS is important because renal outcomes are poor and treatments targeting the underlying clonal disease have been associated with improved renal survival. In this case report, we present a case of a patient with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) subtype of MGRS who underwent a phased clone directed treatment of induction and extended maintenance therapy to achieve renal response.
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http://dx.doi.org/10.4084/MJHID.2019.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328037PMC
January 2019

Health related quality of life for multiple myeloma patients according to treatment strategy after autologous stem cell transplant: a cross-sectional study using EORTC, EQ-5D and MY-20 scales.

Leuk Lymphoma 2019 05 31;60(5):1275-1282. Epub 2018 Oct 31.

l Division of Hematology , The Ottawa Hospital and The University of Ottawa , Ottawa , ON , Canada.

Maintenance (MT) may be prescribed after autologous stem cell transplant (ASCT) but there are often concerns about the impact on quality of life (QoL). QoL was compared between baseline patients (30-100 days post-ASCT and had not commenced MT); MT patients (>100 days post-ASCT and receiving MT), and no MT (>100 days post-ASCT and not receiving MT). Patients completed the EuroQoL five dimension (EQ-5D), the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30), and the QoL Questionnaire Myeloma 20 module (QLQ-MY20). Differences between groups were explored with ordinary least squares regressions. Across US and Canada, 303 patients participated. Regression analyses found few differences between MT and no MT. Only diarrhea (EORTC-QLQ C30) and future perspectives (MY-20) domains differentiated; patients on MT scored worse for diarrhea (+9.43; p = .0358) and future perspectives (-11.39; p = .0196). Collectively, the results suggest that MT is not associated with a notable QoL detriment.
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http://dx.doi.org/10.1080/10428194.2018.1523399DOI Listing
May 2019

Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta-analysis.

Transfusion 2018 10 16;58(10):2437-2452. Epub 2018 May 16.

Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.

Background: Prophylactic immunoglobulin has been used with varying efficacy to reduce complications in hematopoietic stem cell transplant recipients.

Study Design And Methods: A systematic review and meta-analysis was conducted of randomized controlled trials that assessed clinical outcomes (overall survival, transplant-related mortality, graft-versus-host disease [GVHD], veno-occlusive disease [VOD], interstitial pneumonitis, disease relapse, cytomegalovirus [CMV] infection and disease, non-CMV infection) of immunoglobulin prophylaxis versus placebo in hematopoietic stem cell transplant recipients. MEDLINE, EMBASE, EBM Reviews, and the Cochrane Central Register of Controlled Trials were searched up to June 2017. Quality of included studies and outcomes were evaluated via Risk of Bias assessment and Grading of Recommendations, Assessment, Development and Evaluation criteria, respectively.

Results: Of 899 citations screened, 27 studies (n = 3934) were included. Immunoglobulin prophylaxis had no impact on survival (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.88-1.01; 11 studies, n = 1962) but decreased risk of acute GVHD (RR, 0.78; 95% CI, 0.65-0.94; eight studies, n = 1097) and CMV disease (RR, 0.52; 95% CI, 0.28-0.97; two studies, n = 167). Meta-analysis revealed increased risk of VOD (RR, 3.04; 95% CI, 1.10-8.41; three studies, n = 384) and disease relapse (RR, 1.26; 95% CI, 1.07-1.49; seven studies, n = 1647). Other outcomes were small in sample size or nonsignificant. Results should be interpreted cautiously given the low quality of studies and evidence of outcomes.

Conclusion: Immunoglobulin prophylaxis did not have a significant effect on survival. Positive clinical effects were shown for acute GVHD and CMV disease and negative effects against VOD and disease relapse. No studies examined the effect of immunoglobulin treatment in hypogammaglobulinemic patients despite current guidelines, warranting further studies in this population.
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http://dx.doi.org/10.1111/trf.14656DOI Listing
October 2018

Immunoparesis and polyclonal immunoglobulin recovery after auto-SCT for patients with multiple myeloma treated at a single institution.

Leuk Lymphoma 2018 08 21;59(8):1920-1926. Epub 2017 Nov 21.

a Department of Medical Oncology and Hematology , Tom Baker Cancer Center , Calgary , Canada.

Immunoparesis and polyclonal immunoglobulin recovery have been recently described as common indicators of immune dysfunction in patients with multiple myeloma. In the present study, we aimed to assess the impact of immunoparesis and polyclonal immunoglobulin recovery at day-100 post autologous stem cell transplant (auto-SCT) on clinical outcomes. A total of 302 patients were included for the analysis of immunoparesis, and 197 were evaluable for polyclonal immunoglobulin recovery evaluation. Immunoparesis was observed in 93.5% of cases, with 47% of cases having polyclonal immunoglobulin recovery at 12 months post auto-SCT. Median overall and progression-free survival were longer in the group of patients with complete or partial normalization of polyclonal immunoglobulins. Patients receiving consolidation had a lower level of polyclonal reconstitution. In conclusion, polyclonal immunoglobulin recovery by 12 months post-auto-SCT is associated with superior overall and progression free survival in patients with MM. Efforts to better enhance polyclonal recovery deserve further investigation.
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http://dx.doi.org/10.1080/10428194.2017.1403026DOI Listing
August 2018

Early Relapse for Multiple Myeloma Patients Undergoing Single Autologous Stem Cell Therapy: A Single-center Experience.

Clin Lymphoma Myeloma Leuk 2018 01 1;18(1):e69-e75. Epub 2017 Nov 1.

Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address:

Introduction: Multiple myeloma is a heterogeneous disease with diverse clinical courses and patient outcomes. Although the introduction of novel agents has improved the overall survival (OS) of multiple myeloma patients, reports have highlighted that a subset of patients persists who experience early relapse (ER) and whose prognosis is significantly poorer than that of patients with a longer therapy response.

Methods: The purpose of the present study was to understand the effect of ER on OS and identify other predictors of OS. We analyzed the outcomes of 257 patients who had undergone novel agent-based induction and single autologous stem cell therapy at our center from 2010 to 2016.

Results: ER occurred in 35 patients (13.6%), and the group had a greater percentage of high-risk cytogenetics (48.5% vs. 23.3%; P = .0001), a lower percentage of a very good partial response or better (51.4% vs. 80.5%; P = .001), and a shorter median OS (17.8 months vs. not realized; P = .0001) compared with the non-ER group. Multivariate analysis showed that the presence of ER, high-risk cytogenetics, and lactate dehydrogenase > 350 UI/L are independent prognosticators for OS (P < .05).

Conclusions: Our results have demonstrated that ER is an important clinical indicator of patients at high risk. As applications of novel agents evolve, further studies are required to tailor therapy for this patient group.
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http://dx.doi.org/10.1016/j.clml.2017.10.009DOI Listing
January 2018

A national survey of screening and management of hypogammaglobulinemia in Canadian transplantation centers.

Transpl Infect Dis 2017 Aug 24;19(4). Epub 2017 May 24.

Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada.

Background: Infection remains one of the most common transplant-related causes of death in patients undergoing transplantation. Secondary hypogammaglobulinemia (HGG) as a component of immune suppression and deficiency is associated with both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Available data and clinical experience for the supplementation of immunoglobulin (Ig) in these patients is conflicting, and differing clinical opinion accounts for non-uniform practice in the use of Ig treatment. We aimed to survey lead transplant practitioners for current practice around polyvalent Ig use in post-transplant recipients across Canada.

Methods: We performed a survey study using short questionnaires to estimate rate of screening of HGG, use of polyvalent Ig, and physician's opinion on Ig treatment and infection prevention. Directors of 24 SOT and 23 HCT centers across Canada were invited to participate in the survey via an electronic mail.

Results: Overall response rate was 63.8%. Twenty percent of SOT programs routinely measured Ig levels pre-transplant compared to 33% of allogeneic (allo-) and 21% of autologous (auto-) HCT programs. Post-transplant Ig levels were measured in 13%, 75%, and 29% in SOT, allo-HCT, and auto-HCT, respectively. The SOT and auto-HCT groups indicated that they do not prescribe Ig therapy (100% and 86%), contrary to the allo-HCT group (42%). Of the respondents in the SOT, allo-HCT, and auto-HCT groups, 60%, 67%, and 36%, respectively, thought infections could be prevented with intravenous immunoglobulins (IVIg). A majority of respondents indicated they would be interested in participating in a randomized controlled trial evaluating the use of IVIg in the SOT and in both HCT groups (100%, 83%, and 57%, respectively).

Conclusions: Our study shows significant variation in practice between SOT and HCT centers with respect to screening and management of HGG. There is willingness to participate in a randomized controlled trial to address whether Ig treatment reduces infection in post-transplant recipients.
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http://dx.doi.org/10.1111/tid.12706DOI Listing
August 2017

Bortezomib-containing regimens (BCR) for the treatment of non-transplant eligible multiple myeloma.

Ann Hematol 2017 Mar 10;96(3):431-439. Epub 2017 Jan 10.

Department of Medical Oncology and Hematology, Tom Baker Cancer Center, 1331 29th St, NW, Calgary, AB, T2N 4N2, Canada.

In multiple myeloma (MM) patients ineligible for transplant, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor with anti-myeloma effects, have been reported. We aimed to evaluate the impact of different bortezomib-containing regimens (BCR) for the treatment of transplant-ineligible MM. All- consecutive patients treated with BCR at our institution from 01/05 to 02/16 were evaluated. With a median of 6 cycles, an overall response rate of 95.2, 80.9, and 76.3% was observed for patients treated with cyclophosphamide-bortezomib-dexamethasone (CyBorD), bortezomib-melphalan-prednisone (VMP), and bortezomib-dexamethasone (VD), respectively (p = 0.03). The median overall survival was similar between the three different BCR, but a trend for better progression-free survival was noted in favor of CyBorD. BCR are efficacious in the treatment of transplant-ineligible MM. Patients receiving continuous therapy (CT) exhibited better outcomes, suggesting that strategies to prevent toxicity and increase the cumulative dose are warranted.
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http://dx.doi.org/10.1007/s00277-016-2901-xDOI Listing
March 2017

Balancing give and take between patients and their spousal caregivers in hematopoietic stem cell transplantation.

Psychooncology 2017 Dec 2;26(12):2224-2231. Epub 2017 Feb 2.

Tom Baker Cancer Centre, Alberta Health Services, Calgary, AB, Canada.

Objective: Hematopoietic stem cell transplantation (HSCT) is a demanding treatment. Spouses of HSCT patients assume caregiving responsibilities that can induce feelings of burden and disrupt relationship equity. On the basis of equity theory, we propose a conceptual framework examining the individual and dyadic experience of HSCT patients and their caregivers. The model includes feelings of inequity, patient self-perceived burden, caregiver burden, and distress.

Methods: The HSCT patients and their spousal caregivers were recruited prior to HSCT between March 2011 and September 2012. Each member of the dyad self-administered a questionnaire package.

Results: Seventy-two dyads were included in the path analyses. Our model demonstrated an inadequate statistical fit; however, with one modification, an adequate to good fit was obtained: χ (df) = 6.01(5), normed χ  = 1.20, standardized root mean square residual = 0.048, comparative fit index = 0.99, Tucker-Lewis index = 0.96, and root-mean-square error of approximation = 0.05 (90% CI, 0.00-0.18). As hypothesized, pre-HSCT caregiver burden mediates the relationship between caregiver underbenefit and caregiver distress. However, patient self-perceived burden was not associated with patient distress; rather, patient perception of overbenefit was related to patient distress. In our modified model, the results demonstrate that patient overbenefit influenced caregiver burden; however, there was not a reciprocal influence, because caregiver variables did not affect patient variables.

Conclusions: Our proposed theoretical framework describes patients' and caregivers' individual experience of distress before HSCT but does not as clearly encompass the dyadic experience. Addressing perceived imbalances and providing psycho-education on role changes within HSCT dyads before transplantation may be a useful prehabilitation strategy for preventing distress.
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http://dx.doi.org/10.1002/pon.4340DOI Listing
December 2017

Zoster prophylaxis after allogeneic hematopoietic cell transplantation using acyclovir/valacyclovir followed by vaccination.

Blood Adv 2016 Dec 30;1(2):152-159. Epub 2016 Nov 30.

Alberta Blood and Marrow Transplant Program, University of Calgary and Alberta Health Services, Calgary, AB, Canada.

Varicella zoster virus (VZV) disease (usually cutaneous zoster) occurs frequently after hematopoietic cell transplantation (HCT), and postherpetic neuralgia (PHN) results in poor quality of life. The optimal prophylaxis of VZV disease/PHN has not been established. At our center, before 2008, VZV prophylaxis consisted of ∼1 year of post-HCT acyclovir/valacyclovir ("old strategy"), whereas post-2008 prophylaxis consisted of 2 years of acyclovir/valacyclovir followed by immunization using varicella vaccine ("new strategy"). We performed a retrospective study comparing the cumulative incidence of VZV disease and PHN among patients who completed the old strategy (n = 153) vs the new strategy (n = 125). Patients who completed the old strategy had a significantly higher cumulative incidence of VZV disease (33% vs 17% at 5 years, ≤ .01) and PHN (8% vs 0% at 5 years, = .02). In conclusion, VZV prophylaxis with 2 years of acyclovir/valacyclovir followed by vaccination appears to result in a low incidence of VZV disease and may eliminate PHN.
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http://dx.doi.org/10.1182/bloodadvances.2016000836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737163PMC
December 2016

Rationale and design of platelet transfusions in haematopoietic stem cell transplantation: the PATH pilot study.

BMJ Open 2016 10 24;6(10):e013483. Epub 2016 Oct 24.

Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Introduction: In patients with transient thrombocytopenia being treated with high-dose chemotherapy followed by stem cell rescue-haematopoietic stem cell transplantation (HSCT), prophylactic transfusions are standard therapy to prevent bleeding. However, a recent multicentre trial suggests that prophylactic platelet transfusions in HSCT may not be necessary. Additionally, the potential overuse of platelet products places a burden on a scarce healthcare resource. Moreover, the benefit of prophylactic platelet transfusions to prevent clinically relevant haemorrhage is debatable. Current randomised data compare different thresholds for administering prophylactic platelets or prophylactic versus therapeutic platelet transfusions. An alternative strategy involves prescribing prophylactic antifibrinolytic agents such as tranexamic acid to prevent bleeding.

Methods And Analysis: This report describes the design of an open-labelled randomised pilot study comparing the prophylactic use of oral tranexamic acid with platelet transfusions in the setting of autologous HSCT. In 3-5 centres, 100 patients undergoing autologous HSCT will be randomly assigned to either a prophylactic tranexamic acid or prophylactic platelets bleeding prevention strategy-based daily platelet values up to 30 days post-transplant. The study will be stratified by centre and type of transplant. The primary goal is to demonstrate study feasibility while collecting clinical outcomes on (1) WHO and Bleeding Severity Measurement Scale (BSMS), (2) transplant-related mortality, (3) quality of life, (4) length of hospital stay, (5) intensive care unit admission rates, (6) Bearman toxicity scores, (7) incidence of infections, (8) transfusion requirements, (9) adverse reactions and (10) economic analyses.

Ethics And Dissemination: This study is funded by a peer-reviewed grant from the Canadian Institutes of Health Research (201 503) and is registered on Clinicaltrials.gov NCT02650791. It has been approved by the Ottawa Health Science Network Research Ethics Board. Study results will presented at national and international conferences. Importantly, the results of this trial will inform the feasibility and conduct of a larger study.

Trial Registration Number: NCT02650791; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2016-013483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093651PMC
October 2016

Post-Transplant Outcomes in High-Risk Compared with Non-High-Risk Multiple Myeloma: A CIBMTR Analysis.

Biol Blood Marrow Transplant 2016 10 2;22(10):1893-1899. Epub 2016 Aug 2.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National medical Center, Duarte, California.

Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (<45 chromosomes excluding -Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher compared with non-HRM (56% versus 43%, P < .001) with similar pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100 post-transplant, at least a very good partial response was 59% in HRM and 61% in non-HRM (P = .6). More HRM patients received post-transplant therapy with bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were 37% versus 49% (P < .001) and 72% versus 85% (P < .001), respectively. At 3 years, PFS for HRM patients with and without post-transplant therapy was 46% (95% confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus 39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post-transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65) compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM patients with and without post-transplant therapy, respectively. Among patients receiving post-transplant therapy, there was no difference in OS between HRM and non-HRM (P = .08). In addition to HRM, higher stage, less than a CR pretransplant, lack of post-transplant therapy, and African American race were associated with worse OS. In conclusion, we show HRM patients achieve similar day 100 post-transplant responses compared with non-HRM patients, but these responses are not sustained. Post-transplant therapy appeared to improve the poor outcomes of HRM.
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http://dx.doi.org/10.1016/j.bbmt.2016.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090978PMC
October 2016

Optimal transfusion practices after allogeneic hematopoietic cell transplantation: a systematic scoping review of evidence from randomized controlled trials.

Transfusion 2016 Oct 27;56(10):2607-2614. Epub 2016 Jul 27.

Hematology, Department of Medicine, The Ottawa Hospital and University of Ottawa.

Background: Integrating evidence from randomized controlled trials (RCTs) into patient care is needed to optimize patient outcomes. Transfusion support during allogeneic hematopoietic cell transplantation (alloHCT) is a cornerstone of essential supportive care, yet optimal transfusion practices remain unclear.

Study Design And Methods: A scoping review of RCTs in alloHCT was conducted and 14 full-length articles on transfusion practice were identified that reported clinical outcomes after alloHCT.

Results: Eight RCTs compared various interventions related to platelet (PLT) transfusion, addressing product storage duration, dosage, and threshold for transfusion. Restrictive prophylactic PLT transfusion strategies were successful at reducing PLT consumption without impacting clinical outcomes. One study, however, reported increased bleeding associated with a strategy whereby patients did not receive prophylactic PLT transfusions. One study of thrombopoietin was associated with reduced PLT transfusion events but no difference in clinical outcomes compared to placebo. Six RCTs examined the utility of recombinant erythropoietin (EPO) in reducing red blood cell (RBC) transfusion dependence. Four trials reported an increase in hemoglobin levels while five studies demonstrated a reduction in RBC utilization; however, clinical outcomes were variably reported and no differences were identified. There were no RCTs examining RBC transfusion strategies, plasma transfusion, or plasma-derived protein administration.

Conclusion: Prophylactic PLT transfusion when PLTs are fewer than 10 × 10 /L can prevent bleeding and is consistent with recent guidelines. Thrombopoietin and EPO can reduce transfusion requirements; however, potential safety concerns remain and the lack of improvement in clinical outcomes and high cost may limit use. Additional RCTs are needed, particularly with regard to RBC transfusion thresholds, to refine best practices after alloHCT.
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http://dx.doi.org/10.1111/trf.13738DOI Listing
October 2016

Revised International Staging System Applied to Real World Multiple Myeloma Patients.

Clin Lymphoma Myeloma Leuk 2016 09 8;16(9):511-518. Epub 2016 Jun 8.

Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address:

Background: A variety of validated prognostic markers for multiple myeloma has been described to help inform clinical practice. Recently, a robust system has been introduced for clinical use and is being adopted by the International Myeloma Working Group Revised International Staging System (RISS). The RISS was developed using data from patients enrolled in clinical trials. Consequently, its utility is less clear in unselected patients with myeloma.

Materials And Methods: All consecutive patients newly diagnosed with multiple myeloma treated and followed up at Tom Baker Cancer Center from January 2004 to October 2015 were included in the present study. A total of 381 consecutive patients were identified and retrospectively classified as having RISS I, II, and III.

Results: RISS I exhibited a median overall survival and progression-free survival of not reached and 38.9 months compared with 77.9 and 26.9 months and 29.9 and 15.3 months for RISS II and III, respectively. These results correlated well with those seen in the International Staging System (ISS). Multivariate analysis showed that age > 65 years, ISS stage III, abnormal lactate dehydrogenase and high-risk chromosomal abnormalities by fluorescence in situ hybridization [t(4:14), deletion 17p, and t(14;16)] are independent prognostic factors for overall survival and progression-free survival, and β-microglobulin ≥ 5.5 mg/L, C-reactive protein > 20 mg/L, and creatinine > 200 μmol/L are not.

Conclusion: We have confirmed the role of RISS in unselected nonclinical trial patients and suggest that increased serum lactate dehydrogenase and high-risk cytogenetics are very robust prognosticators when combined with the ISS.
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http://dx.doi.org/10.1016/j.clml.2016.06.001DOI Listing
September 2016

Acquired Factor XIII Inhibitor in Hospitalized and Perioperative Patients: A Systematic Review of Case Reports and Case Series.

Transfus Med Rev 2016 07 22;30(3):123-31. Epub 2016 Apr 22.

Department of Anesthesiology, The Ottawa Hospital, Ottawa, Ontario, Canada; Regenerative Medicine Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Electronic address:

Factor XIII (FXIII) cross-links fibrin monomers to support clot stabilization and wound healing. Acquired FXIII deficiency is caused by autoantibodies that inhibit FXIII and can result in bleeding despite normal routine coagulation test results. Given the rarity of this disease, large clinical studies are not feasible. We therefore conducted a systematic review of case reports and case series of acquired FXIII inhibitor to evaluate potential management and treatment strategies for acquired FXIII inhibitor in hospitalized and/or perioperative patients. A systematic search of MEDLINE, Embase, and Web of Science identified reports of hospitalized and perioperative patients with acquired FXIII deficiency. No restrictions were placed on language or publication type. Article screening and data extraction were performed independently by 2 abstractors. Completeness of reporting was evaluated according to modified elements from the CAse REport (CARE) guidelines. A total of 1028 citations were reviewed, with 36 case reports and 3 case series meeting eligibility criteria (63 patients total). The mean age was 60 (range, 9-87) years with balanced sex representation. At presentation, 48 patients (76%) had intramuscular or subcutaneous bleeding, and 34 patients (54%) had external or surgical bleeding. All cases were diagnosed by initially detecting a FXIII deficiency and then identifying the inhibitor. Clinical improvement in bleeding was seen in patients receiving FXIII concentrate (13/17 patients), cryoprecipitate (5/8), and plasma (10/18). Inhibitor reduction was seen in patients who received rituximab (6/6 patients), plasma exchange (2/2), intravenous immunoglobulin (4/5), steroid (15/20), and cyclophosphamide (10/15). Concurrent initiation of multiple therapies and obvious lack of control comparisons made direct association to outcomes difficult to establish. Outcomes were reported for 55 patients, with 25 patients (45%) having complete inhibitor eradication and 15 patients (27%) having partial resolution; 9 of these patients (14%) had a relapse. Thirteen patients (20%) died (7 from internal hemorrhage). Completeness of reporting varied for specific CAse REport items. Patient demographics, clinician-assessed outcomes, and laboratory test results were reported in all case reports. Least reported items included informed consent (6%), patient perspective (3%), and a title containing the words case report (9%). Our systematic review provides the most complete overview of published reports of FXIII acquired inhibitor to date. There is a paucity of data available on FXIII acquired inhibitor, and the available data may be limited by variable reporting. Despite multimodal therapy, a significant proportion of patients with FXIII acquired inhibitor have a large burden of morbidity and mortality.
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http://dx.doi.org/10.1016/j.tmrv.2016.04.001DOI Listing
July 2016
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