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  • American Society of Hematology  (31)
  • 1
    In: Blood Advances, American Society of Hematology, Vol. 5, No. 6 ( 2021-03-23), p. 1648-1659
    Abstract: Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI] , 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 2
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1848-1848
    Abstract: Background Allogeneic hematopoietic stem cell transplantation (HCT) is the optimal and potentially curative therapy in various high-risk hematologic malignancies. Although a human leukocyte antigen (HLA)-matched sibling or unrelated donor is a clinically preferred stem cell source, the use of haploidentical family donors and umbilical cord blood HCT now offers the option of HCT in patients lacking a matched donor. However, many patients lack an appropriate donor, in particular the ethnic minorities. Mismatched unrelated donors (MMUD) have historically been utilized as alternative donor source for these patients due to ease of donor availability but is associated with increased risk of graft versus host disease (GVHD) and non-relapse mortality (NRM). In this systematic review and meta-analysis, we aimed to assess the outcomes with MMUD HCT. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was performed on three databases (PubMed, Cochrane Library, and ClinicalTrials.gov) from date of inception through February 2021 using the MeSH and entry terms for "hematopoietic stem cell transplantation", OR "hematologic neoplasms", AND unrelated donors" AND "treatment outcome". A total of 2477 records were identified and primary and secondary screening was done. After excluding review, duplicate, and non-relevant articles, we included 13 studies (11 retrospective, 2 prospective) reporting outcomes following MMUD HCT. The Joanna Briggs Institute (JBI) critical appraisal checklist for studies reporting prevalence data and randomized control trial was used for quality assessment, and all studies were reported as good. Proportions along with a 95% confidence interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.16-2). The variance between the studies was calculated using Der Simonian-Laird Estimator. Results: We identified 2588 patients from 13 included studies who had MMUD HCT. (Table 1) Median age was 51.7 (18-76) years and 52% (n=1347) were males. Source of primary graft was bone marrow (BM) in 19% (n=478/2508) and peripheral blood (PB) in 81% (n=2030/2508) HCT recipients. Median time to transplant was 10.45 (1.5-139.6) months and median follow up was 41.5 (0.4-136.5) months. Reduced intensity conditioning (RIC) conditioning was used for 73% (n=1884) of the patients while 27.2% (n= 704) patients received myeloablative conditioning (MAC). We estimated a pooled overall survival (OS) of 59% (95% CI 0.52-0.66, I 2 = 92%, n=2563) at one year and 44% (0.36-0.53, I 2=92%, n=1972) at three years. The pooled incidence of acute GVHD (grade II-IV), acute GVHD (grade III-IV), and chronic GVHD were 39% (95% CI 0.33-0.44, I 2=84%, n=2282), 19% (95% CI 0.15-0.23, I 2=65%, n=1417), and 38% (95% CI 0.32-0.47, I 2=93%, n=2477) respectively. Progression free survival (PFS) was 39.5% (95% CI 0.31-0.48, I 2=94% n=2505). The pooled incidence of relapse rate (RR) and NRM were 31% (95% CI 0.25-0.38, I 2=90%, n=2482) and 27% (95% CI 0.21-0.34, I 2 =90% n=2448) respectively. Conclusion: Mismatched unrelated donor HCT has shown favorable outcomes with acceptable toxicity profile. MMUD HCT represents a promising option for patients lacking an HLA-matched donor and has expanded access to HCT in patients with ethnic minorities who often lack a matched donor. Figure 1 Figure 1. Disclosures Abhyankar: Incyte/Therakos: Consultancy, Research Funding, Speakers Bureau. McGuirk: Juno Therapeutics: Consultancy, Honoraria, Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; Gamida Cell: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; EcoR1 Capital: Consultancy; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Astelllas Pharma: Research Funding; Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 3
    In: Blood, American Society of Hematology, Vol. 138, No. 11 ( 2021-09-16), p. 992-996
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 4
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 10545-10546
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 5
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3889-3889
    Abstract: Background: Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells and may be the only allogeneic transplant option for some patients with hematologic malignancies. However, UCB transplantation is associated with delayed blood count recovery and engraftment. In preclinical studies, we have demonstrated that hyperbaric oxygen (HBO) therapy, given prior to cytokine expanded and gene-transduced UCB CD34+ cell infusion, improves peripheral blood, bone marrow, and spleen engraftment in a murine model. Based on these results, we started a pilot clinical trial primarily investigating the safety of HBO in the setting of UCB transplantation. Secondarily, we are evaluating the time to neutrophil and platelet count recovery and engraftment.As a potential marker for effective HBO therapy, we also evaluated serum erythropoietin (EPO) levels in transplanted patients prior to HBO therapy and again at time of transplantation. Materials/methods: Patients with hematological malignancies that require UCB transplantation, either reduced intensity or myeloablative, were included. On day 0, patients received HBO treatment consisting of exposure to 2.5 atmosphere absolutes for a total of 2 hours, in a single hyperbaric chamber, breathing 100% oxygen. Six hours from the start of HBO, single or double UCB units were infused and patients were followed daily for toxicity and blood count recovery. Serum EPO levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: 18 patients were screened for this study, 9 were enrolled, and 9 were treated. The treated subjects were 5 males (56%) and 4 females (44%) with median age of 44 (23-70) who had acute myeloid leukemia (n=6), non-Hodgkin’s lymphoma (n=1), and acute lymphoblastic leukemia (n=2); all patients were in first (n=8) or second (n=1) complete remission. All but two patients received one UCB unit with a median total nucleated cell dose of 3.3 (2.7-4.5) ×107 /Kg recipient body weight and 6 of 9 patients received reduced intensity conditioning. All treated patients completed the planned therapy without a treatment limiting toxicity defined as the occurrence of any of the following complications within 24 hours of HBO: seizure disorder, pneumothorax, death or irreversible grade III or any grade IV toxicity that is determined by the treating physician to be, at least, likely related to HBO therapy. None of the patients experienced an unexpected toxicity. All patients engrafted except for one patient who demonstrated prompt autologous blood count recovery. Platelet count recovery was not assessable in one patient. Time to neutrophil count recovery (defined as the first of 3 consecutive days of an absolute neutrophil count (ANC) of greater than 500/μL) and time to platelet count recovery (defined as the first day of a sustained platelet count greater than 20 K/UL) were 16 (6-25) and 32 (8-87), respectively. 90% or higher donor chimerism was documented in peripheral blood/bone marrow of engrafted patients receiving reduced intensity regimen at a median of 18 (15-31) days post-transplant. Six of the 9 (67%) patients developed acute graft versus host disease at time of engraftment; 50% developed grade I, 33% had grade II and 17% had grade III. In 7 patients who had serum EPO levels assessed, median EPO levels at time of UCB infusion were lower than their median levels prior to HBO therapy (11.3 vs. 25.2 mU/mL). Conclusions: HBO therapy prior to UCB cell infusion appears to be well-tolerated in the setting of clinical umbilical cord blood transplantation. Time to neutrophil recovery/engraftment as well as platelet count recovery appear to be encouraging. HBO therapy resulted in lower EPO serum levels at time of UCB infusion. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 6
    Online Resource
    Online Resource
    American Society of Hematology ; 2022
    In:  Blood Vol. 140, No. Supplement 1 ( 2022-11-15), p. 8374-8375
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 8374-8375
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 7
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 10481-10483
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 8
    In: Blood, American Society of Hematology, Vol. 139, No. 23 ( 2022-06-09), p. 3430-3438
    Abstract: Life-threatening thrombotic events at unusual sites have been reported after vector-based vaccinations against severe acute respiratory syndrome coronavirus 2. This phenomenon is now termed vaccine-induced immune thrombotic thrombocytopenia (VITT). The pathophysiology of VITT is similar to that of heparin-induced thrombocytopenia (HIT) and is associated with platelet-activating antibodies (Abs) against platelet factor 4 (PF4). Therefore, current guidelines suggest nonheparin anticoagulants to treat VITT patients. In this study, we investigated the interactions of heparin, danaparoid, fondaparinux, and argatroban with VITT–Ab/PF4 complexes using an ex vivo model for thrombus formation as well as in vitro assays to analyze Ab binding and platelet activation. We found that immunoglobulin Gs (IgGs) from VITT patients induce increased adherent platelets/thrombus formation in comparison with IgGs from healthy controls. In this ex vivo flow-based model, the procoagulant activity of VITT IgGs was effectively inhibited with danaparoid and argatroban but also by heparin. Interestingly, heparin and danaparoid not only inhibited IgG binding to PF4 but were also able to effectively dissociate the preformed PF4/IgG complexes. Fondaparinux reduced the in vitro generation of procoagulant platelets and thrombus formation; however, it did not affect platelet aggregation. In contrast, argatroban showed no effect on procoagulant platelets and aggregation but significantly inhibited VITT-mediated thrombus formation. Taken together, our data indicate that negatively charged anticoagulants can disrupt VITT–Ab/PF4 interactions, which might serve as an approach to reduce Ab-mediated complications in VITT. Our results should be confirmed, however, in a clinical setting before a recommendation regarding the selection of anticoagulants in VITT patients could be made.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2147-2147
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2147-2147
    Abstract: Introduction: Acute myeloid leukemia (AML) is a disease with poor overall prognosis, about 4.3 per 100,000 men and women per year are diagnosed with AML with a deaths rate of 2.8 per 100,000. The incidence of AML increases with age which leads to an older population with multiple comorbidities and inferior prognosis. Hematopoietic stem cell transplant (HCT) remains the standard of care in most intermediate and high-risk AML patients. However, HCT puts these patients at risk of severe cytopenia, opportunistic infections, acute graft versus host disease and financial stress, especially in the early phases of transplant. The purpose of this study is to identify the annual trends in in-hospital mortality and morbidity associated with patients with AML admitted for HCT and impact of comorbid conditions on the likelihood of death during admission. Method Data was collected from the National Inpatient Sample from the years of 2002 to 2014. Admissions for HCT for acute myeloid leukemia patients were identified using a procedural clinical classification software code for bone marrow transplants in combination with ICD 9 codes for acute myeloid leukemia. Annual trends in mortality, hospital length of stay, and costs of admission were assessed with a linear regression analysis. Univariate logistic regression analysis was used to test for associations between chronic medical conditions and mortality among these patients. Co-morbid conditions were identified using the Agency for Healthcare Research and Quality comorbidity measures for underlying chronic conditions in patients in 2013 to 2014. Results: Between and including the years of 2002 to 2014, a total weighted estimate of transplants for acute myeloid leukemias in the United States totaled 31,811 (N=6,102). Annual transplants increased from 1,761 in 2002 to 3,030 in 2014. In-hospital mortality decreased from 8.4% in 2002 to 4.8% in 2014 (p=0.02). The mean length of stay remained unchanged from 32.8 days in 2002 to 32.7 days in 2014. Costs of admission increased from $226,280 to $474,106. In-hospital mortality in the years 2013 and 2014 were most strongly associated with comorbid conditions of congestive heart failure (Odds ratio (OR)=5.93), weight loss (OR=4.32), coagulopathy (OR=3.84), liver cirrhosis (OR=3.41). Any two of these conditions increased the OR to 8.34. Conclusions: HCTs have traditionally been associated with high upfront including in-hospital mortality. Our data demonstrates that in the last two decades mortality has been reduced by almost 50% while the length of hospital stay has not changed. This could be related to improvements in supportive care and better selection of conditioning regimens for the patients. It also shows that the costs of hospitalization has doubled. Congestive heart failure, weight loss, underlying coagulopathy and liver cirrhosis are most strongly associated with worse outcomes with any combination of these further potentiating risk of death. Careful selection of patients with special attention to the pre-existing comorbidities is the key to improving early outcomes in HCT. Consideration should also be given to expanding infrastructure to perform outpatient transplants to bend the cost curve. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    Online Resource
    Online Resource
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5740-5740
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5740-5740
    Abstract: Introduction: Myelofibrosis is a myeloproliferative neoplasm characterized by ineffective hematopoiesis, inflammation, and increased deposition of reticulin in the bone marrow. It can arise de novo [primary myelofibrosis] or secondary to the transformation of essential thrombocythemia or polycythemia vera. Prognosis in intermediate and high-risk patients is reduced, and allogeneic stem cell transplantation is the only curative option. In this single-center retrospective study, we aim to assess the results of allogeneic stem cell transplantation for the treatment of myelofibrosis patients. Methods: Disease characteristics, treatments, and outcomes data from 23 consecutive myelofibrosis patients receiving allogeneic stem cell transplantation at a single large volume transplant center between 2013-2018 were retrospectively collected. Results: The median age was 57 years (Range: 32-74 years). The diagnosis was primary myelofibrosis in 14 patients, post-ET myelofibrosis in 6 patients, and post-PV myelofibrosis in 3 patients. DIPSS at the time of transplant was Intermediate-1 in 7 patients, Intermediate-2 in 14 patients and High risk in 2 patients. 9 patients underwent HCT from HLA identical siblings, 12 from matched unrelated donors, and 2 from haploidentical donors. 21 patients received reduced-intensity conditioning, whereas 2 patients received myeloablative conditioning regimens. Tacrolimus and methotrexate was the preferred GVHD prophylaxis regimen, which was used in 20 out of 23 patients. JAK-2 was primary driver mutation in 16 patients, CALR in one patient and 6 additional patients were JAK-2 negative with unknown CALR and MPL status. 21 patients received pre-transplant ruxolitinib. The median follow up was 18 months. Median overall survival and relapse-free survival were not reached. 6 months and 1 year OS was 82% and 70% respectively. Treatment-related mortality at 100 days and one-year post-transplant was 8.6% and 26% respectively. Treatment-related mortality was due to GVHD in 5 patients and infection in 2 patients. 3 patients died from disease progression/relapse. Grade II-IV aGVHD developed in 60% of the patients, with 26% of the patients developing grade III-IV aGVHD. Chronic GVHD developed in 65% of the patients. The median time to neutrophil and platelet engraftment was 26 days (Range 12-150 days) and 17 days (Range: 14-38 days) respectively. Two patients developed primary graft failure, and one patient developed secondary graft failure. At the time of data cutoff, 13 patients are alive, all of whom remain in hematological remission. Conclusions: Allogeneic stem cell transplantation offers the chance of long term survival and potential cure for patients with intermediate and high-risk myelofibrosis. However, allogeneic stem cell transplantation is associated with an increased risk of early mortality and graft versus host disease. The above results compare favorably with previously reported literature. Careful selection of patients is of the utmost importance for transplantation in myelofibrosis. Table Disclosures Yacoub: Incyte: Consultancy, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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