Publications by authors named "Santhosh Thyagu"

22 Publications

  • Page 1 of 1

Donor-Recipient Story in Allogeneic Hematopoietic Stem Cell Transplantation.

Curr Oncol 2021 Jan 24;28(1):689-692. Epub 2021 Jan 24.

Stem Cell Club, Toronto, ON M2H 3L2, Canada.

Patients with a variety of blood, immune, and metabolic disorders may require an allogeneic hematopoietic stem cell transplant as part of their treatment. However, over 70% of these patients do not have a matched sibling donor and require an alternative donor, such as a matched unrelated donor. We present a multi-part story of a Canadian stem cell recipient who underwent transplantation for treatment of refractory chronic myelogenous leukemia, and the matched unrelated donor who saved his life. The story segments feature excerpts from interviews with the donor and the recipient, along with representative images of both storytellers. The excerpts were optimized for publication on social media and were arranged to build a story arc that parallels the journey of the donor and recipient together. This donor-recipient story may serve as a resource to help raise awareness about stem cell donation and to encourage eligible individuals to register as donors. The story is one of several developed by Why We Swab, a library of stories in stem cell donation in Canada (Facebook, Twitter, and Instagram; @WhyWeSwab) to support the recruitment of committed unrelated donors.
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http://dx.doi.org/10.3390/curroncol28010067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924398PMC
January 2021

Association of Thoracic CT Measurements and Outcomes in Patients with Hematologic Malignancies Requiring Mechanical Ventilation.

Ann Am Thorac Soc 2021 Jan 12. Epub 2021 Jan 12.

Mount Sinai Hospital/Toronto General Hospital, Interdepartmental Division of Critical Care Medicine, Toronto, Ontario, Canada;

Rationale: Patients with hematologic malignancies (HM) requiring mechanical ventilation have historically experienced poor outcomes.

Objectives: We aimed to determine whether body composition characteristics derived from thoracic Computed-Tomography (CT) were associated with time to liberation from mechanical ventilation.

Methods: We evaluated mechanically ventilated patients with HM admitted between 2014-2018. We included patients with a thoracic-CT completed between one month prior and 48 hours after ICU admission. We assessed the association of carinal skeletal muscle cross-sectional area (CSA), subcutaneous fat CSA and fat index (fat/skeletal muscle) with time to liberation from mechanical ventilation within 28-days. We accounted for the competing event of death within 28-days of mechanical ventilation.

Results: 156 patients were included across whom the mean age was 57 years (SD 14) and 39% were female. Thirty-seven percent had received a hematopoietic stem cell transplant and median PaO2/FiO2 ratio was 134mmHg(IQR 92-205). Median skeletal muscle CSA was 68cm2(IQR 54-88) and subcutaneous fat CSA was 38cm2(IQR 27-52). Forty-two percent of patients were liberated from mechanical ventilation within 28-days and 56% died in the ICU. Subcutaneous fat CSA (subdistribution Hazard Ratio [sHR] 0.81,95% CI-0.68-0.97) and fat index (sHR 0.81,95% CI-0.68-0.97) were significantly associated with longer time to liberation from mechanical ventilation. Skeletal muscle CSA was not associated with time to liberation from ventilation (sHR 1.08, 95% CI-0.94-1.23).

Conclusion: Body composition measurements based on thorax-CT scan were associated with time to liberation from ventilation. These could represent novel surrogate markers of physical frailty in patients with hematologic malignancies receiving mechanical ventilation.
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http://dx.doi.org/10.1513/AnnalsATS.202008-914OCDOI Listing
January 2021

Perspectives on Advance Care Planning for Patients with Hematologic Malignancies: An International Clinician Questionnaire.

Ann Am Thorac Soc 2021 Jan 5. Epub 2021 Jan 5.

University of Toronto, 7938, Interdepartmental Division of Critical Care Medicine, Toronto, Ontario, Canada.

Background: Critical illness is common in hematological malignancy (HM) patients. Advance care planning (ACP) can allow these patients to express their care preferences prior to life-threatening illnesses. The objective of this study was to evaluate physicians' perspectives surrounding ACP in HM patients.

Methods: We administered a survey to intensivists and hematologic oncologists who care for patients with HM across Canada and the United Kingdom. Potential respondents were identified from institutions that have a hematologic oncology program. The survey was disseminated electronically.

Results: 111 physicians completed the survey with a response rate of 19% (39% across those who opened the email); 52% of respondents were intensivists and 48% hematologic oncologists. 15.5% of physicians reported that ACP happens routinely at their institution, while 8.3% of physicians stated that code status is routinely discussed. ACP discussions were most commonly reported at the onset of critical illness (84.3% of respondents), during disease recurrence (52.9% of respondents), or during transition to a strictly palliative approach (54.9% of respondents). Commonly cited barriers to ACP centred on physicians' concern about the reaction of the patient or family.

Conclusion: This study emphasizes the need for earlier and more frequent ACP discussions in this high-risk population with a variety of barriers identified.
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http://dx.doi.org/10.1513/AnnalsATS.202006-678OCDOI Listing
January 2021

Safety of two-hour intermittent intravenous infusions of tacrolimus in the allogeneic hematopoietic stem cell transplantation unit.

J Oncol Pharm Pract 2021 Jan 17;27(1):33-39. Epub 2020 Mar 17.

Messner Allogeneic Transplant Program, University Health Network, Toronto, Canada.

At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit after patients have experienced a serious or intolerable adverse event to cyclosporine. As per our standard practice, tacrolimus is administered via 2-h intermittent IV infusions (IIVs) every 12 h rather than continuous IV infusion. Shorter infusion times are cautioned due to concerns of higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions, although there is a paucity of data to support this claim. Our primary objective was to evaluate the safety of a 2-h IIV of tacrolimus in an adult HSCT population. We retrospectively reviewed the charts of 104 patients who received tacrolimus by IIV (3574 doses; median = 22, range 1-158, IQR = 28) from 2002 to 2016. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and infusion-related reactions. One (0.9%) grade 2 infusion-related reaction occurred and resolved without discontinuation of tacrolimus. Of 16 incidences (13.6%) of nephrotoxicity, all but 10 (8.5%) cases resolved. Precipitating factors for nephrotoxicity unrelated to tacrolimus were identified in all 10 cases. There were 41 incidences (35%) of neurotoxicity, of which, 8 (6.8%) were considered serious. All neurotoxicity reverted to baseline or resolved completely. We propose that a 2-h IIV of tacrolimus is a safe method of administration in the adult HSCT setting.
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http://dx.doi.org/10.1177/1078155220908948DOI Listing
January 2021

A case of secondary acute myeloid leukemia on a background of glycogen storage disease with chronic neutropenia treated with granulocyte colony stimulating factor.

JIMD Rep 2019 Sep 23;49(1):37-42. Epub 2019 Jul 23.

Department of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre University Health Network Toronto Ontario Canada.

Congenital neutropenias due to mutations in ELANE, SBDS or HAX1 or in the setting of glycogen storage disease (GSD) which is caused by mutation, often require prolonged granulocyte colony stimulating factor (G-CSF) therapy to prevent recurrent infections and hospital admission. There has been emerging evidence that prolonged exposure to G-CSF in cases with congenital neutropenia other than GSD is associated with transformation to myelodysplastic syndrome/acute myeloid leukemia.
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http://dx.doi.org/10.1002/jmd2.12069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875697PMC
September 2019

My jamais vu in post allogeneic hematopoietic cell transplant: a review on secondary hemophagocytosis in adults.

Bone Marrow Transplant 2020 05 14;55(5):867-872. Epub 2019 Oct 14.

Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Post allogenic hematopoietic cell transplant (HCT) hemophagocytic lymphohistiocytosis (HLH) is an aggressive disease with unknown etiology. It has a poorly understood pathophysiology and poor outcome if untreated early. It's a state of hypercytokinemia. There are many proposed diagnostic criteria for Post HCT HLH. It usually occurs early in the first 2-6 weeks after allogeneic HCT but can present late. The incidence is highest among cord blood transplant compared with other sources of stem cells with a higher incidence in HLA mismatch donors. Post HCT HLH has a marked low survival rate, when compared with Non-HLH post HCT patients and specifically poor outcome is associated in patients with liver dysfunction, graft failure, and those with endothelial complications. Steroid is the mainstay treatment which can be followed up by cyclosporine and etoposide though an optimal therapy is not known. Intravenous immunoglobulin (IVIg) has been tried in virus associated HLH. Second bone marrow transplant is a rescue procedure in patient with HLH due to graft failure, though a very careful selection of individual patients is mandatory. It has been recently found that etoposide based conditioning regimen may reduce HLH post HCT. A prospective study on post HCT HLH are needed to evaluate this unrecognized condition.
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http://dx.doi.org/10.1038/s41409-019-0711-1DOI Listing
May 2020

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants.

Eur J Haematol 2019 Jun 29;102(6):486-493. Epub 2019 Apr 29.

Messner Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

Introduction: We evaluated the combination of ATG and PTCy for GVHD prophylaxis in matched and mismatched unrelated PBSCTs for high-risk hematological malignancies.

Methods: We treated 102 patients with reduced intensity conditioning (RIC) with fludarabine, busulfan, and TBI 200 cGy. GVHD prophylaxis included rabbit ATG (thymoglobulin at total dose of 4.5 mg/kg divided over days -3 to -1), PTCy (50 mg/kg/day on day +3 and on day +4), and cyclosporine. Clinical and outcome data were collected retrospectively.

Results: Among 102 patients, 76 patients received 10/10 MUD transplants and 26 patients received 9/10 mismatched transplants. The median age was 59 years. At a median follow-up of 15 months (range 0.6 to -33 months), the 1-year OS in MUD and MMUD cohort was 75% and 50%, respectively (P = 0.027). The corresponding one-year PFS was 67% and 35%, respectively (P = 0.0024). The incidence of grade 3-4 acute GVHD was 11.8% in MUD and 3.8% in MMUD group, and that of NIH stage moderate/severe chronic GVHD in the 2 groups was 10.5% and 7.6%, respectively. Cytomegalovirus (CMV) reactivation was seen in 49% patients. The cumulative incidence of relapse was 21.1% in the MUD group and 42.3% in the MMUD group.

Conclusion: Our experience shows that PTCy and ATG can be combined for GVHD prophylaxis in matched unrelated donor PBSCTs with low rates of Gr3-4 acute GVHD and chronic GVHD, and acceptable relapse rates.
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http://dx.doi.org/10.1111/ejh.13230DOI Listing
June 2019

Influence of FLT3-ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML.

Eur J Haematol 2019 Apr 13;102(4):368-374. Epub 2019 Feb 13.

Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Objective: In individuals with cytogenetically normal (CN) AML, disease risk is estimated using molecular features such as the status of NPM1 and FLT3-ITD genes. However, data regarding the impact of NPM1 and FLT3-ITD status on hematopoietic stem cell transplant (HCT) outcomes are limited. We examined the effect of NPM1 and FLT3-ITD status on transplant outcomes in 131 CN AML patients transplanted at Princess Margaret Hospital between 2006 and 2017.

Methods: Overall survival (OS) was calculated using Kaplan-Meier analysis and multivariable Cox proportional hazards regression. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were calculated using competing risk regression.

Results: There was no difference in 3-year OS among NPM1 /FLT3-ITD , NPM1 /FLT3-ITD , NPM1 /FLT3-ITD and NPM1 /FLT3-ITD patients: 56% (95% CI, 29%-76%), 61% (95% CI, 46%-73%), 53% (95% CI, 34%-70%) and 52% (95% CI, 17%-78%), respectively. CIR at 3-years was similar among NPM1 /FLT3-ITD , NPM1 /FLT3-ITD and NPM1 /FLT3-ITD patients-14% (95% CI, 6%-26%), 13% (95% CI, 4%-28%) and 19% (95% CI, 4%-41%), respectively-while there were no relapses in the NPM1 /FLT3-ITD group. NRM at 3 years for NPM1 /FLT3-ITD , NPM1 /FLT3-ITD , NPM1 /FLT3-ITD and NPM1 /FLT3-ITD patients was similar at 44% (95% CI, 19%-67%), 38% (95% CI, 25%-50%), 43% (95% CI, 25%-59%) and 44% (95% CI, 14%-71%), respectively.

Conclusion: NPM1 and FLT3-ITD status may provide limited prognostic information about transplant outcomes in CN AML patients.
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http://dx.doi.org/10.1111/ejh.13216DOI Listing
April 2019

Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies.

Biol Blood Marrow Transplant 2018 11 7;24(11):2259-2264. Epub 2018 Aug 7.

Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada. Electronic address:

Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018. RIC included fludarabine (30 mg/m/day on days -5 to -2), busulfan (3.2 mg/m/day on days -3 and -2), and total body irradiation (200 cGy) on day -1. Unmanipulated PBSCs were infused on day 0. GVHD prophylaxis included ATG (4.5 mg/kg over days -3 to -1), PTCy (50 mg/kg/day on days +3 and +4), and cyclosporine from day +5. Median age was 56 years (range, 22 to 70 years); 25 (73.5%) patients were in first complete remission (CR1), 5 (14.7%) were in second complete remission (CR2), and 8 (23.5%) had active disease. Median time to neutrophil engraftment was 16 days (range, 8 to 43 days). At day +100, the cumulative incidence of acute GVHD of any grade, and grades III to IV was 38.3% and 5.2%, respectively. Mild chronic GVHD was seen in 15.5%. Cytomegalovirus (CMV) reactivation occurred in 37 (74%) cases and CMV disease occurred in 4 (11.5%) cases. Epstein-Barr virus (EBV) reactivation occurred in 21 (61.8%) patients. The incidence of histologically confirmed post-transplantation lymphoproliferative disorder (PTLD) was 5.8%. Four patients received rituximab. There were no CMV, EBV, or PTLD-related deaths. Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD.
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http://dx.doi.org/10.1016/j.bbmt.2018.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110605PMC
November 2018

Fludarabine and busulfan plus low-dose TBI as reduced intensity conditioning in older patients undergoing allogeneic hematopoietic cell transplant for myeloid malignancies.

Ann Hematol 2018 Oct 11;97(10):1975-1985. Epub 2018 Jun 11.

Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, 610 University Ave, Toronto, ON, M5G 2M9, Canada.

We have been using a combination of fludarabine/busulfan plus low-dose total body irradiation (TBI) as the reduced-intensity conditioning (RIC) regimen for patients age ≥ 60 years undergoing allogeneic hematopoietic cell transplantation (HCT) for myeloid malignancies. We retrospectively analyzed outcomes of 116 older patients (median age 64 years) who underwent HCT from 2006 to 2015 for myeloid malignancies, including acute myeloid leukemia (AML) in first complete remission (CR1). On univariate analysis, overall survival (OS) for the cohort at 3 years was 33% (95% CI 25-42). Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 3 years were 24% (95% CI 16-32) and 43% (95% CI 34-52), respectively. Multivariable analysis for OS demonstrated AML patients to have superior outcome (HR 1.60 for other myeloid, 95% CI 1.01-2.54, p = 0.045), as well as related donors (HR 1.92 for unrelated, 95% CI 1.22-3.03, p = 0.005). For NRM, AML patients had superior outcome (HR 1.76 for other myeloid, 95% CI 1.03-3.01, p = 0.038), as well as patients with related donors (HR 1.81 for unrelated, 95% CI 1.07-3.07, p = 0.028). We then demonstrated that AML patients with related donors (n = 45) had superior 3-year OS of 51% (95% CI 36-65), compared to 21% (95% CI 12-32) for all other patients (p = 0.0003). We conclude that the RIC regimen used is effective for older patients, particularly AML patients in CR1 with matched related donors.
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http://dx.doi.org/10.1007/s00277-018-3391-9DOI Listing
October 2018

Efficacy of Cidofovir in Treatment of BK Virus-Induced Hemorrhagic Cystitis in Allogeneic Hematopoietic Cell Transplant Recipients.

Biol Blood Marrow Transplant 2018 09 18;24(9):1901-1905. Epub 2018 Apr 18.

Division of Hematology, Department of Medicine, London Health Sciences Centre, London, Ontario, Canada.

BK virus-associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidences up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC, a retrospective study was undertaken of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada. The primary outcome measure was a reduction in BK-HC severity (graded from 1 to 4); secondary outcomes included overall survival, BK virus titers, and the onset of acute kidney injury. Twelve allo-HCT patients received cidofovir for BK-HC, with pretreatment clinical severity of 3 (50%) or 4 (50%). Cidofovir was administered via intravenous (33%), intravesical (58%), or both modalities (8%). After a median cumulative dose of 10 mg/kg (range, 1 to 37), mean BK-HC grade decreased significantly by 1.8 (3.5 precidofovir, 1.7 postcidofovir, P < .01). Sixty-six percent of patients had at least partial response to cidofovir, with similar response rates between intravenous (66%) and intravesical (62%) administration. Sixty-seven percent of patients died, and 33% of patients experienced renal toxicity, including 2 patients receiving intravesical therapy. In this retrospective series, there was a significant reduction in BK-HC severity after cidofovir administration; most patients achieved at least partial response after cidofovir administration. Even with intravesical instillation, acute kidney injury remains a potential complication of cidofovir. Although cidofovir may be an efficacious therapy for BK-HC, albeit with potential demonstrated toxicities, further prospective trials are needed.
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http://dx.doi.org/10.1016/j.bbmt.2018.04.009DOI Listing
September 2018

Prolonged granulocyte colony stimulating factor use in glycogen storage disease type 1b associated with acute myeloid leukemia and with shortened telomere length.

Pediatr Hematol Oncol 2018 Feb 13;35(1):45-51. Epub 2018 Apr 13.

c Department of Pediatrics , University of British Columbia, BC Children's Hospital , Vancouver , BC . Canada.

Glycogen storage disease (GSD) type 1 is a rare autosomal recessive inherited condition. The 1b subtype comprises the minority of cases, with an estimated prevalence of 1 in 500,000 children. Patients with glycogen storage disease type 1b are often treated with granulocyte colony stimulating factor (G-CSF) for prolonged periods to improve symptoms of inflammatory bowel disease (IBD) and in the face of severe neutropenia to decrease risk of infection. Long-term G-CSF treatment may result in an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) possibly due to increased marrow stress resulting in telomere shortening. To our knowledge, there have been two published cases of AML in GSD type 1b patients following long-term G-CSF exposure. Here, we report two further cases of AML/MDS-related changes in patients GSD type 1b treated with G-CSF. One patient developed AML with complex karyotype after 20 years of G-CSF treatment. The second patient was found to have short telomeres after 10 years of G-CSF exposure, but no evidence of acute leukemia at present. The third patient developed AML/MDS after 25 years of G-CSF use, with short telomeres prior to bone marrow transplant. Together these cases suggest that GSD type 1b patients with prolonged G-CSF exposure may be at an increased risk of MDS/AML states associated with G-CSF-induced shortened telomeres. We recommend that any GSD1b patients with prolonged G-CSF should have routine telomere assessments with monitoring for MDS if telomere shortening is observed, and with particular attention warranted if there is unexplained loss of G-CSF responsiveness.
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http://dx.doi.org/10.1080/08880018.2018.1440675DOI Listing
February 2018

Reduction of severe acute graft-versus-host disease using a combination of pre transplant anti-thymocyte globulin and post-transplant cyclophosphamide in matched unrelated donor transplantation.

Bone Marrow Transplant 2018 03 21;53(3):361-365. Epub 2017 Dec 21.

Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

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http://dx.doi.org/10.1038/s41409-017-0053-9DOI Listing
March 2018

Therapeutic efficacy of azathioprine in addition to prednisone-based regimens as first-line chronic graft-versus-host disease treatment.

Bone Marrow Transplant 2018 03 15;53(3):334-338. Epub 2017 Dec 15.

Allogeneic Blood And Marrow Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, 610 University Ave. Toronto, Ontario, Canada, M5G2M9.

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http://dx.doi.org/10.1038/s41409-017-0025-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861088PMC
March 2018

Outcome following second allogeneic hematopoietic cell transplantation: A single-center experience.

Eur J Haematol 2018 Mar 11;100(3):308-314. Epub 2018 Jan 11.

Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.

Objective: Second allogeneic hematopoietic cell transplantation (HCT) may be indicated following relapse or graft failure following first HCT. Our retrospective single-center study sought to investigate parameters that influence post-second allogeneic HCT survival.

Method: We investigated 92 patients who underwent second allogeneic HCT between 1980 and 2016 for relapse or graft failure following first HCT. Median age at second HCT was 41 years (range 16-68), performed for relapse in 59 patients (64%) and for graft failure in 33 patients (36%).

Results: On univariate analysis, 3-year OS of the entire cohort was 35% (95% CI=25-45). Eastern Cooperative Oncology Group (ECOG) score (3-year OS 48% for ECOG 0-1, 18% for ECOG 2-3, P=.0006), second HCT indication (3-year OS 43% for relapse, 20% for graft failure, P=.02), time from first HCT to relapse/graft failure (3-year OS for <12months 21%, for ≥12months 46%, P=.009), and conditioning intensity (3-year OS for MA 42% vs other regimens 23%, P=.08) significantly influenced OS. Multivariable analysis confirmed ECOG score (HR=2.15 for ECOG 2-3, 95% CI=1.32-3.51, P=.002) and second HCT indication (HR=1.67 for graft failure, 95% CI=1.02-2.75, P=.04) to independently influence survival.

Conclusion: Second HCT may offer long-term survival particularly to patients with good performance status who relapse post-first HCT.
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http://dx.doi.org/10.1111/ejh.13015DOI Listing
March 2018

Incidence and Risk Factors for Nontuberculous Mycobacterial Infection after Allogeneic Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2018 02 3;24(2):366-372. Epub 2017 Oct 3.

Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Allogenic hematopoietic stem cell transplant (HCT) recipients are at risk of many infections. Nontuberculous mycobacteria (NTM) are increasingly recognized as clinically significant pathogens in this population. We investigated the incidence and risk factors for NTM infection after allogeneic HCT. This retrospective cohort study included all patients with allogeneic HCT at our institution during 2001 to 2013. Patients who developed significant NTM infection (NTM disease) were identified. Multivariable modeling was used to identify risk factors for NTM disease, and a risk score model was constructed to identify high-risk patients. Of 1097 allogeneic HCT patients, 45 (4.1%) had NTM isolated and 30 (2.7%) had NTM disease (28 [93.3%] exclusively pulmonary, 2 [6.7%] pulmonary plus another site). Incidence of NTM infection by competing risk analysis was 2.8% at 5 years (95% CI, 1.9% to 4.0%). The median time to diagnosis was 343 days (range, 19 to 1967). In Fine-Gray proportional hazards modeling, only global severity of chronic graft-versus-host disease (cGVHD) (HR, 1.99; 95% CI, 1.12 to 3.53; P = .019,) and cytomegalovirus (CMV) viremia (HR, 5.77; 95% CI, 1.71 to 19.45; P = .004) were significantly associated with NTM disease. Using these variables a risk score was calculated: 1 point for CMV viremia or moderate cGVHD and 2 points for severe cGVHD. The score divided patients into low risk (0 to 1 points, n = 820 [77.3%], 3-year NTM risk 1.2%), intermediate risk (2 points, n = 161 [15.4%], 3-year NTM risk 7.1%), and high risk (3 points, n = 56 [5.4%], 3-year NTM risk 14.3%). NTM disease after allogeneic HCT is common. Severe cGVHD and CMV viremia are associated with increased risk, permitting risk stratification.
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http://dx.doi.org/10.1016/j.bbmt.2017.09.015DOI Listing
February 2018

Extramedullary disease at diagnosis of AML does not influence outcome of patients undergoing allogeneic hematopoietic cell transplant in CR1.

Eur J Haematol 2017 Sep 23;99(3):234-239. Epub 2017 Jun 23.

Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Objective: Extramedullary disease (EMD) at diagnosis of acute myeloid leukemia (AML) has been associated with increased risk of relapse and worse outcomes post-chemotherapy. This study sought to investigate the association of EMD with outcomes following allogeneic hematopoietic cell transplantation (allo-HCT).

Methods: This single-center retrospective study investigated the impact of EMD at diagnosis on the outcome of patients transplanted for AML in first complete remission (CR1). The study included 303 consecutive patients with AML transplanted in CR1, median age 51 years (range 18-71).

Results: EMD at diagnosis was documented in 39 patients (13%), either histologically (26 patients) or clinically/radiologically (13 patients). Among the 39 EMD patients, 16 had CNS disease, seven had gingival infiltration, and five had leukemia cutis. On univariate analysis, EMD had no significant impact on survival, with a 3-year OS of 55% (95% CI 38-69) compared to 48% for the non-EMD group (95% CI 42%-55%) (P=.84). Likewise, 3-year CIR was 18% vs 19% (P=.86) and 3-year NRM was 26% vs 33% (P=.83) for EMD vs non-EMD groups, respectively. Multivariate analysis confirmed these results.

Conclusions: We conclude that EMD at diagnosis of AML does not seem to influence outcomes following allo-HCT performed in CR1.
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http://dx.doi.org/10.1111/ejh.12909DOI Listing
September 2017

Progressive multifocal leukoencephalopathy due to John Cunningham (JC) virus following allogeneic haematopoietic cell transplantation.

Antivir Ther 2017 ;22(8):721-725

Allogeneic Blood and Marrow Transplant Program, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.

Progressive multifocal leukoencephalopathy (PML) is an uncommon infectious complication post allogeneic stem cell transplant. We present a case report of a patient developing this complication with a review of the current literature. It also describes the first use of artesunate in a clinical case of PML with no beneficial effect.
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http://dx.doi.org/10.3851/IMP3162DOI Listing
July 2019

Quality of life following completion of treatment for adult acute lymphoblastic leukemia with a pediatric-based protocol.

Leuk Res 2013 Dec 27;37(12):1632-5. Epub 2013 Sep 27.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Using multiple validated self-report instruments, we evaluated the health-related quality of life (HRQoL) of 29 adult ALL patients a median of 28 months after completing a pediatric-based treatment regimen. Global health was similar to normative data, but leukemia survivors had lower cognitive and social function, and reported more financial difficulty. Fatigue and pain affected 83% and 53% of patients, respectively, and both showed significant inverse correlation with overall health and all functional scales. Vincristine-related peripheral neuropathy was reported by 43%. Although therapy-related symptoms were persistent, long-term ALL survivors have a global HRQoL similar to the general population.
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http://dx.doi.org/10.1016/j.leukres.2013.09.018DOI Listing
December 2013

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia with imatinib combined with a paediatric-based protocol.

Br J Haematol 2012 Aug 1;158(4):506-14. Epub 2012 Jun 1.

Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada.

Although the combination of tyrosine kinase inhibitors with chemotherapy is widely used for young adults with Philadelphia chromosome positive-acute lymphoblastic leukaemia (Ph+ ALL), the outcome and safety of this combination using intensive paediatric-based protocols has not been well described. The clinical course of 32 adults age 18-60 years with Ph+ ALL treated with a paediatric-based protocol plus imatinib was evaluated. The complete response rate was 94%. Grade 3-4 infections, neuropathy, myopathy and liver function abnormalities were common, resulting in major treatment delays and dose reductions, and declines in performance status (physical deconditioning), particularly in patients aged 41-60 years. Median and 3-year overall survival (OS) was 40·7 months and 53%, respectively, and median and 3-year even-free survival (EFS) was 30·1 months and 50%, respectively. OS and EFS were inferior in deconditioned patients. Of 16 patients who underwent haematopoietic stem cell transplantation (HSCT) in first complete remission, six died of non-relapse complications. There was no significant difference in OS and EFS between transplanted and non-transplanted patients, based on an intention-to-treat and time-to-donor identification analysis. The combination of imatinib with a paediatric-based regimen in adults produced high response rates, but was associated with considerable toxicity and high non-relapse mortality post-HSCT.
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http://dx.doi.org/10.1111/j.1365-2141.2012.09182.xDOI Listing
August 2012

Plasma cell leukemia of the breast.

Breast J 2008 Mar-Apr;14(2):204-5

Imageology Division, Regional Cancer Centre, Trivandrum, Kerala, India.

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http://dx.doi.org/10.1111/j.1524-4741.2008.00559.xDOI Listing
April 2008