Days Of Hematopoietic Cell Transplantation Research Articles

Outcomes within 100 days of hematopoietic cell transplantation in pediatric patients: insights from an intensive care unit in Colombia.

Hematopoietic cell transplantation (HCT) has become an essential therapeutic modality for pediatric patients with malignant and non-malignant conditions. Despite its effectiveness, many patients experience post-transplant complications often leading into life-threatening conditions requiring specialized care in a Pediatric Intensive Care Unit (PICU). This study aims to describe clinical characteristics associated with mortality in pediatric HCT patients who needed PICU care within 100 days post-transplant in a resource-limited country. A retrospective cohort study was conducted involving pediatric HCT patients (<18 years old) admitted to our PICU from January 2012 to December 2021. Variables were characterized according to their nature, employing appropriate measures of central tendency and dispersion. The relationship between mortality and patient clinical characteristics was assessed using the Chi-square test or the Mann-Whitney U test, as applicable. A p-value of <0.05 was considered statistically significant. A Kaplan Meier survival curve was performed considering the days from HCT to death during PICU admission and a Cox regression analysis was conducted to analyze the association between PRISM III score and risk of death. Data analysis was executed utilizing the STATA SE v18 statistical software package. Of 316 HCTs, 69 patients required admission to the PICU. Haploidentical transplants from related donors were performed in 72.5% of these patients. The primary cause of PICU admission was infection, accounting for 68.1% (n = 47) of cases. Factors significantly associated with mortality included a PRISM III score > 20 (p < 0.002), mechanical ventilation (p < 0.007), renal replacement therapy (p < 0.002) and vasoactive support (p < 0.001). A total of 27 patients succumbed during their PICU stay. Kaplan Meier curve showed a survival rate of 51.6% at100-days post-transplant. A PRISM III score higher than 20 points was related with mortality (Hazard ratio 5.71 CI 95% 2.09-15.5). This study examines critical factors associated with mortality in pediatric HCT recipients who required admission to our PICU within the first 100 days post-transplant. Our findings indicate that infectious complications, alongside the need for advanced cardiovascular, respiratory, and renal support are strongly correlated with mortality. These results underscore the importance of early risk factor identification and targeted interventions to optimize patient outcomes.

Monoallelic Pathogenic Variants in Hemophagocytic Lymphohistiocytosis Genes Are Uncommon and Not Associated with Hematopoietic Cell Transplantation Outcomes in Severe Aplastic Anemia

Introduction: Severe aplastic anemia (SAA) is primarily an immune-mediated disease, but a subset of patients have a germline genetic predisposition. Germline genetic testing for patients with SAA is recommended to guide patient treatment, including adjustment for hematopoietic cell transplantation (HCT) modalities. Hemophagocytic lymphohistiocytosis (HLH) is a life threatening hyperinflammatory condition often associated with cytopenias. HLH etiology is genetically variable with X-linked or autosomal recessive (XLR or AR) modes of inheritance. The role of monoallelic pathogenic/likely pathogenic (P/LP) variants in recessive HLH-associated genes in SAA etiology or outcomes is unclear. In this study, we determined the frequency of monoallelic HLH-associated gene variants in a large cohort of patients with acquired SAA and evaluated their association with HCT outcomes. Methods: The Transplant Outcomes in Aplastic Anemia (TOAA) project is a collaboration between the NCI and the Center for International Blood and Marrow Transplant Research and consists of genomic and clinical data from 824 patients with SAA who received HCT between 1989-2015. We excluded 140 patients with inherited bone marrow failure syndrome (92 with a clinical diagnosis and 48 genetically identified; McReynolds, Blood, 2022). We used exome sequencing data from the remaining 684 non-inherited SAA patients and used ACMG/AMP criteria to curate variants in 14 HLH-associated genes (AR: PRF1, UNC13D, STX11, STXBP2, ITK, CD27, LYST, RAB27A, AP3B1, BLOC1S6, SLC7A7; and XLR: XIAP, SH2D1A, MAGT1). Variants were deemed deleterious variants of uncertain significance (del-VUS) if there were damaging predictions in &amp;gt;3/5 in-silico meta-predictors (BayesDel, REVEL, CADD, MetaSVM and EIGEN). Follow-up started at the day of HCT and ended at outcome of interest, death, loss to follow-up, or end of study period (August 2017). We used the Kaplan-Meier estimator to calculate the probability of overall survival (OS) after HCT, using a log-rank test for statistical comparisons. For other HCT outcomes, we used cumulative incidence calculator accounting for competing risk of death. Results: There were 57 HLH variants in 49 of the 684 (7.2%) patients: 17 variants present in 19 patients (2.8%) were pathogenic or likely pathogenic (P/LP) and 40 were del-VUS. Eight of 17 P/LP variants were loss of function (3 frameshift, 3 splice site loss, and 2 nonsense). Among the 19 patients with P/LP variants, 16 (84%) had monoallelic variants in genes with AR inheritance, and PRF1 was the most frequently affected (in 8/19 patients). The median age at HCT was comparable in patients with (median=20 years; range=5-62) and without (median=20 years; range=0.2-77) P/LP HLH variants. We did not observe statistically significant differences in other demographics or transplant-related factors in the two groups, except for a higher frequency of male in patients with P/LP variants (79% vs. 55%, in those with and without HLH variants, respectively; p=0.04). All patients with P/LP HLH variants achieved neutrophil engraftment by day 30 compared with 92% of patients without HLH variants. The cumulative incidence of neutrophil engraftment at day 20 was 89%, 95% CI=70-99% for patients with HLH variants and 64%, 95% CI=60-67% in those without variants (p=0.01) (Figure 1A). No statistically significant associations between HLH variants and other key HCT outcomes were noted (p&amp;gt;0.05). The 5-year OS probability in all patients with P/LP variants was 89% (95% CI=72-99) compared to 66% (95% CI=63-70) in those without variants (p=0.06) (Figure 1B). When restricting the analysis to patients receiving reduced intensity/non-myeloablative regimen, the 5-year OS was 92% (95% CI=72-100%) in those with P/LP HLH variants versus 75% (95% CI=70-79%) in those without variants. Conclusions: We found that 7.2% of patients undergoing HCT for acquired SAA carried potentially deleterious variants in HLH genes, with 2.8% carrying a P/LP variant. HCT outcomes in patients with monoallelic P/LP variants was similar to those without P/LP HLH variants. Our data suggest that identification of monoallelic P/LP variants in HLH genes does not influence HCT outcomes, and no special treatment consideration, other than that used for SAA, is warranted.

Toxicities Associated with Tyrosine Kinase Inhibitor Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Background Use of tyrosine kinase inhibitor (TKI) maintenance following allogeneic hematopoietic cell transplantation (HCT) in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia may help to prevent post HCT relapse but is difficult to administer due to toxicity. However, these toxicities and their impact on maintenance is not fully characterized. Herein, we report our experience at a single, large transplant center to describe toxicities encountered with post HCT TKI maintenance in Ph+ ALL. Methods Ph+ ALL patients (pts) who underwent 1st allogeneic HCT at City of Hope between 2003-2021 and received at least one dose of TKI maintenance were included in this retrospective analysis. Baseline characteristics and toxicities were summarized via descriptive analysis, and groups were compared via Fischer test. Survival analyses were calculated from the time of TKI initiation. Results Baseline characteristics are described in Table 1. Of the 186 pts studied, 50 (26.8%) received imatinib and 136 (73.2%) received a newer generation TKI (NG-TKI: 112 dasatinib, 6 nilotinib, 1 bosutinib, 17 ponatinib) at a median time of 78 days (IQR, 41-134) and 91 days (IQR, 58-129), respectively. A total of 96 patients (51.6%) began TKI maintenance within 90 days of HCT. Post HCT TKI was started prophylactically in 149 patients (80.1%) while 37 patients (19.9%) received TKI preemptively for positive MRD. The MRD status at time of HCT differed between the imatinib group and NG-TKI group. In the imatinib group MRD was negative in 33 of 50 patients (66.0%) compared with 78 of 136 patients (57.4%) in the NG-TKI group (P&amp;lt;0.01). There were 12 (24.0%) vs 18 (13.2%) with an unknown MRD-status at HCT in the imatinib vs NG-TKI groups, respectively ( P&amp;lt;0.01). The median follow-up duration for surviving patients in the entire cohort was 5.5 years (range, 1.0-17.5). The median cumulative TKI exposure was 413.5 days (range, 4-2740). The median cumulative imatinib exposure in patients initially receiving imatinib was 328 days (range, 3-2216), while the median cumulative NG-TKI exposure in patients initially receiving NG-TKI was 268.5 days (range, 3-2740), respectively. The median cumulative exposure of dasatinib, nilotinib, bosutinib and ponatinib were 249 days (range, 3-2740), 222 days (range, 114-839), 371 days, and 576 days (range, 72-921), respectively. Twenty-seven (54.0%) vs 75 (55.2%) patients completed &amp;gt;12 months of initial imatinib and NG-TKI maintenance (P=1.0), respectively. Of the treated patients, 78 pts (41.9%) required at least one dose reduction of their initial TKI due to toxicity; 19 of them (10.2%) required ≥2 dose reductions. When imatinib maintenance was used as the initial TKI, a dose reduction due to toxicity was required in 18 patients (36.0%), of whom 7 patients (14.0%) required ≥2 dose reductions. Initial NG-TKI maintenance required a dose reduction due to toxicity in 60 (44.1%), of whom 12 (8.8%) required ≥2 dose reductions. One hundred and thirty-nine patients (74.7%) had their maintenance TKI therapy interrupted, 122 (65.6%) due to toxicity. Sixty-seven patients (36.0%) did not complete their pre-determined maintenance period owing to toxicity; 70 pts (37.6%) discontinued one TKI, and 11 (5.9%) discontinued two TKIs, due to toxicity. The most common reasons for discontinuing the initial TKI are listed in Table 2, including 45.2% of patients due to toxicity, and 12.9% due to progressive disease. Toxicity-related discontinuations occurred within 6 months on that TKI in 63.0% of patients, and 75.3% within the first 12 months. Five-year overall survival and progression-free survival from the start of TKI were similar between the imatinib and NG-TKI group; 83.1% vs 76.9% (P=0.74) and 72.8% vs 70.5% (P=0.63), respectively (Figure 1). Conclusion Toxicities resulting in dose reductions, interruptions, and discontinuation are common in TKI maintenance post HCT. The toxicity profile (mainly GI and blood count related), frequency, and severity of TKIs in the post HCT setting appears to be different than what has been previously reported in the pre-HCT setting, making it a formidable challenge to meet the recommended cumulative TKI maintenance exposure (2 years) per the NCCN guidelines. While the choice of TKI did not appear to impact on long-term outcomes and relapse rates were not excessive in our analysis, further studies are needed to develop tolerable and personalized TKI maintenance strategies.

432 Safety of skin biopsies for rash within 100 days of hematopoietic cell transplantation

432 Safety of skin biopsies for rash within 100 days of hematopoietic cell transplantation

Prognostic Biomarkers for Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Myeloablative Allogeneic Hematopoietic Cell Transplantation: Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT). This study aimed to determine a blood biomarker signature early post-HCT that identifies patients at high risk for VOD/SOS. A set of 23 plasma biomarkers, selected from the VOD/SOS literature, was measured on days 0, 7, and 14 after myeloablative HCT using blood samples from patients enrolled in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 1202. Eligible cases were diagnosed with VOD/SOS in BMT CTN 1202 using the Baltimore criteria. Controls (without VOD/SOS) were matched to cases for conditioning regimen and age. Significant biomarkers were identified using the Bonferroni-adjusted Wilcoxon rank-sum test (P ≤ .002). Thirty-three patients with mild or severe VOD/SOS were identified (cases) and matched to 107 controls. Two, 8, and 5 biomarkers measured from the plasma of these patients were significantly associated with the development of VOD/SOS at days 0, 7, and 14, respectively, with the strongest associations on days 7 and 14. Biomarker associations were stronger for severe VOD/SOS risk and were stronger prognostic markers for VOD/SOS cases occurring within 28 days of HCT. Hyaluronan was most strongly associated with VOD/SOS risk, with an area under the receiver operating characteristic curve (AUC) of .81 on day 7 and .79 on day 14. Multivariate models of up to 5 biomarkers generated AUCs ranging from .82 to .85. All associations with VOD/SOS risk were independent of clinical risk factors. This study confirms previously identified biomarkers of VOD/SOS risk and identified novel prognostic biomarker signatures that identify patients at risk for VOD/SOS shortly after HCT. Multivariate analysis suggests that a combination of up to 5 of these protein biomarkers may provide a prognostic tool for identifying patients at risk for VOD/SOS.

RGI-2001 Infusion for Prevention of Acute Gvhd after Allogeneic Hematopoietic Cell Transplantation

Background Acute graft-versus-host disease (aGvHD) is a major cause of early morbidity after allogeneic hematopoietic cell transplantation (alloHCT). Despite the use of prophylactic immunosuppressive therapy, aGvHD occurs in 40% -60% of matched related and unrelated alloHCT and severe cases contribute to non-relapse mortality. RGI-2001 is a liposomal glycolipid that binds CD1d receptor of antigen-presenting cells (APC) resulting in activation of invariant natural killer (iNKT) cells. This interaction results in a cytokine-dependent Treg proliferation with subsequent modulation of the GvHD pathogenic cascade. RGI-2001 is being evaluated for the potential to reduce or prevent aGvHD after alloHCT. Earlier studies had shown that a single dose of RGI-2001 given on the day of hematopoietic cell transplantation was safe and potentially contributed to aGvHD prevention. Methods: RGI-2001-003 (NCT04014790) is an open-label, multi-center phase 2b study to evaluate the potential efficacy and safety of RGI-2001 when added to calcineurin inhibitor with methotrexate or mycophenolate mofetil (without T-cell depletion) for the prevention of aGvHD in subjects following myeloablative alloHCT. RGI-2001 was administered in a 30-minute infusion at a dose of 100 ug/kg IV infusion weekly x 6 doses, starting on the day of transplant (Days 0, 7, 14, 21, 28, 35). The primary endpoint of the phase 2b study was grade II-IV acute GVHD by Day 100. Results: A total of 53 subjects were screened and 49 treated at 7 U.S. transplant centers. Median age was 52 (range 21-65). The most common underlying indications for alloHCT were AML(n=27, 55%), ALL (n=11, 22%), and MDS (n=7, 14%). Donors were HLA-matched related (n=15), match unrelated (n=28) or mismatched unrelated (n=6, 5 HLA DQ and 1 HLA-A). Graft source was peripheral blood progenitor cells (n=40) or bone marrow (n=9). Common myeloablative conditioning regimens included Fludarabine/ Busulfan (81.6%), Cyclophosphamide/TBI (12.2%), and Cytarabine/Cyclophosphamide/TBI (4%). All subjects received tacrolimus/methotrexate for GvHD prophylaxis. Preliminary results are reported herein with all 49 subjects having completed study day 100. There were no reported serious infusion reactions and one subject received 5 of 6 doses due to a treatment related AE (increased ALT, grade 3). Treatment-emergent AE (TEAE) related to RGI-2001 (> 5%) were diarrhea (12%), nausea (12%), abdominal pain (8%), increased ALT (6%), increased alkaline phosphatase (6%), and rash (6%). Grade 3/4 related TEAE (>1 subject) were decreased neutrophil count (6%), decreased platelet count (4%), anemia (4%), stomatitis (4%) and decreased appetite (4%). Serious adverse events reported were sepsis, upper respiratory tract infection, diarrhea, headache, VOD, pelvic pain and DVT; none were deemed related to RGI-2001. There were no cases of engraftment failure. All 49 patients had at least 100 days of follow-up (FU), and 39 of 49 had complete FU to day 180. The median FU of survivors was 310 days (range, 111-365). Through day 100, there were 10 cases of grades II-IV aGvHD [20.4% (95% confidence interval 10.2-34.3%)], two of which were grades III-IV aGvHD [(4.1% (0.5-14.0%)]. One subject died from aGvHD due to GI bleed. There have been 3 relapses, 3 deaths, and 7 cases of moderate (0 severe cases) chronic GVHD (cGVHD) by last contact. Day-180 estimates of overall survival (OS), grades II-IV aGvHD-free survival (GFS), and relapse were 93.6% (81.6-97.9%), 75.2% (60.5-85.1%), and 4.1% (0.7-12.6%), respectively. Figure 1 summarizes the probability of OS and GFS as a function of time. Conclusions: Intravenous administration of RGI-2001 added to standard-of-care tacrolimus / methotrexate showed promising efficacy in the prevention of clinically significant aGVHD with a favorable safety profile. A phase 3 study is planned. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Acute kidney injury within 100 days post allogeneic hematopoietic cell transplantation is associated with increased risk of post-transplant complications and poor transplant outcomes.

Allogeneic hematopoietic cell transplantation (HCT) offers cure for some patients with hematological diseases but is associated with significant risk of morbidity and mortality. We investigated the incidence of AKI and its impact on transplant outcomes among 408 patients transplanted at Princess Margaret Hospital Cancer Centre, Toronto, Canada. The overall incidence of AKI at 100 days was 64.2%. Compared to those with no AKI, patients who developed AKI had inferior 2-y overall survival (OS), 44.7% vs. 62.4% (P = 0.0004), higher 2-y transplant related mortality (TRM) 36.8% vs. 18.7% (P = 0.0003), lower 2-y graft-vs-host disease (GVHD)- and relapse-free survival (GRFS), 21.0% vs. 39.8% (P = 0.0002), and higher 100-day grade 3-4 acute GVHD (aGVHD), 12.4% vs. 6.3% (P = 0.01). There was no difference in 2-y incidence of relapse between the AKI and non-AKI groups, 24.2% vs. 24.3% (P = 0.84), 100-day grade 2-4 aGVHD, 27.7% vs. 25.7 (P = 0.41) or 2-y moderate-severe chronic GVHD, 24.0% vs. 21.6% (P = 0.79). Patients who develop AKI within 100 days of HCT have inferior OS and GRFS with higher rates of TRM and grade 3-4 aGVHD. These results highlight the importance of close monitoring of renal function, multidisciplinary collaboration, and implementation of protective strategies throughout HCT to optimize transplant and kidney outcomes.

End-of-Life Care in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.

Background: Patients receiving allogeneic hematopoietic cell transplantation (HCT) have high morbidity and mortality risk, but literature is limited on factors associated with end-of-life (EOL) care intensity. Objectives: Describe EOL care in patients after allogeneic HCT and examine association of patient and clinical characteristics with intense EOL care. Design: Retrospective chart review. Setting/Subjects: A total of 113 patients who received allogeneic HCT at Mayo Clinic Arizona between 2013 and 2017 and died before November 2019. Measurements: A composite EOL care intensity measure included five markers: (1) no hospice enrollment, (2) intensive care unit (ICU) stay in the last month, (3) hospitalization >14 days in last month, (4) chemotherapy use in the last two weeks, and (5) cardiopulmonary resuscitation, hemodialysis, or mechanical ventilation in the last week of life. Multivariable logistic regression modeling assessed associations of having ≥1 intensity marker with sociodemographic and disease characteristics, palliative care consultation, and advance directive documentation. Results: Seventy-six percent of patients in our cohort had ≥1 intensity marker, with 43% receiving ICU care in the last month of life. Median hospital stay in the last month of life was 15 days. Sixty-five percent of patients died in hospice; median enrollment was 4 days. Patients with higher education were less likely to have ≥1 intensity marker (odds ratio 0.28, p = 0.02). Patients who died >100 days after HCT were less likely to have ≥1 intensity marker than patients who died ≤100 days of HCT (p = 0.04). Conclusions: Death within 100 days of HCT and lower educational attainment were associated with higher likelihood of intense EOL care.

Influence of Total Body Irradiation Dose Rate on Idiopathic Pneumonia Syndrome in Pediatric Patients With Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

<h3>Purpose/Objective(s)</h3> To evaluate the relationship between total body irradiation (TBI) and other factors in the development of idiopathic pneumonia syndrome (IPS) in pediatric patients undergoing allogeneic hematopoietic cell transplantation (HCT) for acute leukemia. <h3>Materials/Methods</h3> Between 2006-2019, 121 pediatric patients with acute leukemia (84 lymphoblastic, 37 myeloid), ranging in age from 1 to 21 years (median 12), underwent allogeneic HCT at a single institution with matched sibling (n = 33), single unrelated cord blood (sUCB; n = 57), or double unrelated cord blood (dUCB; n = 31) donor. Pretransplantation conditioning included cyclophosphamide (100-120 mg/kg) with (n = 89) or without fludarabine (75 mg/m²) (n = 32). TBI was delivered in 8 b.i.d. fractions of 1.65 Gy over 4 days via opposed lateral beams of 6, 18, or 25 MV prescribed to midplane at umbilicus, with the patient in a semi-recumbent position, and without lung shielding. Aluminum lung compensator was utilized if predicted mid-lung point dose was ≥3% higher than prescription dose (n = 28). Dose rate was specified at 9-20 cGy/min and depended on linear accelerator availability. Patients were stratified by receipt of high-dose-rate (HDR; > 15 cGy/min; 36%) or low-dose-rate (LDR; ≤15 cGy/min; 64%) delivery. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. The association between treatment factors and IPS was examined. <h3>Results</h3> Overall, IPS developed in 22 (18%) patients from day 6 to 83 (median 20) after HCT. On univariate analysis, factors associated with IPS included donor type (matched sibling 12%, sUCB 12%, dUCB 35%, <i>P</i> < 0.01), HDR TBI (35% vs 9% for LDR, <i>P</i> < 0.01), and lower beam energy (35% for 6 MV and 15% for 18/25 MV, <i>P</i> = 0.04). The finding of beam energy significance is likely the result of the 6 MV cohort having a greater dose rate (median 16 cGy/min) than the 18/25 MV cohort (11 cGy/min). On competing risk regression analysis, the pre-specified factors of dose rate, beam energy, lung compensator, age, HCT comorbidity index, and donor type were included in the model. All factors except age (hazard ratio [HR] 1.09, <i>P</i> = 0.20) and lung compensator (HR 1.8, <i>P</i> = 0.17) showed an independent statistically significant association with IPS. Kaplan-Meier estimated 1-year survival was 73% for the entire cohort. Time-dependent effect of IPS did not show an association with overall survival (HR 1.2, <i>P</i> = 0.76). <h3>Conclusion</h3> TBI dose rate is an important variable in the risk of pulmonary toxicity in children treated with allogeneic HCT. TBI dose rates ≤15 cGy/min reduced the risk of posttransplantation IPS and should be strongly considered as an easily implemented parameter in pre-transplantation TBI-based conditioning.

Pro-Tmune, the Next Generation Graft for Allogeneic Hematopoietic Cell Transplantation: Phase 1 Safety and Efficacy Data

ProTmune, an ex vivo modulated mobilized peripheral blood (mPB) graft, has FDA fast track designation for the reduction of incidence and severity of acute graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT). Despite the use of standard protocols to prevent its occurrence, 50 to 60% of patients receiving an unrelated allogeneic HCT experience acute GvHD within 60 days post-HCT.Here we report early Phase 1 safety and efficacy data from PROTECT, the ongoing Phase 1 open-label / Phase 2 blinded and randomized controlled trial (RCT) of ProTmune in adult subjects with hematologic malignancy undergoing HCT following myeloablative conditioning using a matched unrelated donor and receiving standard GvHD prophylaxis of methotrexate and tacrolimus.As of July 31, 2017, five subjects were administered ProTmune in the Phase 1 portion of PROTECT. Underlying hematologic diseases included ALL, AML and MDS. Subjects were predominantly female (80%), with mean age of 54 (range 34 to 66) and mean weight of 75.2 +/- 14.7 kg. All subjects remain on study as of July 31, 2017 with a median follow-up of 53 days (range 33 to 224 days).ProTmune was manufactured on-site the day of HCT (Day 0) by pharmacologically modulating a mPB graft ex vivo with two small molecules (FT1050 and FT4145) to enhance the biologic properties and therapeutic function of the graft. All manufacturing runs have been successful, maintaining high cell viability (87.9 +/- 10.9%) and CD34+ cell recovery (87.7 +/- 13.5%). Successful pharmacologic modulation was confirmed by the marked increase in the percentage of cells positive for the potency marker CXCR4 (5.0 +/- 0.1% pre-manufacture to 67.3 +/- 7.9% post-manufacture). ProTmune, containing on average 6.8 +/- 3.6 x106 CD34+ cells/kg and 2.5 +/- 0.5 x108 CD3+ cells/kg, was administered on Day 0.ProTmune has been well tolerated in these five subjects. ProTmune-related AEs were limited to two cases of Grade 1 vomiting on the day of administration. No ProTmune-related SAEs have been reported. All subjects engrafted with no reports of secondary graft failure. Median time to neutrophil engraftment was Day 15 (range Day 14 to Day 21). There have been no disease relapse or deaths.The primary efficacy endpoint is incidence of acute GvHD through Day 100. In Phase 1, one subject was reported to have an acute GvHD event by Day 100 (limited to skin with complete recovery on methylprednisolone).The Phase 1 portion of PROTECT is projected to enroll 6-10 subjects. By the 2017 ASH meeting, enrollment will be complete with at least six subjects projected to have reached Day 100+, and the safety and efficacy results will be updated. [Display omitted] DisclosuresMaziarz:Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Honoraria; Juno Therapeutics: Honoraria; Kite Therapeutics: Honoraria; Athersys, Inc: Patents & Royalties. Saad:Spectrum: Honoraria; Actinium: Consultancy. Diaz:Fate Therapeutics, Inc: Employment. Medcalf:Fate Therapeutics, Inc: Employment, Equity Ownership. Fremgen:Fate Therapeutics, Inc.: Employment. Storgard:Fate Therapeutics, Inc: Employment.

41. Impact of Gut Microbiome Changes on Hematopoietic Stem Cell Transplantation Outcomes in Children

BackgroundIn adults undergoing allogeneic hematopoietic cell transplantation (HCT), higher gut microbiome diversity is associated with reduced bloodstream infections (BSI) and improved overall survival (OS). Rifaximin prophylaxis in adult HCT helps to maintain microbiome diversity. We examine changes in microbiome in a cohort of pediatric patients undergoing HCT.MethodsPatients were enrolled in an institutional biorepository (n=82) with a subset enrolled in an ongoing trial using rifaximin (n=21) between 2013–2020. All patients had HCT for a hematologic malignancy, using myeloablative conditioning. Patients in the rifaximin trial received rifaximin starting 7 days before HCT (D-7) through D+28, otherwise, no prophylactic antibiotics were used. Systemic antibiotic timing was categorized as none, early (≤ Day 0, day of HCT), and late (> D0). We performed 16s rRNA sequencing from stool for 73 subjects, at baseline (D-7), and weekly through D+28 (engraftment). Microbiome diversity was assessed by Shannon index.ResultsMedian age was 9 years (range 1–20), 59% male, 41% Caucasian and 29% Black. There were no differences in BSI or mortality by age, sex, or race.Microbiome diversity changed significantly over time (p=0.008). Drop in diversity was most notable in patients who had early antibiotics (Mean=1.4, CI -0.15, 2.94, p=0.077). Higher diversity was seen when patients received none or late versus early antibiotics, but this was not statistically significant (Figure 1, p=0.23). Piperacillin-tazobactam was used empirically in 91% of patients. OS at 1 year was 88.5% (CI 68.4%, 96.1%) for patients with high (≥ median) D+28 diversity compared to 60% (CI 38.4%, 76.1%) for patients with low diversity (Figure 2, p=0.018) Only 1 of 21 (4.8%) in the rifaximin group developed a BSI with a gut bacterium compared to 8 of 61 (13.1%) not on rifaximin within the first 30 days (trial enrollment ongoing).Figure 1. Effect of systemic antibiotic timing on microbiome diversity over time. Figure 2. One-year overall survival of patients with high (>2.77) versus low (<2.77) diversity defined by median Shannon-Index.ConclusionWe have shown a significant correlation between engraftment microbiome diversity and 1-year OS. Early antibiotic exposure was detrimental to microbiome diversity. Approaches to preserve microbiome diversity and prevent BSI are likely to improve HCT outcomes. Our ongoing trial using rifaximin will provide preliminary data regarding this approach. Disclosures All Authors: No reported disclosures

Healthcare Resource Utilization in Transplant Patients Who Are at a Higher-Risk to Develop Cytomegalovirus Infection during Their Primary Transplant-Related Hospitalization

Healthcare Resource Utilization in Transplant Patients Who Are at a Higher-Risk to Develop Cytomegalovirus Infection during Their Primary Transplant-Related Hospitalization

Early CD4+ T cell reconstitution as predictor of outcomes after allogeneic hematopoietic cell transplantation

Background: An association between early CD4+ T cell immune reconstitution (CD4+ IR) and survival after T-replete allogeneic hematopoietic cell transplantation (HCT) has been previously reported. Here we report validation of this relationship in a separate cohort that included recipients of ex vivo T-cell-depleted (TCD) HCT. We studied the relationship between CD4+ IR and clinical outcomes.Methods: A retrospective analysis of children/young adults receiving their first allogeneic HCT for any indication between January 2008 and December 2017 was performed. We related early CD4+ IR (defined as achieving >50 CD4+ T cells/µL on two consecutive measures within 100 days of HCT) to overall survival (OS), relapse, non-relapse mortality (NRM), event-free survival (EFS) and acute graft-versus-host disease (aGVHD). Fine and Gray competing risk models and Cox proportional hazard models were used.Results: In this analysis, 315 patients with a median age of 10.4 years (interquartile range 5.0–16.5 years) were included. The cumulative incidence of CD4+ IR at 100 days was 66.7% in the entire cohort, 54.7% in TCD (N = 208, hazard ratio [HR] 0.47, P < 0.001), 90.0% in uCB (N = 40) and 89.6% in T-replete (N = 47) HCT recipients. In multi-variate analyses, not achieving early CD4+ IR was a predictor of inferior OS (HR 2.35, 95% confidence interval [CI] 1.46–3.79, P < 0.001) and EFS (HR 1.80, 95% CI 1.20–2.69, P = 0.004) and increased NRM (HR 6.58, 95% CI 2.82–15.38, P < 0.001). No impact of CD4+ IR on relapse or aGVHD was found. Within the TCD group, similar associations were observed.Conclusion: In this HCT cohort, including recipients of TCD HCT, we confirmed that early CD4+ IR was an excellent predictor of outcomes. Finding strategies to predict or improve CD4+ IR may influence outcomes.

Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation.

Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence of lower respiratory tract infection, and hypoxemia. We described IPS incidence and mortality within 120 and 365 days after HCT. We examined conditioning intensity (nonmyeloablative versus myeloablative with high-dose total body irradiation [TBI] versus myeloablative with low-dose TBI) as an IPS risk factor in a time-to-event analysis using Cox models, controlled for age at transplant, HLA matching, stem cell source, and pretransplant Lung function Score (a combined measure of impairment in Forced Expiratory Volume in the first second (FEV1) and Diffusion capacity for carbon monoxide (DLCO)). Among 1829 HCT recipients, 67 fulfilled IPS criteria within 120 days (3.7%). Individuals who developed IPS were more likely to be black/non-Hispanic versus other racial groups and have severe pulmonary impairment but were otherwise similar to participants without IPS. In adjusted models, myeloablative conditioning with high-dose TBI was associated with increased risk of IPS (hazard ratio, 2.5; 95% confidence interval, 1.2 to 5.2). Thirty-one patients (46.3%) with IPS died within the first 120 days of HCT and 47 patients (70.1%) died within 365 days of HCT. In contrast, among the 1762 patients who did not acquire IPS in the first 120 days, 204 (11.6%) died within 120 days of HCT and 510 (29.9%) died within 365 days of HCT. Our findings suggest that although the incidence of IPS may be declining, it remains associated with post-transplant mortality. Future study should focus on early detection and identifying pathologic mediators of IPS to facilitate timely, targeted therapies for those most susceptible to lung injury post-HCT.

P688Cardiac dysfunction as a predictor of hepatic sinusoidal obstruction syndrome after hematopoietic cell transplantation

Abstract Background Hepatic sinusoidal obstruction syndrome (HSOS) is a well-known fatal complication of hematopoietic cell transplantation (HCT), but the impact of cardiac abnormalities on the occurrence of HSOS has been poorly evaluated. Therefore, the authors investigated whether the structural changes or dysfunction of the heart before HCT is associated with the future occurrence of HSOS. Methods A total of 92 patients who underwent HCT were divided into 2 groups; HSOS group (n=11, 6 males, 53.8±15.9 years) vs no HSOS group (n=81, 51 males, 48.6±14.7 years). According to the modified Seattle criteria, HSOS was defined as otherwise unexplained occurrence of 2 or more of the following events within 20 days of HCT; serum total bilirubin &gt;2 mg/dL, hepatomegaly or right upper quadrant pain, sudden weight gain due to fluid accumulation (&gt;2% of baseline body weight). Echocardiography examinations were performed 1 month before HCT, and echocardiographic findings were compared between the groups. Results HSOS was developed in 11 patients (12.0%). HSOS group had significantly larger left ventricular end-diastolic volume index (LVEDVI) (65.2±4.9 vs 53.2±6.9 ml/m2, p&lt;0.001) and relatively worse systolic function than no HSOS group (LV ejection fraction: 56.4±3.4 vs 65.1±5.9%, p&lt;0.001, LV global longitudinal strain: −17.9±1.4 vs −20.1±2.0%, p=0.001). LV diastolic functional parameters were also significantly worse in HSOS group than in no HSOS group (E/E' ratio: 11.3±1.8 vs 9.1±2.0, p=0.002, left atrial global longitudinal strain: 27.7±3.3 vs 34.9±5.9%, p&lt;0.001). However, left atrial volume index was not different between the groups (30.8±2.8 vs 29.0±3.3 ml/m2, p=0.078). By receiver operation characteristic curve analysis, among significantly different variables, LVEDVI was the most powerful predictor for HSOS, and the optimal cutoff value was 59.25 mL/m2. (81.8% sensitivity and 77.8% specificity, AUC 0.909). Predictor of HSOS: ROC analysis Conclusions The present study demonstrated that structural changes or dysfunction of the heart are more prevalent in patients with HSOS after HCT and larger LVEDVI, among them, can be a useful predictor of upcoming HSOS. Routine echocardiographic study before HCT would be useful to identify high risk group for HSOS, and the development of HSOS should be carefully monitored in HCT patients with cardiac structural changes or dysfunction on echocardiography.

Feasibility and Clinical Utility of Electronic Geriatric Assessment (eGA) in Older Patients Undergoing Hematopoietic Cell Transplantation

BackgroundThe prevalence of age-related impairments in older patients (pts) undergoing hematopoietic cell transplantation (HCT), and its relationship with transplant outcomes is largely unknown.MethodsIn a pilot quality improvement project, assessment of functional, social, emotional, cognition, sensory, nutritional and polypharmacy domains was performed using an electronic rapid fitness assessment (eRFA) developed at MSKCC (Shahrokni JNCCN 2017). Older adults (age ≥ 60 years) undergoing HCT for hematologic malignancies from 2015 through 2018 in 2 transplant clinics were included. The prevalence of geriatric impairments, transplant-associated toxicities and survival were analyzed under an IRB approved waiver of authorization.ResultsPatient characteristics are shown in Table 1. The median day from eRFA to HCT was 45 days (range 14-162). Median time to complete eRFA was 10 minutes. Table 2 has a summary of geriatric impairments. Majority of pts (n=33) had at least 1 impairment. The most prevalent were social, emotional, polypharmacy and functional. Median number of geriatric impairments per patient was 4 (range 0-9). Median toxicities per patients was 4 (range 0-12). The most common toxicities were: 25 metabolic, 22 infections, 21 oral/gastrointestinal, and 16 cardiopulmonary. The only pt admitted to the ICU was an allo-HCT pt with 5 impairments. Amongst the 8 pts (4 AHCT, 4 allo-HCT) readmitted to the hospital within the first 100 days of HCT, the median number of impairments was 4 (range 0-9). Seven patients died, 5 from disease, and 2 from GvHD. With a median follow up of 9 months (range 1-38) among survivors, the 18-months progression-free and overall survival were 0.71 (0.55-0.91) and 0.7 (0.51-0.95) respectively (Figure 1).ConclusionsPerforming pre-HCT eRFA among older transplant patients is feasible. With the median completion time of 10 minutes, the eRFA can identify geriatric impairments of this vulnerable population. Future larger studies should assess whether these impairments have association with the outcomes, and whether interventions to improve geriatric impairments also improve transplant outcomes. The prevalence of age-related impairments in older patients (pts) undergoing hematopoietic cell transplantation (HCT), and its relationship with transplant outcomes is largely unknown. In a pilot quality improvement project, assessment of functional, social, emotional, cognition, sensory, nutritional and polypharmacy domains was performed using an electronic rapid fitness assessment (eRFA) developed at MSKCC (Shahrokni JNCCN 2017). Older adults (age ≥ 60 years) undergoing HCT for hematologic malignancies from 2015 through 2018 in 2 transplant clinics were included. The prevalence of geriatric impairments, transplant-associated toxicities and survival were analyzed under an IRB approved waiver of authorization. Patient characteristics are shown in Table 1. The median day from eRFA to HCT was 45 days (range 14-162). Median time to complete eRFA was 10 minutes. Table 2 has a summary of geriatric impairments. Majority of pts (n=33) had at least 1 impairment. The most prevalent were social, emotional, polypharmacy and functional. Median number of geriatric impairments per patient was 4 (range 0-9). Median toxicities per patients was 4 (range 0-12). The most common toxicities were: 25 metabolic, 22 infections, 21 oral/gastrointestinal, and 16 cardiopulmonary. The only pt admitted to the ICU was an allo-HCT pt with 5 impairments. Amongst the 8 pts (4 AHCT, 4 allo-HCT) readmitted to the hospital within the first 100 days of HCT, the median number of impairments was 4 (range 0-9). Seven patients died, 5 from disease, and 2 from GvHD. With a median follow up of 9 months (range 1-38) among survivors, the 18-months progression-free and overall survival were 0.71 (0.55-0.91) and 0.7 (0.51-0.95) respectively (Figure 1). Performing pre-HCT eRFA among older transplant patients is feasible. With the median completion time of 10 minutes, the eRFA can identify geriatric impairments of this vulnerable population. Future larger studies should assess whether these impairments have association with the outcomes, and whether interventions to improve geriatric impairments also improve transplant outcomes.

Real World Experience of Letermovir (LTV) Prophylaxis (Px) for the Prevention of Cytomegalovirus Infection (CMVi) in the Adult CMV Seropositive Recipients (R+) of Allogeneic Hematopoietic Cell Transplantation (HCT) Patients (pts).

CMVi leads to significant morbidity in R+ HCT and preemptive therapy (PET) has been the standard of care. LTV was FDA-approved in Nov. 2017 for CMVi prevention in R+ HCT. Besides the clinical trials, there is are real world data on LTV. Upon IRB approval, we retrospectively studied consecutive R+ HCT pts with their first HCT between 1/1/2017 and 6/30/2018. LTV group included pts with HCT between 2/20/18 and 6/30/2018, who had LTV Px started within 28 days of HCT (n=59), and R+ HCT between 1/1/2017 and 2/19/2018 (n=307) served as control (ctrl). We compared CMVi rates in first 100 days of HCT, and time to engraftment between the 2 groups. Risk stratification: high risk - haplo/cord HCT & ATG use, low risk - all others. CMVi was defined as viral load (VL) of 625 IU/ml to 1250 IU/ml or higher (CMV assay conversion factor of 1 genomic copy/ml = 2.5 IU/ml). CMV VL less than 625 IU/ml is reported negative, VL between 625 and 1250 IU/ml is qualitative positive but numeric value is provided only for VL ≥ 1250 IU/ml. PET was recommended for VL >1250 IU/ml (500 copies/ml) in high risk and > 3750 IU/ml (1500 copies/ml) in low risk HCT (including those on LTV requiring PET). Descriptive statistics was done for baseline characteristics. Cumulative incidence curves were generated for CMVi within 100 days post-HCT and Gray's test was used to compare the difference between the 2 groups. In both groups, median age was 54 years and HCT indications were similar. Donor type in LTV/ Ctrl groups: MRD (27 vs 36%), MUD (44 vs 47%), haplo (27 vs 15%), cord (1.7 vs 1.6%). PBMC was graft source in 90% of both groups. Myeloablative conditioning: 40.7% in LTV and 35% in Ctrl. GVHD Px: Cellcept (32 vs 25%), methotrexate (7 vs 9%), tacro/siro (58 vs 65), and others (3.4 vs 0.3%) in LTV & Ctrl respectively. A majority (n=36) received both intravenous & oral LTV formulation while 23 received oral only. Median time from HCT to LTV start was 13 days (range: 4-26). LTV group had significant reduction in CMVi rate (22.4% [95%CI: 12.7-34.0]) compared with ctrl group (41.1% [95%CI: 35.4-46.7], p=0.008, Fig 1). In a subgroup of high-risk HCT LTV was significantly reduced CMVi rate (22.2%) compared with ctrl (62.8%, p=0.004, Fig 2) while statistical difference was not reached in low-risk HCT pts (22.8% vs. 35.6%, p=0.11). In the LTV Px, clinically significant (CS)-CMVi requiring PET occurred in 8.4% (n=5) and on excluding 2 pts who were not on LTV at the time of CMVi, the rate was 5% (Fig 1). CMVi cleared without PET in 8/13 LTV pts and LTV was continued; all pts had VL LTV use in a real world setting is associated with significant reduction of CMVi and CS-CMVi without any discernible myelosuppression. The low level CMVi resolved spontaneously in majority with continued LTV Px and PET was not necessary. The high-risk HCT had most benefit with LTV Px.

Protmune, a Next-Generation Graft for GvHD Prophylaxis in Allogeneic Hematopoietic Cell Transplantation: 1-Year Safety and Efficacy Phase 1 Data

▪ProTmune is an ex vivo pharmacologically-modulated, next-generation mobilized peripheral blood (mPB) cell graft with FDA fast track designation for the reduction of incidence and severity of acute graft versus host disease (GvHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT).Here we report the 1-year safety and efficacy data from the Phase 1 stage of PROTECT, an ongoing Phase 1 open-label / Phase 2 blinded, randomized and controlled trial of ProTmune in adult subjects with hematologic malignancy undergoing matched unrelated donor HCT following myeloablative conditioning and receiving standard GvHD prophylaxis of methotrexate and tacrolimus.Seven subjects were administered ProTmune in the Phase 1 stage of PROTECT. Underlying hematologic diseases included ALL (n=3), AML (n=3) and MDS (n=1). Subjects were predominantly female (n=5) with a median age of 56 (range 34 to 69) and a median weight of 79 kg (range 53 to 133). As of July 23, 2018, five subjects remain on study with a median follow up of 390 days (range 342 to 490 days).ProTmune was manufactured on-site on the day of HCT by pharmacologically-modulating a conventional mobilized peripheral blood (mPB) cell graft ex vivo with 16,16-dimethyl prostaglandin E2 and dexamethasone, to enhance the biologic properties and therapeutic function of the graft. All ProTmune units were manufactured successfully with a mean of 6.6 (range 3.0 to 11.0) x106 CD34+ cells/kg and 2.3 (range 1.2 to 3.1) x108 CD3+ cells/kg.ProTmune was well tolerated. ProTmune-related AEs were all mild to moderate and consisted of nausea, vomiting and non-cardiac chest pain on the day of administration. No ProTmune-related SAEs have been reported. All subjects engrafted with no primary or secondary graft failure. Average time to neutrophil engraftment was 17 days (range 14 to 22).Day 100 acute GvHD assessment revealed three of the seven subjects had steroid responsive acute CIBMTR Grade 2-4 GvHD with median time of seven days [range 5 to 8 days] to resolution of the maximum GvHD grade.Since therapeutic approaches intended to reduce acute GvHD may increase disease relapse risk, composite endpoints are being explored by the HCT community to more thoroughly define transplant success. 1-year current GvHD-free, relapse-free survival (CGRFS) is one endpoint under study measuring proportion of subjects that are alive without relapse and without active moderate or severe chronic GvHD per NIH consensus criteria at Day 365.We intend to present final 1-year CGRFS on the seven Phase 1 subjects at the ASH Annual Meeting. To date, non-relapse mortality, deemed not attributable to ProTmune, occurred in two subjects (Subject 1 on Day 228 from pulmonary edema; Subject 3 on Day 151 from cardiac arrhythmia). There has been no disease relapse, and no moderate / severe chronic GvHD at Day 365. Two subjects are pending the 1-year assessment.The Phase 2 stage of PROTECT is currently enrolling a planned 60 subjects at 15 U.S. centers. Subjects with hematologic malignancies undergoing matched unrelated donor HCT following myeloablative conditioning are randomized 1:1 to receive in a blinded manner, either ProTmune or a conventional matched unrelated donor mPB unit as the cell graft. [Display omitted] DisclosuresMaziarz:Athersys, Inc.: Patents & Royalties; Incyte: Consultancy, Honoraria; Kite Therapeutics: Honoraria; Juno Therapeutics: Consultancy, Honoraria; Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Saad:Actinium: Consultancy. Diaz:Fate Therapeutics, Inc.: Employment. Medcalf:Fate Therapeutics, Inc.: Employment. Storgard:Fate Therapeutics, Inc.: Employment, Equity Ownership. Deol:Kite Pharmaceuticals: Consultancy; Novartis: Consultancy.

A Case Report of Refractory Immune Thrombocytopenia (ITP) Following Reduced Intensity Conditioning (RIC) Hematopoietic Cell Transplantation (HCT) for Myelodysplastic Syndrome (MDS) Successfully Treated with Off-Label Use of Daratumumab

Background:A source of treatment refractoriness in immune cytopenias appears to be residual CD138/38 positive lymphocyte populations (Audia S et al, Blood 118:4394-400,2011; Mahevas M et al, J Clin Invest 123:432-442, 2013). Persistence of recipient's plasma cells can lead to prolonged refractory thrombocytopenia following RIC-HCT. (Fasano RM et al, Br J Haematol 166(3):425-34, 2014). Daratumumab was effective in the treatment of a child with refractory autoimmune hemolytic anemia after HCT (Tolbert et al, Blood 128:4819, 2016).Case Report:The patient is a 60-year-old man with intermediate-high risk MDS who underwent RIC-HCT with total lymphoid irradiation and antithymocyte globulin with peripheral blood graft from a fully matched unrelated male donor. The patient had mild thrombocytopenia prior to HCT consistent with MDS and had not received platelet transfusions. He had not received any prior therapy for MDS. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. Cytomegalovirus (CMV) serologic testing for exposure was negative for the recipient and positive for the donor. Both the patient and the donor had evidence for prior exposure to Epstein-Barr virus (EBV). He achieved engraftment on day +12. His peripheral blood chimerism on day + 30 showed full donor origin (WB 98%,CD3 96%,CD15 95%, CD19 98%, CD56 95%) and has been maintained to date. Acute skin GVHD responded to corticosteroids. While on corticosteroid therapy, he developed an abrupt decline in platelet count from 156,000/mcl on day +152 to 9, 000/mcl on Day + 166 without evidence for recurrent or active GVHD. While this was initially attributed to simultaneous EBV and CMV reactivations, severe thrombocytopenia persisted after viral clearance. An extensive work up for other etiologies of thrombocytopenia was negative. Repeated bone marrow biopsies were normal, including adequate megakaryocytosis and no MDS recurrence. Platelet associated antibody testing and platelet antigen genotyping were not conclusive for autoimmune versus alloimmune etiology. Testing for platelet HLA antibodies showed calculated Panel Reactive Antibody of 31% and unsatisfactory corrected count increment after transfusion of HLA compatible platelets units. The patient experienced prolonged severe thrombocytopenia for over 26 weeks with platelet count less than 5000/mcl for 22 weeks and only above 10,000 /mcl on 6 occasions. Potentially responsible medications were discontinued serially, but testing for drug inducted ITP was not conducted. Therapy included high dose corticosteroids, high dose immune globulin, rituximab, plasma exchange, splenectomy, romiplostim 10 mcg/kg/week, eltrombopag 100 mg to 150 mg daily for over 24 weeks, and low dose danazol. Fostamatinib was not available. Prednisone dose was tapered over many weeks to 5 mg daily. The patient experienced recurrent life-threatening and vision-threatening bleeding. Cumulative transfusions following Day + 166 were 133 single donor platelet units and 42 red cell units. All products were from CMV negative donors. Eltrombopag and danazol were deemed ineffective and tapered to discontinuation. CD38 positive cells were present in spleen and marrow by immunohistochemistry. Daratumumab 1300 mg was infused weekly x 4. Four weeks after the last dose of daratumumab, his platelet count increased to 91,000/mcl. Platelet count normalized to 150,000/mcl in week 5 or HCT Day + 383. Hypogammaglobulinemia has been the only detectable toxicity. Testing to determine autoimmune versus alloimmune origin is ongoing.Conclusion: Clinical trials of daratumumab for the treatment of severe refractory ITP are indicated. DisclosuresNo relevant conflicts of interest to declare.

Non‐transferrin‐bound iron and oxidative stress during allogeneic hemopoietic stem cell transplantation in patients with or without iron overload

Non‐transferrin‐bound iron and oxidative stress during allogeneic hemopoietic stem cell transplantation in patients with or without iron overload