Distinguishing ASH Clinical Practice Guidelines from Other Forms of ASH Clinical Advice.

The American Society of Hematology (ASH) develops a variety of resources that provide guidance to clinicians on the diagnosis and management of blood diseases. These resources include clinical practice guidelines (CPGs) and other forms of clinical advice. While both ASH CPGs and other forms of clinical advice provide recommendations, they differ with respect to the methods underpinning their development, the principal type of recommendations they offer, their transparency and concordance with published evidence, and the time and resources required for their development. It is crucial that end users be aware of the differences between CPGs and other forms of clinical advice and that producers and publishers of these resources use clear and unambiguous terminology to facilitate their distinction. The objective of this article is to highlight similarities and differences between ASH CPGs and other forms of ASH clinical advice and to discuss the implications of these differences for end users.

Determining the impact of current Canadian stem cell registry policy on donor availability via dynamic registry simulation.

BACKGROUND AND OBJECTIVES: When a haematopoietic stem cell registry size is constrained by limits on recruiting, as in Canada, identifying the right person to recruit is a critical determinant of effectiveness. The aim of this study was to evaluate the impact of changes to donor recruitment effort, within ethnic groups, on the matching effectiveness of the Canadian registry as it evolves over time. MATERIALS AND METHODS: Simulation methods are applied to create a cohort of donor recruits and patients over a 10-year time horizon. New recruits are added to the registry each year, while some existing donors 'age-out' upon reaching their 36th birthday. In a similar fashion, simulated patient lists are created. At the end of each simulated year, simulated patients are matched against the simulated registry. RESULTS: There are increased matches in non-White populations when diverse registrants are preferentially recruited, but there are larger decreases in the number of matches for Caucasian patients. Additionally, ethnic communities that have limited registrants in the Canadian registry in 2021 do not benefit from increased recruiting efforts as much as communities with a larger initial number of registrants. CONCLUSION: Preferentially recruiting from non-Caucasian populations reduces the number of matches from Canadian sources because increases in non-Caucasian populations will not fully counterbalance decreases to Caucasian patient matches. Nevertheless, more than 80% of all matches are for Caucasian patients, regardless of the donor recruiting effort within ethnic groups.

Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis.

Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes. METHODS: Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model. RESULTS: By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4.5%) for SibCy, and 1.9% (99% CI, 1.1% to 2.9%) for SibCNI (P = .001), and that of mold FI was 2.9% (99% CI, 1.5% to 4.7%), 3.7% (99% CI, 91.7% to 6.6%), and 1.7% (99% CI, 1.0% to 2.6%), respectively (P = .040). FI was associated with an increased risk of death, with an adjusted hazard ratio (HR) of 4.06 (99% CI, 2.2 to 7.6) for HaploCy, 4.7 (99% CI, 2.0 to 11.0) for SibCy, and 3.4 (99% CI, 1.8 to 6.4) for SibCNI compared with SibCNI without FI (P < .0001 for all). Similar associations were noted for transplantation-related mortality. FI did not impact rates of relapse or chronic GVHD. CONCLUSIONS: Rates of FI by day 180 ranged between 1.9% and 5.2% for yeast FI and from 1.7% to 3.7% for mold FI across the 3 cohorts. The use of PTCy was associated with higher rates of yeast FI only in HaploHCT and with mold FI in both HaploHCT and SibHCT. The presence of FI by day 180 was associated with increased risk for overall mortality and transplant-related mortality at 2 years regardless of donor type or PTCy use. Although rates of FI were low with PTCy, FI is associated with an increased risk of death, underscoring the need for improved management strategies.

Post-transplantation cyclophosphamide is associated with increased bacterial infections.

Post-transplant cyclophosphamide (PTCy) is increasingly used to reduce graft-versus-host disease after hematopoietic cell transplantation (HCT); however, it might be associated with more infections. All patients who were ≥2 years old, receiving haploidentical or matched sibling donor (Sib) HCT for acute leukemias or myelodysplastic syndrome, and either calcineurin inhibitor (CNI)- or PTCy-based GVHD prophylaxis [Haploidentical HCT with PTCy (HaploCy), 757; Sibling with PTCy (SibCy), 403; Sibling with CNI-based (SibCNI), 1605] were included. Most bacterial infections occurred within the first 100 days; 953 patients (34.5%) had at least 1 infection and 352 patients (13%) had ≥2 infections. Patients receiving PTCy had a greater incidence of bacterial infections by day 180 [HaploCy 46%; SibCy 48%; SibCNI 35%; p < 0.001]. Compared with the SibCNI without infection cohort, 1.99-fold, 3.33-fold, 2.78-fold, and 2.53-fold increased TRM was seen for the HaploCy cohort without infection and HaploCy, SibCy, and SibCNI cohorts with infection, respectively. Bacterial infections increased mortality [HaploCy (HR1.84, 99% CI: 1.45-2.33, p < 0.0001), SibCy cohort (HR,1.68, 99% CI: 1.30-2.19, p < 0.0001), and SibCNI cohort (HR,1.76, 99% CI: 1.43-2.16, p < 0.0001). PTCy was associated with increased bacterial infections regardless of donor, and bacterial infections were associated with increased mortality irrespective of GVHD prophylaxis. Patients receiving PTCy should be monitored carefully for bacterial infections following PTCy.

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.

Canadian Blood Services traceback investigation of a suspected case of transfusion-transmitted malaria.

BACKGROUND: A 4-month-old infant hospitalized since birth received multiple blood transfusions. In March 2022, Plasmodium falciparum was confirmed with nucleic acid testing. As the mother was assessed as unlikely to be the source of infection, the blood operator initiated a traceback investigation for a potential blood donor source. The patient had received 13 red blood cell (RBC) transfusions (aliquoted from 11 donors), 4 apheresis platelet (PLT) transfusions and 16 buffy coat pooled PLT transfusions. The blood operator medical team developed a supplementary malaria infection risk questionnaire to identify donors at highest risk of life-time malaria infection, based on birthplace, residence, or travel in malaria-endemic regions. RESULTS: With 79 donors initially implicated, initial focus was on donors of RBC components. The 11 RBC donors were contacted and assessed using the supplementary questionnaire. Three donors, all of whom met current malaria-related donor eligibility criteria, were deemed high risk of prior malaria infection. These donors consented to P. falciparum serology and nucleic acid testing (NAT). One donor who was born and had resided in an endemic West African country for 14 years, was positive for P. falciparum by serology (indirect fluorescent antibody test) and NAT-(Ct ≥32). Lookback of this donor's transfused fresh co-components and prior donation identified no other malaria cases. CONCLUSION: This was a probable transfusion-transmitted malaria (TTM) case from an eligible donor who in retrospect was found to have unrecognized, asymptomatic, semi-immune malaria infection, and who was potentially infectious. Blood donor lack of recall of prior malaria infection does not negate the risk of TTM from those who have lived in malaria-endemic countries.

HLA-haplotype redundancy and rareness in Canadian Blood Services' Stem Cell Registry and Cord Blood Bank: Novel metrics for optimizing utility.

BACKGROUND: The utility of unrelated donor registries that support allogeneic hematopoietic cell transplantation could be optimized through greater understanding of redundancy and rareness of HLA phenotypes. METHODS: HLA phenotype rareness was determined using known HLA haplotype frequencies. Donor redundancy was determined through pairwise comparison of donor HLA profiles within an inventory. RESULTS: Among 61,730 registrants in the Canadian Blood Services (CBS) Stem Cell Registry (SCR) with high resolution HLA typing at 5 loci, 6.6% of HLA phenotypes were redundant with variation across ethnic groups (8.3% of Caucasian phenotypes; 8% of Native American/First Nations, 4.4% of Asia-Pacific Islanders (API), 2.1% of Hispanic, 0.7% of African-American (AFA), and 4.5% of other ethnicities). A total of 18.5% of registrants had redundant HLA phenotypes with variation across ethnic groups. All 3716 cord blood units in the CBS's cord blood bank (CBB) had high resolution HLA typing at 5 loci and 202 units were redundant (5.4%) comprising 78 HLA phenotypes, with varying rareness. Repeated HLA phenotypes were from Caucasian donors (77%), multiple ethnicity (13%), API (9%), and AFA (1%). Registrants and CBUs with AFA ethnicity had the rarest phenotypes while Caucasian ethnicity was associated with the most common HLA phenotypes. CONCLUSIONS: Redundancy was greater in the SCR compared to the CBB and was most common with CAU ethnicity. Recruiting non-Caucasian registrants and continued cord blood banking should reduce redundancy. A sub-inventory of redundant donors and cord blood units could support new uses for donor-supported cellular therapies that do not require HLA matching.

Modeling unrelated blood stem cell donor recruitment using simulated registrant cohorts: Assessment of human leukocyte antigen matching across ethnicity groups.

BACKGROUND: Human leukocyte antigen (HLA)-matched unrelated donors are not available for some patients considered for allogeneic hematopoietic cell transplantation, particularly among certain ethnic groups. Simulated recruitment modeling can inform efforts to find new matches for more patients. METHODS: Simulated recruits were generated by assigning a pair of donor HLA haplotypes from historical data files and matched against HLA data of patient searches in the Canadian Blood Services Stem Cell Registry. Recruitment cohorts reflected the proportion of five specific ethnic groups in the 2016 Canadian census data. RESULTS: Novel 8/8 HLA matches between simulated recruits and patients increased linearly with larger recruitment cohorts. The proportion of novel 8/8 HLA matches from Caucasian, Hispanic, and Native American/First Nations recruits was equal to or greater than their relative proportion in the recruited cohort (match to: recruit ratio (MRR) ≥ 1). In contrast, African American and Asian & Pacific Islander recruits represented a smaller proportion of novel matches relative to their percentage of the recruited cohort (MRR <1). The proportion of novel 7/8 HLA-matches from each ethnic group was approximately the same as their proportion in the recruited cohort (MRR ~ 1) and high rates of 7/8 HLA-matching already exist within the Canadian Blood Services registry for all ethnic groups. CONCLUSION: Continued large recruitment cohorts are needed to add new 8/8 HLA matches to registry inventories. Likelihoods of novel HLA matches varied across ethnic groups, reflecting varied HLA haplotype frequencies across groups. Simulated cohort modeling can inform recruitment strategies that will generate new donor options for patients.

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.

A Portrait of Cord Blood Units Distributed for Transplantation from Canadian Blood Services' Cord Blood Bank: First Analysis.

BACKGROUND: The Canadian Blood Services Cord Blood Bank (CBS CBB) was created to improve access to stem cell products for transplantation for patients across ethnic groups. An analysis of distributed units is needed to assess the effectiveness of the bank to meet the needs of patients from different ethnic groups. METHODS: A descriptive analysis was performed on all cord blood units distributed from the CBS' CBB as of 30 June 2022. RESULTS: Distribution of the first 60 units based on CBS' CBB inventory has been linear over time. A similar proportion of cord blood unit (CBU) recipients were pediatric or adult. More than half of the cord blood units (56.7%) were distributed to recipients outside of Canada, and CBUs were used to treat a broad range of hematologic and immune disorders. 43.3% of distributed CBUs were of non-Caucasian ethnicity and 18% were from donors self-reporting as multi-ethnic. The mean total nucleated cell counts and total CD34+ cell counts were 1.9 ± 0.1 × 109 cells and 5.3 ± 0.5 × 106 CD34+ cells, respectively. CD34+ cells per kg (recipient weight) varied significantly between pediatric (age 0-4), adolescent (age 5-17) and adult recipients (age 18 and older) (3.1 ± 0.5, 1.4 ± 0.5 and 0.9 ± 0.07 × 105 CD34+ cells/kg, respectively). HLA matching was 6/6 (15%), 5/6 (47%) or 4/6 (38%). CONCLUSIONS: The CBS' CBB has facilitated the utilization of banked units for patients across a broad range of ages, geographic distribution, ethnicity, and diseases. Distributed units were well matched for HLA alleles and contained robust cell counts, reflecting a high-quality inventory with significant utility.

Demand and usage of unrelated donor products for allogeneic haematopoietic cell transplantation during the COVID-19 pandemic: A Canadian Blood Services Stem Cell Registry analysis.

BACKGROUND AND OBJECTIVES: Understanding changes in the demand and usage of unrelated allogeneic haematopoietic cell transplantation (HCT) donors during the COVID-19 pandemic is needed to optimize pandemic preparedness of registry and donor collection services. The aim of this study was to understand the extent to which the pandemic has impacted the demand and usage of unrelated donors and cord blood units (CBUs) at Canadian Blood Services (CBS). MATERIALS AND METHODS: Data regarding stem cell donor interest and product usage for unrelated allogeneic HCT were retrieved from the database at CBS using de-identified anonymous information. RESULTS: Unrelated donor searches for Canadian patients remained unchanged by the pandemic, reflecting stable demand. The number of unrelated allogeneic transplants performed within Canada also remained stable, while the number of cord blood transplants increased, chiefly for paediatric patients. Requests for donor verification typing, a first signal of potential interest, increased from domestic centres during the first 6 months of the pandemic and decreased from international centres, before returning to baseline levels. The proportion of transplants for Canadian patients who used stem cell products procured from Canadian donors increased between 3 and 6 months after the start of the pandemic before returning to baseline and appears to be increasing again more than 1 year after the start of the pandemic. Use of CBUs for Canadian paediatric patients increased and remains elevated. CONCLUSION: Demand for unrelated adult HCT donors has remained stable despite the evolving pandemic with a transient and recurring increased interest and usage of domestic adult donors. Use of CBUs for paediatric patients has increased and remains elevated. Registries and donor collection centres should maintain the capacity to expand services for domestic donor collection during pandemics to offset threats to international donor usage.

Systematic Scoping Review of Studies Reporting Unexpected Donor-Derived Abnormalities from Recipients of Allogeneic Hematopoietic Cell Transplantation: A Proposed Framework for Donor Disclosure.

Allogeneic hematopoietic cell transplantation (HCT) is used increasingly to treat blood and immune-based disorders. Post-transplantation testing of HCT recipients can lead to unexpected molecular, cytogenetic, and other information in donor-derived cells, raising questions regarding the potential impact on donor health. This study was conducted to identify the breadth of donor-derived abnormalities identified by testing HCT recipients and to determine the extent to which disclosure and donor follow-up are described. A systematic search and scoping review were conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping review guidelines in OVID MEDLINE and Embase (1947 to May 24, 2021). We identified 38 studies (63 donor-recipient pairs) addressing nonleukemic abnormalities to complement existing literature describing donor cell leukemia and donor-derived myelodysplasia. Donors were unrelated adults (n = 20), related family members (n = 28), cord blood donors (n = 6), or not reported (n = 9). Acquired cytogenetic, molecular, and morphologic abnormalities were reported. Donor origin was confirmed by cytogenetic analysis via karyotyping, fluorescence in situ hybridization, single tandem repeat PCR, and other techniques. A disease in donor-derived cells was described in 35 recipients (56.5%). Despite the relevance for testing and disclosure to donors, only 22 cases (32%) mentioned donor follow-up, and in 5 cases the donor developed a disease associated with the identified abnormality. Unrelated donor disclosure was mentioned in 3 of 26 cases (12%), with the findings reported back to the registry. Incidental abnormalities identified in transplanted donor cells may contribute to the post-transplantation risk of illness in the recipient and may be relevant to donor health. A framework for donor disclosure is proposed that incorporates consideration of analytic validity of the testing, potential significance of the finding, and the extent to which the abnormality is actionable. Adoption of effective processes to safeguard both donor and recipient health outcomes related to this issue is needed.

Predictors of poor haematopoietic stem cell mobilisation in patients with haematological malignancies at a South African centre.

BACKGROUND: Autologous stem cell transplant (ASCT) is an established consolidation strategy in the treatment of haematological malignancies, however poor mobilisation (PM) can contribute to patient morbidity and high resource utilisation. Identifying the incidence, risk factors for PM and engraftment outcomes are important goals in our resource limited setting. METHODS: We retrospectively analyzed patients with haematological malignancies that consecutively underwent ASCT at Groote Schuur hospital, Cape Town, South Africa from January 2013 to January 2019. RESULTS: 146 patients - majority with multiple myeloma (MM)(41,8%), F:M= 1:2, underwent leukapheresis with median age of 32 years (range, 9 - 66 years). PM occurred in 25/146 (17%), mobilisation failure (MF) in 3/146 (2%) and super mobilisation (SMs) in 99/146 (68%), respectively. Risk factors for PM were: diagnosis of acute leukaemia (RR = 25, 95% CI 3.4 - 183, p = 0.002) and Hodgkin lymphoma (RR = 19, 95% CI 2.6 - 142, p = 0.004); low white cell count (WCC) at harvest (WCC < 9 × 109/L (RR=4.3, 95% CI 2.3 - 8.3, p < 0.0001) and two vs one line of prior therapy (RR = 3.1, 95% CI 1.45 - 6.7, p = 0.0037). Median days to neutrophil and platelet engraftment were 14 days (95% CI 14-15 days) and 16 days (95% CI 15-16 days) respectively. CONCLUSION: PM occurred in 17% of a contemporary South African ASCT cohort, albeit with a low MF rate (2%). There was surprisingly high rate (68%) of SMs, possibly reflective of superfluous mobilisation strategy in MM patients. We identified predictive factors for PM that will lead to enhanced cost-effective use of plerixafor.

Cost-Effectiveness of Brexucabtagene Autoleucel versus Best Supportive Care for the Treatment of Relapsed/Refractory Mantle Cell Lymphoma following Treatment with a Bruton's Tyrosine Kinase Inhibitor in Canada.

For patients with Mantle Cell Lymphoma (MCL), there is no recognized standard of care for relapsed/refractory (R/R) disease after treatment with a Bruton's tyrosine kinase inhibitor (BTKi). Brexucabtagene autoleucel (brexu-cel) represents a promising new treatment modality in MCL. We explored whether brexu-cel was cost-effective for the treatment of R/R MCL. We developed a partitioned survival mixture cure approach to model the costs and outcomes over a lifetime horizon. The clinical data were derived from the ZUMA-2 clinical trial. The costs were estimated from the publicly available Canadian databases, published oncology literature, and pan-Canadian Oncology Drug Review economic guidance reports. The health state utilities were sourced from the ibrutinib submission to the National Institute for Health and Care Excellence for R/R MCL and supplemented with values from the published oncology literature. In the base case over a lifetime horizon, brexu-cel generated an incremental 9.56 life-years and an additional 7.03 quality-adjusted life-years compared to BSC, while associated with CAD 621,933 in additional costs. The resultant incremental cost-utility ratio was CAD 88,503 per QALY gained compared with BSC. Based on this analysis, we found brexu-cel to be a cost-effective use of healthcare resources relative to BSC for treatment of adult patients with R/R MCL previously treated with a BTKi in Canada, though additional research is needed to confirm these results using longer follow-up data.

Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia.

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

Is Haploidentical Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide Feasible in Sub-Saharan Africa?

Identifying a suitable volunteer unrelated donor (UD) in South Africa is challenging due to the highly diverse ethnic groups and mixed-race populations in this region. Haploidentical hematopoietic cell transplantation (haploHCT) is thus an attractive procedure for patients with high-risk hematologic malignancies. This study was conducted to assess the safety and feasibility of haploHCT in South Africa. We retrospectively analyzed the outcome of 134 patients with hematologic malignancies who received unmanipulated haploHCT with post-transplantation cyclophosphamide at 2 high-volume HCT centers between 2014 and 2019. We assessed overall survival (OS), disease-free survival (DFS), nonrelapse mortality (NRM), relapse incidence (RI), and incidence of acute GVHD. The median recipient age was 44 years (range, 15 to 73 years) and the median donor age was 36 years (range, 9 to 68 years). Acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS) and acute lymphoblastic leukemia (ALL) were the most common indications for haploHCT (61.2%). The European Society for Blood and Marrow Transplantation risk score was ≥5 in 44 patients (32.8%). Seventy-seven patients (57.4%) received a myeloablative conditioning regimen. The majority of patients received a sex-matched transplant (57.4%) and had peripheral blood stem cells (PBSCs) as the stem cell source (70.9%). Sixteen patients (11.9%) had an incongruent cytomegalovirus serostatus at transplantation. The median duration of follow-up was 10.8 months (range, 0.36 to 70.8 months). OS was 56% (95% confidence interval [CI], 47% to 64%) at 1 year and 37% (95% CI, 28% to 47%) at 3 years. DFS was 47% (95% CI, 38% to 55%) at 1 year and 32% (95% CI, 24% to 41%) at 3 years. The 100-day and 3-year cumulative incidence of NRM was 18% (95% CI, 11% to 25%) and 41% (95% CI, 32% to 50%), respectively, and the 1- and 3-year cumulative RI was 16% (95% CI, 11% to 24%) and 21% (95% CI, 14% to 29%), respectively. The 1-year OS was 55% (95% CI, 40% to 67%) for the patients with AML/MDS versus 41% (95% CI, 21% to 60%) for those with ALL. Forty-five patients (41.7%) developed acute GVHD by day +100; of these, 80% had grade I-II disease. Fifty patients (37.5%) developed cytomegalovirus infection that required therapy. On multivariable analysis, older donor age was an independent risk factor for lower DFS. RI was higher for diagnoses other than acute leukemia/MDS (relative risk [RR], 2.62; 95% CI, 1.12 to 6.15; P = .027), decreased for PBSC versus bone marrow (RR, 0.43; 95% CI, 0.19 to 0.95; P = .038) and decreased for offspring donors (RR, 0.25; 95% CI, 0.09 to 0.67; P = .006). These data support the feasibility of haploHCT and suggest that unmanipulated haploHCT using a younger parent or offspring donor is a viable option for adults in sub-Saharan Africa with acute leukemia and MDS who lack a suitable related or unrelated donor.