-
1.
A Portrait of SARS-CoV-2 Infection in Patients Undergoing Hematopoietic Cell Transplantation: A Systematic Review of the Literature
Bailey, A. J. M., Kirkham, A. M., Monaghan, M., Shorr, R., Buchan, C. A., Bredeson, C., Allan, D. S.
Current oncology (Toronto, Ont.). 2022;29(1):337-349
Abstract
The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better understand the presenting features, prognostic factors, and treatment options. Of 897 records, 29 studies were identified in our search. Most studies reporting on adults and pediatric recipients described signs and symptoms that were typical of COVID-19. Overall, the mortality rates were high, with 21% of adults and 6% of pediatric HCT recipients succumbing to COVID-19. The factors reported to be associated with increased mortality included age (HR = 1.21, 95% CI 1.03-1.43, p = 0.02), ICU admission (HR = 4.42, 95% CI 2.25-8.65, p < 0.001 and HR = 2.26, 95% CI 1.22-4.20, p = 0.01 for allogeneic and autologous HCT recipients), and low platelet count (OR = 21.37, 95% CI 1.71-267.11, p = 0.01). Performance status was associated with decreased mortality (HR = 0.83, 95% CI 0.74-0.93, p = 0.001). A broad range of treatments was described, although no controlled studies were identified. The risk of bias, using the Newcastle-Ottawa scale, was low. Patients undergoing HCT are at a high risk of severe morbidity and mortality associated with COVID-19. Controlled studies investigating potential treatments are required to determine the efficacy and safety in this population.
-
2.
Can GCSF-stimulated donor lymphocyte infusions improve outcomes for relapsed disease following allogeneic hematopoietic cell transplantation? A systematic review and meta-analysis
Kirkham, A. M., Bailey, A. J. M., Masurekar, A., Shorr, R., Bredeson, C., Sabloff, M., Allan, D. S.
Leukemia & lymphoma. 2022;:1-12
Abstract
Donor lymphocyte infusions (DLI) can produce graft-versus tumor effects to treat relapse after allogeneic hematopoietic cell transplantation, however, durable responses remain uncommon. A systematic review and meta-analysis are needed to clarify whether DLI collected after stimulation with granulocyte colony-stimulating factor (GCSF; G-DLI) can improve clinical outcomes. Sixteen studies (4 controlled) involving 585 patients were identified in a systematic search up to 17 September 2020. A meta-analysis demonstrated no significant difference in the risk of all-cause mortality (RR: 0.94, 95% CI 0.52-1.68, p = 0.82; n = 3 studies) or relapse-related mortality (RR: 0.72, 0.44-1.18, p = 0.19; n = 3 studies) between G-DLI and conventional DLI (C-DLI) groups. G-DLI products had similar mean CD3+ cells compared to C-DLI products, but median CD34+ cells/kg were increased. No improvement in disease progression, complete response rates, or risk of developing GVHD was observed with G-DLI, however, greater non-relapse mortality was observed compared to C-DLI. Alternative approaches to enhancing graft-versus-tumor effects are needed.
-
3.
First-line therapy, autologous stem-cell transplantation, and post-transplantation maintenance in the management of newly diagnosed mantle cell lymphoma
Bhella, S., Varela, N. P., Aw, A., Bredeson, C., Cheung, M., Crump, M., Fraser, G., Sajkowski, S., Kouroukis, T.
Current oncology (Toronto, Ont.). 2020;27(6):e632-e644
Abstract
BACKGROUND In Ontario, no clearly defined standard of care for the management of mantle cell lymphoma (mcl) has been developed, and substantial variability from centre to centre is evident. This guidance document was prompted by the need to harmonize practice in Ontario with respect to first-line, conditioning, and post-transplantation maintenance therapy for patients newly diagnosed with transplantation-eligible mcl. METHODS The medline and embase databases were systematically searched from January 2013 to January 2020 for evidence, and the best available evidence was used to draft recommendations relevant to first-line therapy, autologous stem-cell transplantation, and post-transplantation maintenance in the management of transplantation-eligible newly diagnosed mcl. Final approval of this guidance document was obtained from the Stem Cell Transplant Advisory Committee. RECOMMENDATIONS These recommendations apply to all cases of transplantation-eligible newly diagnosed mcl:¦ Alternating cycles of r-chop (rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisolone) and r-dhap [rituximab plus dexamethasone-high-dose cytarabine-cisplatin] is the recommended first-line treatment for symptomatic patients newly diagnosed with mcl before autologous stem-cell transplantation (asct).¦ Rituximab plus hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone (r-hypercvad), alternating with methotrexate and cytarabine, is not recommended for the treatment of patients with newly diagnosed mcl.¦ beam (carmustine-etoposide-cytarabine-melphalan), beac (carmustine-etoposide-cytarabine-cyclophosphamide), and total-body irradiation-based regimens are reasonable conditioning options for patients with mcl who have responded to first-line therapy and who are undergoing asct.¦ Maintenance therapy with rituximab is recommended for patients with newly diagnosed mcl who have undergone asct.
-
4.
Network geometry of evidence from randomised controlled trials addressing donor selection and source of haematopoietic progenitor cells used in allogeneic transplantation: a systematic scoping review
Monaghan, M., Rizk, M., Pilon, S., Iyengar, A., Shorr, R., Tay, J., Maze, D., Bredeson, C., Hutton, B., Allan, D. S.
Transfusion medicine (Oxford, England). 2018
Abstract
BACKGROUND AND METHODS A scoping review of randomised controlled trials (RCTs) addressing source of cells and choice of donor for allogeneic haematopoietic cell transplantation (HCT) was performed to create a network of best evidence that allows us to identify new potential indirect comparisons for the strategic development of future studies that connect to the existing evidence network. RESULTS A total of 19 eligible RCTs (2589 total patients) were identified. Nine studies (1566 patients) compared clinical outcomes following the use of peripheral blood progenitor cells (PBPCs) with bone marrow (BM) from matched related donors (eight studies) or matched unrelated donors (one study). The remaining studies compared BM or PBPCs with various methods of BM stimulation or manipulation (six studies), compared different methods of surface molecule-based selection and/or depletion of grafts (two studies) or compared the optimal number of units for paediatric cord blood transplantation (two studies). No published RCTs compared different types of donors. The geometry of the evidence network was analysed to identify opportunities for potential novel indirect comparisons and to identify opportunities to expand the network. Few indirect comparisons are currently feasible due to small sample size and heterogeneity in patient diagnoses and demographics between treatment nodes in the network. CONCLUSION More RCTs that enrol greater numbers of similar patients are needed to leverage the current evidence network concerning donor choice and source of cells used in allogeneic HCT.
-
5.
Eltrombopag after allogeneic haematopoietic cell transplantation in a case of poor graft function and systematic review of the literature
Dyba, J., Tinmouth, A., Bredeson, C., Matthews, J., Allan, D. S.
Transfusion Medicine (Oxford, England). 2016;26(3):202-7
Abstract
BACKGROUND Late graft failure after allogeneic haematopoietic cell transplantation (HCT) can result from the failed engraftment of long-term engrafting cells. The use of thrombopoietin (TPO) receptor agonists (TRA) has been extensively studied and remains an important component of experimental ex vivo stem cell expansion protocols, but its use in allogeneic transplantation is still evolving. METHODS We describe the use of eltrombopag, a TRA, to stimulate the rescue of late graft failure in a patient following allogeneic HCT, and we performed a systematic review of published studies describing the use of TRAs following allogeneic transplantation. RESULTS A total of eight publications were identified from our systematic search and included observational case studies (five studies, total of seven patients) that primarily addressed ITP or isolated thrombocytopenia at various time points after allogeneic HCT and prospective clinical trials (three studies, total of 177 patients with 95 patients receiving TRAs). No studies reported specifically on the use of TRAs for the treatment of trilineage graft failure as a means of in vivo stem cell expansion. The use of TRAs following allogeneic HCT appears safe and promising. CONCLUSION The use of eltrombopag or other TRAs to treat poor graft function after allogeneic HCT is intriguing and warrants further study.
-
6.
Optimal transfusion practices after allogeneic hematopoietic cell transplantation: a systematic scoping review of evidence from randomized controlled trials
Christou, G., Iyengar, A., Shorr, R., Tinmouth, A., Saidenberg, E., Maze, D., Tay, J., Bredeson, C., Allan, D. S.
Transfusion. 2016;56(10):2607-2614
Abstract
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 x 109 /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. Copyright © 2016 AABB.
-
7.
Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario
Kouroukis, C. T., Varela, N. P., Bredeson, C., Kuruvilla, J., Xenocostas, A.
Current Oncology. 2016;23(4):e409-30
Abstract
BACKGROUND High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony-stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10-18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. METHODS The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. RECOMMENDATIONS These recommendations apply to adult patients considered for asct: Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available. For patients with a low peripheral blood CD34+ cell count (for example, <10/muL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the mobilization regimen to maximize stem-cell collection and to prevent the need for remobilization. It is recommended that patients who have failed a previous mobilization attempt undergo remobilization with g-csf and plerixafor, with or without chemotherapy.
-
8.
Systematic review of randomized controlled trials of hematopoietic stem cell mobilization strategies for autologous transplantation for hematologic malignancies
Sheppard, D., Bredeson, C., Allan, D., Tay, J.
Biology of Blood & Marrow Transplantation. 2012;18(8):1191-203
Abstract
Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplantation; however, a proportion of patients fail to collect the minimum number of cells required. We summarized the efficacy and safety of HSC mobilization strategies. We performed a systematic review of randomized controlled trials comparing HSC mobilization strategies before autologous transplantation for hematologic malignancies. The primary outcome was CD34+ cell yield. Secondary outcomes included number of aphereses, proportion of failures, rate of count recovery, and adverse events. We identified 28 articles within 3 broad strategies. Using a cyclophosphamide with growth factor strategy (10 articles), CD34+ cell yield is improved by addition of molgramostim to cyclophosphamide (1.4 vs 0.5 x 10(6)/kg; P = .0165), addition of cyclophosphamide to filgrastim (7.2 vs 2.5 x 10(6)/kg; P = .004), and addition of ancestim to cyclophosphamide and filgrastim (12.4 vs 8.3 x 10(6)/kg; P = .007). Within a growth factor-based strategy (6 articles), addition of plerixafor improves CD34+ cell yield over filgrastim alone in multiple myeloma (MM; 11.0 vs 6.2 x 10(6)/kg; P < .001) and non-Hodgkin lymphoma (5.69 vs 1.98 x 10(6)/kg; P < .01). With combination or noncyclophosphamide-based chemotherapy (12 articles), higher-dose filgrastim (8.2 vs 4.7 x 10(6)/kg for 16 vs 8/mcg/kg daily of filgrastim, respectively; P < .0001) and addition of rituximab to etoposide and filgrastim (9.9 vs 5.6 x 10(6)/kg; P = .021) improve CD34+ cell yield. Growth factor alone after chemotherapy, ancestim, or plerixafor provide adequate autologous HSC grafts for the majority of patients. Although some strategies result in higher CD34+ cell yield, this potentially comes at the expense of increased toxicity. As all strategies are reasonable, programmatic, and patient-specific considerations must inform the approach to autologous graft mobilization. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.