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Introduction: Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common types of cutaneous T-cell lymphoma. Although many available treatments offer temporary disease control, allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative treatment option for advanced stage MF and SS. CAR T-cell therapy is a promising new avenue for treatment., Areas Covered: In this review, we discuss the evidence supporting the use of allo-HSCT for the treatment of MF/SS, including disease status at the time of transplant, conditioning regimen, total body irradiation (TBI), and donor lymphocyte infusion (DLI). We also address the potential role for CAR T-cell therapy in CTCL., Expert Opinion: Allo-HSCT is an effective treatment for patients with advanced MF and SS. However, significant research is required to determine optimal treatment protocols. Data support the use of reduced-intensity conditioning regimens and suggests that the use of TBI for debulking of skin disease may result in more durable remissions. Donor lymphocyte infusions (DLI) appear to be particularly effective in inducing complete remission in MF/SS patients with relapsed or residual disease. Challenges with CAR-T therapies in T-cell lymphoma include T-cell fratricide due to shared antigens on malignant and nonmalignant T-cells, penetrance into the skin compartment, and CAR-T cell persistence.

Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been noted to be a potential curative treatment in cases of advanced-stage mycosis fungoides (MF) or Sezary syndrome (SS). To assess outcomes of allo-HSCT for MF/SS we performed a systematic review and meta-analysis including 15 manuscripts and 557 patients, published from 2010-2023. Meta-analysis revealed 1-year and 3+year overall survival (OS) of 51% (95% CI 39-64%) and 40% (32-49%). Progression-free survival at 1 year and 3+years were 42% (31-53%) and 33% (25-42%). Non-relapse mortality was 18% (13-23%). Relapse occurred in of 47% (40-53%) with a median time to relapse of 7.9 months (range 1.6-24 months). Rates of acute and chronic graft-versus-host disease (GVHD) were 45% (35-55%) and 40% (33-48%). Reduced-intensity conditioning (RIC) was associated with superior OS compared to myeloablative conditioning (MAC) (58% vs. 30%, p < 0.001). Of patients with relapse after allo-HSCT, 46% treated with donor lymphocyte infusion (DLI) achieved complete remission. These data support use of allo-HSCT for treatment of advanced-stage MF/SS and suggest superiority of RIC over MAC. Rates of GVHD were comparable to allo-HSCT in general. The improved OS for RIC and high rate of CR with DLI underscore the importance of the graft-versus-lymphoma effect in allo-HSCT for MF/SS., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

We report results on 23 patients with cutaneous T cell lymphoma (7 primary cutaneous γδ T cell lymphoma [PCGDT], 16 mycosis fungoides/Sézary syndrome [MF/SS]) who underwent allogeneic stem cell transplantation. All pts had skin involvement, 14 had total skin electron beam before conditioning. Donors were 10/10 HLA matched related (13), 5/10 haploidentical (4), and matched unrelated (5) or mismatched unrelated (1). Thirteen were in a clinical complete remission at the time of transplant. The 100-day transplant related mortality for the MF/SS and PCGDT patients was 12% and 29%, respectively. At a median follow up of 5.5 years, the overall survival and disease-free survival for MF/SS patients was 75% and 64%, respectively, and 6 of 10 MF/SS pts in long term complete response had a partial response at the time of transplant. Of seven PCGDT patients, four of seven are alive at a median follow up of 5 years and three are disease-free.

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has a high death rate in patients with comorbidities or in an immunocompromised state. We report a mild and attenuated SARS CoV-2 infection in a patient who is 17 months post stem cell transplantation and maintained on the JAK/STAT inhibitor ruxolitinib, a proposed novel therapy for SARS CoV-2 pneumonia., (Copyright © 2020. Published by Elsevier Inc.)

Background: Extracorporeal photopheresis (ECP) is an immunomodulatory cellular therapy which has been shown to induce a tolerogenic state in patients with acute and chronic graft-vs-host disease. ECOG-ACRIN explored the activity of ECP as a part of a reduced intensity conditioning regimen in two multicenter trials in patients with MDS (E1902) and lymphomas (E1402). While both studies closed before completing accrual, we report results in 23 patients (17 MDS and 6 lymphoma)., Study Design and Methods: Patients received 2 days of ECP followed by pentostatin 4 mg/m2 /day for two consecutive days, followed by 600 cGy of total body irradiation prior to stem cell infusion. Immunosuppression for aGVHD was infusional cyclosporine A or tacrolimus and methotrexate on day +1, +3, with mycophenolate mofetil starting on day 100 for chronic GVHD prophylaxis., Results: All patients engrafted, with median time to neutrophil and platelet engraftment of 15-18 days and 10-18 days respectively. Grade 3 or 4 aGVHD occurred in 13% and chronic extensive GVHD in 30%., Conclusions: These studies demonstrate that ECP/pentostatin/TBI is well tolerated and associated with adequate engraftment of neutrophils and platelets in patients with lymphomas and MDS., (© 2020 AABB.)

The T Cell Project was the largest prospective trial to explore the incidence, treatment patterns, and outcomes for T cell lymphomas. The rare subtypes of T cell lymphomas, including hepatosplenic T cell lymphoma (HSTCL), enteropathy associated T cell lymphoma (EATL), and peripheral gamma delta T cell lymphomas (PGDTCLs) are poorly represented in most studies and there is little data regarding treatment patterns. We report results from 115 patients with hepatosplenic (n = 31), enteropathy associated (n = 65), and PGDTCLs (n = 19). While anthracycline regimens were most commonly used as first line therapy, response rates ranged from 20%-40% and were suboptimal for all groups. Autologous stem cell transplantation was performed as a consolidation in first remission in a small number of patients (33% of HSTCL, 7% of EATL, and 12% of PGDTCL), and four patients with HSTCL underwent allogeneic stem cell transplantation in first remission. The progression free survival at 3 years ranged from 28%-40% for these rare subtypes, and the overall survival at 3 years was most favorable for PGDTCL (70%). These data highlight the need for novel treatment approaches for rare subtypes of T cell lymphomas and for their inclusion in clinical trials., (© 2019 Wiley Periodicals, Inc.)

Background: The role of autologous stem cell transplantation (ASCT) in the first complete remission (CR1) of peripheral T-cell lymphomas (PTCLs) is not well defined. This study analyzed the impact of ASCT on the clinical outcomes of patients with newly diagnosed PTCL in CR1., Methods: Patients with newly diagnosed, histologically confirmed, aggressive PTCL were prospectively enrolled into the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE) study, and those in CR1 were included in this analysis., Results: Two hundred thirteen patients with PTCL achieved CR1, and 119 patients with nodal PTCL, defined as anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or PTCL not otherwise specified, were identified. Eighty-three patients did not undergo ASCT, whereas 36 underwent consolidative ASCT in CR1. At the median follow-up of 2.8 years, the median overall survival was not reached for the entire cohort of patients who underwent ASCT, whereas it was 57.6 months for those not receiving ASCT (P = .06). ASCT was associated with superior survival for patients with advanced-stage disease or intermediate-to-high International Prognostic Index scores. ASCT significantly improved overall and progression-free survival for patients with AITL but not for patients with other PTCL subtypes. In a multivariable analysis, ASCT was independently associated with improved survival (hazard ratio, 0.37; 95% confidence interval, 0.15-0.89)., Conclusions: This is the first large prospective cohort study directly comparing the survival outcomes of patients with nodal PTCL in CR1 with or without consolidative ASCT. ASCT may provide a benefit in specific clinical scenarios, but the broader applicability of this strategy should be determined in prospective, randomized trials. These results provide a platform for designing future studies of previously untreated PTCL., (© 2019 American Cancer Society.)

Background: Current guidelines recommend adding vancomycin to empiric treatment of FN in patients who meet specific criteria. After 48 hours, the guidelines recommend discontinuing vancomycin if resistant Gram-positive organisms are not identified. Based on these recommendations, a vancomycin stewardship team defined criteria for discontinuation of vancomycin at 48 hours and increased surveillance of vancomycin usage through a multimodal approach. The purpose of this retrospective analysis is to assess the impact of this multimodal approach on the discontinuation of empiric vancomycin at 48 hours in FN., Methods: This retrospective analysis included a pre- and post-intervention cohort of 200 HSCT recipients with FN from 2015 to 2018. Criteria for continued vancomycin use beyond 48 hours included culture-documented resistant Gram-positive infection, positive Methicillin-Resistant S aureus (MRSA) nasal swab with evidence of pneumonia, or hemodynamic instability with concern for sepsis. The following patient characteristics were collected: previous MRSA infection, MRSA nasal swab collection and results, culture results, duration of vancomycin use, rationale for continuation of vancomycin beyond 48 hours, and re-initiation of vancomycin., Results: In the post-intervention cohort, vancomycin discontinuation at 48 hours increased from 31% (95% CI 21.94-40.05) to 70% (95% CI 61.02-78.97; P < 0.0001). An additional 23% of vancomycin orders were discontinued at 72 hours. Off criteria vancomycin use decreased from 33% in pre to 1% in the post-implementation cohort., Conclusion: Establishing define criteria for vancomycin use in FN patients with a multimodal approach of physicians from hematology and infectious diseases, clinical pharmacists and the antibiotic stewardship team significantly improved vancomycin discontinuation., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Primary cutaneous aggressive epidermotropic cytotoxic CD8 positive T-cell lymphoma (CD8 + PCAETL) is a rare subtype of peripheral T-cell lymphoma with poor outcomes and without a standardized treatment strategy. Allogeneic hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy., Patients and Methods: We conducted a retrospective case series. We identified 8 patients with the diagnosis of CD8 + PCAETL, 4 of whom also underwent allogeneic HSCT., Results: Eight patients were treated at our center with combination chemotherapy and several novel agents, including histone deacetylase inhibitors, brentuximab, and pralatrexate. Patients underwent a median of 8.5 treatments before HSCT. Six of the 8 patients examined, including all 4 who received an HSCT, were alive at their last follow-up., Conclusion: Allogeneic HSCT is a promising treatment modality for CD8 + PCAETL. Because of the aggressive nature of this disease and lack of sustained remission with currently available therapies, HSCT should be considered early in the course of treatment. Two novel agents, brentuximab and pralatrexate, showed significant activity against CD8 + PCAETL, and may be incorporated earlier in the treatment course., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recognizing the significant biological and clinical heterogeneity of mature T cell and natural killer (NK)/T cell lymphomas, the American Society for Blood and Marrow Transplantation invited experts to develop clinical practice recommendations related to the role of autologous hematopoietic cell transplantation (auto-HCT) and allogeneic HCT (allo-HCT) for specific histological subtypes. We used the GRADE methodology to aid in moving from evidence to decision making and ultimately to generating final recommendations. Auto-HCT in front-line consolidation is recommended in peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK)-negative, NK/T cell (disseminated), enteropathy-associated T cell lymphoma (EATL), and hepatosplenic lymphomas. Auto-HCT in relapsed-sensitive disease is recommended for NK/T cell (localized and disseminated), EATL, subcutaneous panniculitis-like T cell, and ALCL-ALK-positive lymphomas. Auto-HCT is also recommended for PTCL-NOS, AITL, and ALCL-ALK-negative lymphomas if not performed as front-line therapy. Auto-HCT in refractory (primary or relapsed) disease is not recommended for any of the histological subtypes discussed. Allo-HCT in front-line consolidation is recommended for NK/T cell (disseminated), adult T cell leukemia/lymphoma (ATLL; acute and lymphoma type), and hepatosplenic lymphomas. Allo-HCT for relapsed-sensitive disease is recommended for PTCL-NOS, AITL, ALCL-ALK-negative, ALCL-ALK-positive, NK/T cell (localized and disseminated), ATLL (acute, lymphoma type, smoldering/chronic), mycosis fungoides/Sezary syndrome (advanced stage IIB-IVB or tumor stage/extracutaneous), EATL, subcutaneous panniculitis-like T cell, and hepatosplenic lymphoma. Allo-HCT in refractory (primary or relapsed refractory) disease is recommended for any aforementioned histological subtypes. Emerging novel therapies will likely be incorporated into the pretransplantation, peritransplantation, and post-transplantation algorithms (auto-HCT or allo-HCT) with the goals of optimizing efficacy and improving outcomes. We acknowledge that there are unique clinical scenarios not covered by these recommendations that may require individualized decisions., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The panniculitic T-cell lymphomas (TCLs) comprise 2 distinct entities, αβ subcutaneous panniculitis-like TCL (SPTCL) and the γδ cutaneous TCLs with pannicular involvement primary cutaneous γδ (PCGD)-TCL. Although outcomes for most patients with SPTCL are favorable, those with PCGD-TCLs generally have an inferior outcome, and treatment strategies have not been well defined. Allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to be a potentially curative strategy in aggressive TCLs and in refractory and advanced-stage mycosis fungoides., Objective: We sought to analyze the outcomes of HSCT for panniculitic cutaneous TCL., Results: Fourteen patients (4 SPTCL, 10 PCGD-TCL) presented with primarily pannicular T-cell infiltrates. Seven patients underwent allogeneic HSCT from matched-related donors and matched-unrelated donors of which 4 (57%) are alive (1 SPTCL, 3 PCGD-TCL) at 7.8, 6.9, 6.2, and 0.25 years. Two patients underwent autologous HSCT (1 SPTCL, 1 PCGD-TCL) and both are alive at a median follow-up of 1.91 years., Limitations: This study is limited by its retrospective nature and small sample size because of the rarity of SPTCL and PCGD-TCL., Conclusion: Aggressive therapy followed by allogeneic HSCT is a promising treatment modality for patients with PCGD-TCL., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Host conditioning prior to allogeneic bone marrow transplantation (BMT) has traditionally involved the use of high-dose, myeloablative chemotherapy and irradiation, focusing on maximal tumor cytoreduction as well as adequate immunosuppression to allow engraftment of allogeneic stem cells. High-dose chemoradiation conditioning regimens have been associated with a significant incidence of organ toxicity and acute and chronic graft-versus-host disease (GVHD). Recent efforts to diminish the acute transplant-associated toxicities have focused on the development of relatively nontoxic, nonmyeloablative, or less myeloablative conditioning regimens, with the emphasis being predominantly on induction of immunosuppression to enable engraftment. Without ablative chemotherapy, disease control in these regimens is largely relegated to the graft-versus-leukemia/lymphoma (GVL) effect. While the evolution these regimens has resulted in successful engraftment of allogeneic stem cells with minimal toxicity, acute and chronic GVHD occurs in 20% to 50% of patients and remains a major cause of transplant-associated morbidity. Strategies to lower the incidence of acute GVHD have primarily focused on more precise molecular donor/recipient matching, alternative stem cell sources, and T-cell depletion of the graft. While successful in lowering the frequency and severity of GVHD, T-cell-depleted grafts have been associated with compromised the graft-versus-disease effect. Recent studies have suggested that, in addition to T-effector cells within the graft, donor and host dendritic cells may play a role in GVHD. Purine analogues have been evaluated as part of these regimens. While fludarabine and cladribine have been shown to be effective, these agents have been associated with an increased incidence of serious infection and severe acute GVHD. Pentostatin has a different mechanism of action and was also investigated as part of these preparative regimens. Regimens using pentostatin/extracorporeal photopheresis (ECP)/total body irradiation (TBI) have been shown to be well tolerated and associated with early full donor engraftment with a predominance of donor dendritic cell (DC)2 cells and a low incidence of acute GVHD. Further investigation evaluating this preparative regimen is warranted.

Reduced-intensity allogeneic transplantations for myelodysplastic syndrome (MDS) patients have been limited by significant graft-versus-host disease (GVHD), treatment-related mortality, and disease relapse. We treated 18 MDS patients ineligible for standard allogeneic transplantation with a preparative regimen of photopheresis day -7 and -6, pentostatin 4 mg/m(2) by continuous infusion day -5 and -4, and total body irradiation 600 cGy in 3 fractions day -3 and -2, followed by allogeneic stem cell infusion from 6/6 or 5/6 HLA-matched related donors or 6/6 HLA-matched unrelated donors. GVHD prophylaxis consisted of cyclosporin A and a short course of methotrexate. The median age was 54 years (range, 30-70 years). Diagnoses included refractory anemia (n = 2), refractory anemia with ringed sideroblasts (n = 2), refractory anemia with excess blasts (n = 10), refractory anemia with excess blasts in transformation (n = 3), and chronic myelomonocytic leukemia (n = 1). Sixteen of 18 patients developed full donor chimerism with no day +100 transplant-related mortality. Grade II to IV acute GVHD and extensive chronic GVHD developed in 19% and 18% of patients, respectively. Disease relapse occurred in 2 patients. At a median follow-up of 14 months (range, 1-35 months), the 1-year failure-free and overall survival were 64% and 65%, respectively. Our photopheresis and pentostatin-based reduced-intensity preparative regimen for allogeneic bone marrow transplantation in high-risk MDS patients achieves successful donor engraftment and disease remission with less transplant toxicity and grade II to IV acute GVHD.

Background HSCT patients are at an increased risk of developing PJP after transplant due to treatment induced immunosuppression. Given the risk of cytopenias with co-trimoxazole, AP is utilized as an alternative for PJP prophylaxis. A prior study revealed a 0% (0/19 patients) incidence when AP prophylaxis was given for one year post autologous HSCT. Current guidelines recommend a duration of 3 – 6 months for PJP prophylaxis in autologous HSCT. The primary endpoint of this study was to assess the incidence of PJP infection within one year post autologous HSCT in patients who received 3 months of AP. Secondary endpoint was a cost comparison of 3 months compared with 6 months of AP. Methods A single-center, retrospective study of adult autologous HSCT patients at Yale New Haven Hospital between February 2013 and December 2017 was performed. Patients were excluded if: <18 years of age, received < or >3 months of AP, changed to alternative PJP prophylactic agent or received no PJP prophylaxis, received tandem HSCT, deceased prior to one year post-transplant from a non PJP-related infection, HIV positive, or lost to follow-up. Pentamidine was given as a 300 mg inhalation monthly for 3 months starting Day +15 after autologous HSCT. Results A total of 288 patients were analyzed, no PJP infections occurred within one year post HSCT. Additionally, 187 (65%) patients received treatment post HSCT with 135/215 (63%) receiving maintenance immunomodulatory drugs for myeloma and 40/288 (14%) patients developing relapsed disease. 43% of the chemotherapy regimens for relapsed disease included high dose corticosteroids. The cost difference of using 3 months vs. 6 months of AP is $790, reflecting the cost of drug and its administration. Applying our incidence of 0%, potential cost savings of 3 months vs. 6 months of AP would be $330,000 over 5 years or $66,000 per year. Conclusion Three months of AP for PJP prophylaxis in autologous HSCT patients is safe and effective as well as cost-effective compared with a 6 month regimen. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Introduction T-cell lymphomas are heterogenous group of neoplasms associated with generally unfavorable outcomes. High dose chemotherapy and autologous stem cell transplant (SCT) consolidation is a standard approach in first remission while allogeneic SCT (alloSCT) is recommended in the relapsed/refractory setting. Data on outcomes after alloSCT are limited, particularly in the era of brentuximab. Methods We retrospectively analyzed data from patients (pts) with T-cell lymphomas who underwent alloSCT in our institution from 11/2010–6/2018. Patient and disease characteristics were summarized using median and range for continuous data, and frequency and percentage for categorical data. Kaplan-Meier analysis was used to estimate progression free survival (PFS) and overall survival (OS) from the day of receipt of transplant. Survival probabilities were expressed by 95% confidence limits (CI). Results Thirty-three pts received alloSCT. Median age at transplant was 57 years (range [R], 22-73). T-cell lymphoma types included: cutaneous T-cell lymphoma, n = 12; NK-T cell, n = 4; peripheral T-cell lymphoma subtypes, n = 9; angioimmunoblastic T lymphoma, n = 6; T-cell rich B-cell, n = 2. Median lines of therapy prior to alloSCT were 4 (R, 2-13), including six with prior autologous SCT. Sixteen pts were transplanted in CR1, five in CR2, and three in CR3. Pentostatin/TBI was the most common pretransplant conditioning regimen (n = 23) followed by haplo regimen of Flu/TBI/Cy (n = 4). Donor transplant sources were MRD (16), MUD (8); Haplo (4), MMUD (5). Median days to neutrophil and platelet engraftment were 12 (R, 10-19) and 13 (R, 10-30), respectively. Cumulative incidence of grade II-IV acute and chronic GVHD were 24.2% and 45.4%, respectively. One-year PFS and OS probabilities were 69.5% (95% CI, 54.7- 88.4) and 87.1% (95% CI, 54.7-88.4), respectively. With a median follow up of 53 months (R, 2-97), 25 (75%) are alive and 24 are disease free. Four died from transplant related mortality (TRM) and 3 from relapse. The median time to relapse was 3.9 months [R, 2.2-12.5]). The cumulative incidence of GVHD was higher among patients who were relapse-free (71% vs 22% in relapsed pts, p=0.02). Seven of the 9 who relapsed were treated with brentuximab vedotin; of these 4 responded, including two patients who had haplo transplants. Conclusions Results from our study suggest that alloSCT in T-cell lymphomas with reduced intensity regimens are associated with overall favorable outcomes. Treatment of post-transplant relapse with brentuximab is feasible and should be explored further in long-term prospective studies. [ABSTRACT FROM AUTHOR]

Introduction Blood management and infectious disease mitigation are essential for success with allogeneic stem cell transplant (alloSCT). We sought to investigate the safety profile of a proactive infection mitigation strategy with the use of pathogen-inactivated (PI) platelets (PLT) during the alloSCT peri-engraftment period in the era of restrictive blood transfusion. Methods We retrospectively analyzed data from patients undergoing alloSCT that received prophylactic red blood cell (RBC) and PLT transfusion triggered by a hemoglobin of 8 g/dL and PLT count of 15,000 PLT/mL. When available, PI PLT (non-irradiated) were used starting November 2016 until March 2018 (study timeframe). Statistical analysis was performed using SAS 9.4 (Cary, NC). Patients characteristics and clinical parameters were summarized using mean and standard deviation or median and range for continuous data, and frequency and percentage for categorical data. Kaplan-Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS) from day of transplant. A two-sided logrank test was used to compare across strata using p<0.05 as significance cut-off. Univariate Cox proportional hazard regression analyses were performed to assess the effect of continuous explanatory variables. Results Sixty-eight patients received alloSCT. Median age at transplant was 55 years (range [R], 18-73). Peripheral blood stem cells were the graft source in all but one patient. Donor source was a matched related, 10/10 matched unrelated (MUD), 9/10 MUD and haploidentical donor in 30.9%, 44.1%, 2.9%, and 22.1% of cases, respectively. Myeloablative conditioning was used in 45.6% of patients. Indication for alloSCT was a myeloid or lymphoid disorder in 64.7% and 35.3% of cases. Median time to neutrophil and PLT engraftment was 12 (R, 10-35) and 12 days (R, 8-120), respectively. Pre-alloSCT RBC alloimmunization was present in 11.8% of patients. Cumulative incidence of grades II-IV acute and chronic graft-versus-host disease (GVHD) was 20.6% and 22.1%, respectively. PI PLT were used in 73.5 % patients. There were no cases of transfusion associated graft failure (GF) or GVHD. Bacteremia occurred in 10.0% and 22.1% of patients by 30 days and 100 days post-alloSCT, respectively, and were both associated with worse OS (both p<0.001). Persistent RBC transfusions beyond 30 days post-transplant was associated with both inferior PFS and OS (p=0.04 and p=0.0009, respectively). Conclusions Restrictive prophylactic transfusion thresholds in alloSCT recipients is feasible. Limited PI PLT transfusion was not associated with transfusion-attributable GVHD, GF or infectious complications. Future prospective studies should determine the short term hemostatic efficacy and long term post-alloSCT outcomes with restrictive transfusion criteria in an era of expanding PI product use. [ABSTRACT FROM AUTHOR]