Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors.

Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-Governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (six WHO regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT number increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/ten million population was observed for autologous HCT (r=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation (r=0.51) was detected from related donors. The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.

Evaluating the economic burden of acute myeloid leukemia in Canada.

Background Acute myeloid leukemia (AML) represents a significant burden for patients and their families, and to the healthcare system. This study estimated the total cost of illness associated with newly diagnosed AML patients in Canada. Methods The economic burden of AML was estimated using an incidence-based model, analyzing different types of AML cases in Canada. Direct and indirect costs were calculated using scientific literature and Canadian clinical experts' inputs. Patients were categorized depending on their eligibility for intensive chemotherapy (fit and unfit patients) as well as according to age and cytogenetic markers. Results The total average cost of AML per patient is estimated to be $178,073 with a cost of $210,983 and $145,163 for fit and unfit patients, respectively. The costs related to treatment represent half of the total average cost (52%), followed by hematopoietic stem cell transplant (23%), best supportive care (16%), productivity loss (6%) and wastage (4%) Conclusions For patients with AML, the costs associated with fit patients are higher than unfit patients. Hospitalization and best supportive care costs are key cost drivers for the total costs of fit and unfit patients, respectively. This study highlights that AML is associated with a significant economic burden in Canada.

Final report of TKI discontinuation trial with dasatinib for the second attempt of treatment-free remission after failing the first attempt with imatinib: Treatment-free Remission Accomplished by Dasatinib (TRAD) study.

Multiple studies have reported a significant treatment-free remission (TFR) rate of 50%-60% in patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitor (TKI) therapy. However, the remaining half of these patients still require re-initiation of TKI therapy for leukaemia control. It remains unclear if TKI drugs should be switched for re-therapy in patients who failed the first TFR (TFR1) attempt. Our study attempted to determine whether dasatinib therapy after TFR1 failure post-imatinib discontinuation could improve the likelihood of TFR2. Of 59 patients who lost molecular response after imatinib discontinuation for TFR1, 55 patients (93.2%) were treated with dasatinib, of whom 49 (89.1%) regained MR4.5 or deeper response, with a median time of 1.85 months to achieve MR4.5. Dasatinib was discontinued in 35 patients for TFR2 attempt, of whom 26 patients (74.28%) lost MMR and 6 (17.14%) MR4. Risk factor analysis for the TFR2 after dasatinib discontinuation suggested three significant factors: (1) doubling time of BCR::ABL1 transcript following TFR1 attempt, (2) rapid regaining of molecular response following dasatinib therapy and (3) undetectable BCR::ABL1 transcript prior to TFR2 attempt. The present study showed that dasatinib does not increase the TFR2 rate in general, but a selected group of patients could benefit from this approach.

Updates in hematopoietic cell transplant and cellular therapies that enhance the risk for opportunistic infections.

BACKGROUND: Infectious disease physicians may be asked to evaluate and manage a variety of infections in immunocompromised hosts undergoing hematopoietic cell transplant (HCT) and cellular therapies. Over the last decade, several advances in cellular therapy have occurred, with implications for the types of infectious complications that may be seen. AIMS: The purpose of this review is to update the infectious disease physician on newer advances in HCT and cellular therapy, including haploidentical transplant, expanding indications for transplant in older individuals and children, and chimeric antigen receptor T-cells. We will review how these advances might influence infectious disease complications following HCT. We will also provide a perspective that infectious disease physicians can use to evaluate the degree of immune suppression in an individual patient to help determine the type of infections that may be encountered.

BCR-ABL1 transcript doubling time as a predictor for treatment-free remission failure after imatinib discontinuation in chronic myeloid leukaemia in chronic phase.

The doubling time (DT) of the BCR-ABL1 quantitative polymerase chain reaction (qPCR) transcript level reflects the re-growing fraction of leukaemic cells after discontinuation of tyrosine kinase inhibitor (TKI). The present study analyzed monthly DT within six months after imatinib discontinuation in 131 patients. Monthly DT was calculated as x = ln(2)/K, where x is the DT and K is the fold BCR-ABL1 change from the previous value divided by the number of days between each measurement. The optimal DT value was determined as 12·75 days at two months using a recursive partitioning method. The patients were stratified into three groups: the high-risk group (DT<12·75 days but >0, with rapidly proliferating chronic myeloid leukaemia (CML) cells; n = 26) showed the lowest molecular relapse-free survival (mRFS) of 7·7% at 12 months, compared to 53·6% in the intermediate-risk group (DT≥12·75 days, with slowly proliferating CML cells; n = 16) or 90·0% in the low-risk group (DT≤0, i.e., without proliferating CML cells; n = 71; P < 0·001). Monthly assessment of DT helps identify high-risk patients for treatment-free remission failure with an imminent risk of molecular recurrence, and to define low-risk patients who can be spared the frequent monitoring of monthly molecular tests.

One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors.

The Worldwide Network of Blood and Marrow Transplantation (WBMT) pursues the mission of promoting hematopoietic cell transplantation (HCT) for instance by evaluating activities through member societies, national registries and individual centers. In 2016, 82,718 first HCT were reported by 1,662 HCT teams in 86 of the 195 World Health Organization member states representing a global increase of 6.2% in autologous HCT and 7.0% in allogeneic HCT and bringing the total to 1,298,897 procedures. Assuming a frequency of 84,000/year, 1.5 million HCT were performed by 2019 since 1957. Slightly more autologous (53.5%) than allogeneic and more related (53.6%) than unrelated HCT were reported. A remarkable increase was noted in haploidentical related HCT for leukemias and lymphoproliferative diseases, but even more in non-malignant diseases. Transplant rates (TR; HCT/10 million population) varied according to region reaching 560.8 in North America, 438.5 in Europe, 76.7 in Latin America, 53.6 in South East Asia/Western Pacific (SEA/WPR) and 27.8 in African/East Mediterranean (AFR/EMR). Interestingly, haploidentical TR amounted to 32% in SEA/WPR and 26% in Latin America, but only 14% in Europe and EMR and 4.9% in North America of all allogeneic HCT. HCT team density (teams/10 million population) was highest in Europe (7.7) followed by North America (6.0), SEA/WPR (1.9), Latin America (1.6) and AFR/EMR (0.4). HCT are increasing steadily worldwide with narrowing gaps between regions and greater increase in allogeneic compared to autologous activity. While related HCT is rising, largely due to increase in haploidentical HCT, unrelated HCT is plateauing and cord blood HCT is in decline.

Optimal duration of imatinib treatment/deep molecular response for treatment-free remission after imatinib discontinuation from a Canadian tyrosine kinase inhibitor discontinuation trial.

Although total duration of tyrosine kinase inhibitor (TKI) therapy and of molecular response at 4 log reduction or deeper (MR4) correlates with treatment-free remission (TFR) success after TKI discontinuation, the optimal cut-off values of the duration remain unresolved. Thus, 131 patients were enrolled into the Canadian TKI discontinuation study. The molecular relapse-free survival (mRFS) was defined from imatinib discontinuation till molecular recurrence, that is, major molecular response (MMR) loss and/or MR4 loss. We evaluated mRFS at 12 months after imatinib discontinuation, analyzed it according to the imatinib treatment duration and MR4 duration, and calculated P value, positive (PPV) and negative predictive value (NPV) in the yearly cut-off period of time. The shortest cut-off was sought that met the joint criteria of a P value ≤ 0·05, PPV ≥ 60% and NPV ≥ 60%. We propose six years as the shortest imatinib duration cut-off with a P value 0·01, PPV 68% and NPV 62%: The patients treated with imatinib duration ≥ 6 years showed a superior mRFS rate (61·8%) compared to those with less treatment (36·0%). Also, 4·5 years MR4 duration as the shortest cut-off with a P value 0·003, PPV 63% and NPV 61%: those with MR4 duration ≥ 4·5 years showed a higher mRFS rate (64·2%) than those with a shorter MR4 duration (41·9%).

Regional differences in access to hematopoietic stem cell transplantation among pediatric patients with acute myeloid leukemia.

INTRODUCTION: Indications for hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML) are primarily dependent on risk stratification at diagnosis and relapse status. We sought to determine whether access to HSCT is influenced by regional and socioeconomic factors. METHODS: Children with newly diagnosed AML aged < 15 years between 2001 and 2015 were identified using the Cancer in Young People in Canada national population-based registry. Factors potentially associated with the receipt of HSCT were studied using univariate and multivariable logistic regression models. RESULTS: Overall, 568 children with newly diagnosed AML were included and 262 (46%) received HSCT. A greater proportion of patients, 103/157 (65.6%), underwent HSCT after first or subsequent relapse compared to 159/411 (38.7%) patients who underwent transplant before relapse. Among patients for whom HSCT would be considered before relapse, factors associated with higher odds of HSCT in a multivariable analysis were: poor versus good-risk cytogenetics (Odds ratio [OR]: 30.0, 95% confidence interval [CI]: 7.7-117.0), diagnosis during 2012-2015 versus 2001-2006 (OR: 3.2, 95% CI: 1.6-6.3), diagnosis in eastern Canada versus central Canada (OR: 3.7, 95% CI: 1.9-7.3), and age 10-14 years versus age < 1 year (OR: 5.4, 95% CI: 2.3-12.8). Among patients for whom HSCT would be considered after first relapse, higher odds of HSCT was associated with diagnosis at a HSCT center (OR: 2.1, 95% CI: 1.1-4.1). CONCLUSION: Patients diagnosed at a HSCT performing center and patients from eastern Canada had higher odds of receiving HSCT. This may suggest preferential access to HSCT for certain patients.

Access to Hematopoietic Stem Cell Transplantation among Pediatric Patients with Acute Lymphoblastic Leukemia: A Population-Based Analysis.

Access to hematopoietic stem cell transplantation (HSCT) in pediatric acute lymphoblastic leukemia (ALL) primarily depends on disease-related factors but may be influenced by social and economic determinants. We included all children aged < 15 years with newly diagnosed ALL in Canada between 2001 and 2018 using the Cancer in Young People in Canada national registry. We examined factors potentially associated with the likelihood of receiving HSCT using univariate and multivariable logistic regression models. A total of 3992 patients with newly diagnosed ALL were included. Three hundred twenty-five (8.1%) received an HSCT and formed the transplant cohort. In multivariable analysis factors independently associated with an increased odds of receiving HSCT were male sex (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.05 to 1.93), initial WBC ≥ 50,000 × 109/L (OR, 1.58; 95% CI, 1.09 to 2.28), mixed phenotype acute leukemia relative to B-precursor ALL (OR, 34.32; 95% CI, 16.64 to 70.79), T cell relative to B-precursor ALL (OR, 1.77; 95% CI, 1.07 to 2.91), unfavorable relative to standard cytogenetics (OR, 3.96; 95% CI, 2.56 to 6.12), and relapse before HSCT (OR, 32.77; 95%, 23.89 to 44.96). No association was found between race, neighborhood income quintile or region at diagnosis, and receipt of HSCT. Diagnosis at an HSCT treating center (OR, 1.51; 95% CI, 1.09 to 2.09) and residential distance from the ALL treating center (OR, 1.84 for ≥300 km compared with <100 km; 95% CI, 1.17 to 2.91) were associated with higher odds of receiving HSCT. In a publically funded healthcare system, children with ALL had equitable access to HSCT, which was largely governed by biologic disease-related factors. Patients diagnosed at an HSCT performing center and patients who live farthest away from their treatment center had higher odds of receiving HSCT, although the effect was small, possibly suggesting preferential referral to HSCT for some patients.

Inferior Access to Allogeneic Transplant in Disadvantaged Populations: A Center for International Blood and Marrow Transplant Research Analysis.

Allogeneic hematopoietic cell transplantation (alloHCT) is offered in a limited number of medical centers and is associated with significant direct and indirect costs. The degree to which social and geographic barriers reduce access to alloHCT is unknown. Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for International Blood and Marrow Transplant Research (CIBMTR) were integrated to determine the rate of unrelated donor (URD) alloHCT for acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS) performed between 2000 and 2010 in the 612 counties covered by SEER. The total incidence of AML, ALL, and MDS was determined using SEER, and the number of alloHCTs performed in the same time period and geographic area were determined using the CIBMTR database. We then determined which sociodemographic attributes influenced the rate of alloHCT (rural/urban status, median family size, percentage of residents below the poverty line, and percentage of minority race). In the entire cohort, higher levels of poverty were associated with lower rates of alloHCT (estimated rate ratio [ERR], .86 for a 10% increase in the percentage of the population below the poverty line; P < .01), whereas rural location was not (ERR, .87; P = .11). Thus, patients from areas with higher poverty rates diagnosed with ALL, AML, and MDS are less likely patients from wealthier counties to undergo URD alloHCT. There is need to better understand the reasons for this disparity and to encourage policy and advocacy efforts to improve access to medical care for all.

Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission.

For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. Am. J. Hematol. 91:322-329, 2016. © 2015 Wiley Periodicals, Inc.

Routine filtration of hematopoietic stem cell products: the time has arrived.

BACKGROUND: Most blood products are infused at the time of transfusion through a standard blood filter, designed to capture macroaggregates and cellular debris that might be harmful to the patient if infused. Hematopoietic stem cell products are not universally filtered, likely due to concern about loss of viable stem cells in the filtration process. STUDY DESIGN AND METHODS: We conducted a two-phase study to better understand the safety of routine filtration. First, surplus cryopreserved stem cell products were thawed and filtered, with markers of viability and potency measured. Second, routine filtration was implemented as part of routine practice at our center, and date of neutrophil and platelet (PLT) recovery was compared to historical controls. RESULTS: In the first phase, there was no difference seen in any markers of viability or potency for products after routine filtration. Based on those results, routine filtration was implemented. There was no difference in neutrophil or PLT engraftment. Thus, in this study, routine filtration did not impact the number of viable stem cells and did not delay engraftment. CONCLUSION: Given the very real harm posed by infusion of macroaggregates and cellular debris, and no clear disadvantage to filtration, routine filtration of stem cell products should be considered the standard of care.

Effect of postremission therapy before reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission.

The impact of pretransplant (hematopoietic cell transplantation [HCT]) cytarabine consolidation therapy on post-HCT outcomes has yet to be evaluated after reduced-intensity or nonmyeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia in first complete remission (CR1) reported to the Center for International Blood and Marrow Transplant Research who received a reduced-intensity or nonmyeloablative conditioning HCT from an HLA-identical sibling, HLA-matched unrelated donor, or umbilical cord blood donor from 2000 to 2010. We compared transplant outcomes based on exposure to cytarabine postremission consolidation. Three-year survival rates were 36% (95% confidence interval [CI], 29% to 43%) in the no consolidation arm and 42% (95% CI, 37% to 47%) in the cytarabine consolidation arm (P = .16). Disease-free survival was 34% (95% CI, 27% to 41%) and 41% (95% CI, 35% to 46%; P = .15), respectively. Three-year cumulative incidences of relapse were 37% (95% CI, 30% to 44%) and 38% (95% CI, 33% to 43%), respectively (P = .80). Multivariate regression confirmed no effect of consolidation on relapse, disease-free survival, and survival. Before reduced-intensity or nonmyeloablative conditioning HCT, these data suggest pre-HCT consolidation cytarabine does not significantly alter outcomes and support prompt transition to transplant as soon as morphologic CR1 is attained. If HCT is delayed while identifying a donor, our data suggest that consolidation does not increase transplant treatment-related mortality and is reasonable if required.

Acute promyelocytic leukaemia is characterized by stable incidence and improved survival that is restricted to patients managed in leukaemia referral centres: a pan-Canadian epidemiological study.

Timely diagnosis and care are major determinants of the outcome in acute promyelocytic leukaemia (APL), a malignancy whose incidence may be increasing. The Canadian Cancer Registry (CCR) and health system represent valuable settings to study APL epidemiology. We analysed the CCR, which contains data on all Canadians with APL. To provide clinical information lacking in the CCR, we obtained data from five leukaemia referral centres during a similar time period. Between 1993 and 2007, there were 399 APL in Canada. Age-standardized incidence was 0·083/100,000 and was stable over time. The early death (ED) rate was 21·8% (10·6% in patients <50 years old and 35·5% for those aged >50 years), with no improvement over time. Five-year overall survival (OS) was 54·6% (73·3% in patients <50 years; 29·1% older patients). In the referral cohort, 131 patients were diagnosed between 1999 and 2010. ED was 14·6% and 2-year OS was 76·5%. Within this cohort, ED and OS improved over time, although advanced patient age remained an adverse determinant of OS. In Canada, APL incidence is unexpectedly low and temporally stable. ED was higher than reported in clinical trials, but similar to reports from other registries. In contrast, ED was lower in referral centres and improved with time.

Cell Therapy Transplant Canada (CTTC) Consensus-Based Guideline 2024 for Management and Treatment of Chronic Graft-Versus-Host Disease and Future Directions for Development.

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD. This document will provide comprehensive and practical guidance that can be applied across Canada by healthcare professionals caring for patients with cGvHD. Hopefully, this guideline, based on input from GvHD treaters across the country, will aid in standardizing cGvHD care and facilitate access to much-needed novel therapies. This consensus paper aims to discuss the optimal approach to the initial assessment of cGvHD, review the severity scoring and global grading system, discuss systemic and topical treatments, as well as supportive therapies, and propose a therapeutic algorithm for frontline and subsequent lines of cGvHD treatment in adults and pediatric patients. Finally, we will make suggestions about the future direction of cGvHD treatment development such as (1) a mode-of-action-based cGvHD drug selection, according to the pathogenesis of cGvHD, (2) a combination strategy with the introduction of newer targeted drugs, (3) a steroid-free regimen, particularly for front line therapy for cGvHD treatment, and (4) a pre-emptive approach which can prevent the progression of cGvHD in high-risk patients destined to develop severe and highly morbid forms of cGvHD.

Publication bias is present in blood and marrow transplantation: an analysis of abstracts at an international meeting.

Publication bias is the preferential publication of research with positive results, and is a threat to the validity of medical literature. Preliminary evidence suggests that research in blood and marrow transplantation (BMT) lacks publication bias. We evaluated publication bias at an international conference, the 2006 Center for International Blood and Marrow Transplant Research (CIBMTR)/American Society for Blood and Marrow Transplantation (ASBMT) "tandem" meeting. All abstracts were categorized by type of research, funding status, number of centers, sample size, and direction of the results. Publication status was then determined for the abstracts by searching PubMed. Of 501 abstracts, 217 (43%) were later published as complete manuscripts. Abstracts with positive results were more likely to be published than those with negative or unstated results (P = .001). Furthermore, positive studies were published in journals with a mean impact factor of 6.92, whereas journals in which negative/unstated studies were published had an impact factor of only 4.30 (P = .02). We conclude that publication bias exists in the BMT literature. Full publication of research, regardless of direction of results, should be encouraged and the BMT community should be aware of the existence of publication bias.

The Effect of the COVID-19 Pandemic on Unrelated Allogeneic Hematopoietic Donor Collections and Safety.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic profoundly influenced unrelated donor (UD) allogeneic peripheral blood stem cell (PBSC) collections. Changes included efforts to minimize COVID-19 exposure to donors and cryopreservation of products. The extent to which the efficacy and safety of PBSC donations were affected by the pandemic is unknown. METHODS: Prospective cohort analysis of PBSC collections comparing pre-pandemic (01 April 2019-14 March 2020) and pandemic (15 March 2020-31 March 2022) eras. RESULTS: Of a total of 291 PBSC collections, cryopreservation was undertaken in 71.4% of pandemic donations compared to 1.1% pre-pandemic. The mean requested CD34+ cell dose/kg increased from 4.9 ± 0.2 × 106 pre-pandemic to 5.4 ± 0.1 × 106 during the pandemic. Despite this increased demand, the proportion of collections that met or exceeded the requested cell dose did not change, and the mean CD34+ cell doses collected (8.9 ± 0.5 × 106 pre-pandemic vs. 9.7 ± 0.4 × 106 during the pandemic) remained above requested targets. Central-line placements were more frequent, and severe adverse events in donors increased during the pandemic. CONCLUSION: Cryopreservation of UD PBSC products increased during the pandemic. In association with this, requested cell doses for PBSC collections increased. Collection targets were met or exceeded at the same frequency, signaling high donor and collection center commitment. This was at the expense of increased donor or product-related severe adverse events. We highlight the need for heightened vigilance about donor safety as demands on donors have increased since the pandemic.

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-Based Cohort Study.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 7571 were allogeneic and 10,475 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post-transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of the continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

Access to Hematopoietic Stem Cell Transplant in Canada for Patients with Acute Myeloid Leukemia.

Hematopoietic stem cell transplant is a complicated intervention only offered in specialized centers. Access to transplants may vary based on the location of primary residence, income levels, age, and reported race or ethnicity. Using data from the Canadian Institute of Health (CIH) Discharge abstract database (DAD), all non-Quebec Canadians under the age of 65 with a diagnosis of AML between 2004 and 2015 were included in this study. Descriptive statistics were produced for the variables of interest: time period, age, sex, rurality, transplant status, proportion of visible minorities, proportion identifying as indigenous, and proportion of low-income families. Transplant rates were compared and reported using univariable and multivariable analysis. In multivariable analysis, time period, province of residence, gender, and age were significantly associated with the receipt of an allogeneic hematopoietic stem cell transplant. However, differences in transplant rates observed in indigenous patients, low-income families, and visible minorities were not found to be statistically significant. In non-Quebec Canada, transplant rates vary significantly with province of residence, with the highest rates recorded in Alberta. Contrary to findings previously reported in studies exploring access to transplant in the United States, a low-income level was not associated with lower rates of transplants. This might suggest that Canada's universal health care insurance program is protective against socioeconomic barriers that impact access to health care services.

Real-World Treatment Patterns and Clinical Outcomes in Canadian Patients with AML Unfit for First-Line Intensive Chemotherapy.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.