Conditioning Hematopoietic Cell Transplantation Research Articles

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.

Reproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation

Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues. The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant. This was a secondary analysis of gonadal hormone production, future infertility risk assessment, and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (interquartile range [IQR]) or percentages. There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 to 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3388 to 9706 mg/m2. The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent proxies (for patients <18 years old) and patients ≥18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty-five percent of parent proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant. There are high rates of gonadal dysfunction post-HCT, but many parent proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-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.

Treosulfan- Versus Busulfan-based Conditioning in Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A Single-center Retrospective Propensity Score-matched Cohort Study

Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia (CMML) at Princess Margaret Hospital, Toronto 2015-2022. Using propensity score matching, we compared transplant outcomes between two well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n=46) or fludarabine-busulfan with total body irradiation (FBT200) (n=92). A scoring system based on patient age, Karnofsky performance score and hematopoietic cell transplant comorbidity index was used to assign patients based on fitness to low-dose (30 g/m2) or high-dose (42 g/m2) treosulfan: 32 (69.6%) received high-dose treosulfan. The racial composition of the two groups was similar, with 27.2% and 21.7% of FBT200 and FT recipients, respectively, identifying as non-Caucasian (P=0.61). Primary outcomes were analyzed at a median follow-up of 747 days. Of all participants, 116 (84.0%) received graft-vs-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCY) and anti-thymocyte globulin (ATG) . Patients who received FT had a superior 2-y overall survival (OS) compared to those who received FBT200: 66.9% (95% confidence interval (CI): 46.1-81.2) vs. 44.5% (95% CI: 34-54.4), hazards ratio (HR): 0.43, 95% CI: 0.22-0.84 (P=0.013). In multivariate analysis (MVA), only the use of fresh grafts (P=0.02) and FT (P=0.01) were associated with improved OS. FT was associated with superior 2-y relapse-free survival (RFS) compared to FBT200: 63.1% (95% CI: 42.6-77.9) vs. 39.1% (95% CI: 29.1-49.1), HR: 0.44 (95% CI: 0.24-0.81), P=0.008. In MVA, the use of fresh grafts (P=0.03) and FT (P=0.009) were associated with improved RFS. Recipients of FT demonstrated superior 2-y graft versus host disease relapse-free survival (GRFS) compared to those who received FBT200: 57.4% (95% CI: 37.8-72.8) vs. 35.1% (95% CI: 25.5-45). In MVA, only FT was associated with superior GRFS (P=0.02). FT recipients exhibited markedly superior 1-y event-free survival (EFS) compared to recipients of FBT200 in univariate analysis (40.3% (95% CI: 25.9-54.2) vs. 9.2% (95% CI: 4.4-16.3), HR: 0.47 (95%CI: 0.30-0.72), P<0.001) and MVA (P=0.004). FT was associated with lower 1-y non-relapse mortality (NRM) compared to FBT200 in univariate analysis (9.9% (95% CI: 3.0-21.8) vs. 29.7% (95% CI: 20.6-39.3), HR: 0.41 (95% CI: 0.17-0.96), P=0.04) and MVA (P=0.04). Our study utilized propensity score matching to demonstrate superiority of treosulfan- over busulfan-based conditioning in stem cell transplantation of patients with MDS and is the first to evaluate the performance of treosulfan-based conditioning in combination with ATG and PTCY. As such, it contributes to the increasing body of evidence supporting the safety of treosulfan, even at the dose of 42 g/m2.

Non-conditioned cord blood transplantation for infection control in athymic CHARGE syndrome.

CHARGE syndrome is a congenital malformation syndrome caused by heterozygous mutations in the CHD7 gene. Severe combined immunodeficiency (SCID) arises from congenital athymia called CHARGE/complete DiGeorge syndrome. While cultured thymus tissue implantation (CTTI) provides an immunological cure, hematopoietic cell transplantation (HCT) is an alternative option for immuno-reconstitution of affected infants. We aimed to clarify the clinical outcomes of patients with athymic CHARGE syndrome after HCT. We studied the immunological reconstitution and outcomes of four patients who received non-conditioned unrelated donor cord blood transplantation (CBT) at Kyushu University Hospital from 2007 to 2022. The posttransplant outcomes were compared with the outcomes of eight reported patients. Four index cases received CBT 70-144days after birth and had no higher than grade II acute graft-versus-host disease. One infant was the first newborn-screened athymic case in Japan. They achieved more than 500/μL naïve T cells with balanced repertoire 1month post transplant, and survived more than 12months with home care. Twelve patients including the index cases received HCT at a median 106days after birth (range: 70-195days). One-year overall survival rate was significantly higher in patients who underwent non-conditioned HCT than in those who received conditioned HCT (100% vs. 37.5%, p=.02). Nine patients died, and the major cause of death was cardiopulmonary failure. Athymic infants achieved a prompt reconstitution of non-skewing naïve T cells after non-conditioned CBT that led to home care in infancy without significant infections. Non-conditioned CBT is a useful bridging therapy for newborn-screened cases toward an immunological cure by CTTI.

Favorable Fertility Outcome in a Large Cohort of Sickle Cell Disease Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Fertility preservation is an important consideration for individuals with sickle cell disease (SCD) who may face reproductive challenges. While SCD itself does not directly affect fertility, certain complications and its treatment such as hematopoietic cell transplantation (HCT) can impact the reproductive health in SCD patients. HCT is a potential curative therapy for SCD, however, one of the negative outcomes is the premature gonadal failure and infertility. Both male and female patients have different risk factors that may impact the fertility post-transplant. Therefore, these patients should undergo fertility preservation counselling pre transplant. In this study, we report the fertility outcome of large transplant cohort undergoing Non-myeloablative (NMA) conditioning regimen. Methods: We retrospectively collected the data for all SCD patients who were ≥ 14 years old and who underwent allogeneic HCT in our center from 2015 until 2022 with a minimum of 1 year follow up post-transplant. All patients received hydroxyurea for 2 to 3 months pre- transplant at maximum tolerated dose. The conditioning regimen was alemtuzumab 1 mg /kg divided over 5 days from day - 7 to day -3 and Total Body Irradation 200 cGy on day -2 (with testicular shielding for male patients). Graft versus host disease prophylaxis with sirolimus started from day -1 and continued for at least 1 year post-transplant. We started the fertility program in October 2019 where all patients get counselled for fertility preservation methods. Male patients undergo sperm cryopreservation after holding hydroxyurea for 3 months and female patients were referred to a specialized oncology fertility clinic for either oocyte cryopreservation or treatment with Gonadotropin-releasing hormone (GnRH) agonists pre transplant. Primary objective of the study was to assess post-transplant fertility (defined by either ability to conceive for married patients, or development of azoospermia for male patient or secondary amenorrhea for female patients). Secondary objectives were to assess pre transplant fertility, assess the success of different fertility preservations methods and finally to assess for risk factors (pre- transplant and transplant) that affect the fertility potential. Results: We identified a total of 200 SCD patients who underwent HCT. Out of these 200 patients, 107 (54%) were included in our fertility program. The median post-transplant follow up was 3.5 years (1 - 7.5). One hundred and twelve patients (56%) were male, and eighty eight (44%) were female patients. All patients were on hydroxyurea pre transplant with average dose 1000 mg and a duration of less than 2 years in 47 (23.5%) patients, 2 to 5 years in 94 (47%) patients and more than 5 years in 59 (39.5%) patients. Other baseline characteristics are shown in table 1. In the pre-transplant fertility assessment; 58 patients were married and 48 (82%) of them had children pre transplant. 36 male patients attempted sperm cryopreservation and were successful in 33 (91%). 39 female patients received Leuprolide (GNRH agonists) pre-transplant with no complications and 6 female patients attempted oocyte cryopreservation and all were successful. One patient developed cerebral venous thrombosis during the oocyte cryopreservation course. For the post-transplant fertility assessment; out of 57 married patients 26 (45%) were able to conceive. From these 26 pregnancies; 20 ended with successful live-births, 1 ended with abortion and 5 are still pregnant. 6 patients were able to conceive twice and one patient had one twin babies. For male patients 74 did semen analysis at minimum 1 year post-transplant; 35 (47%) had azoospermia and 39 (53%) had viable sperms. Majority recovered spermatogenesis after 1 year (24 patients), at 2 years (9 patients) and after 3 years (3 patients). Three male patients had Azoospermia at one year but was able to conceive successfully without repeating the test. For female patients 71 (80.7%) were able to regain menses and 17 (19.3%) developed secondary amenorrhea. Table 2 shows the pre and post-transplant fertility measures outcome. In conclusion In this study, we have shown the fertility outcomes of male and female patients with SCD undergoing NMA conditioning HCT can be preserved in a significant proportion of patients. All adult patients should be counselled for fertility preservation methods before undergoing curative allogeneic HCT.

Role of Splenic Irradiation Prior to Transplant for Myelofibrosis: A Global Collaboration

JAK inhibitors and novel agents have shown promising reduction of spleen size in newly diagnosed myelofibrosis. However, not all patients will respond or they eventually progress at some point. Despite hematopoietic cell transplantation (HCT) being the only curative treatment option to date, splenomegaly prior to HCT remains a particular challenge. On the other hand, numbers of patients eligible for HCT continue to increase worldwide, and thus management of splenomegaly becomes more and more relevant. One approach to reduce spleen size prior to HCT could be splenic irradiation. However, evidence on its role remains scarce. We took advantage of a global collaboration between European, US, and Latin American centers to investigate the role of splenic irradiation as part of the HCT platform for patients with myelofibrosis. Radiation therapy had to be given within 3 months prior to or be part of conditioning therapy for HSCT. Detailed information on irradiation as well as post-HCT safety profiles was collected in addition to usual patient-, disease-, and transplant-related variables. This global collaborative study included 52 patients, of whom 71% had primary myelofibrosis, 17% post polycythemia vera and 12% post essential thrombocythemia myelofibrosis. Median age at HCT was 60 years (range, 32-76). Risk category according to DIPSS prior to irradiation was intermediate-1 in 20%, intermediate-2 in 52%, and high in 28%. Driver mutation status was JAK2 in 44%, CALR in 40%, MPL in 4%, and triple negative in 12%. Four patients had portal vein thrombosis before irradiation. Ruxolitinib before irradiation was received by 76% and 4% received fedratinib. Reduced intensity conditioning HCT was received by 73% and 85% were matched related or matched unrelated donor transplants. Median time from irradiation to HCT was 2 weeks (range, 0.9-12 weeks) and median spleen size prior to irradiation was 23 cm (range, 14-35). Spleen size was measured by ultrasound in 70%, CT scan in 20%, and physical examination in 10%. Median total irradiation dose was 7 Gy (range, 3-12), fractionated in a median of 5 administrations (range, 2-12). Splenic irradiation resulted in a significant spleen reduction prior to HCT but was also associated with significant reduction in platelet and leukocyte counts ( Table). Spleen size did not correlate with blood counts prior or after irradiation. Higher platelet count prior to irradiation correlated with higher counts after irradiation (r=0.83; P&amp;lt;0.001). There was no correlation between irradiation dose and post-irradiation hematological toxicities. Only 1 patient had non-hematological adverse events (tumor lysis syndrome). Neutrophil engraftment was achieved by 90% within a median of 18 days after HCT and platelet engraftment was achieved by 81% within a median of 38 days. Median follow-up of the total cohort was 2.7 years and 3-year overall survival was 66% (95% CI, 52-80%; Figure). Non-relapse mortality was 27% (95% CI, 15-39%) and cumulative incidence of relapse was 11% (95% CI, 2-20%; Figure). Incidence of acute GVHD grade II-IV and chronic GVHD was 25% and 38%, respectively. Increased spleen size (as continuous variable) prior to irradiation was associated with worse outcome (P=0.05), showing 3-year survival of 73% for spleen ≤25cm vs 42% for &amp;gt;25cm, and non-relapse mortality of 58% vs 14%, respectively (P=0.02). No effect of spleen size after irradiation on outcomes was observed. All 4 patients with portal vein thrombosis died (2-year survival 25%). A multivariable model showed that larger spleen size before irradiation, lower hemoglobin levels, CALR/MPL-unmuated driver mutation genotype, and presence of portal vein thrombosis were significantly associated with worse survival ( Table). This first international and largest study to date on splenic irradiation as part of the HCT algorithm for patients with myelofibrosis and splenomegaly showed a significant impact of spleen size on overall survival and non-relapse mortality, while relapse rates were low. In addition, lower hemoglobin levels and presence of portal vein thrombosis at time of irradiation predicted worse outcomes.

Cryopreservation of Growth Factor-Mobilized Peripheral Blood Stem Cells Does Not Compromise Major Outcomes after Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience

During the COVID-19 pandemic, cryopreservation of allogeneic donor stem cell products ensured availability of products at the start of conditioning for hematopoietic cell transplantation (HCT). Following recommendations from unrelated donor registries, including the National Marrow Donor Program (NMDP), many centers started to cryopreserve related donor peripheral blood stem cell (PBSC) products. Throughout the process, several centers have published outcomes with cryopreserved versus fresh products, some with conflicting results. Even though cryopreservation was initially considered only a temporary measure driven by the pandemic, potential advantages include greater flexibility of transplant timing. However, concern about detrimental effects of cryopreservation including increased risks of graft rejection, relapse and consequently mortality remained. The primary objective was to describe our center's experience comparing outcomes following PBSC transplantation with cryopreserved versus fresh grafts. This was an observational case study with retrospective review comparing cryopreserved grafts (N=213), to a recent historical cohort (controls) using fresh grafts (N=167). In multivariable analyses, the adjusted hazard ratio (fresh vs. cryo) we for overall mortality was HR= 1.20 (95% confidence interval (CI), 0.79-1.82; p=0.40), for non-relapse mortality HR=0.99 (95% CI, 0.55-1.77; p=0.98), and for relapse HR=0.94 (95% CI, 0.60 -1.48; p=0.80). The adjusted hazard ratio for platelet engraftment was HR=1.31 (95% CI, 1.05-1.63; p=.02) and the odds ratio of grades III-IV acute GVHD was OR=1.75 (95% CI 1.01-3.04; p=.05) with fresh compared to cryopreserved grafts. There was no demonstrable difference in the risk of chronic GHVD. Although longer-term follow-up is needed, these data provide preliminary reassurance that in the event of another pandemic or should the logistical need arise in individual patients, cryopreservation of PBSC products constitutes a reasonably safe alternative.

Optimization of Radiolabeling of a [90Y]Y-Anti-CD66-Antibody for Radioimmunotherapy before Allogeneic Hematopoietic Cell Transplantation.

For patients with acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia, allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. In addition to standard conditioning regimens for HCT, high-dose radioimmunotherapy (RIT) offers the unique opportunity to selectively deliver a high dose of radiation to the bone marrow while limiting side effects. Modification of a CD66b-specific monoclonal antibody (mAb) with a DTPA-based chelating agent should improve the absorbed dose distribution during therapy. The stability and radioimmunoreactive fraction of the radiolabeled mAbs were determined. Before RIT, all patients underwent dosimetry to determine absorbed doses to bone marrow, kidneys, liver, and spleen. Scans were performed twenty-four hours after therapy for quality control. A radiochemical purity of >95% and acceptable radioimmunoreactivity was achieved. Absorbed organ doses for the liver and kidney were consequently improved compared to reported historical data. All patients tolerated RIT well with no treatment-related acute adverse events. Complete remission could be observed in 4/5 of the patients 3 months after RIT. Two patients developed delayed liver failure unrelated to the radioimmunotherapy. The improved conjugation and radiolabeling procedure resulted in excellent stability, radiochemical purity, and CD66-specific radioimmunoreactivity of 90Y-labeled anti-CD66 mAb. RIT followed by conditioning and HCT was well tolerated. Based on these promising initial data, further prospective studies of [90Y]Y-DTPA-Bn-CHX-A″-anti-CD66-mAb-assisted conditioning in HCT are warranted.

Alemtuzumab and CXCL9 levels predict likelihood of sustained engraftment after reduced-intensity conditioning HCT.

Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism <5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n= 25) and other IEIs (n= 8) who underwent HCTs with T-cell-replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32μg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32μg/mL (P= .008). Impending or established secondary GF was only observed in patients with day 0 alemtuzumab levels >0.32μg/mL (P= .08). Unexpectedly, patients with impending or established secondary GF had lower CXCL9 levels. The cumulative incidence of impending or established secondary GF in patients with a day 14+ CXCL9 level ≤2394 pg/mL (day 14+ median) was 73.6% vs 0% in patients with a level >2394 pg/mL (P= .002). CXCL9 levels inversely correlated with alemtuzumab levels. These data suggest a model in which higher levels of alemtuzumab at day 0 deplete donor T cells, inhibit the graft-versus-marrow reaction (thereby suppressing CXCL9 levels), and adversely affect sustained engraftment in the nonmyeloablative HCT setting. This trial was registered at www.clinicaltrials.gov as #NCT01998633.

Prognostic impact of resting heart rate on outcomes after allogeneic hematopoietic cell transplantation

Abstract Funding Acknowledgements Type of funding sources: None. Background Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for patients with hematologic malignancies, but is associated with life-threatening toxicities which contribute to prolonged hospitalization and chronic comorbidities. The presence of life-threatening toxicities results in variable length of survival. In this context, identifying appropriate prognostic biomarkers of HCT response is of clinical importance. Pre-treatment elevated resting heart rate (RHR) has been associated with increased risk of toxicities and worse survival in patients with solid tumors, but this has not been studies in patients undergoing HCT. Purpose To examine the association between pre-HCT RHR and outcomes after allogeneic HCT. Methods This was a retrospective cohort study of patients who underwent allogeneic HCT for acute leukemia or myelodysplastic syndrome as adults (≥18 years old). RHR was obtained from pre-HCT screening electrocardiogram or echocardiogram after a 5-minute rest in the supine position. RHR was first divided into quartiles: 50-66 beat per minutes (bpm), 67-75 bpm, 76-85 bpm, 86-163 bpm. There was no significant association between RHR and 2-year mortality among the three lowest quartiles, and they were combined in our analyses (lower RHR [&amp;lt;86 bpm] vs. elevated RHR [≥86 bpm]). Outcomes of interest included length of hospitalization, major adverse cardiovascular events (MACE: myocardial infarction, coronary artery stenosis, congestive heart failure), and cause-specific (relapse, non-relapse) and all-cause mortality, at 2 years. Results There were 792 consecutive patients who underwent HCT between 2007-2014. Median age was 51 years (range 18–74 years); 53.8% were male and 57.1% were non-Hispanic white. Average length of hospitalization was significantly longer in patients with elevated RHR compared to those with lower RHR (35.6 [21.2] vs 32.0 [18.7] days; P = 0.003). However, there was no association between RHR and the development of MACE after HCT. Patients with elevated RHR had significantly worse 2-year overall survival (50.2% vs. 66.1%, p&amp;lt;0.001; Figure 1) compared to those with lower RHR. In the multivariable model (adjusted for age at HCT, sex, diagnosis, stem cell donor source, risk of relapse, HCT conditioning intensity, hypertensive medication, and hemoglobin), elevated RHR was associated with increased risk of all-cause (HR:1.41, 95% CI 1.11–1.79; P=0.005), relapse related (HR: 1.60 95% CI 1.11–2.31; P= 0.012), and non-relapse-related (HR:1.58, 95% CI 1.13–2.21; P = 0.007) mortality. Conclusion This study is the first to demonstrate the association between pre-treatment RHR and clinically important outcomes in patients with acute leukemia or myelodysplastic syndrome undergoing HCT. This information may be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT.

Similar Risk of Relapse and Survival with Post-Transplant Cyclophosphamide Compared to Standard Gvhd Prophylaxis after Allogeneic Hematopoietic Cell Transplantation for AML and MDS

Similar Risk of Relapse and Survival with Post-Transplant Cyclophosphamide Compared to Standard GVHD Prophylaxis after Allogeneic Hematopoietic Cell Transplantation for AML and MDS Background: Post-transplant cyclophosphamide (PTCy) is frequently used after allogeneic hematopoietic cell transplant (HCT) as it results in lower rates of graft versus host disease (GVHD). In addition to its predominant use in haploidentical and HLA mismatched donor HCT, PTCy showed potential to become the standard of care GVHD prophylaxis in a setting of HLA matched related and unrelated donor HCT as well (Bolaños-Meade, Lancet 2019). However, recent registry study reported higher risk of relapse after PTCy-based vs.calcineurin inhibitor (CNI) and methotrexate (MTX) GVHD prophylaxis in patients with acute myeloid leukemia (AML) receiving matched sibling donor HCT (Nagler, Transplant Cell Ther 2022). Thus, additional studies are needed to determine whether the benefit of GVHD prevention with PTCy comes at the cost of compromising the graft versus leukemia effect yielding higher relapse of AML and myelodysplastic syndromes (MDS) after HCT. In this retrospective study, we compared the HCT outcomes of PTCy-based vs. CNI-based GVHD prophylaxis in patients with AML and MDS. Methods: We included patients with AML and MDS who received an allogeneic HCT in first or second complete remission at our institution from 1/1/2014 to 12/31/2019. Patients received either a PTCy-based or a CNI-based GVHD prophylaxis regimen. CNI-based regimen consisted of either CNI/sirolimus +/- other (CNI/Siro group) or CNI/MTX +/- other (CNI/MTX group). The graft source in all the patients was peripheral blood (n=582) or bone marrow (n=23). Results: Total of 605 patients were identified: 442 with AML and 163 with MDS (Table 1.). GVHD prophylaxis with PTCy was used in 137 (23%), CNI/Siro in 402 (66%) and CNI/MTX in 66 (11%) patients. The PTCy group had higher proportion of patients who were Caucasian, received haploidentical donor HCT, reduced intensity (RIC) or non-myeloablative (NMA) conditioning or a bone marrow graft. Otherwise, baseline characteristics were similar between the GVHD prophylaxis groups. With a median follow up of 47 months, 149 (25%) patients relapsed, and 265 (44%) patients died. The probability of relapse at 2 years after HCT was similar between the GVHD prophylaxis groups: 23% in PTCy, 26% in CNI/Siro and 23% in CNI/MTX (p=0.94) (Figure 1). Similarly, there were no significant differences in 2-year overall survival (OS) between the groups: 58% in PTCy, 62% in CNI/Siro and 69% in CNI/MTX (p=0.33). We also observed no differences in non-relapsed mortality (NRM) between the groups. Median time to post-HCT relapse was 175 days in PTCy group, 180 days in CNI/Siro group and 131 days in CNI/MTX group. Management for post-HCT relapse included chemotherapy alone (n=58), chemotherapy +/- targeted therapy (n=53), chemotherapy + donor lymphocyte infusion (n=6), second HCT (n=3) and supportive care (n=29). GVHD prophylaxis groups did not differ by type of treatment used for relapse. Post-relapse OS at 2 years was 6% in PTCy, 20% in CNI/Siro and 31% in CNI/MTX groups (p=0.34). In multivariable analysis, the type of GVHD prophylaxis regimen did not significantly influence the post-HCT relapse, NRM, OS or post-relapse survival. Relapse was affected by DRI (p<0.001) and by type of conditioning regimen (p=0.002). NRM was influenced by HCT-CI (p=0.007) and by type of conditioning regimen (p=0.006). OS was inferior with high/very high risk DRI (p<0.001) and HCT-CI ≥ 3 (p<0.001). Survival after post-HCT relapse was better in patients relapsing >12 months after receiving HCT (p=0.003) and in those receiving treatment other than supportive care (p<0.001). Conclusion: In patients with AML and MDS receiving allogeneic HCT, we found similar risk of relapse and survival with PTCy-based and standard GVHD prophylaxis regimens. Survival after post-HCT relapse was also similar between the GVHD prophylaxis groups. The findings of this study support the use of PTCy-based regimen as GVHD prophylaxis after allogeneic HCT in patients with AML and MDS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Immunoregulatory effects of RGMb in gut inflammation.

Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT). Current strategies to prevent GvHD with immunosuppressive drugs carry significant morbidity and may affect the graft-versus-tumor (GVT) effect. Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Current strategies to prevent colitis with immunosuppressive drugs carry significant morbidity. Recently, Repulsive Guidance Molecule b (RGMb) has been identified as part of a signaling hub with neogenin and BMP receptors in mice and humans. In addition, RGMb binds BMP-2/4 in mice and humans as well as PD-L2 in mice. RGMb is expressed in the gut epithelium and by antigen presenting cells, and we found significantly increased expression in mouse small intestine after total body irradiation HCT conditioning. We hypothesized that RGMb may play a role in GvHD and IBD pathogenesis by contributing to mucosal inflammation. Using major-mismatched HCT mouse models, treatment with an anti-RGMb monoclonal antibody (mAb) that blocks the interaction with BMP-2/4 and neogenin prevented GvHD and improved survival compared to isotype control (75% versus 30% survival at 60 days after transplantation). The GVT effect was retained in tumor models. Using an inflammatory bowel disease dextran sulfate sodium model, treatment with anti-RGMb blocking monoclonal antibody but not isotype control prevented colitis and improved survival compared to control (73% versus 33% at 21 days after treatment) restoring gut homeostasis. Anti-RGMb mAb (9D1) treatment decreased IFN-γ and significantly increased IL-5 and IL-10 in the gut of the treated mice compared to the isotype control treated mice.

Total marrow irradiation (TMI): Addressing an unmet need in hematopoietic cell transplantation - a single institution experience review.

PurposeTMI utilizes IMRT to deliver organ sparing targeted radiotherapy in patients undergoing hematopoietic cell transplantation (HCT). TMI addresses an unmet need, specifically patients with refractory or relapsed (R/R) hematologic malignancies who have poor outcomes with standard HCT regimens and where attempts to improve outcomes by adding or dose escalating TBI are not possible due to increased toxicities. Over 500 patients have received TMI at this center. This review summarizes this experience including planning and delivery, clinical results, and future directions.MethodsPatients were treated on prospective allogeneic HCT trials using helical tomographic or VMAT IMRT delivery. Target structures included the bone/marrow only (TMI), or the addition of lymph nodes, and spleen (total marrow and lymphoid irradiation, TMLI). Total dose ranged from 12 to 20 Gy at 1.5-2.0 Gy fractions twice daily.ResultsTrials demonstrate engraftment in all patients and a low incidence of radiation related toxicities and extramedullary relapses. In R/R acute leukemia TMLI 20 Gy, etoposide, and cyclophosphamide (Cy) results in a 1-year non-relapse mortality (NRM) rate of 6% and 2-year overall survival (OS) of 48%; TMLI 12 Gy added to fludarabine (flu) and melphalan (mel) in older patients (≥ 60 years old) results in a NRM rate of 33% comparable to flu/mel alone, and 5-year OS of 42%; and TMLI 20 Gy/flu/Cy and post-transplant Cy (PTCy) in haplo-identical HCT results in a 2-year NRM rate of 13% and 1-year OS of 83%. In AML in complete remission, TMLI 20 Gy and PTCy results in 2-year NRM, OS, and GVHD free/relapse-free survival (GRFS) rates of 0%, 86·7%, and 59.3%, respectively.ConclusionTMI/TMLI shows significant promise, low NRM rates, the ability to offer myeloablative radiation containing regimens to older patients, the ability to dose escalate, and response and survival rates that compare favorably to published results. Collaboration between radiation oncology and hematology is key to successful implementation. TMI/TMLI represents a paradigm shift from TBI towards novel strategies to integrate a safer and more effective target-specific radiation therapy into HCT conditioning beyond what is possible with TBI and will help expand and redefine the role of radiotherapy in HCT.

Relationship Between Pretransplantation Nutritional Status and Outcome in Adults with Acute Myelogenous Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

Pretransplantation nutritional status may impact outcome after allogeneic hematopoietic cell transplantation (HCT). Various simple screening tools have been developed and used to identify patients at risk of malnutrition; however, how best to use these screening tools is unclear, and their accuracy for the prediction of adverse outcomes is unknown. To investigate how these different measures contribute to outcome prediction, we examined a large cohort of adults with acute myelogenous leukemia (AML) who underwent allogeneic HCT in first or second remission at our institution between April 2006 and May 2021. We assessed the prognostic role of the Nutrition Risk Index (NRI), which combines weight loss and serum albumin, in 970 adults with AML in first or second remission who had usual body weight information available at AML diagnosis or relapse and before HCT. A low NRI at the time of conditioning for HCT was associated with higher nonrelapse mortality (hazard ratio [HR], .97; 95% confidence interval [CI], .95 to .98; P < .001) and relapse risk (HR, .98; 95% CI, .96 to .99; P < .001) and decreased relapse-free survival (HR, .97; 95% CI, .96 to .98; P < .001) and overall survival (HR, .97; 95% CI, .96 to .98; P < .001), as was a low pre-HCT serum albumin level. After multivariable adjustment, NRI, but not weight loss alone, was associated with outcome. The predictive ability of NRI was overall relatively low and comparable to that of serum albumin, with a C-statistic not exceeding .59. Taken together, our data indicate that pre-HCT level of serum albumin, an acute-phase protein recognized to more accurately reflect the severity of the inflammatory response compared with poor nutritional status, but not weight loss, is independently associated with post-HCT outcome in patients with AML. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Comparison of Dose Adjustment Strategies for Obesity in High-dose Cyclophosphamide Among Adult Hematopoietic Cell Transplantation Recipients: Pharmacokinetic Analysis

Cyclophosphamide (CY) is an alkylating agent widely used in the field of oncology and hematopoietic cell transplantation (HCT). It is recommended to use an adjusted body weight with an adjustment factor of 0.25 (ABW25) for dosing of CY in obese patients undergoing HCT. However, evidence based on the pharmacokinetics (PK) of CY to support this recommendation is lacking. We aimed to identify a dosing strategy of CY that achieves equivalent exposures among obese and nonobese patients. The present study is a secondary analysis of a previously conducted observational PK study of phosphoramide mustard (PM), the final cytotoxic metabolite of CY. Data were collected from 85 adults with hematologic malignancy who received a single infusion of CY 50 mg/kg, fludarabine, ± anti-thymocyte globulin, and a single fraction of total body irradiation as HCT conditioning therapy. A previously developed population PK model in these patients was used for simulations. Using individualized PK parameters from that analysis, simulations were performed to assess cumulative exposures of PM (i.e., area-under-the-curve [AUC]) resulting from 8 different dosing strategies according to various measures of body size: (1) “mg/kg” by total body weight (TBW); (2) “mg/kg” by ideal body weight (IBW); (3) “mg/kg” by fat free mass; (4) “mg/m2” by body surface area (BSA); (5) “mg/kg” by TBW combined with ABW25 (TBW-ABW25); (6) “mg/kg” by IBW combined with ABW25 (IBW-ABW25); (7) “mg/kg” by TBW combined with ABW by adjustment factor of 0.50 (TBW-ABW50); and (8) “mg” by fixed-dose. We defined equivalent exposure as the effect of obesity on PM AUC within ±20% from the PM AUC in the nonobese group, where obesity is defined based on TBW/IBW ratio (i.e., nonobese, <1.2; mildly obese, 1.2-1.5; and moderately/severely obese, >1.5). Primary and secondary outcomes were PM AUC0-8hours and PM AUC0-infinity, respectively. In the 85 patients, with the median age of 63 years (range 21-75), 46% were classified as mildly and 25% were moderately/severely obese based on the TBW/IBW ratio. Negative correlations (i.e., higher the extent of obesity, lower the PM AUC) were shown when dosing simulations were based on IBW, TBW-ABW25, and fixed dosing (P < .05). Positive correlations were shown when dosing was simulated by TBW (P < .05). None of the 8 dosing strategies attained equivalent PM AUC0-8hours between patients with versus without obesity, whereas dosing by BSA and TBW-ABW50 attained equivalent PM AUC0-infinity (P < .05). Our study predicted that the recommended ABW25 dose adjustment may result in lower exposure of CY therapy in obese patients than in nonobese. A CY dosing strategy that would result in similar PM concentrations between obese and nonobese was not identified for early exposure (i.e., PM AUC0-8hours). The data suggest though that CY dosing based on “mg/m2” by BSA or “mg/kg” by TBW-ABW50 would result in similar total exposure (i.e., PM AUC0-infinity) and may minimize exposure differences in obese and nonobese patients.

Feasibility of a Novel Sparse Orthogonal Collimator-Based Preclinical Total Marrow Irradiation for Enhanced Dosimetric Conformality.

Total marrow irradiation (TMI) has significantly improved radiation conditioning for hematopoietic cell transplantation in hematologic diseases by reducing conditioning-induced toxicities and improving survival outcomes in relapsed/refractory patients. Recently, preclinical three-dimensional image–guided TMI has been developed to enhance mechanistic understanding of the role of TMI and to support the development of experimental therapeutics. However, a dosimetric comparison between preclinical and clinical TMI reveals that the preclinical TMI treatment lacks the ability to reduce the dose to some of the vital organs that are very close to the skeletal system and thus limits the ability to evaluate radiobiological relevance. To overcome this limit, we introduce a novel Sparse Orthogonal Collimator (SOC)–based TMI and evaluate its ability to enhance dosimetric conformality. The SOC-TMI–based dose modulation technique significantly improves TMI treatment planning by reducing radiation exposures to critical organs that are close to the skeletal system that leads to reducing the gap between clinical and preclinical TMI.

Association Between the Magnitude of Intravenous Busulfan Exposure and Development of Hepatic Veno-Occlusive Disease in Children and Young Adults Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation

Intravenous busulfan is widely used as part of myeloablative conditioning regimens in children and young adults undergoing allogeneic hematopoietic cell transplantation (HCT). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious clinical problem observed with busulfan-based conditioning HCT. The development of VOD/SOS may be associated with busulfan exposure. Getting more insight into the association between busulfan exposure and the development of VOD/SOS enables further optimization of dosing and treatment strategies. The objective of this study was to assess the association between the magnitude of busulfan exposure and the occurrence of VOD/SOS in children and young adults undergoing myeloablative conditioning with a busulfan-containing regimen before allogeneic HCT. In this observational study we included all patients who underwent allogeneic HCT with intravenous busulfan as part of the conditioning regimen at 15 pediatric transplantation centers between 2000 and 2015. The endpoint was the development of VOD/SOS. The magnitude of busulfan exposure was estimated using nonlinear mixed effect modeling and expressed as the maximal concentration (Cmax; day 1 and day 1 to 4 Cmax), cumulative area under the curve (AUC; day 1, highest 1-day AUC in 4 days, and 4-day cumulative AUC), cumulative time above a concentration of 300 µg/L, and clearance on day 1. A total of 88 out of 697 patients (12.6%) developed VOD/SOS. The number of alkylators in the conditioning regimen was a strong effect modifier; therefore we stratified the regression analysis for the number of alkylators. For patients receiving only busulfan as one alkylator (36.3%, n = 253), cumulative busulfan exposure (>78 mg × h/L) was associated with increased VOD/SOS risk (12.6% versus 4.7%; odds ratio [OR] = 2.95, 95% confidence interval [CI] 1.13 to 7.66). For individuals receiving busulfan with one or two additional alkylators (63.7%, n = 444), cumulative busulfan exposure (≤78 and >78 mg × h/L) did not further increase the risk of VOD/SOS (15.4% versus 15.2%; OR = 1.03, 95% CI 0.61 to 1.75). The effect of the magnitude of busulfan exposure on VOD/SOS risk in children and young adults undergoing HCT is dependent on the number of alkylators. In patients receiving busulfan as the only alkylator, higher cumulative busulfan exposure increased the risk of VOD/SOS, whereas in those receiving multiple alkylators, the magnitude of busulfan exposure did not further increase this risk.

Cryopreservation of Allogeneic Hematopoietic Cell Grafts Did Not Adversely Affect Early Post-Transplant Survival during the First Six Months of the COVID-19 Pandemic

▪Introduction: During the COVID-19 pandemic, concerns regarding travel logistics and donor safety necessitated a substantial increase in the use of cryopreserved hematopoietic stem cell (HSC) grafts from both related (RD) and unrelated donors (URD) to ensure patients have a graft available prior to the start of conditioning for hematopoietic cell transplantation (HCT). However, pre-pandemic data beyond single center or small multi-center reports are lacking to reassure clinicians that cryopreservation of allogeneic grafts does not adversely impact post-HCT outcomes including hematopoietic engraftment and overall survival (OS). The Center for International Blood and Marrow Transplant Research (CIBMTR) has recently published three retrospective analyses of outcomes in recipients of cryopreserved compared to fresh grafts administered prior to the pandemic. Results have been conflicting and reasons for receipt of cryopreserved grafts were not routinely collected, rendering interpretation of the impact of cryopreservation on clinical outcomes problematic. Since the pandemic provided a unifying rationale (including mandatory cryopreservation required by the National Marrow Donor Program (NMDP) and other major registries) for the majority of patients to receive cryopreserved allografts, we sought to evaluate early post-HCT clinical outcomes in patients reported to the CIBMTR database who received a first allogeneic HCT using cryopreserved grafts from March through August 2020.Methods: Key study endpoints were hematopoietic engraftment and overall survival (OS). We compared these outcomes to those in patients allografted using fresh products transplanted between March through August 2019. Additional patient selection criteria included: 1) recipients in US only, 2) peripheral blood stem cell (PBSC) or bone marrow (BM) grafts, 3) consented to research, and 4) availability of both CIBMTR product infusion and post-HCT day 100 (D100) follow-up form. The Pearson chi-square test was used for comparing discrete variables; the Kruskal-Wallis test was used for comparing continuous variables. Multivariate analysis (MVA) using a Cox proportional hazards model was performed for OS after adjusting for confounders and testing the proportional hazards assumption. Neutrophil engraftment by D28 and platelet engraftment by D100 were analyzed using multivariate logistic regression.Results: This study included 959 and 2,499 recipients of cryopreserved and fresh products, respectively. Patient characteristics are presented in Table 1. Recipients of cryopreserved grafts were older, more likely to receive URD grafts, PBSC as the graft source and post-transplant cyclophosphamide (PTCy) for graft versus host disease (GVHD) prophylaxis. They received lower infused PBSC and BM cell doses. Due to differences in duration of follow-up between the cohorts, follow up for the OS analysis was censored at Days 100 and 180. MVA results are presented in Table 2. No impact of cryopreservation on OS at either D100 (HR 0.93, p=0.72) or D180 (HR 1.10, p=0.34) post HCT was detected (see also Figure 1). When we performed the MVA for OS limiting the analysis to URD recipients only, the results were unchanged. Median time to neutrophil and platelet engraftment were both delayed by 1 day in recipients of cryopreserved grafts (16 vs. 15 days and 21 vs. 20 days, respectively) but there was no difference in the risk of primary graft failure by D28 (OR 1.38, p=0.96). Some delay in D100 platelet engraftment was observed in recipients of cryopreserved grafts (OR 0.67, p<0.005). There were no interactions identified between donor or graft type for OS or engraftment. Other important clinical outcomes such as secondary graft failure, acute GVHD, and early relapse are being analyzed and will be included at the time of abstract presentation.Conclusion: The shift in clinical practice to cryopreserved products necessitated during the pandemic did not adversely impact early post HCT OS or risk of primary graft failure. We caution that follow up is short and it will be critical to follow this cohort and subsequent recipients of cryopreserved grafts for much longer periods to determine the ultimate impact of cryopreservation on outcomes. Nevertheless, this large multi-center study will be useful to inform clinical decision making both during and following the pandemic. [Display omitted] DisclosuresDevine: Sanofi: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Orca Bio: Consultancy, Research Funding; Be the Match: Current Employment. Stefanski: Novartis: Honoraria. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy.

Assessment of Serology after Sars-Cov-2 Vaccine in Allogeneic HCT Recipients

Introduction: Randomized trials demonstrated ~95% efficacy of SARS-CoV-2 spike messenger RNA (mRNA) vaccines. Patients (pts) after allogeneic hematopoietic cell transplant (HCT) have a variable period of immune deficiency and the impact of diagnosis, treatment regimens, GvHD, and immunosuppression on vaccine (vacc) immunogenicity is unknown.Methods: We performed a retrospective analysis of 149 consecutive pts (Table) who received a SARS-CoV-2 vacc between 12/17/2020, and 5/21/21, and were tested for anti-SARS-CoV-2 S1/S2 antibodies. Serology testing was performed with the Liaison® SARS-CoV-2 S1/S2 IgG assay (DiaSorin) with ≥15 AU/mL defined as a positive result. Pts with prior COVID-19 infection were excluded. Pts received mRNA-1273/Moderna (n= 46), BNT162b2/Pfizer-BioNTech (n= 100) or Jannsen vacc (n= 3). Reactogenicity was not investigated. Demographic and treatment variables were tested for prediction of vaccine response using Chi-square test or Fisher's exact test for categorical variables and two-sample t test for continuous variables. Univariate and multivariable logistic regression analyses with backward selection using Akaike information criterion (AIC) were used to examine interdependence of those variables and odds ratios (OR) with 95% confidence intervals (CI).Results: Pts underwent HCT from a related HLA matched sibling (n=36), related haploidentical (n= 23), or matched/mismatched unrelated donor (n= 89). 93% received fludarabine in the HCT conditioning regimen (data not shown). All pts received a calcineurin inhibitor (CNI) and 76 pts received ATG for GvHD prophylaxis. All pts achieved at least mixed donor lymphoid engraftment (data not shown). Median time from HCT to 1st vaccination was 26 months (range, 3-258 months). Median age at time of vaccination was 61 years (range, 24-78) and 75 (50%) were female. Serology was tested at a median of 37 days (range, 6-119 days) after the second vacc dose. Serology was tested <14 days in 3 pts; all were seropositive. No pt developed COVID-19 during the period of observation.101 pts (67%) tested positive for anti-SARS-CoV-2 S1/S2 antibodies (vacc responders). Of the responders, the median time from HCT to 1st vacc was 45.5 months (range, 3-258, SD 39.78). Among the 23 pts between 3-9 months after HCT, 26% (n=6) had a positive antibody response, but all were receiving ongoing immunosuppression at time of vaccination. 29% (n=29) vacc responders were receiving prednisone (pred) in the management of cGvHD at the time of vaccination. 48 pts did not mount an antibody response (vacc non-responders). Of the non-responders, 30 pts were receiving cGvHD treatment at the time of vacc, 31 pts were taking pred, and 20 pts were taking CNIs.In univariate analysis, we found a history of prolonged use of pred (>8 weeks) and/or CNIs, on current treatment for cGvHD at time of vacc, and receipt of rituximab in the preceding 12 months predicted for lack of response (Table). Active use of pred and treatment with pred >8 weeks in the preceding 12 months prior to vacc predicted vacc non-response [OR 0.221; 95% CI (0.106 - 0.456); p<0.001] and [OR 0.408; 95% CI (0.197 - 0.844); p=0.016] in univariate analysis, respectively, however, active use of pred was predictive [OR 0.07; 95% CI (0.016-0.304; p<0.001] while pred treatment >8 weeks was not [OR 2.00; 95% CI (0.55-7.298; p=0.293] in multivariable analysis. Other significant predictors for non-response in the multivariable analysis include pt use of ruxolitinib [OR, 0.233, 95% CI, (0.067-0.808); p=0.022], and rituximab within 1 year [OR, 0.026, 95% CI, (0.007-0.099); p<0.001].Discussion: In this study, we found that 67% allogeneic HCT pts developed anti-SARS-CoV-2 S1/S2 antibodies after SARS-CoV-2 vaccination. Predictors of non-response after adjustment for potential confounders, were factors that are expected to suppress immune response including active use of immunosuppressive medications. Consistent with prior studies, anti-CD20 therapy likely impairs humoral response to vaccination. Ruxolitinib also appears to impair response. However, a proportion of pts being actively treated for cGvHD responded to vaccination and these pts should still be encouraged to receive vaccination in consideration of the COVID-19 mortality risk. Many questions remain including the protective benefit of immune response, the duration of response, and the potential value of booster vaccinations in non-responders. [Display omitted] DisclosuresRowley: ReAlta Life Sciences: Consultancy.