Autologous Hematopoietic Stem Cell Transplantation for Liver Transplant Recipients With Recurrent Primary Sclerosing Cholangitis: A Pilot Study.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an indication for liver transplantation, but recurrence after liver transplantation is associated with poor outcomes often requiring repeat transplantation. We investigated whether autologous hematopoietic stem cell transplantation (aHSCT) could be used to stop progression of recurrent PSC and promote operational tolerance. METHODS: Twelve patients with recurrent PSC were fully evaluated and 5 were selected for aHSCT. Autologous hematopoietic stem cells were collected, purified by CD34 immunomagnetic selection, and cryopreserved. Immunoablation using busulfan, cyclophosphamide, and rabbit antithymocyte globulin was followed by aHSCT. The primary endpoint of the study was the establishment of operational tolerance defined as lack of biochemical, histologic, and clinical evidence of rejection while off immunosuppression at 2 y post-aHSCT. RESULTS: Two of the 5 patients achieved operational tolerance with no clinical or histologic evidence of PSC progression or allorejection. A third patient developed sinusoidal obstruction syndrome following aHSCT requiring repeat liver transplantation but has no evidence of PSC recurrence while on sirolimus monotherapy now >3 y after aHSCT. A fourth patient was weaned off immunosuppression but died 212 d after aHSCT from pericardial constriction. A fifth patient died from multiorgan failure. Immunosuppression-free allograft acceptance was associated with deletion of T-cell clones, loss of autoantibodies, and increases in regulatory T cells, transitional B cells, and programmed cell death protein-1 expressing CD8+ T cells in the 2 long-term survivors. CONCLUSIONS: Although operational tolerance occurred following aHSCT, the high morbidity and mortality observed render this specific protocol unsuitable for clinical adoption.

CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies.

Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada's publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin's lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 106 CAR-T cells/kg (range 0.13-3.6 × 106/kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03765177, identifier NCT03765177.

Autologous Hematopoietic Stem Cell Transplantation for Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) refractory to conventional therapy can lead to marked disability and represents a therapeutic challenge. OBJECTIVE: To report five cases of treatment-refractory disabling CIDP treated with autologous hematopoietic stem cell transplantation (AHSCT). METHODS: This was a retrospective cohort study from a tertiary care referral center for both neuromuscular disease and AHSCT. Patients with CIDP treated with AHSCT between 2008 and 2020 were included. All patients had major persistent and disabling neuropathic deficits despite combinations of intensive immunosuppressive therapy. The primary outcome measures were: Medical Research Council sum score, Overall Neuropathy Limitations Scale and requirement for ongoing CIDP immunotherapy after transplantation. We also analyzed safety outcomes by documenting all severe AHSCT-related complications. RESULTS: Five patients with refractory CIDP underwent AHSCT. Three were classified as manifesting a typical syndrome, two were classified as the multifocal Lewis Sumner variant. The mean age at time of CIDP diagnosis was 33.4 years (range 24-46 years), with a median delay of 46 months (range 21-135 months) between diagnosis and AHSCT. The median follow-up period was 41 months. All five patients were able to wean off CIDP-related immunotherapy. Marked improvements in Medical Research Council scale and overall Neuropathy Limitations Scale were noted in 4/5 patients. One patient with longstanding neurogenic atrophy showed no improvement in disability scales. There were no treatment-related deaths or critical illnesses. CONCLUSIONS: AHSCT can achieve marked sustained clinical improvement of refractory CIDP and may allow for weaning off long-term complex immunotherapies.

Time to rethink vascular access in patients with breast cancer.

Breast cancer management is a rapidly evolving field. Diagnosis and treatment options have changed dramatically over the years, as have options for vascular access devices used to administer therapies. We now need to critically rethink vascular access device options for our breast cancer patients. Breast cancer (BC) is the most commonly diagnosed cancer among Canadian women. Although BC incidence continues to rise, the overall mortality rate in Canada is the lowest it has been for 70 years. The five-year net survival is 87%, and 83% of women are alive at 10 years. New oral therapies, shorter dose-dense treatments, and decreased use of anthracycline-base regimens are reducing the need for central venous access devices during acute treatment phases. However, these survivors go on to develop other health issues requiring routine venipuncture and insertion of vascular access devices. Breast cancer-related lymphedema (BCRL) is a chronic complication that has no cure and no proven prevention strategies. Approximately 21% of breast cancer survivors are at risk of developing BCRL. Of those patients who do develop BCRL, 70% do so within two years of surgery, 90% within three years, and another one percent per year thereafter. The literature supports axillary lymph node dissection, mastectomy, administration of chemotherapy or radiotherapy, and obesity, as risk factors for the development of BCRL. However, 40% of patients who develop BCRL have no identifiable risk factors. Broader risk reduction strategies developed are not evidence based, the most commonly cited being avoidance of needle sticks. Large cohort studies have found no significant association between blood draws and intravenous infusion in the surgical arm with the development of BCRL. Recommendations that effectively eliminate vascular access on the surgical side for the patient's entire lifetime are neither necessary nor realistic. Vascular access specialists can provide leadership by developing standardized, evidence-informed recommendations for safe vascular access and infusion practices for this patient population.

Comparison of complication rates and incidences associated with different peripherally inserted central catheters (PICC) in patients with hematological malignancies: a retrospective cohort study.

Patients with hematological malignancies (HM) or undergoing hematopoietic cell transplantation (HCT) require reliable vascular access. Peripherally inserted central catheters (PICC) meet this need, however, studies suggest these patients have higher rates of PICC-associated complications. This retrospective cohort study evaluates the influence of PICC type on the rates and incidences of complications. Four hundred and eighty-five dual lumen PICCs were inserted into 469 complex patients with HM or undergoing HCT: 161 Groshong®, 60 PowerPICC® Solo, 165 BioFlo®, and 99 Arrow®. The rates and incidences of complications differed significantly across the PICC types. The overall rate of complication ranged from 7.40 to 26.4/1000 catheter days (CDs). The rate of deep vein thrombosis (0.31-1.48/1000 CDs) and occlusion differed across the PICC types, while the rate of central line-associated bloodstream infection (0.53-0.74/1000 CDs) did not. Following multivariate adjustment, PICC type was associated with complication rate. This highlights that PICC type should be considered in clinical decisions.

Anaphylaxis and anaphylactoid reactions associated with the insertion of peripherally inserted central catheters: A multiyear comparative retrospective cohort study.

OBJECTIVE: Peripherally inserted central catheters (PICCs) are a mainstay of nonpermanent vascular access devices. In this study, we assessed patients displaying anaphylaxis or anaphylactoid reactions to the PowerPICC SOLO and Groshong PICC (Bard Access Systems) using the Sherlock tip locating system (TLS). METHODS: Patients from 2 tertiary-care hospitals were systematically monitored over 4 years for adverse events following the insertion of a PICC using the Sherlock TLS. Insertion data were also collected using the BioFlo PICC (Angiodynamics)from a third hospital site and from The Ottawa Hospital over 4 years as an additional comparator. Three definitions of anaphylaxis and anaphylactoid reactions were utilized, and the Cohen κ was used to assess interrater agreement. Analysis of reactions among the patient cohorts was performed using the χ2 test with Yates correction or the Fisher exact test as appropriate. RESULTS: Among 8,257 insertions using the TLS PICCs, 37 potential reactions (0.45%) were recorded. Using specific definitions for anaphylaxis or anaphylactoid reactions, 54.1%-91.9% met criteria. Comparator populations using data from Calgary (n = 491) and Ottawa (n = 7,889) using the BioFlo PICC insertion found no reactions. Anaphylactic or anaphylactoid reactions were significantly associated with the PowerPICC SOLO and Groshong PICC with the TLS compared to the BioFlo PICC (P < .0001) across all definitions. The largest subset of patients experiencing adverse reactions had cystic fibrosis (CF) (n = 4, 10.8%). CONCLUSION: Our study results demonstrate significant adverse events associated with the PowerPICC SOLO and Groshong PICC using the Sherlock TLS inserted across a range of patient populations. The incidence rate of anaphylaxis or anaphylactoid reactions in the CF population at our center is significantly higher than in non-CF patients (P < .001).

Implanted vascular access device related deep vein thrombosis in oncology patients: A prospective cohort study.

BACKGROUND: Implanted vascular access devices (IVADs) have significantly improved the management of cancer patients. These patients are at an increased risk of venous thromboembolism and IVADs are a known risk factor. We sought to assess the incidence of IVAD-related upper extremity deep vein thrombosis (IVAD-related UEDVT) associated with BioFlo® IVADs (Angiodynamics, Inc.). METHODS: A total of 394 cancer patients were enrolled over 12 months. The primary outcome was the incidence of IVAD-related UEDVT confirmed by diagnostic imaging. IVAD-related UEDVT was defined as symptomatic ipsilateral upper extremity (axillary vein or proximal) deep vein thrombosis and symptomatic pulmonary embolism (PE). Patients were followed until initiation of therapeutic anticoagulation, catheter removal, death, or up to 12 months. RESULTS: 389 patients were included in the analysis. The median age of the cohort was 58.2 years; 68% (n = 273) were females. Sixty-six percent had gastrointestional cancer (including pancreatic cancer) and 68% had metastases. Eighty four percent of IVADs were right sided insertions. Ninety eight percent of catheter tip placements were distal superior vena cava (n = 237), cavo-atrial junction (n = 67) or atrium (n = 90). Overall, 5 patients had symptomatic IVAD-related UEDVT (1.29%, 95% CI 0.2 to 2.4%). CONCLUSION: IVAD-related UEDVT is an infrequent complication in cancer patients with BioFlo® IVADs.

The legacy of lymphedema: Impact on nursing practice and vascular access.

Breast cancer is the most common cancer in women. Breast cancer related lymphedema (BCRL) is a chronic condition characterized by an abnormal accumulation of protein-rich fluid in tissues resulting in swelling of the upper limb or trunk after treatment. Lack of consensus on definition, classification and grading of BCRL has led to subjective and objective parameters estimating incidence and severity. Prospective studies estimate the risk of BCRL to be approximately 21.4% (14.9-29.8). In patients with axillary lymph node dissection (ALND), the estimated risk of 19% (13.5-28.2) was about four times higher than those patients who had sentinel lymph node biopsy (5.6%, 6.1-7.9). Seventy percent of these patients will experience BCRL within two years of surgery, 90% within three years, and a 1% rate per year thereafter. Many patients who have no high-risk variables such as mastectomy, ALND and radiation therapy develop BCRL. Patients fear this complication, which has no cure and no proven prevention strategies. Risk reduction strategies, primarily focused on reducing trauma to the surgical arm, are based on anecdotal information and effectively restrict the use of the at-risk limb for the patient's lifetime. Although broad risk reduction strategies have been recommended, the avoidance of needle sticks has become the most common strategy practised, enforced through institutional policies and procedures and reinforced through patient education initiatives and breast cancer support groups. Large cohort studies have found no significant association between blood draws and intravenous infusions in the surgical arm and the development of BCRL. Current literature supports that approximately 21% of patients will develop BCRL, leaving 79% free of the complication. Due to increased survival, breast cancer survivors go on to develop other healthcare issues that may require vascular access. Therefore, long-held beliefs with regards to risk factors and preventative measures need to be challenged. Education of healthcare providers, patients and support groups through the dissemination of evidence-based information on the diagnosis, prevention and treatment of BCRL is necessary to ensure that patients receive the best care possible with the least risk.

Optimal vascular access strategies for patients receiving chemotherapy for early-stage breast cancer: a systematic review.

IMPORTANCE: Systemic chemotherapy can be administered either through a peripheral vein (IV), or centrally through peripherally inserted central catheter (PICC), totally implanted vascular access devices (PORTs) or tunnelled cuffed catheters. Despite the widespread use of systemic chemotherapy in patients with breast cancer, the optimal choice of vascular access is unknown. OBJECTIVE: This systematic review evaluated complication rates and patient satisfaction with different access strategies for administering neo/adjuvant chemotherapy for breast cancer. EVIDENCE REVIEWED: Ovid Medline, EMBASE and the Cochrane Central Register of Controlled Trials were searched from 1946 to September 2017. Two reviewers independently assessed each citation. The Newcastle-Ottawa scale was used to assess the quality of cohort and case-control studies. FINDINGS: Of 1584 citations identified, 15 unique studies met the pre-specified eligibility criteria. There were no randomised studies comparing types of vascular access. Reports included six single-institution retrospective cohort studies, one retrospective multi-institution cohort, one retrospective cohort database study, five prospective single-institution studies, one prospective multi-institution study and one nested case-control study. Median complication rates were infection: 6.0% PICC (2 studies) versus 2.1% PORT (8 studies); thrombosis: 8.9% PICC (2 studies) versus 2.6% PORT (9 studies); extravasation: 0 PICC (1 study) versus 0.4% PORT (4 studies) and mechanical issues: PICC 3.8% (1 study) versus 1.8% PORT (9 studies). Satisfaction/quality of life appeared high with each device. CONCLUSION: In the absence of high-quality data comparing vascular access strategies, randomised, adequately powered, prospective studies would be required to help inform clinical practice and reduce variation.

Outcomes in a nurse-led peripherally inserted central catheter program: a retrospective cohort study.

BACKGROUND: Peripherally inserted central catheters (PICCs) provide enormous benefit to patients. However, recent publications have highlighted relatively high PICC-associated complication rates. We report on patient and device outcomes from a nurse-led program. METHODS: We performed a retrospective analysis of a prospective cohort of consecutive patients undergoing PICC insertion at The Ottawa Hospital between Jan. 1, 2013 and Dec. 31, 2014. Of the 8314 BioFlo PASV PICCs inserted, we randomly selected a sample of 700 and obtained a complete data set for 656. We measured the cumulative incidence of major complications (catheter-related bloodstream infections and deep vein thrombosis) and use of a thrombolytic to alleviate occlusions. RESULTS: The total number of catheter days was 58 486, and the median dwell time 45 days. We observed 4 cases of catheter-related bloodstream infection (0.6% [95% CI 0.17%-1.55%]) (0.07/1000 catheter days). Ten patients (1.5% [95% CI 0.83%-2.78%]) (0.17/1000 catheter days) had catheter-related deep venous thrombosis. At least 1 dose of thrombolytic was required in 75 catheters (11.4% [95% CI 8.61%-13.39]), 31 (7.1%) of the 436 single-lumen catheters and 113 (25.7%) of the 440 lumina of dual-lumen catheters (p < 0.001). INTERPRETATION: We attribute our low rates of major complications to a nurse-led expert insertion team, standardized care and maintenance protocols, high insertion volumes, novel catheter material and continuous quality-improvement initiatives that are implemented and evaluated regularly. We conclude that the considerable benefits PICCs provide to patients are attained with a low risk of major complications.

Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial.

BACKGROUND: Strong immunosuppression, including chemotherapy and immune-depleting antibodies followed by autologous haemopoietic stem-cell transplantation (aHSCT), has been used to treat patients with multiple sclerosis, improving control of relapsing disease. We addressed whether near-complete immunoablation followed by immune cell depleted aHSCT would result in long-term control of multiple sclerosis. METHODS: We did this phase 2 single-arm trial at three hospitals in Canada. We enrolled patients with multiple sclerosis, aged 18-50 years with poor prognosis, ongoing disease activity, and an Expanded Disability Status Scale of 3.0-6.0. Autologous CD34 selected haemopoietic stem-cell grafts were collected after mobilisation with cyclophosphamide and filgrastim. Immunoablation with busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin was followed by aHSCT. The primary outcome was multiple sclerosis activity-free survival (events were clinical relapse, appearance of a new or Gd-enhancing lesion on MRI, and sustained progression of Expanded Disability Status Scale score). This study was registered at ClinicalTrials.gov, NCT01099930. FINDINGS: Between diagnosis and aHSCT, 24 patients had 167 clinical relapses over 140 patient-years with 188 Gd-enhancing lesions on 48 pre-aHSCT MRI scans. Median follow-up was 6.7 years (range 3.9-12.7). The primary outcome, multiple sclerosis activity-free survival at 3 years after transplantation was 69.6% (95% CI 46.6-84.2). With up to 13 years of follow-up after aHSCT, no relapses occurred and no Gd enhancing lesions or new T2 lesions were seen on 314 MRI sequential scans. The rate of brain atrophy decreased to that expected for healthy controls. One of 24 patients died of transplantation-related complications. 35% of patients had a sustained improvement in their Expanded Disability Status Scale score. INTERPRETATION: We describe the first treatment to fully halt all detectable CNS inflammatory activity in patients with multiple sclerosis for a prolonged period in the absence of any ongoing disease-modifying drugs. Furthermore, many of the patients had substantial recovery of neurological function despite their disease's aggressive nature. FUNDING: Multiple Sclerosis Scientific Research Foundation.

Myasthenia Gravis Treated With Autologous Hematopoietic Stem Cell Transplantation.

IMPORTANCE: Some patients with myasthenia gravis (MG) do not respond to conventional treatment and have severe or life-threatening symptoms. Alternate and emerging therapies have not yet proved consistently or durably effective. Autologous hematopoietic stem cell transplant (HSCT) has been effective in treating other severe autoimmune neurologic conditions and may have similar application in MG. OBJECTIVE: To report 7 cases of severe MG treated with autologous HSCT in which consistent, durable, symptom-free, and treatment-free remission was achieved. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study reports outcomes at The Ottawa Hospital, a large, Canadian, tertiary care referral center with expertise in neurology and HSCT, from January 1, 2001, through December 31, 2014, with a median follow-up of 40 months (range, 29-149 months). Data collection and analysis were performed from February 1 through August 31, 2015. All patients with MG treated with autologous HSCT at The Ottawa Hospital were included. All had persistent severe or life-threatening MG-related symptoms despite continued use of intensive immunosuppressive therapies. INTERVENTIONS: Autologous hematopoietic stem cell grafts were mobilized with cyclophosphamide and granulocyte colony-stimulating factor, collected by peripheral blood leukapheresis, and purified away from contaminating lymphocytes using CD34 immunomagnetic selection. Patients were treated with intensive conditioning chemotherapy regimens to destroy the autoreactive immune system followed by graft reinfusion for blood and immune reconstitution. MAIN OUTCOMES AND MEASURES: The primary outcome was MG disease activity after autologous HSCT measured by frequency of emergency department visits and hospitalizations and Myasthenia Gravis Foundation of America (MGFA) clinical classification, MGFA therapy status, and MGFA postintervention status. Safety outcomes included all severe autologous HSCT-related complications. RESULTS: Seven patients underwent autologous HSCT, 6 for MG and 1 for follicular lymphoma with coincident active MG. Mean (SD) ages at MG diagnosis and at autologous HSCT were 37 (11) and 44 (10) years, respectively. Five patients (71%) had concurrent autoimmune or lymphoproliferative illnesses related to immune dysregulation. All patients had distinct clinical and electromyographic evidence of MG (MGFA clinical classification IIIb-V). All patients achieved durable MGFA complete stable remission with no residual MG symptoms and freedom from any ongoing MG therapy (MGFA postintervention status of complete stable remission). Three patients (43%) experienced transient viral reactivations, and 1 (14%) developed a secondary autoimmune disease after autologous HSCT, all of which resolved or stabilized with treatment. There were no treatment- or MG-related deaths. CONCLUSIONS AND RELEVANCE: Autologous HSCT results in long-term symptom- and treatment-free remission in patients with severe MG. The application of autologous HSCT for this and other autoimmune neurologic conditions warrants prospective study.

Improved Prediction of CD34+ Cell Yield before Peripheral Blood Hematopoietic Progenitor Cell Collection Using a Modified Target Value-Tailored Approach.

The most commonly used stem cell source for both autologous and allogeneic transplantation is mobilized peripheral blood hematopoietic progenitor cells collected by apheresis. In the 1990s, an Italian group used the correlation between the preapheresis peripheral blood CD34+ cell count and the final number of CD34+ cells collected to devise a formula for "target value-tailored" (TVT) apheresis. Using local patient data, the Canadian Blood Services Stem Cell Laboratory created a similar model to determine the blood volume to process during apheresis collection. The objectives of this study were to determine the correlation between the number of CD34+ cells predicted by the TVT formula and the actual number of CD34+ cells collected and to determine whether the TVT formula remains predictive when applied to an external data set. All apheresis collections performed at the Ottawa Hospital between January 1, 2003 and October 2, 2013 were reviewed. The primary outcome was the correlation between the number of CD34+ cells predicted by the TVT formula and the actual number of CD34+ cells collected on day 1 of apheresis. For the external data set, all autologous collections performed at the London Health Sciences Centre between December 1, 2008 and December 1, 2013 were reviewed. The external data set was divided into test and validation sets to determine whether a model could be created to predict the final number of CD34+ cells collected on day 1 based on the preapheresis CD34+ count. A total of 1252 collections were included in the analysis. The Ottawa data set included 1012 collections, 836 of which were autologous and 176 of which were from donors. Of the autologous collections in Ottawa, 764 (92.5%) were first collections. In 759 (91%) collections, chemotherapy plus granulocyte colony-stimulating factor (G-CSF) was used as the mobilization regimen. In 747 collections (89%), only 1 collection day was required to achieve the desired number of CD34+ cells. The TVT estimate was highly predictive of the number of CD34+ cells × 10(6)/kg actually collected on apheresis day 1 (r = .90, P < .0001). The London data set included 240 autologous collections. All mobilizations were with G-CSF alone. For the test set, the precollection CD34+ count was highly predictive of the number of CD34+ cells × 10(6)/kg collected on day 1 of apheresis. Applying this model to the validation set, the correlation between the predicted and final and day 1 CD34+ cells × 10(6)/kg count was .9186 (P < .0001). Using a modified TVT approach, the preapheresis CD34+ count can be used to accurately predict the number of CD34+ cells × 10(6)/kg collected on day 1. This approach can be applied at other centers and for different diseases and mobilization regimens. This method can be used to individualize the blood volume processed and, thus, optimize resource utilization.

Outcomes of both abbreviated hyper-CVAD induction followed by autologous hematopoietic cell transplantation and conventional chemotherapy for mantle cell lymphoma: a 10-year single-centre experience with literature review.

We retrospectively evaluated consecutive patients diagnosed with Mantle cell lymphoma (MCL) between 01 January 2000 and 31 December 2009. Eighty eight patients with MCL were included in the analysis of whom 46 (52%) received abbreviated Hyper-CVAD (a total of two cycles; with addition of Rituximab since 2005) with an intention of proceeding to autologous hematopoietic cell transplantation (auto-HCT), with a median age of 58 years. Response rate to induction at auto-HCT time was 89% and complete response was 61%. Forty four patients received an auto-HCT with a 5-year progression-free survival (PFS) and overall survival (OS) were 31.2% and 62.5%, respectively. There were 42 nontransplant eligible patients with a median age of 72 years, and 5-year PFS and OS were 0.0% and 39.9%, respectively. The median survival and PFS in the auto-HCT eligible group were 68 and 33 months, compared to 32 and 12 months in nontransplant eligible group, without a plateauing of the survival curves in either group. Treatment-related mortality in the auto-HCT eligible group was 10.9% (n = 5); two patients died during R-Hyper-CVAD and 3 (6.8%) experienced transplant-related mortality. An abbreviated R-Hyper-CVAD-based induction strategy followed by consolidative auto-HCT is feasible and provides moderate potential of long-term survival. Further research to define risk-adapted strategies; to optimize disease control, is required.

Impact of platelet transfusion on toxicity and mortality after hematopoietic progenitor cell transplantation.

BACKGROUND: Thrombocytopenia occurs commonly after hematopoietic progenitor cell transplantation (HPCT) and is associated with potential morbidity and mortality. Few studies have examined the impact of platelet (PLT) transfusion on clinical outcomes in HPCT while optimal PLT transfusion strategies after HSCT remain uncertain. STUDY DESIGN AND METHODS: A retrospective single-center cohort study was conducted on 522 patients undergoing HPCT between January 2002 and December 2007. Associations between PLT transfusion events and clinical characteristics with transplant-related outcomes were assessed using univariate and multivariate analysis. RESULTS: Mean number of PLT transfusion events before Day +60 posttransplant was 7.5 (95% confidence interval, 6.7-8.4) with greater number of events after allogeneic compared with autologous HPCT (p < 0.01). Univariate and multivariate analysis confirmed that the number of PLT transfusion events was associated with increased 100-day nonrelapse mortality (p < 0.01), posttransplant length of hospital stay (p < 0.01), need for intensive care unit admission (p < 0.01), and number of organs affected by severe toxicity (p < 0.01). CONCLUSION: HPCT-related toxicity and mortality are associated with increased PLT transfusion events. Alternative strategies to reduce PLT transfusions after HPCT may warrant future study.

Incidence and risk factors of symptomatic venous thromboembolism related to implanted ports in cancer patients.

INTRODUCTION: The true incidence of symptomatic implanted port related venous thromboembolism (VTE) in cancer patients is unclear and there is very limited data on its associated risk factors. MATERIALS AND METHODS: We performed a retrospective cohort study of consecutive cancer outpatients who received an ultrasound guided implanted port insertion for the administration of chemotherapy. The primary outcome measure was symptomatic VTE. Univariable and multivariable logistic regression analyses were used to identify risk factors for symptomatic VTE. RESULTS: A total of 400 cancer patients with a newly inserted implanted port for deliverance of chemotherapy were included in the study. Median age was 58years (range of 21 to 85years) and 120 (30%) were males. Patients were followed for a median of 12months and none received thrombophrophylaxis. Of the 400 patients included in the analysis, 34 patients (8.5%; 95% CI: 6.0 to 11.7%) had symptomatic VTE (16 DVTs, 16 PEs, and 2 with both). In the univariate analyses, metastatic disease, male gender and right sided implanted port insertion were significantly associated with the risk of VTE. In the multiple-variable analysis, male gender (OR 2.17, p=0.04) and presence of metastases (OR 8.22, p<0.01) were the two significant independent predictors of implanted port related VTE. CONCLUSION: Symptomatic VTE is a frequent complication in cancer patients with implanted port receiving chemotherapy. Gender and presence of metastatic disease are independent risk factors for symptomatic VTE. Future trials assessing the role of thromboprophylaxis among these higher risk patients are needed.

Is cytomegalovirus testing of blood products still needed for hematopoietic stem cell transplant recipients in the era of universal leukoreduction?

Hematopoietic stem cell transplantation (HSCT) recipients are a high-risk, immunocompromised group of patients who receive frequent transfusions after transplantation. Transfusion of cytomegalovirus (CMV)-negative blood products has long been the standard of care to prevent transfusion-transmitted CMV in this patient population. Leukoreduction of blood products before transfusion has been shown to significantly reduce the risk of transfusion-transmitted CMV. In the era of universal leukoreduction in Canada, the need for CMV testing of blood products remains unclear. We sought to identify whether there is a difference in transfusion-transmitted CMV viremia in patients receiving only leukoreduced versus CMV-negative and leukoreduced blood products in HSCT recipients. Patients who were CMV negative and received an allogeneic HSCT from a CMV-negative donor between October 1, 1999 and June 30, 2012 were included in the analysis. Transfusion data were collected from The Ottawa Hospital Blood Bank and Canadian Blood Services. CMV viremia was defined as PCR positivity. One hundred sixty-six patients were identified who met the inclusion criteria. Of these, 89 patients received an HSCT before January 2007, during the time when patients received leukoreduced and CMV-negative blood products. Seventy-seven patients received an HSCT after this time, receiving only leukoreduced blood products. The 2 groups did not differ in terms of age, gender, diagnosis, graft type, graft source, conditioning regimen, or ABO compatibility (P > .05). CMV viremia was detected in 3 patients who received CMV-negative leukoreduced blood products (3.37%) and in 1 patient who received only leukoreduced blood products (1.30%, P = .6244). Of the patients who developed CMV viremia, 2 developed suspected CMV disease. Both of these patients were transfused with CMV-negative blood products. Secondary outcomes, including total length of stay in hospital, admission to the intensive care unit, acute and chronic graft versus host disease, and 100-day nonrelapse mortality, did not differ between the groups. In the era of universal leukoreduction of blood products, this study demonstrates that testing for CMV-negative blood products is not needed for HSCT recipients.

The use of intravenous antibiotics at the onset of neutropenia in patients receiving outpatient-based hematopoietic stem cell transplants.

Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program.

Incidence and predictive factors of symptomatic thrombosis related to peripherally inserted central catheters in chemotherapy patients.

INTRODUCTION: The incidence of symptomatic catheter-related deep vein thrombosis (DVT) in cancer patients remains unclear and there is a lack of reliable data on the risk factors of PICC-related DVT. MATERIALS AND METHODS: We performed a retrospective cohort study of consecutive cancer patients who received an ultrasound guided PICC line for the administration of chemotherapy. Univariable and multivariable logistic regression analyses were performed to identify risk factors for symptomatic PICC-related DVT. RESULTS: In total, 340 cancer patients obtained PICC lines for the administration of chemotherapy. Of these patients, 19 (5.6%; 95% CI: 3.6-8.6) developed symptomatic PICC-related DVT. Factors previously associated with catheter-related DVT, including side of catheter placement, lumen size, tip location, need for repositioning, and number of insertion attempts, were not significant determinants in our analysis. Patients with diabetes were three times more likely to develop PICC-related DVT (OR 3.0, p=0.039), while the presence of COPD and metastatic cancer also increased the odds (OR 3.3, p=0.078 and OR 2.3, p=0.083 respectively). Diabetes remained a significant risk factor after adjustment for effect of metastases and COPD (OR 3.175, p=0.039). Further, the presence of metastases was a significant predictor (OR 3.34, p=0.024) in our multivariable model. CONCLUSIONS: Symptomatic PICC-related DVT are frequent in cancer patients receiving chemotherapy. Previously described factors associated with catheter-related thrombosis were not predictive of PICC-related DVT in our study. Diabetes, advanced disease and COPD appear to increase the risk of developing PICC-related DVT in chemotherapy patients.