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  1. Article ; Online: Reduced-Intensity Compared to Nonmyeloablative Conditioning in Patients with Non-Hodgkin Lymphoma Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

    Nath, Karthik / Peterson, Kristen / Brown, Samantha / Devlin, Sean / Rodriguez, Natasia / Barker, Juliet / Giralt, Sergio / Gyurkocza, Boglarka / Jakubowski, Ann / Papadopoulos, Esperanza / Ponce, Doris / Scordo, Michael / Shah, Gunjan / Perales, Miguel-Angel / Sauter, Craig / Lin, Andrew / Dahi, Parastoo B

    Transplantation and cellular therapy

    2023  Volume 30, Issue 1, Page(s) 81–92

    Abstract: Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning are preferred for patients with non-Hodgkin lymphoma (NHL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). Although prior studies have suggested that ... ...

    Abstract Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning are preferred for patients with non-Hodgkin lymphoma (NHL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). Although prior studies have suggested that higher-intensity regimens in RIC-NMA conditioning are associated with inferior outcomes in patients with NHL, the optimal conditioning regimen remains unknown. We performed a retrospective single-center analysis to determine outcomes of adult patients with B cell and T cell NHL who underwent allo-HCT and received either RIC or NMA conditioning between March 2008 and December 2019. RIC regimens included fludarabine-cyclophosphamide-thiotepa-4 Gy-total body irradiation (Flu-Cy-TT-4Gy-TBI), fludarabine-melphalan (Flu-Mel), fludarabine-cyclophosphamide-4 Gy-total body irradiation (Flu-Cy-4Gy-TBI), and fludarabine-busulfan-4 (Flu-Bu-4). The NMA regimen comprised fludarabine-cyclophosphamide-2 Gy-total body irradiation (Flu-Cy-2Gy-TBI). The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), nonrelapse mortality (NRM), and the incidence of acute and chronic graft-versus-host-disease (GVHD). Of 279 transplants recipients (median age, 58 years), 110 received RIC (55% Flu-Mel, 38% Flu-Cy-TT-4Gy-TBI, 6% Flu-Bu-4, 1% Flu-Cy-4Gy-TBI) and 169 received NMA conditioning with Flu-Cy-2Gy-TBI. With a median of 64 months of follow-up post-allo-HCT, there was no significant difference in OS between the NMA and RIC groups (median, not reached [NR] versus 103 months; P = .1), and this was maintained on multivariable analysis. Similarly, after adjustment for all independently significant covariates (age, Karnofsky Performance Status [KPS], Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI], and disease histology), the regression analysis showed no significant difference in PFS with RIC compared to NMA conditioning (hazard ratio [HR] 1.38; 95% confidence interval [CI], .92 to 2.09; P = .24). On univariable analysis, there was no significant difference in NRM between the RIC and NMA arms (100-day estimate, 10.0% versus 1.8%; P = .5). After adjustment for age, ethnicity, KPS, HCT-CI, GVHD prophylaxis, and donor source, RIC conditioning was associated with a significantly higher incidence of NRM compared to NMA conditioning (HR, 2.61; 95% CI, 1.04 to 6.52; P = .039). On multivariable analysis, compared with the NMA arm, the RIC arm had higher rates of grade II-IV (HR, 2.25; 95% CI, 1.31 to 3.86; P = .002) and grade III-IV acute GVHD (HR, 5.62; 95% CI, 2.03 to 15.6; P < .001). The findings of this study suggest that NMA conditioning with Flu-Cy-TBI-2Gy may be considered over more intensive RIC regimens for patients with NHL undergoing allo-HCT.
    MeSH term(s) Adult ; Humans ; Middle Aged ; Retrospective Studies ; Transplantation, Homologous/adverse effects ; Survival Analysis ; Hematopoietic Stem Cell Transplantation/adverse effects ; Lymphoma, Non-Hodgkin/complications ; Lymphoma, Non-Hodgkin/drug therapy ; Cyclophosphamide/therapeutic use ; Graft vs Host Disease/epidemiology ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Busulfan/therapeutic use ; Thiotepa
    Chemical Substances Cyclophosphamide (8N3DW7272P) ; Busulfan (G1LN9045DK) ; Thiotepa (905Z5W3GKH)
    Language English
    Publishing date 2023-10-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2023.09.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5082: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Oral Proteasome Inhibitor Ixazomib for Switch-Maintenance Prophylaxis of Recurrent or Late Acute and Chronic Graft-versus-Host Disease after Day 100 in Allogeneic Stem Cell Transplantation.

    Rodriguez, Natasia / Lee, Jasme / Flynn, Lisa / Murray, Fiona / Devlin, Sean M / Soto, Cristina / Cho, Christina / Dahi, Parastoo / Giralt, Sergio / Perales, Miguel-Angel / Sauter, Craig / Ponce, Doris M

    Transplantation and cellular therapy

    2021  Volume 27, Issue 11, Page(s) 920.e1–920.e9

    Abstract: Graft-versus-host disease (GVHD) is a frequent complication in the first year after allogeneic stem cell transplantation (allo-HCT). Recipients of reduced-intensity (RI) or nonmyeloablative (NMA) conditioning combined with calcineurin inhibitor (CNI)- ... ...

    Abstract Graft-versus-host disease (GVHD) is a frequent complication in the first year after allogeneic stem cell transplantation (allo-HCT). Recipients of reduced-intensity (RI) or nonmyeloablative (NMA) conditioning combined with calcineurin inhibitor (CNI)-based GVHD prophylaxis frequently develop GVHD in the context of immunosuppression taper. Ixazomib is an oral proteasome inhibitor with a wide safety profile that has demonstrated immunomodulatory properties, inhibition of pro-inflammatory cytokines, and anti-tumor activity. We hypothesized that switch-maintenance GVHD prophylaxis using ixazomib would facilitate CNI taper without increased GVHD frequency and severity while maintaining graft-versus-tumor (GVT) effect and an acceptable safety profile. We conducted an open-label, prospective, single-center pilot study in patients with hematologic malignancies who received an RI or NMA conditioning and CNI-based GVHD prophylaxis that were within day 100 to 150 after HCT (n = 18). Patients were treated with ixazomib once weekly on a 28-day cycle (3 weeks on, 1 week off). Treatment was safe; most adverse events were grade 1 or 2, with cytopenia and elevation in transaminases the most common. Five patients were removed from the study because of toxicity or side effects. Only 5 of 18 patients developed GVHD during the study, and its severity was driven by acute manifestations while chronic involvement was mild. The cumulative incidence of grade II-IV acute and chronic GVHD at 1-year after HCT was 33% (95% confidence interval [CI], 13-55). No patients died during the study, and only 1 had malignant relapse. An additional patient relapsed after completion of the study but within 1 year after HCT. The probability of progression-free survival and GVHD-free/relapse-free survival (composite endpoint) at 1 year were 89% (95% CI, 75-100) and 78% (95% CI, 61-100), respectively. Immune reconstitution analysis showed a rapid and sustained recovery in T-cell subpopulations and B cell reconstitution, and vaccine response in a subset of patients demonstrated continuing or de novo positive protective antibody titers. This study demonstrated low incidence of recurrent and late acute and chronic GVHD within 1 year after HCT possible associated with switch-maintenance GVHD prophylaxis using ixazomib. This approach allowed for CNI taper while preserving GVT effect, without aggravating GVHD. Our findings support further development of this approach and provide a proof-of-concept for switch-maintenance GVHD prophylaxis.
    MeSH term(s) Boron Compounds ; Glycine/analogs & derivatives ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Neoplasm Recurrence, Local ; Pilot Projects ; Prospective Studies ; Proteasome Inhibitors/therapeutic use
    Chemical Substances Boron Compounds ; Proteasome Inhibitors ; ixazomib (71050168A2) ; Glycine (TE7660XO1C)
    Language English
    Publishing date 2021-05-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2021.05.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5082: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: A prospective study of dysgeusia and related symptoms in patients with multiple myeloma after autologous hematopoietic cell transplantation.

    Scordo, Michael / Shah, Gunjan L / Adintori, Peter A / Knezevic, Andrea / Devlin, Sean M / Buchan, Marissa L / Preston, Elaina V / Lin, Andrew P / Rodriguez, Natasia T / Carino, Caroline A / Nguyen, Linh K / Sitner, Nancy Cruz / Barasch, Andrei / Klang, Mark G / Maloy, Molly A / Mastrogiacomo, Brooke / Carlow, Dean C / Schofield, Ryan C / Slingerland, Ann E /
    Slingerland, John B / Stein-Thoeringer, Christoph K / Lahoud, Oscar B / Landau, Heather J / Chung, David J / van den Brink, Marcel R M / Peled, Jonathan U / Giralt, Sergio A

    Cancer

    2022  Volume 128, Issue 21, Page(s) 3850–3859

    Abstract: Background: Dysgeusia is a common but understudied complication in patients undergoing autologous hematopoietic cell transplantation (auto-HCT). We assessed the feasibility of using chemical gustometry (CG) to measure dysgeusia and explored its ... ...

    Abstract Background: Dysgeusia is a common but understudied complication in patients undergoing autologous hematopoietic cell transplantation (auto-HCT). We assessed the feasibility of using chemical gustometry (CG) to measure dysgeusia and explored its associations with symptom burden, nutrition, chemotherapy pharmacokinetics (PK), and the oral microbiome.
    Methods: We conducted a single-center, prospective feasibility study (NCT03276481) of patients with multiple myeloma undergoing auto-HCT. CG was performed longitudinally testing five flavors (sweet, sour, salty, bitter, umami) to calculate a total taste score (maximum score, 30). We measured caloric intake and patient-reported symptoms, assessing their correlation with oral microbiota composition and salivary and blood melphalan PK exposure.
    Results: Among all 45 patients, 39 (87%) completed at least four (>60%) and 22 (49%) completed all six CG assessments. Median total CG scores remained stable over time but were lowest at day +7 (27, range 24-30) with recovery by day +100. Symptom burden was highest by day +10 (area under the curve, 2.9; range, 1.0-4.6) corresponding with the lowest median overall caloric intake (1624 kcal; range, 1345-2267). Higher serum/salivary melphalan levels correlated with higher patient-reported dysgeusia and lower caloric intake. Oral microbiota α-diversity was stable early and increased slightly by day +100.
    Conclusions: Assessment of dysgeusia by CG is feasible after auto-HCT. Most dysgeusia, symptom burden, and lowest caloric intake occurred during the blood count nadir. Higher melphalan concentrations correlated with more dysgeusia and poorer caloric intake. Future studies will aim to modulate melphalan exposure by PK-targeted dosing and characterize patient taste preferences to personalize diets for improved nutritional intake.
    Lay summary: Taste changes after cancer treatments are very common. We used chemical gustometry (taste testing) to study taste changes and to better understand why patients with multiple myeloma experience this symptom after autologous hematopoietic cell transplantation. We found that taste testing was feasible, taste changes peaked when blood counts were lowest, and most patients recovered their taste by 100 days after transplantation. Taste changes correlated with lower food intake and with higher levels of chemotherapy in the body. Future work will focus on using personalized chemotherapy doses to reduce taste changes and to match patients' individual taste preferences with their diets.
    MeSH term(s) Dysgeusia/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Melphalan ; Multiple Myeloma/therapy ; Prospective Studies ; Transplantation, Autologous/adverse effects
    Chemical Substances Melphalan (Q41OR9510P)
    Language English
    Publishing date 2022-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1429-1
    ISSN 1097-0142 ; 0008-543X ; 1934-662X
    ISSN (online) 1097-0142
    ISSN 0008-543X ; 1934-662X
    DOI 10.1002/cncr.34444
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.146: Show issues Location:
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  4. Article ; Online: Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse.

    DeWolf, Susan / Elhanati, Yuval / Nichols, Katherine / Waters, Nicholas R / Nguyen, Chi L / Slingerland, John B / Rodriguez, Natasia / Lyudovyk, Olga / Giardina, Paul A / Kousa, Anastasia I / Andrlová, Hana / Ceglia, Nick / Fei, Teng / Kappagantula, Rajya / Li, Yanyun / Aleynick, Nathan / Baez, Priscilla / Murali, Rajmohan / Hayashi, Akimasa /
    Lee, Nicole / Gipson, Brianna / Rangesa, Madhumitha / Katsamakis, Zoe / Dai, Anqi / Blouin, Amanda G / Arcila, Maria / Masilionis, Ignas / Chaligne, Ronan / Ponce, Doris M / Landau, Heather J / Politikos, Ioannis / Tamari, Roni / Hanash, Alan M / Jenq, Robert R / Giralt, Sergio A / Markey, Kate A / Zhang, Yanming / Perales, Miguel-Angel / Socci, Nicholas D / Greenbaum, Benjamin D / Iacobuzio-Donahue, Christine A / Hollmann, Travis J / van den Brink, Marcel R M / Peled, Jonathan U

    Science translational medicine

    2023  Volume 15, Issue 706, Page(s) eabq0476

    Abstract: T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across ... ...

    Abstract T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.
    MeSH term(s) Humans ; Mice ; Animals ; T-Lymphocytes/pathology ; Hematopoietic Stem Cell Transplantation ; Graft vs Host Disease/pathology ; Receptors, Antigen, T-Cell
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-07-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abq0476
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6941: Show issues Location:
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