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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 < 2500 IU/ml with 50% having VL <1250 IU/ml. There was no difference in time to WBC and platelet engraftment in 2 groups (Fig 3). 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. [ABSTRACT FROM AUTHOR]

Highlights • Ruxolitinib use was associated with a reduction in prednisone dose. • The rate of infectious/bacterial infections was high and contributed to the overall mortality. • Ruxolitinib as salvage therapy is promising for chronic graft-versus-host disease refractory to steroids. Abstract Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval,.388 to.673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost. [ABSTRACT FROM AUTHOR]

Background Allogeneic hematopoietic cell transplant (allo-HCT) recipients often require substantial but variable transfusion support. Few studies have quantified their transfusion burden, or identified prognostic factors for increased transfusions to guide patient counseling or inventory management. Data on haploidentical HCT (Haplo-HCT) patients are especially scarce. Objectives To identify factors associated with increased RBC and platelet (PLT) transfusions, and provide for the first time data on a large cohort of Haplo-HCT patients. Methods We retrospectively evaluated 1803 consecutive first time adult allo-HCT patients transplanted at our center in 2011-17. Multivariate linear regression and Fine-Gray subdistribution hazards models were used to examine the associations between baseline characteristics (age, sex, disease stage, graft type, donor type, ABO compatibility and conditioning regimen) and log-transformed transfusion units in the first 30 days after HCT and time to reach transfusion independence respectively. Results The median age of the cohort was 53(18-78); 56.2% were male. Most common diagnoses were AML (38.8%), ALL (19.6%), and lymphoma (14.8%); 50.2% had advanced disease. Patients received nonmyeloablative/reduced intensity (58.9%) or myeloablative conditioning regimens (MAC, 41.1%), followed by peripheral blood stem cell (88.4%), bone marrow (6.9%) or umbilical (UC, 4.7%) HCT. Most grafts were from matched related (MRD, 38.7%) or unrelated (MUD, 49.1%) donors, and 7.6% were haploidentical. ABO incompatibility (Major 15.8%, minor 18.6%, bi-directional 8.5%) was present in 42.9% of the cases (Table 1). Most of the 1764 patients who survived 30+ days received RBC (88.2%) or PLT (97.2%) transfusions during the first 30 days, with a median of 3 (0-37) RBC and 5(0-144) apheresis PLT units. RBC and PLT transfusion independence was reached in 28 (95%CI: 26-31) and 12 (95%CI: 12-13) days respectively. Multivariate analyses showed that Haplo-HCT and UC graft were independently associated with more RBC and PLT transfusions, as were advanced disease, ABO incompatibility, older age, and MAC (P<0.001 for all variables). Prolonged PLT or RBC transfusion dependence was independently associated with Haplo-HCT, UC graft and advanced disease (P<0.001 for all three), older age (P=0.003) and ABO incompatibility (P<0.001 for RBC, P=0.008 for PLT), but not sex or conditioning regimen. Haplo-HCT patients needed fewer transfusions than UC, but more than MRD/MUD recipients; they also became transfusion-independent faster than UC, but slower than MRD/MUD recipients regardless of graft type (Table 2 & 3). Conclusions We identified patient and transplant factors strongly associated with increased transfusions in the first 30 days after allo-HCT, and quantified the transfusion burden of Haplo-HCT relative to other types of HCT. [ABSTRACT FROM AUTHOR]

Identification of anti-apoptotic properties of the Bcl2 protein has offered novel treatment options in many malignancies including AML. Venetoclax, a Bcl2 inhibitor, has shown promising results as upfront therapy in elderly patients (pts) and relapse/refractory (R/R) AML, when combined with hypomethylating agents (HMA). Yet, due to the high relapse risk, allogenic HCT remains as the only curative option for these high risk populations. To date, outcomes of HCT after prior therapy with Venetoclax + HMA have not been described. Also, as Venetoclax induces aplasia of antigen presenting cells expressing Bcl2, we hypothesized that pre-HCT treatment with venetoclax may be associated with a lower risk for GvHD. We retrospectively analyzed 26 consecutive AML pts who underwent HCT at our institution from 2016 to 2018 with final line of systemic therapy of venetoclax + HMA. Pts were not eligible for upfront standard induction chemotherapy (n=8) or had R/R disease (n=18). Fifteen pts received ≥2 lines of therapy and 3 had previous HCT. CR/CRi was achieved in 62% (n=16), of which 3 pts had minimal residual disease and the rest (n=10) had persistent disease prior to HCT. Donors were matched related (n=8), matched unrelated (n=16), or haploidentical (n=2). Conditioning regimen was myeloablative (38.5%) or reduced intensity (61.5%). Most pts (n=24, 92.3%) received PBMCs as the graft source. Tacrolimus/Sirolimus (Tac/Sir) was administered in most pts (n=20, 77%) for GvHD prophylaxis. Descriptive statistics were used for baseline characteristics. Kaplan-Meier and cumulative incidence curves were constructed for overall survival (OS), progression-free survival (PFS), relapse, none-relapse mortality (NRM), and aGvHD. Median age at the time of HCT was 59 years (range: 18-73). Median time to neutrophil and platelet engraftment were 17 days (range: 14-20) and 20 days (range: 16-61), respectively. With a median follow up of 4.5 months (range: 1.4-18.6), 6 months relapse rate was 12% (95% CI: 0.16-0.54) and 100 day NRM was 4% (95% CI: 0.02-0.34). Grade II-IV aGvHD at 100 days was noted in 34% (95% CI: 0.15-0.51). One-year OS and PFS for all pts were 72% (95% CI: 0.43-0.88) and 40% (95% CI: 0.16-0.63), respectively. For patients in CR at the time of HCT, 1-year OS was 80% (95%CI: 37-95) and PFS was 38% (95%CI: 0.08-0.69) (Fig 1). Only one patient who had been treated with three lines of systemic therapy prior to HCT experienced veno-occlusive disease. Thus, administration of Venetoclax-based salvage regimen as a bridge to HCT is safe with no added immediate toxicities post-HCT. Our early outcome data are promising for this otherwise high-risk population. Our data also justify further studies on the role and impact of Venetoclax and its anti-Bcl2 properties as a component of the conditioning regimen or as post-HCT maintenance. [ABSTRACT FROM AUTHOR]

Chronic GVHD remains as the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Systemic corticosteroids are the first line of therapy, but outcomes are poor in steroid refractory (SR) patients. Previous reports show that in SR patients, IL-2 therapy results in partial response (PR) associated with increase in regulatory T cells (Tregs). ECP has been used for cGVHD with skin response rates of 40-100%. Based on non-overlapping toxicities and, we prospectively studied a combination of low dose IL-2 + ECP to treat SR-cGVHD. Patients with SR-cGVHD, were treated with low dose IL-2 (1 × 106 U/m2, daily) + ECP for 12 weeks. IL-2 was provided by Prometheus Laboratories. ECP was administered 2 times/week for 4 weeks followed by 2 treatments every 2 weeks for the next 8 weeks. The NIH consensus criteria was used to assess cGVHD severity. PBMC and plasma samples were banked at baseline and on 3-week intervals to assess regulatory T cell (Tregs) and reactive oxygen species (ROS). Of the 12 consented patients, 9 completed the study (2 were not treated due to rapid disease progression before enrollment and 1 died from sepsis at week 11). All enrolled patients (n=10) had scleroderma as the predominant cGVHD manifestation. Median age was 45.6 years (range: 23-66). Median prior lines of therapy were 4.2(range 3-6), 5 patients had prior exposure to ruxolitinib and 4 were on ECP at the enrollment. Donors were fully matched unrelated (n=8), matched sibling (n=1) or mismatched unrelated (n=1). Conditioning regimen was myeloablative (n=5) or reduced intensity (n=4). GVHD prophylaxis was tacrolimus/Sirolimus (tac/sir) (n=6), tac/methotrexate (MTX) (n=2), or Tac/sir/MTX (n=1). Of the 10 enrolled patients, 9 responded to IL-2 + ECP combination (all classified as PR). A 37% dose reduction in steroid dose was noted among 7 patients. The remaining 3 patients were on stable steroid dose at end of study. Only 1 patient had progressive cGVHD in form of scleroderma. ECP+IL-2 therapy was well tolerated with no drug related serious adverse events (SAE). Grade 3-4 AEs included grade 3 metabolic and nutrition (n=8), grade 3 anemia (n=3), and grade 4 atrial flutter (n=1). Infectious complications were noted in 3 patients (one grade 4 [sepsis]). There was a robust increase in Tregs from the baseline mean of 0.755% (range 0.08-1.88) to end of treatment 6.999% (range 0.78-17.13) [p=0.02] Fig 1. Increment in Tregs was seen in patients who were on ECP therapy prior to enrollment (n=4) and in one patient who progressed while on therapy. No correlation was found between the treatment response and ROS levels. In conclusion, the combination of ECP +IL-2 is well tolerated in patients with SR-cGVHD with no apparent increase in infectious complications or other toxicities. Clinical response correlates with a robust increase in Tregs, but no correlation was found with ROS levels. [ABSTRACT FROM AUTHOR]

Background AlloHCT is the only curative therapy for primary and secondary myelofibrosis (MF). Pulmonary arterial hypertension (PAH) can be seen in 30% of patients with MF. PAH can eventually lead to right heart failure and may be associated with complications after alloHCT. The primary objective was to determine the association of PAH with alloHCT outcome in patients with MF. Secondary objectives included the effect of HCT on the underlying PAH as well as incidence of specific transplant-related complications in these patients. Methods All patients with MF who underwent alloHCT from 2008 to early 2018 at the City of Hope Medical Center with evaluable pre-HCT echocardiography were considered for this retrospective analysis. Pre and postHCT echocardiograms were reviewed to evaluate the pulmonary arterial systolic pressure (PASP). Descriptive statistics were used for baseline patient and transplant related characteristics stratified by PAH. Paired t-test was used to detect the change in the pulmonary vascular pressure after HCT. Kaplan-Meier and cumulative incidence curves were constructed for OS and NRM), respectively. Log-rank test and Gray's test were used whenever appropriate. Results 65 patients with MF that met the inclusion criteria were studied. Median age at HCT was 61 years with 36 (55%) males. 39 (60%) patients had intermediate 2 or high DIPPS score at the time of HCT. 37 (57%) had JAK2 positive MF.. Median PASP was 37.0 mmHg (range: 16.0-57.9) prior to HCT with 37 out of 65 patients (57%) meeting the diagnostic criteria for PAH. With median follow-up of 35.0 months (range: 3.3 – 119.4), PAH was significantly associated with inferior OS (58.9% vs. 88.8%, p=0.025), primarily due to increased NRM (21.6% vs. 7.1%, p= 0.007). 57% of deaths (8 of 14) in patients with PAH occurred within day 100 after HCT. In patients with available post-HCT echocardiogram (n=33) eight patients (24%) had persistent PAH with the median pulmonary artery pressure of 30mmHg. Compared with pre-HCT values pulmonary arterial pressure was significantly reduced after HCT (p<0.001). Conclusion PAH is associated with inferior survival due to increased NRM in patients with MF undergoing alloHCT. About half of deaths in patients with PAH occurred within 100 days of HCT. PAH appears at least partially reversible after successful alloHCT. Based on our data, PAH should be considered a risk factor for early mortality after alloHCT and surveillance of pulmonary artery pressure in MF patients being considered for alloHCT may be useful. [ABSTRACT FROM AUTHOR]

Therapy-related myelodysplastic syndrome is a long-term complication of cancer treatment in patients receiving cytotoxic therapy, characterized by high-risk genetics and poor outcomes. Allogeneic hematopoietic cell transplantation is the only potential cure for this disease, but the prognostic impact of pre-transplant genetics and clinical features has not yet been fully characterized. We report here the genetic and clinical characteristics and outcomes of a relatively large cohort of patients with therapy-related myelodysplastic syndrome (n=67) who underwent allogeneic transplantation, comparing these patients to similarly treated patients with de novo disease (n=199). The 5-year overall survival was not different between patients with therapy-related and de novo disease (49.9% versus 53.9%; P =0.61) despite a higher proportion of individuals with an Intermediate-2/High International Prognostic Scoring System classification (59.7% versus 43.7%; P =0.003) and high-risk karyotypes (61.2% versus 30.7%; P<0.01) among the patients with therapy-related disease. In mutational analysis, TP53 alteration was the most common abnormality in patients with therapy-related disease (n=18: 30%). Interestingly, the presence of mutations in TP53 or in any other of the high-risk genes ( EZH2 , ETV6 , RUNX1 , ASXL1 : n=29: 48%) did not significantly affect either overall survival or relapse-free survival. Allogeneic stem-cell transplantation is, therefore, a curative treatment for patients with therapy-related myelodysplastic syndrome, conferring a similar long-term survival to that of patients with de novo disease despite higher-risk features. While TP53 alteration was the most common mutation in therapy-related myelodysplastic syndrome, the finding was not detrimental in our case-series., (Copyright© 2017 Ferrata Storti Foundation.)