Dual T cell depletion for graft versus host disease prevention in peripheral blood haploidentical hematopoietic cell transplantation for adults with hematological malignancies.

The ideal immunosuppressive agents to complement post-transplant cyclophosphamide (PTCy) in PBSC-based haploidentical hematopoietic cell transplantation (haplo-HCT) remain debated. This study looks at our experience with ATG-PTCy-Cyclosporine (CsA) prophylaxis in PB haplo-HCT since 2015. Between October 2015 and December 2021, 157 adults underwent haploidentical hematopoietic cell transplantation (haplo-HCT) using a GVHD prophylaxis regimen comprising rabbit-ATG, PTCy, and CsA. Among these patients, 76.4% received a total ATG dose of 4.5 mg/kg, and 23.5% received 2 mg/kg. T-cell replete peripheral blood stem cell (PBSC) grafts were infused on day 0. The study reported a median follow-up of 32 months (range 0.3-61.64) for survivors. The cumulative incidence of grade II-IV and grade III-IV acute GVHD at day +100 was 26.3% and 9.5%, respectively. Moderate/severe chronic GVHD at 1 year was 19.9%. The 2-year overall survival (OS) was 49.4%, with a relapse-free survival (RFS) of 44.6%. In multivariate analysis, older patients, and those with high/very-high disease risk indices (DRI) were at higher risk for worse OS and higher non-relapse mortality (NRM). The study confirms that using PTCy and ATG (4.5 mg/kg), alongside CsA is safe and effective in preventing GVHD when using peripheral blood as the stem cell source in haploidentical hematopoietic cell transplantation (haplo-HCT).

Late-onset Pneumocystis jirovecii pneumonia post-allogeneic stem cell transplantation after time-dependent discontinuation of prophylaxis.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is a rare complication of hematopoietic stem cell transplantation (HSCT). Primary prophylaxis for 6-12 months post-HSCT is the standard approach. However, there is no consensus regarding the optimal duration of prophylaxis. METHODS: We identified patients who developed PJP more than 1-year post-HSCT. All patients had previously received 12 months of PJP prophylaxis. PJP was diagnosed based on clinical findings and the detection of P. jirovecii in bronchoalveolar lavage (BAL) using polymerase chain reaction (PCR). The CD4+ T-cell percentage was determined using flow cytometry. Data expressed as median (interquartile range). RESULTS: Ten patients developed PJP at 17.5 months (16-24 months) post-HSCT. PJP diagnosis occurred 5.5 months (3-15 months) after discontinuing prophylaxis. Eight patients received anti-thymocyte globulin (ATG) as graft versus host disease (GVHD) prophylaxis. At diagnosis, only one patient had lymphopenia; all patients had CD4+ T-lymphocyte counts ≥0.2 × 109 /L (median 0.337 × 109 /L). Three patients had concomitant bacterial infections. The clinical presentation was mild; only three required hospitalization, none of them required intensive care and there were no deaths. CONCLUSION: There is a need to develop risk-adapted prophylactic strategies in the contemporary era using ATG-based GVHD prophylaxis.

HCT frailty scale for younger and older adults undergoing allogeneic hematopoietic cell transplantation.

The HCT Frailty Scale is an easy prognostic tool composed of (a) Clinical Frailty Scale; (b) Instrumental Activities of Daily Living; (c) Timed-up-and-Go test; (d) Grip Strength; (e) Self-Health Rated Questionnaire; (f) Falls tests; (g) Albumin and C-reactive protein levels. This scale was designed to classify allogeneic hematopoietic cell transplant (alloHCT) candidates into fit, pre-frail and frail groups, irrespective of age. This study evaluates the ability of this frailty classification to predict overall survival (OS) and non-relapse mortality (NRM) in adult patients of all ages, in a prospective sample of 298 patients transplanted between 2018 and 2020. At first consultation, 103 (34.6%) patients were fit, 148 (49.7%) pre-frail, and 47 (15.8%) were frail. The 2-year OS and NRM of the three groups were 82.9%, 67.4%, and 48.3% (P < 0.001), and 5.4%, 19.2%, and 37.7% (P < 0.001). For patients younger than 60 years (n = 174), the 2-year OS and NRM of fit, pre-frail, and frail groups were 88.4%, 69.3% and 53.1% (P = 0.002), and 5.8%, 22.8%, and 34.8% (P = 0.005), respectively; and in patients older than 60 (n = 124), OS and NRM were 75.5%, 63.8% and 41.4% (P = 0.006), and 4.9%, 16.4%, and 42.1% (P = 0.001). In conclusion, frailty predicted worse transplant outcomes in both younger and older adults.

Interaction Between High-Dose Intravenous Busulfan and Post-Transplantation Cyclophosphamide on Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplantation.

This study investigates the incidence and predictors of hemorrhagic cystitis (HC) in 960 adults undergoing allo- hematopoietic stem cell transplantation. Two hundred fifty-two (26.5%) patients received myeloablative conditioning regimens, and 81.4% received high-dose intravenous busulfan (HD Bu). Six hundred ninety-five (72.4%) patients received post-transplantation cyclophosphamide (PTCY)-based prophylaxis, and 91.4% additionally received anti-thymocyte globulin (ATG) and Cyclosporine A (CsA) (PTCY-ATG-CsA). Two hundred twenty-eight (23.8%) patients developed HC. The day 100 cumulative incidences of grades 2-4 and 3-4 HC were 11.1% and 4.9%. BK virus was isolated in 58.3% of urinary samples. Using HD BU myeloablative regimens increased the risk for grade 2-4 HC (hazard ratio [HR] = 1.97, P = .035), and HD BU combined with ATG-PTCY-CsA increased this 4 times (HR = 4.06, P < .001) for grade 2-4 HC compared to patients who received neither of these drugs. A significant correlation was documented between grade II-IV acute graft-versus-host disease and grade 2-4 HC (HR = 2.10, P < .001). Moreover, patients with BK-POS grade 2-4 HC had lower 1-year overall survival (HR = 1.51, P = .009) and higher non-relapse mortality (HR = 2.31, P < .001), and patients with BK-NEG grade 2-4 HC had comparable post-transplantation outcomes. In conclusion, intravenous HD Bu was identified as a predictor for grade 2-4 HC. Moreover, when HD Bu was combined with PTCY-ATG-CsA, the risk increased 4-fold. Based on the results provided by this study, preventing the onset of HC, especially in high-risk patients, is mandatory because its presence significantly increases the risk for mortality.

Mutational profile, outcomes, and impact of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia and inconclusive cytogenetic analysis.

BACKGROUND: Inconclusive cytogenetic analysis (IC) at baseline has been reported as a predictor of poor prognosis in patients with acute myeloid leukemia (AML). The mutational profile in this group of patients, and its impact on outcomes have not been reported. METHODS: We retrospectively analyzed adult patients (≥18 years) with newly diagnosed AML treated with intensive induction chemotherapy between 2015 and 2019. Patients with any documented cytogenetic abnormalities were excluded. Targeted next generation sequencing (NGS) was performed in all patients. Baseline characteristics, mutation profile, and outcomes were compared between patients with normal cytogenetics(NC) and those with IC. RESULTS: Sixty-one patients (males 39.3%; median age 59 years) had IC at diagnosis. The proportion of patients with mutations in genes with proven prognostic impact were not different between AML patients with IC and NC. AML patients with NC were more likely to harbor the prognostically favorable NPM1mut /FLT3-ITDwt mutational combination conferring "favorable" risk status. As a result, a larger proportion of patients in the IC group underwent allogeneic hematopoietic stem cell transplantation (allo HCT; 54.1% vs. 39.6%; p = .02). The 2-year RFS (55.9% vs. 58.5%; p = .29) and OS (61.9% vs. 66.9%; p = .48) were similar in IC and NC patients. There was no difference in survival of patients who underwent allo HCT when compared with patients who did not (p = .99). CONCLUSIONS: Inconclusive cytogenetic analysis may not be an independent prognostic indicator in AML. In such patients, molecular abnormalities detected through NGS or whole genome sequencing are more likely to be informative.

Impact of hematopoietic cell transplant frailty scale on transplant outcome in adults.

This prospective study designs an HCT Frailty Scale to classify alloHCT candidates into groups of frail, pre-frail, and fit, and to be implemented in the first consultation at no additional cost. The present scale is composed of the following eight variables: Clinical Frailty Scale, Instrumental Activities of Daily Living, Timed Up and Go Test, Grip Strength, Self-Health Rated, Falls, Albumin, and C-Reactive Protein. The Frailty score of a patient is the weighted sum of scores for each item, with weights assigned according to the hazard ratios of a multivariable Cox proportional hazards model estimated and validated with data on OS as the dependent variable, and the scores of the eight variables as explanatory ones, from 298 adults split into training (n = 200) and validation (n = 98) sets. For clinical use, the scale scores were transformed into three categories: scale score ≤1: fit; 15.5 frail. The estimated probabilities of 1-year OS in each group of frailty, were, respectively: 83.7%, 48.5%, and 16.5% (p < 0.001). In the validation cohort, the respective values were 90.3%, 69.5%, and 46.2% (p < 0.001). Pending further external validations, the HCT Frailty Scale is a low cost-highly informative prognostic signal of outcomes at the pre-transplant stage.

Relationship between certain HLA alleles and the risk of cytomegalovirus reactivation following allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Evidence is emerging to support an association between certain human leukocyte antigen (HLA) alleles and the risk of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplant (allo-HSCT). The primary aim of this study was to identify HLA alleles associated with resistance or susceptibility to CMV reactivation. METHODS: We studied 586 adults who underwent allo-HSCT for high-risk hematological malignancies. High-resolution HLA typing data were available for recipients and donors. HLA class I and II alleles observed at a frequency of >5% in our population were included in the analysis. A CMV viremia level of more than 200 IU/ml on weekly monitoring was considered to be indicative of CMV reactivation. RESULTS: The median follow-up time in surviving patients was 21 months (range 4-74 months). The cumulative incidence of CMV reactivation at 6 months in the entire cohort was 55% (95% confidence interval [CI] 50.8%-59.2%). Mismatched donors, increasing recipient age, occurrence of acute graft versus host disease and recipient CMV seropositivity were associated with an increased risk of CMV reactivation. HLA B*07:02 (hazard ratio 0.59, 95% CI 0.40-0.83) was associated with a decreased risk of CMV reactivation. Patients who developed CMV reactivation had a lower incidence of relapse, higher transplant-related mortality (TRM) and lower overall survival (OS) than those without CMV reactivation. There was an adverse correlation of OS and TRM with increasing numbers of CMV reactivations. CONCLUSION: We observed that HLA B*07:02 was associated with a decreased risk of CMV reactivation. CMV reactivation was associated with lower relapse post-transplant, but this did not translate into a survival benefit due to higher TRM.

Improving Safety and Outcomes After Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience.

The implementation of dual T-cell depletion comprising 4.5 mg/kg of antithymocyte globulin (ATG), post-transplantation cyclophosphamide, and cyclosporine A for reduced-intensity allogeneic hematopoietic cell transplantation (HCT) independent of donor source in 2015 significantly improved graft-versus-host disease (GVHD) control at our Institution. Further advances were made between 2017 to 2020 in supportive care of allogeneic HCT recipients and were the subject of this study, with 651 adults included. Transplant outcomes were compared between patients who underwent transplantation during Period 1 (2017-2018) and Period 2 (2019-2020). Main changes implemented during the study period were reduction of ATG dose from 4.5 to 2 mg/kg in matched unrelated donor transplants, abandoning of dual T-cell depletion in matched related donor transplants, combining dual T-cell depletion with myeloablative conditioning for selected patients, and reduction of the target therapeutic cyclosporine level from 200 to 400 ng/L to 150 to 250 ng/L. Other improvements included addition of ursodiol until day 100, implementation of a double responsible physician model, and personalized patient supportive care plan focused on activity and calorie intake. The reduction in intensity of GVHD prophylaxis provided comparable acute GVHD and moderate-severe chronic GVHD between both time periods. Altogether the described improvements in transplant methodology and supportive care showed that compared to Period 1, patients transplanted in Period 2 had superior 1-year overall survival, relapse-free survival, and non-relapse mortality and showed a trend toward better GVHD- and relapse-free survival, without an increase in relapse risk. This study reports the results of outcomes-directed improvements in transplantation design, GVHD prophylaxis, and supportive care, highlighting how transplantation outcomes can be improved through careful modifications in response to meticulously monitored outcomes.

Allogeneic hematopoietic stem cell transplantation in patients with therapy-related hematologic malignancies developing after multiple myeloma.

INTRODUCTION: Increasing survival of patients with multiple myeloma (MM) has resulted in an increased recognition of therapy-related hematological malignancies (t-MDS/AML, t-ALL, and t-CMML). There are limited data on the role of allogeneic hematopoietic stem cell transplantation (HCT) in this patient population. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent HCT for t-MDS/AML, t-ALL, and t-CMML developing after receiving treatment for MM at our center. Patients were analyzed for myeloma characteristics and therapy, time to diagnosis of therapy-related hematological neoplasms, clinical, laboratory characteristics, transplant details, relapse-free survival (RFS), and overall survival (OS). RESULTS: Twenty patients underwent HCT for therapy-related hematological malignancies after MM (t-MDS/AML = 13, t-ALL = 6, t-CMML = 1). Median(range) age at time of transplant was 62.5 (49-73) years and 70% (n = 14) were male. The most common cytogenetic abnormality was complex/monosomal karyotype in 30% (n = 6) followed by monosomy/deletion of chromosome 5 or 7 in 15% (n = 3) of patients each. Donors were human leukocyte antigen matched (10/10 or 6/6) siblings in 30% (n = 6), unrelated in 60% (n = 12) and haploidentical in 10% (n = 2) patients. Estimated 2-year OS and RFS for the whole cohort were 53.1% and 47.2% respectively. There was a trend toward better survival in patients with t-ALL when compared to t-MDS/AML; however, the difference was not statistically significant. We did not find any pre-transplant or post-transplant factors that were predictive of survival outcomes after multivariate analysis. CONCLUSIONS: Allogeneic HCT provides substantial long-term disease-free survival in a proportion of patients with MM-associated therapy-related hematological malignancies. Multicenter studies with more patients and longer follow-up may provide additional information about factors affecting outcomes.

Bloodstream Infections and Outcomes Following Allogeneic Hematopoietic Cell Transplantation: A Single-Center Study.

This study investigated the single-center incidence and risk factors for bloodstream infections (BSIs) in 651 adults who underwent allogeneic hematopoietic cell transplantation (alloHCT) between 2015 and 2019 and explored the impact of these BSIs on post-transplantation outcomes. Antibiotic prophylaxis with ciprofloxacin was given during the aplastic phase. Overall, the median patient age was 57 years, 79.7% of patients received an alternative donor graft, and 68.7% received post-transplantation cyclophosphamide (PTCy) as part of their graft-versus-host disease (GVHD) prophylaxis. Of the 651 patients, 358 (55.0%) had at least 1 episode of BSI, and the overall mortality rate secondary to this complication was 7.5% (12.6% among those diagnosed with at least 1 episode of BSI). BSI was more often diagnosed during the first 30 days (58.7%), and gram-positive bacteria were the most prevalent microorganisms isolated during the entire post-transplantation follow-up (62%). A high Disease Risk Index (hazard ratio [HR], 1.47; P < .029) and receipt of PTCy-based GVHD prophylaxis (HR, 3.33; P < .001) were identified as risk factors for BSI. Additionally, univariate analysis showed that patients diagnosed with a BSI during post-transplantation follow-up had worse overall survival (HR, 2.48; P < .001) and higher nonrelapse mortality (HR, 2.68; P < .001) than those without BSI. In conclusion, alloHCT recipients with a BSI had a higher risk of mortality compared with those who did not develop BSI. The inclusion of PTCy as part of GVHD prophylaxis was identified as an independent risk factor for BSI during early post-transplantation follow-up. Single-center analyses focused on reporting the incidence and risk factors for BSI highlight the need for active implementation of preemptive strategies to decrease BSI incidence in the alloHCT setting. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Predictors of Outcomes of Therapy-Related Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND/OBJECTIVE: Existing literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in therapy-related acute myeloid leukemia (t-AML) is confounded by the inclusion of patients with secondary AML and t-MDS. We aim to report our 20-year experience of HSCT in t-AML. METHODS: We retrospectively reviewed patients with t-AML who underwent HSCT. Patients were analyzed for prior malignancy, therapy, time to diagnosis of t-AML, transplant details, relapse-free survival (RFS), overall survival (OS), and predictors of outcomes. RESULTS: In total, 68 patients (59.9% female; median age, 56.5 years) underwent HSCT. Acute and chronic graft-versus-host disease (GVHD) occurred in 39 (57.4%) and 23 (33.8%) patients, respectively. Cumulative incidence of relapse, nonrelapse mortality, RFS, and OS at 2 years were 17.9%, 34.5%, 47.6%, and 49.3%, respectively. Significant predictors of reduced OS were presence of 11q23 rearrangement (hazard ratio [HR], 3.24), using induction regimens other than FLAGI-da or 7 + 3 (HR, 3.65), haploidentical donors (HR, 3.48), Eastern Cooperative Oncology Group performance status 2 or higher (HR, 5.83), and using cyclosporine A-methotrexate as GVHD prophylaxis (HR, 2.41). A significant decrement in survival was seen with an increasing number of any of these prognostic factors. CONCLUSION: Outcomes of t-AML are satisfactory after allo-HSCT. Patients with t-AML with good-risk karyotypes, good performance status, having HLA-matched donors, and receiving intensive induction regimens have better outcomes after HSCT.

Lower dose of ATG combined with post-transplant cyclophosphamide for HLA matched RIC alloHCT is associated with effective control of GVHD and less viral infections.

This study compares the outcomes before and after reducing the ATG dose from 4.5 to 2 mg/kg, in a combination of PTCy and CsA for GVHD prevention, in 250 patients treated with HLA matched RIC PB-alloHCT (70% received 4.5 mg/kg and 30% received 2 mg/kg). The incidences of grade II-IV and III-IV aGVHD at day +100, and moderate/severe cGVHD at 1-year were 12.6% vs. 20% (p = 0.431), 3.6% vs. 4.5% (p = 0.935), and 10.9% vs. 26.1% (p = 0.480), respectively. PTLD (9.1% vs. 1.3%, p = 0.026) and viral infections (30.3% vs. 12%; p = 0.001) were lower for those treated with 2 mg/kg of ATG. The reduction of the ATG dose resulted in a comparable OS (2-year: 64.7% vs. 64.7%), GRFS (2-year: 48.0% vs. 44.5%), RFS (2-year: 57.0% vs. 62.0%), and NRM (2-year: 17.8 vs. 14.9). The use of (2 mg/kg) ATG-PTCy-CsA for HLA matched RIC alloHCT results in lower viral infections, and incomparable GVHD preventive effect and survival rates.

Efficacy and cost analysis of eltrombopag in thrombocytopenia and poor graft function post allogeneic hematopoietic cell transplantation.

Eltrombopag has shown efficacy in the treatment of thrombocytopenia and poor graft function (PGF) after allogeneic hematopoietic cell transplantation (HCT) in retrospective observational studies, but is not approved for this indication. The cost of this drug is also a major concern in publicly funded health care systems. We collected data about patients who received eltrombopag for thrombocytopenia or PGF after HCT. Post-HCT thrombocytopenia, PGF, and eltrombopag response were defined as per previously published criteria. Primary outcome was treatment efficacy and secondary outcome was cost comparison between estimated treatment cost prior to and after initiation of eltrombopag. Seventeen patients (males 70.6%; median age = 58) received eltrombopag. Isolated thrombocytopenia was present in 11.8% (n = 2) patients while PGF was present in 88.2% (n = 15) of patients. After 8 weeks of treatment at the maximum dose of 150 mg orally daily, overall response rate (ORR) was seen in 76.5% (13/17) of patients: complete response (CR) in 10/13 patients and partial response (PR) in 3/13 patients. The use of eltrombopag was associated with an overall decrease in the total weekly care costs (5021 vs 2,524 CA$; P = 0.04). Thus, Eltrombopag is an efficacious and possibly cost-effective therapy for thrombocytopenia and PGF after allogeneic HCT.

Experience Using Anti-Thymocyte Globulin With Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Peripheral Blood Haploidentical Stem Cell Transplantation.

Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option for patients without a suitable 10/10 HLA matched donor. We share an updated experience at our center of using in vivo dual T-cell depletion with anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) in peripheral blood haploHCT and report the impact of reducing the dose of ATG from 4.5 mg/kg to 2 mg/kg on post-transplantation complications and outcomes. Ninety-five consecutive adults underwent haploHCT at our center between August 2016 and February 2020, all of whom were included in the study. Nine (9.5%) patients received myeloablative conditioning, and 86 (90.5%) patients underwent reduced-intensity haploHCT. All patients received thymoglobulin, PTCy and cyclosporine (CsA) for graft-versus-host disease (GVHD) prophylaxis: Sixty (63.2%) patients received 4.5 mg/kg, and 35 (36.8%) patients received 2 mg/kg of ATG. Clinical information was collected retrospectively and updated in June 2020. The median age was 57 (18-73), and acute myeloid leukemia was the most prevalent diagnosis (58.9%). The day 100 cumulative incidence of grade II-IV and grade III-IV aGVHD, and 1-year moderate/severe cGVHD were 22.3%, 11.1%, and 20.2%, respectively. Those patients who received 2 mg/kg of ATG had higher incidence of grade III-IV aGVHD (23.9% vs 3.5%, P = .006) and comparable moderate/severe cGVHD (1-year 20.6% vs 19.8%, P = .824) than those patients who received 4.5 mg/kg. Overall, the 18-month overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) were 43.8%, 38.4%, and 40.2%, respectively. The reduction of the ATG dose did not have a significant impact in OS (hazard ratio [HR] 1.06, P = .847), RFS (HR 0.984, P = .955), and in NRM (HR 1.38; P = .348). The reduction of the ATG resulted in a negative impact on aGVHD without conferring any benefit in OS, RFS, and NRM. Consequently, the ATG dose used at our institution in combination with PTCy and CsA for haploHCT continues to be 4.5 mg/kg.

Prolactin, a potential biomarker for chronic GVHD activity.

INTRODUCTION: The polypeptide prolactin (PRL) is a peptide hormone and a cytokine mostly secreted from the anterior pituitary gland. PRL is also synthesized in extra pituitary tissues including thymocytes and T lymphocytes. Considering the need for chronic GVHD (cGVHD) biomarkers, we explored the relationship between hyperprolactinemia and active cGVHD in a cohort of long-term post-alloHCT survivors. METHODS: Three-hundred sixteen adults underwent alloHCT between 2010 and 2016, survived more than 1 year and were included. All patients underwent a regular annual assessment that includes a hormone profile with serum PRL levels. RESULTS: Overall, 236 (74.7%) patients had cGVHD, and in 199 (63%), the grade was moderate or severe. Sixty-five (21%) recipients had active cGVHD at the time of the annual evaluation, and hyperprolactinemia was documented in 63 (19.9%) patients. Hyperprolactinemia correlated with cGVHD activity (Odds Ratio 6.9 (95% CI; 3.6-13.1); P < .001) in the multivariate analysis. In conclusion, patients with hyperprolactinemia were 6.4 times more likely to have active cGVHD in comparison with those patients with normal levels of PRL (P < .001). CONCLUSION: Prolactin may serve as a biomarker for cGVHD activity. Further studies are required to confirm these findings, and to explore if hyperprolactinemia has an impact on cGVHD severity and prognosis.

Outcomes of adult patients with acute myeloid leukemia and unsuccessful cytogenetic analysis undergoing allogeneic hematopoietic stem cell transplantation.

OBJECTIVE/BACKGROUND: Unsuccessful cytogenetic (US) analysis at baseline has been reported to be a poor prognostic feature in patients with acute myeloid leukemia (AML). We conducted this study to examine the prognostic impact of UC/inconclusive cytogenetic analysis on outcomes in patients with AML undergoing allogeneic hematopoietic stem cell transplantation (Allo HSCT). METHODS: We retrospectively analyzed all adults undergoing Allo HSCT for AML from January 2011 to August 2019. Patients with any documented cytogenetic abnormalities were excluded. Baseline characteristics and transplant outcomes were compared between patients with normal cytogenetics and those with UC. RESULTS: Overall, 243 AML patients (median age, 55 years; 55.1% female) were included. UC were reported in 79 patients, whereas 164 patients had a normal karyotype. The two groups were similar to each other in terms of baseline demographics, treatment received, and transplant related variables. There was no difference between patients with UC and normal cytogenetics in terms of relapse-free survival (66 months vs. 42 months, p = .53) or overall survival (OS; 77 months vs. 76 months, p = .72). Survival parameters remained similar even in subgroup analysis based on NPM1 and FLT3 mutation status. Significant predictors of OS after Allo HSCT in AML patients with UC were increased age at time of Allo HSCT (hazard ratio [HR] = -1.049; 95% confidence interval [CI], 1.005-1.095), favorable (NPM1Mut/FLT3wt) mutation profile (HR = 0.11; 95% CI, 0.01-0.84), neutrophil engraftment < 17 days, and absence of chronic graft-versus-host disease (HR = 3.27; 95% CI, 1.20-8.60). CONCLUSION: Outcomes after Allo HSCT are comparable between AML patients with UC analysis and patients with normal cytogenetics even after stratification based on molecular risk factors. Allogeneic Allo HSCT may mitigate the poor prognosis of UC analysis in patients with AML.

Pilot prospective study of Frailty and Functionality in routine clinical assessment in allogeneic hematopoietic cell transplantation.

A Frailty and Functionality evaluation for alloHCT was implemented using existing resources. We describe the implementation of this evaluation across all ages and at first consultation, and correlate results with posttransplant outcomes in 168 patients. The evaluation consists of: Clinical Frailty Scale (CFS), Instrumental Activities of Daily Living (IADL), grip strength (GS), timed up and go test (TUGT), self-rated health question (SRH), Single question of Falls, albumin and C-Reactive Protein (CRP) levels. Median time to perform the evaluation was 5-6 min. Median age was 58 years (range: 19-77) and median follow-up was 5.3 months. TUGT > 10 s (HR 2.92; p = 0.003), raised CRP (HR 4.40; p < 0.001), and hypoalbuminemia (HR 2.10; p = 0.043) were significant risk factors for worse overal survival (OS). CFS ≥ 3 (HR 3.11; p = 0.009), TUGT > 10 s (HR 3.47; p = 0.003), GS (HR 2.56; p = 0.029), SRH ( 10 s and raised CRP were significant predictors for worse OS and NRM. SRH (

High incidence but low mortality of EBV-reactivation and PTLD after alloHCT using ATG and PTCy for GVHD prophylaxis.

We explore risk factors and impacts of post-transplant EBV-Reactivation (EBV-R) and PTLD in 270 patients that underwent RIC alloHCT using ATG-PTCy and cyclosporine for GVHD prophylaxis. Twenty-five (12%) patients had probable (n = 7) or proven (n = 18) PTLD. Patients were managed with reduction of immunosuppression and 22 with weekly rituximab (375 mg/m2 IV). ORR was 84%; 8 (32%) recipients died, and one-year OS and NRM of patients with PTLD was 59.7% and 37%, respectively. One hundred seventy-two (63.7%) recipients had EBV-R. One-year OS and RFS of patients with EBV-R were 68.2% and 60.6%, and of EBV-Negative patients were 62.1% and 50.1%, respectively. High incidence but low mortality of EBV-R and PTLD was documented. EBV-R induced a protective effect on RFS in multivariable analysis (HR 0.91, p = .011). Therefore, EBV-R may have a protective effect on RFS in this setting. Further research is necessary to evaluate the interplay of EBV-R, immune reconstitution, and post-transplant outcomes.

Less Is More: Superior Graft-versus-Host Disease-Free/Relapse-Free Survival with Reduced-Intensity Conditioning and Dual T Cell Depletion in Acute Myelogenous Leukemia.

In this study, we compared the outcomes of patients with acute myelogenous leukemia (AML) in complete remission treated with myeloablative conditioning (MAC) and those treated with reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HCT). In addition, we explored the efficacy of dual T cell depletion using anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) for the prevention of graft-versus-host disease (GVHD) in patients undergoing RIC allo-HCT. Our study cohort comprised 356 adults with AML in complete remission who underwent allo-HCT between 2013 and 2018. One hundred eleven patients (31.2%) received a MAC regimen, and 245 (68.8%) received an RIC regimen. One hundred seventy-one of the patients who received an RIC regimen (68.4%) received ATG, PTCy, and cyclosporine (ATG-PTCY-CsA) for GVHD prophylaxis in accordance with our institutional protocol. Data were collected retrospectively and updated in July 2019. With a median follow-up of 14.5 months (range, 0 to 76 months), 161 patients (45.2%) died, and 66 (18.5%) relapsed. Two-year overall survival (OS), relapse-free survival (RFS), and GVHD-free/RFS (GRFS) were 55%, 52.6%, and 35%, respectively. The intensity of the conditioning regimen, with or without ATG-PTCY-CsA, did not have a significant impact on OS and RFS. However, RIC in combination with ATG-PTCY-CsA was associated with a significantly lower cumulative incidence of acute GVHD and chronic GVHD. The use of RIC with ATG-PTCy-CsA was a significant predictor for higher GRFS secondary to the reduction of clinically relevant GVHD (P= .0001). In patients with AML, RIC allografts and dual T cell modulation with ATG and PTCy led to superior GRFS. The use of this GVHD prophylaxis strategy, along with mitigation of conditioning toxicity using RIC, may result in better long-term quality of life for allo-HCT recipients.