Hematopoietic Cell Transplant Patients Research Articles

Use of T2Bacteria Panel in Pediatric Hematopoietic Stem Cell Transplant Patients: A Single Center Experience

Abstract Background Bloodstream infection is a common complication following hematopoietic cell transplant (HCT), occurring in 10-40% of patients (1,2). Rapid identification of causative bacteria is imperative to provide proper empiric therapy and ensure optimal patient outcomes. The T2Bacteria Panel detects five bacterial pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli) using T2 magnetic resonance (T2MR, T2Biosystems, Lexington MA, USA) directly from blood specimens. Previous studies have reported per-patient sensitivity, specificity, and negative predictive value (NPV) of 84-90%, 85.9-90%, and 99.7%, respectively, as well as 100% positive agreement and 98.4% negative agreement when compared to blood culture (3-5). To date, there have been no studies on the use of this test in pediatric HCT recipients. Methods We reviewed all pediatric HCT patients at St. Jude Children’s Research Hospital who had a T2Bacteria Panel performed for fever and suspected infection between January 2019 and September 2022. A total of 706 T2Bacteria Panel results and concurrent blood culture results from 251 unique patients were analyzed to determine assay performance for detection of the 5 targeted pathogens. Results T2Bacteria PCR and blood culture showed concordant results in 97% of cases. Overall, our study revealed 65% positive percent agreement with blood culture and 95% negative percent agreement for bacteremia caused by any of the target pathogens. PPV, NPV, sensitivity and specificity for each organism detected by the panel, and the panel overall, are presented in Table 1. Positive predictive value ranged from 28-73%. Negative predictive value was high for all organisms (98-100%). Sensitivity was highest for Pseudomonas aeruginosa (88%), and lowest for Escherichia coli (44%). Specificity was high for all organisms (97-99%). Conclusion In pediatric HSCT patients, the T2Bacteria Panel was most useful for rapidly ruling out the presence of target pathogens, with high negative percent agreement, NPV, and specificity. Positive percent agreement was lower than noted in previous studies. Positive predictive value and sensitivity varied per pathogen.

CAR T-cell therapy combined with autologous hematopoietic cell transplantation in patients with refractory/relapsed Burkitt Lymphoma

Burkitt lymphoma (BL) is a highly aggressive type of non-Hodgkin lymphomas that have a high likelihood of relapse and are highly refractory to initial treatment. While high-intensity chemotherapy has improved the outcomes, many adult patients still experience treatment failure, and effective salvage therapies are limited. This study retrospectively analyzed the outcomes of 21 relapsed or refractory (R/R) adult BL patients treated with chimeric antigen receptor T-cell (CAR-T) therapy, combined or not with hematopoietic cell transplantation (HCT), across four Chinese hospitals. Patients were grouped based on treatment strategies: autologous HCT followed by CAR T-cell therapy (auto-HCT+CART group, n=8), and CAR T-cell therapy alone (CART group, n=13). The auto-HCT+CART group demonstrated superior outcomes, with an overall response rate (ORR) of 87.5% and significantly higher 1-year overall survival (OS) and progression-free survival (PFS) rates compared to the CART group (p=0.014 and p=0.045, respectively). These findings suggest that combining auto-HCT with CAR-T therapy may enhance long-term disease control in R/R BL patients. These encouraging results highlight the need for further prospective studies to validate our data.

Frailty and pre-frailty associated with long-term diminished physical performance and quality of life in breast cancer and hematopoietic cell transplant survivors.

Physical frailty as a sign of accelerated aging is not well characterized in breast cancer (BC) and hematopoietic cell transplant (HCT) survivors and its correlation with outcomes and quality of life (QOL) is not defined. We conducted a prospective study to determine the prevalence of frailty in adult BC and HCT survivors, examine its impact on QOL, and determine its association with p16INK4a, a molecular biomarker for biological aging. The study included 59 BC and 65 HCT survivors. Median age was 60 years (range 27-81), 68.5% were female and 49.2% were 18-59 vs. 51.8% ≥60 years old. A total of 71 (57.3%) were "fit" (frailty score 0) vs. 53 (42.7%) were pre-frailty/frail (frailty scores ≥1), and of the latter 17 (32.1%) were BC and 36 (67.9%) HCT patients. On multivariate analysis, patients >60 years were twice as likely to be frail (OR 2.04, 95% CI, 0.96-4.33; p=0.07), HCT were more likely to be frail compared to BC patients, and female HCT had 2.43 (95% CI, 0.92-6.40) and male HCT patients had 3.25 (95% CI, 1.37-7.72) times higher risk of frail; p=0.02. Frailty was associated with significant decline in QOL, measured by Medical Outcomes Study (MOS) Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), and FACT (Functional Assessment of Cancer Therapy) scores. p16INK4a expression was higher in those who were frail, older than 60, and with higher expression in frail vs. fit patients who are 18-59 years. Our study highlights the high prevalence of frailty in survivors with detrimental effects on physical and overall wellbeing, and supports an association between frailty and the senescence marker p16INK4a.

Successful Allogeneic Hematopoietic Cell Transplantation for Patients with IL10RA Deficiency in Japan.

IL10RA (IL10 receptor subunit alpha) deficiency is an autosomal recessive disease that causes inflammatory bowel disease during early infancy. Its clinical course is often fatal and the only curative treatment is allogeneic hematopoietic cell transplantation (HCT). In Japan, only case reports are available, and there are no comprehensive reports of treatment outcomes. We retrospectively analyzed patients with IL10RA deficiency in Japan. Two newly identified and five previously reported patients were included in this study. Five patients underwent HCT; one untransplanted patient survived to age 14, and one died of influenza encephalopathy before transplantation. All five HCT recipients underwent HCT at the age before 2 years. They all were conditioned with fludarabine/busulfan- or fludarabine /melphalan-based regimens. The donor source was human leukocyte antigen haploidentical donor bone marrow (BM) for two patients and unrelated umbilical cord blood (CB) for two patients. One patient experienced graft failure with unrelated CB and required a second transplant with unrelated BM. All patients who underwent HCT survived and demonstrated an improved performance status. In cases of IL10RA deficiency, the need for transplantation should be promptly assessed, and early transplantation should be considered. (190/250).

Abstract 8: Facilitating Hematopoietic Cell Transplant for Patients with Infantile Krabbe Disease Identified by Newborn Screening

Abstract 8: Facilitating Hematopoietic Cell Transplant for Patients with Infantile Krabbe Disease Identified by Newborn Screening

Predictors of fluid overload in allogeneic hematopoietic cell transplant patients receiving post-transplant cyclophosphamide.

Fluid overload (FO) commonly occurs during hospitalization for allogeneic hematopoietic cell transplantation (HCT). Grade 2-4 FO is associated with day +100 non-relapse mortality.1 Post-transplant cyclophosphamide (PTCY) for graft-versus-host disease prevention requires aggressive IV hydration to prevent hemorrhagic cystitis. This is a single-center, retrospective, observational study conducted at an academic medical center via electronic chart review. Included patients received allogeneic HCT followed by PTCY on days +3 and +4. Patients were excluded for age < 18 years or incarceration. Primary endpoints are incidence of Grade 2-4 FO and associated risk factors. Descriptive and inferential statistics (i.e., Fisher's exact test, multivariable regression analysis) were used. Of 97 patients screened, 95 were included and 2 were excluded due to absence of weight measurements needed to grade FO. Median age was 60 years, 66.3% were male, 91.6% received reduced-intensity conditioning, 72.6% received haploidentical HCT, 44.2% were ECOG 0, and 11.6% had diastolic dysfunction. Incidence of grade 2-4 FO was 33.7% (n = 32). Univariate analyses found age (continuous; p = 0.04) and BSA < 1.7 m2 (p = 0.006) as independent factors associated with grade 2-4 FO. Multivariable regression analysis found 3.3% higher risk with every 1-year increase in age ranging from f 20 to 78 years (OR 1.033, 95% CI 1.001, 1.006; p = 0.0453) and 82.8% lower risk with BSA ≥ 1.7 m2 (OR 0.172, 95% CI 0.051, 0.588; p = 0.005) after adjusting for co-variates. Increasing age and BSA < 1.7 m2 are risk factors associated with grade 2-4 FO during hospitalization for allogeneic HCT with PTCY.

Early Toxicity and Efficacy of Four Different Conditioning Regimens for Autologous Hematopoietic Cell Transplantation in Patients With Lymphoma: Impact of Drug Shortages in a Resource-Constrained Country

High-dose therapy followed by autologous hematopoietic cell transplant (AHCT) remains a viable consolidation strategy for a subset of patients with relapsed or refractory (R/R) lymphomas. BEAM (carmustine, etoposide, cytarabine, and melphalan) is widely recognized as the predominant conditioning regimen due to its satisfactory efficacy and tolerability. Nevertheless, shortages of carmustine and melphalan have compelled clinicians to explore alternative conditioning regimens. The aim of this study was to compare the toxicity and transplant outcomes following BEAM, CBV (carmustine, etoposide, cyclophosphamide), BuMel (busulfan, melphalan), and BendaEAM (bendamustine, etoposide, cytarabine, melphalan). We retrospectively analyzed data from 213 patients (CBV 65, BuMel 42, BEAM 68, BendaEAM 38) with R/R lymphomas undergoing AHCT between 2014 and 2020. Multivariate models were employed to evaluate toxicity and transplant outcomes based on conditioning type. Among grade III to IV toxicities, oral mucositis was more frequently observed with BuMel (45%) and BendaEAM (24%) compared to BEAM (15%) and CVB (6%, P ≤ .001). Diarrhea was more common with BendaEAM (42%) and less frequent with BuMel (7%, P = .01). Acute kidney injury was only found after BendaEAM (11%). Febrile neutropenia and infectious complications were more frequent following BendaEAM. Frequencies of other treatment-related toxicities did not significantly differ according to conditioning type. BendaEAM (odds ratio [OR] 3.07, P = .014) and BuMel (OR 4.27, P = .002) were independently associated with higher grade III to IV toxicity up to D+100. However, there were no significant differences in relapse/progression, nonrelapse mortality, progression-free survival, or overall survival among the four regimens. BuMel and BendaEAM were associated with a higher rate of grade III to IV toxicity. Carmustine-based regimens appeared to be less toxic and safer; however, there were no significant differences in transplant outcomes. The utilization of alternative preparative regimens due to drug shortages may potentially lead to increased toxicity after AHCT for lymphoma.

Challenges with sirolimus experimental data to inform QSP model of post-transplantation cyclophosphamide regimens.

Dose optimization of sirolimus may further improve outcomes in allogeneic hematopoietic cell transplant (HCT) patients receiving post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD). Sirolimus exposure-response association studies in HCT patients (i.e., the association of trough concentration with clinical outcomes) have been conflicting. Sirolimus has important effects on T-cells, including conventional (Tcons) and regulatory T-cells (Tregs), both of which have been implicated in the mechanisms by which PTCy prevents GVHD, but there is an absence of validated biomarkers of sirolimus effects on these cell subsets. Considering the paucity of existing biomarkers and the complexities of the immune system, we conducted a literature review to inform a quantitative systems pharmacology (QSP) model of GVHD. The published literature presented multiple challenges. The sirolimus pharmacokinetic models insufficiently describe sirolimus distribution to relevant physiological compartments. Despite multiple publications describing sirolimus effects on Tcons and Tregs in preclinical and human exvivo models, consistent parameters relating sirolimus concentrations to circulating Tcons and Tregs could not be found. Each aspect presents a challenge in building a QSP model of sirolimus and its temporal effects on T-cell subsets and GVHD prevention. To optimize GVHD prevention regimens, phase I studies and systematic studies of immunosuppressant concentration-effect association are needed for QSP modeling.

Impact of dexamethasone on transplant-related mortality in pediatric patients: a multi-site, propensity score-weighted, retrospective assessment.

Dexamethasone use during hematopoietic cell transplant (HCT) conditioning varies between pediatric centers. This study aimed to estimate the difference in 1-year treatment-related mortality (TRM) between patients who did or did not receive dexamethasone during HCT conditioning. Secondary objectives were to estimate the difference between dexamethasone-exposed and dexamethasone-unexposed groups in 1-year event-free survival (EFS), time to neutrophil engraftment, acute graft-versus-host disease (aGVHD), and invasive fungal disease (IFD) at day + 100. This was a seven-site, international, retrospective cohort study. Patients < 18years old undergoing their first allogeneic or autologous myeloablative HCT for hematologic malignancy or aplastic anemia between January 1, 2012, and July 31, 2017, were included. To control for potential confounders, propensity score weighting was used to calculate the standardized mean difference for all endpoints. Among 242 patients, 140 received dexamethasone during HCT conditioning and 102 did not. TRM was unaffected by dexamethasone exposure (1.7%; 95% CI - 7.4, 10.2%). Between-group differences in secondary outcomes were small. However, dexamethasone exposure significantly increased possible, probable, and proven IFD incidence (9.0%, 95% CI 0.8, 17.3%). TRM is not increased in pediatric patients who receive dexamethasone during HCT conditioning. Clinicians should consider potential IFD risk when selecting chemotherapy-induced vomiting prophylaxis for pediatric HCT patients.

Pediatric Hematology and Oncology Patients on Extracorporeal Membrane Oxygenation: Outcomes in a Multicenter, Retrospective Cohort 2009-2021.

To describe characteristics associated with survival for pediatric patients with an oncologic diagnosis or hematopoietic cell transplant (HCT) supported with extracorporeal membrane oxygenation (ECMO). Multicenter, retrospective study. Sixteen PICUs in the United States and Israel. We included patients aged younger than 19 years with an oncologic diagnosis or HCT who required ECMO support between 2009 and 2021. None. A total of 149 patients were included in the study cohort. There were 118 patients with an oncologic diagnosis and 31 that received HCT. The indications for ECMO were respiratory failure (46%), combined respiratory and cardiac failure (28%), and cardiac failure (25%). Venovenous (V-V) ECMO was used in 45% of patients, with 53% of patients being placed on venoarterial (V-A) ECMO. For oncologic and HCT groups, survival to ECMO decannulation was 52% (62/118) and 64% (20/31), and survival to hospital discharge was 36% (43/118) and 42% (13/31), respectively. After adjusting for other factors, requiring cardiopulmonary resuscitation was associated with greater odds ratio of mortality (3.0 [95% CI, 1.2-7.7]). Survival to ECMO decannulation of pediatric oncologic and HCT patients in this study was 52-64%, depending upon diagnosis. However, survival to hospital discharge remains poor. Future research should prioritize understanding factors contributing to this survival gap within these patient populations.

Clinical Pharmacokinetics and Pharmacodynamics of Letermovir in Allogenic Hematopoietic Cell Transplantation.

Letermovir is a newly developed antiviral agent used for the prophylaxis of human cytomegalovirus infections in patients undergoing allogeneic hematopoietic cell transplantation. This novel anti-cytomegalovirus drug, used for the prophylaxis of cytomegalovirus reactivation until approximately 200 days after transplantation, effectively reduces the risk of clinically significant cytomegalovirus infection. No human counterpart exists for the terminase complex; letermovir is virus specific and lacks some toxicities previously observed with other anti-cytomegalovirus drugs, such as cytopenia and nephrotoxicity. The absolute bioavailability of letermovir in healthy individuals is estimated to be 94% based on a population-pharmacokinetic analysis. In contrast, oral administration of letermovir to patients undergoing hematopoietic cell transplantation results in lower exposure than that in healthy individuals. Renal or hepatic impairment does not influence the intrinsic clearance of letermovir. Co-administration of letermovir may alter the plasma concentrations of other drugs, including itself, as it acts as a substrate and inhibitor/inducer of several drug-metabolizing enzymes and transporters. In particular, attention should be paid to the drug-drug interactions between letermovir and calcineurin inhibitors or azole antifungal agents, which are commonly used in patients undergoing hematopoietic cell transplantation. This article reviews and summarizes the clinical pharmacokinetics and pharmacodynamics of letermovir, focusing on patients undergoing hematopoietic cell transplantation, healthy individuals, and specific patient subsets.

Incidence of venous thromboembolic disease and risk of bleeding in critically ill patients with hematologic malignancies: A retrospective study

ObjectiveOur objectives were to describe the use of thromboprophylaxis and the incidence of VTE/bleeding in critically ill patients with hematologic malignancies (HM). DesignRetrospective cohort study (2014–2022). SettingMedic-Surgical Intensive Care Unit (ICU) in a tertiary care academic center. PatientsAdult patients admitted to ICU with a concomitant diagnosis of a hematological malignancy. InterventionsNone. Main variables of interestWe analyzed demographic data, use of thromboprophylaxis and secondary outcomes that included incidence of VTE (venous thromboembolism), bleeding, mortality, severity scores and organ support. We applied a multivariable logistic regression model to examine the risk of thrombosis in the ICU. ResultsWe included 862 ICU admissions (813 unique patients). Thromboprophylaxis was given during 65% of admissions (LMWH 14%, UFH 8%, and SCDs 43%); in 21% it was contraindicated due to thrombocytopenia; 14% of cases lacked documentation on prophylaxis. There were 38 unique incident cases of VTE (27 DVT, 11 PE), constituting 4.4% of ICU episodes. Most of VTE cases happened in patients with various degrees of thrombocytopenia. In the multivariable analysis, SOFA score on the first ICU day was independently associated (OR 0.85, 95% CI 0.76−0.96) with the risk of VTE. Bleeding occurred in 7.2% (minor) and 14.4% (major) of episodes; most frequent sites being CNS, abdomen/GI and pulmonary. ConclusionsIn this cohort of critically ill patients with HM, there was considerable variability in the utilization of DVT prophylaxis, with predominant use of SCDs. The incidence of VTE was 4.4% and major bleeding 14%. Clinical Trial RegistrationNCT05396157. Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study (https://clinicaltrials.gov/).

Clinical impact of clonal hematopoiesis in hematopoietic cell transplantation: a review, metaanalysis, and call to action.

Hematopoietic cell transplantation (HCT) is the only potentially curative treatment option for many patients with hematologic malignancies. While HCT outcomes have improved drastically over the years, patients and clinicians continue to face numerous survivorship challenges, such as relapse, graft-versushost disease, and secondary malignancies. Recent literature suggests that clonal hematopoiesis (CH), the presence of a recurrent somatic mutation in hematopoietic cells, in HCT patients or donors may be associated with outcomes in autologous and allogeneic HCT. Herein, we perform a review of the literature and summarize reported associations between CH and clinical outcomes in HCT. For commonly reported outcomes, we used meta-analysis methods to provide estimates of effect sizes when combining results. A total of 32 articles with relevant and independent contributions were included, covering both autologous (n = 19) and allogeneic (n = 13) HCT. The articles report variable risk for developing outcomes according to CH characteristics, patient disease status, and method of HCT. Using meta-analysis of available results, HCT outcomes with statistically significant effects by CH status include therapy-related myeloid neoplasms (OR 3.65, 95%CI 2.18-6.10) and overall survival (HR 1.38, 95%CI 1.20-1.58) in autologous HCT and relapse (HR 0.80, 95%CI 0.68-0.94) in allogeneic HCT. However, heterogeneity, biases, and limitations in the literature provide challenges for informing the translation of CH to clinical decision-making. We conclude with a call to action and discussion of next steps to build upon the current literature and provide granularity to the true clinical impact of CH in the setting of HCT.

Photobiomodulation minimizes taste changes during hematopoietic cell transplantation: A randomized clinical trial.

Prevention and treatment protocols for taste changes observed during hematopoietic cell transplantation (HCT) are not well-established. The purpose of this study was to assess the efficacy of photobiomodulation (PBM) in relieving taste changes and preventing lingual papillae atrophy. HCT patients received PBM (n = 42) on the tongue dorsum using an InGaAIP laser (660 nm, 100 mW, 1.1 W/cm2, 8.8 J/cm2). During the HCT conditioning (T0), severe neutropenia (T1), and after neutrophil engraftment (T2), taste acuity for sweet, bitter, sour, and salty solutions, and clinical appearance of lingual papillae were compared with those of a placebo group (n = 43). PBM significantly reduced hypogeusia, ageusia, and parageusia at T1 and T2, and also successfully prevented papillae atrophy during all the analyzed HCT periods. In conclusion, PBM enhanced taste acuity during HCT. The decrease in papillae atrophy indicated a potential regenerative effect of this therapy on tongue mucosa.

Acute Endothelial Complications Post-Allogeneic Hematopoietic Cell Transplant in Patients with Pre-Cellular Therapy SARS-CoV-2 Infection.

Acute Endothelial Complications Post-Allogeneic Hematopoietic Cell Transplant in Patients with Pre-Cellular Therapy SARS-CoV-2 Infection.

Telemedicine With Wearable Technologies in Patients Undergoing Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy (TEL-HEMATO Study): Prospective Noninterventional Single-Center Study.

Patients with hematological malignancies receiving hematopoietic cell transplantation (HCT) or chimeric antigen receptor (CAR) T-cell therapy are at risk of developing serious clinical complications after discharge. The aim of the TEL-HEMATO study was to improve our telehealth platform for the follow-up of patients undergoing HCT or CAR T-cell therapy during the first 3 months after discharge with the addition of wearable devices. Eleven patients who received autologous (n=2) or allogeneic (n=5) HCT or CAR T-cell therapy (n=4) for hematological malignancies were screened from November 2022 to July 2023. Two patients discontinued the study after enrollment. The telehealth platform consisted of the daily collection of vital signs, physical symptoms, and quality of life assessment up to 3 months after hospital discharge. Each patient received a clinically validated smartwatch (ScanWatch) and a digital thermometer, and a dedicated smartphone app was used to collect these data. Daily revision of the data was performed through a web-based platform by a hematologist or a nurse specialized in HCT and CAR T-cell therapy. Vital signs measured through ScanWatch were successfully collected with medium/high adherence: heart rate was recorded in 8/9 (89%) patients, oxygen saturation and daily steps were recorded in 9/9 (100%) patients, and sleeping hours were recorded in 7/9 (78%) patients. However, temperature recorded manually by the patients was associated with lower compliance, which was recorded in 5/9 (55%) patients. Overall, 5/9 (55%) patients reported clinical symptoms in the app. Quality of life assessment was completed by 8/9 (89%) patients at study enrollment, which decreased to 3/9 (33%) at the end of the third month. Usability was considered acceptable through ratings provided on the System Usability Scale. However, technological issues were reported by the patients. While the addition of wearable devices to a telehealth clinical platform could have potentially synergic benefits for HCT and CAR T-cell therapy patient monitoring, noncomplete automation of the platform and the absence of a dedicated telemedicine team still represent major limitations to be overcome. This is especially true in our real-life setting where the target population generally comprises patients of older age with a low digital education level.

Evidence into practice: Changes in haploidentical versus double umbilical cord blood graft utilization for hematopoietic cell transplantation in the U.S. in relation to a pivotal randomized clinical trial.

e23306 Background: Randomized clinical trials are the “gold standard”, but expensive and not always practice changing. Umbilical cord blood (UCB) and haploidentical (haplo) are donor sources for hematopoietic cell transplant (HCT) patients who do not have a fully matched donor. The Blood and Marrow Transplant Clinical Trials Network (CTN) 1101 trial (2012-2018) compared outcomes of double UCB and haplo bone marrow (BM) transplantation. The trial showed a lower two-year overall survival after UCB compared to haplo (46% vs 57%, p = 0.04). Here, we quantified the change in graft selection in clinical practice in the U.S. after publication of the trial’s primary results. Methods: 11,190 U.S. HCT recipients 18-70 years of age who received either UCB (single or double units) or haplo transplants (BM or peripheral blood stem cells), for leukemias, lymphomas, myelodysplastic syndrome, myeloproliferative neoplasms, who reported to the Center for International Blood and Marrow Transplant Research database, were analyzed. Graft utilization was analyzed in 3 time periods: 2010-2012 (pre-study), 2013-2018 (during study), and 2019-2022 (post-study), using Chi-square test and multivariable logistic regression. Results: Over the 3 time periods, there was a practice change with an increasing proportion of haplo transplants vs UCB (32%, 68% and 91% of transplants, p &lt; 0.001; odds ratio (OR) of 4.67 and 21.38 for during-study and post-study periods, respectively, both with p &lt; 0.001, compared to pre-study period). Males and older patients were more likely to receive haplo (OR = 1.32, p &lt; 0.001, and OR = 1.74, p &lt; 0.001, respectively). Compared to White recipients, Black recipients were more likely to receive haplo (OR = 1.74, p &lt; 0.001), whereas Asian recipients were less likely to receive haplo (OR = 0.75, p = 0.002). Hispanic recipients had a similar likelihood of receiving haplo to White patients (OR = 1.03, p = 0.665). Conclusions: Practice change toward haploidentical graft utilization had begun before the CTN 1101 trial’s publication and continued to increase over time. Black patients were more likely than White patients to receive haplo, and Asian patients were more likely than White patients to receive UCB. Availability of both UCB and haplo as alternative graft sources allowed for HCT for a diverse population. [Table: see text]

A phase 1 trial of TSC-100 and TSC-101, engineered T cell therapies that target minor histocompatibility antigens to eliminate residual disease after hematopoietic cell transplantation.

TPS2678 Background: Engineered T cell therapies such as CAR-T cell therapies have transformed the treatment of B-cell but not non-B cell hematologic malignancies. Allogeneic hematopoietic cell transplantation (HCT) remains the best curative option for hematologic malignancies but ~40% of patients relapse post-HCT with up to 90% mortality due to residual disease post-HCT. A potential solution is targeting minor histocompatibility antigens (MiHAs) that are homogenously expressed on all hematopoietic cells and are genetically mismatched between donors and patients undergoing HCT. These mismatches enable engineered T cells to selectively eliminate residual patient hematopoietic cells, normal or malignant, leaving donor cells untouched. TScan has developed allogeneic donor derived T-cell products TSC-100 and TSC-101, targeting MiHAs HA-1 and HA-2 respectively, both presented on HLA-A*02:01. By choosing HCT patients who are HLA-A*02:01 positive (&gt;98% of whom are either HA-1 or HA-2 positive) and donors who are either HLA-A*02:01 or MiHA negative, TSC-100 or TSC-101 can potentially eliminate all residual patient-derived hematopoietic cells after HCT, to prevent disease relapse. Methods: Study NCT05473910 is a multi-center, multi-arm, non-randomized controlled Phase 1 umbrella study evaluating the feasibility, safety and preliminary efficacy of TSC-100 and TSC-101. Inclusion criteria include adults with AML, MDS or ALL eligible for reduced intensity conditioning-based haploidentical donor transplantation from HLA or MiHA mismatched donors. HLA-A*02:01-positive patients undergo HA-1/ HA-2 testing and are assigned to either TSC-100 or TSC-101 treatment arms in addition to HCT. HLA-A*02:01-negative patients in the control arm receive HCT alone. Upon count recovery after HCT, patients in treatment arms receive either TSC-100 or TSC-101, administered as single or two doses. Primary endpoints include adverse event profiles and dose limiting toxicities. Secondary endpoints include relapse rates, disease-free survival and overall survival. Exploratory endpoints include surrogates of efficacy such as donor chimerism rates and kinetics and minimal residual disease (MRD) rates. Donor chimerism is measured by standard STR-based and novel high-sensitivity NGS-based assays to quantify residual patient-derived hematopoietic cells. MRD is measured before and after HCT using flow cytometry and NGS. Together, these assays measure elimination of residual patient hematopoietic cells, malignant or normal, and could provide early evidence of biological activity. Clinical trial information: NCT05473910 .

Timing of intubation of pediatric hematopoietic cell transplant patients: an international survey.

Retrospective data suggest that pediatric hematopoietic cell transplant (HCT) patients placed on non-invasive ventilation (NIV) prior to intubation have increased risk of mortality compared to patients who are intubated earlier in their course. The HCT-CI subgroup of the PALISI Network set out to gain a better understanding of factors that influence clinician's decisions surrounding timing of intubation of pediatric HCT patients. We validated and distributed a brief survey exploring potential factors that may influence clinician's decisions around timing of intubation of pediatric HCT patients with acute lung injury (ALI). One hundred and four of the 869 PALISI Network's members responded to the survey; 97 of these respondents acknowledged caring for HCT patients and were offered the remainder of the survey. The majority of respondents were PICU physicians (96%), with a small number of Advanced Practice Providers and HCT physicians. As expected, poor prognosis categories were perceived as a factors that delay timing to intubation whereas need for invasive procedures was perceived as a factor shortening timing to intubation. Concerns for oxygen toxicity or NIV-associated lung injury were not believed to influence timing of intubation. Our survey indicates increased risk of ALI from prolonged NIV and oxygen toxicity in HCT patients are not a concern for most clinicians. Further education of pediatric ICU clinicians around these risk factors could lead to improvement in outcomes and demands further study. Additionally, clinicians identified concerns for the patient's poor prognosis as a common reason for delayed intubation.

InsT-ALLing CD7 chimeric antigen receptors before transplantation.

In their paper, the authors present their experience with the use of chimeric antigen receptor T cells targeting CD7 as a bridge to allogeneic haematopoietic cell transplantation in patients with relapsed/refractory T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma. Commentary on: Cao etal. A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy. Br J Haematol 2024;204:2351-2364.