137 results on '"Bejanyan N"'
Search Results
2. Oral Mucosal Sparing in High-Dose Total Body Irradiation (TBI) prior to Stem Cell Transplantation (SCT) for Acute Leukemia
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Liveringhouse, C., primary, Sandoval, M.L., additional, Dohm, A.E., additional, Weygand, J., additional, Garcia, G., additional, Peters, J., additional, Nieder, M., additional, Faramand, R., additional, Jain, M.D., additional, Locke, F.L., additional, Bejanyan, N., additional, Kim, S., additional, Robinson, T.J., additional, and Latifi, K., additional
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- 2022
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3. MDS disease characteristics, not donor source, predict hematopoietic stem cell transplant outcomes
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Pourhassan, H, DeFor, T, Trottier, B, Dolan, M, Brunstein, C, Bejanyan, N, Ustun, C, and Warlick, E D
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- 2017
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4. Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival
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Lunde, L E, Dasaraju, S, Cao, Q, Cohn, C S, Reding, M, Bejanyan, N, Trottier, B, Rogosheske, J, Brunstein, C, Warlick, E, Young, J A H, Weisdorf, D J, and Ustun, C
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- 2015
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5. Immunotherapy: ZEDENOLEUCEL (MT-401, MUTLI-TUMOR ASSOCIATED ANTIGEN-SPECIFIC T CELLS) UTILIZED FOR TREATMENT FOR MRD+ AML PATIENTS
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Arslan, S., primary, Liu, H., additional, silverman, M., additional, Bejanyan, N., additional, McCallum, R., additional, Quintero, S., additional, Garrett, G., additional, Wang, K., additional, Smith, E., additional, Hoang, T., additional, Shahim, T., additional, Crisostomo, J., additional, Wilga-Savitski, A., additional, Pickering, J., additional, Angelo, L., additional, Smith, A., additional, Vera, J., additional, and Koneru, M., additional
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- 2022
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6. Clinical outcomes of AML patients relapsing after matched-related donor and umbilical cord blood transplantation
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Bejanyan, N, Oran, B, Shanley, R, Warlick, E, Ustun, C, Vercellotti, G, Verneris, M, Wagner, J E, Weisdorf, D, and Brunstein, C
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- 2014
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7. TP53 mutations in myeloid malignancies are either homozygous or hemizygous due to copy number-neutral loss of heterozygosity or deletion of 17p
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Jasek, M, Gondek, L P, Bejanyan, N, Tiu, R, Huh, J, Theil, K S, O'Keefe, C, McDevitt, M A, and Maciejewski, J P
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- 2010
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8. Lower Graft-versus-Host Disease and Relapse Risk in Post-Transplant Cyclophosphamide Based Haploidentical versus Matched Sibling Donor Reduced-Intensity Conditioning Transplant for Hodgkin Lymphoma
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Ahmed, S, Kanakry, JA, Ahn, KW, Litovich, C, Abdel-Azim, H, Aljurf, M, Bacher, VU, Bejanyan, N, Cohen, JB, Farooq, U, Fuchs, EJ, Bolanos-Meade, J, Ghosh, N, Herrera, AF, Hossain, NM, Inwards, D, Kanate, AS, Martino, R, Munshi, PN, Murthy, H, Mussetti, A, Nieto, Y, Perales, MA, Romee, R, Savani, BN, Seo, S, Wirk, B, Yared, JA, Sureda, A, Fenske, TS, and Hamadani, M
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Haploidentical transplantation ,hemic and lymphatic diseases ,Allogeneic transplantation ,Hodgkin lymphoma ,Alternative donor - Abstract
Classic Hodgkin lymphoma (cHL) patients with relapsed or refractory disease may benefit from allogeneic hematopoietic cell transplantation (allo-HCT), but many lack a matched sibling donor (MSD). Herein, we compare outcomes of 2 reduced-intensity conditioning (RIC) Ha platforms in cHL: T cell-replete related donor haploidentical (haplo) HCT with a post-transplant cyclophosphamide (PTCy)-based approach versus an MSD/calcineurin inhibitor (CNI)-based approach. The study included 596 adult patients who underwent a first RIC allo-HCT for cHL between 2008 and 2016 using either a haplo-PTCy (n = 139) or MSD/CNI-based (n = 457) approach. Overall survival (OS) was the primary endpoint. Secondary endpoints included acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). On multivariate analysis, there was no significant difference between haplo/PTCy and MDS/CNI-based approaches in terms of OS (hazard ratio [HR], 1.07; 95% confidence interval [CI], .79 to 1.45; P = .66) or PFS (HR, .86; 95% CI, .68 to 1.10; P=.22). Haplo/PTCy was associated with a significantly higher risk of grades II to IV aGVHD (odds ratio [OR], 1.73, 95% CI, 1.16 to 2.59; P=.007), but the risk of grades III to IV aGVHD was not significantly different between the 2 cohorts (OR, .61; 95% Cl, .29 to 1.27; P=.19). The haplo/PTCy platform provided a significant reduction in cGVHD risk (HR, .45; 95% CI, .32 to .64; P < .001), and a significant reduction in relapse risk (HR, .74; 95% CI, .56 to.97; P=.03). There was a statistically nonsignificant trend toward higher NRM with a haplo/PTCy approach (HR, 1.65; 95% Cl, .99 to 2.77; P = .06). Haplo/PTCy-based approaches are associated with lower incidences of cGVHD and relapse, with PFS and OS outcomes comparable with MSD/CNI-based approaches. There was a leaning toward higher NRM with a haplo/PTCy-based platform. These data show that haplo/PTCy allo-HCT in cHL results in survival comparable with MSD/CNI-based allo-HCT. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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- 2019
9. Importance of conditioning regimen intensity, MRD positivity, and KIR ligand mismatch in UCB transplantation
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Ustun, C, primary, Brunstein, C, additional, DeFor, T, additional, Rashidi, A, additional, Yohe, S, additional, Bejanyan, N, additional, Cooley, S, additional, Warlick, E, additional, Miller, J, additional, Linden, M A, additional, and Weisdorf, D, additional
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- 2017
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10. MDS disease characteristics, not donor source, predict hematopoietic stem cell transplant outcomes
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Pourhassan, H, primary, DeFor, T, additional, Trottier, B, additional, Dolan, M, additional, Brunstein, C, additional, Bejanyan, N, additional, Ustun, C, additional, and Warlick, E D, additional
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- 2016
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11. Umbilical cord blood transplantation is a suitable option for consolidation of acute myeloid leukemia with FLT3-ITD
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Eckfeldt, C. E., primary, Randall, N., additional, Shanley, R. M., additional, Yohe, S., additional, Bejanyan, N., additional, Dolan, M., additional, Warlick, E. D., additional, Verneris, M. R., additional, Brunstein, C. G., additional, Wagner, J. E., additional, Weisdorf, D. J., additional, and Ustun, C., additional
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- 2016
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12. Improved graft-versus-host disease-free, relapse-free survival associated with bone marrow as the stem cell source in adults
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Mehta, R. S., primary, de Latour, R. P., additional, DeFor, T. E., additional, Robin, M., additional, Lazaryan, A., additional, Xhaard, A., additional, Bejanyan, N., additional, de Fontbrune, F. S., additional, Arora, M., additional, Brunstein, C. G., additional, Blazar, B. R., additional, Weisdorf, D. J., additional, MacMillan, M. L., additional, Socie, G., additional, and Holtan, S. G., additional
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- 2016
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13. Predictive Factors for Adverse Outcomes After Use of Donor Cell Infusion (DCI) in Patients with Relapsed Hematological Malignancies Treated with Allogeneic Hematopoietic Cell Transplantation (alloHCT)
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Bejanyan, N., primary, Bolwell, B., additional, Rybicki, L., additional, Abounader, D., additional, Duong, H., additional, Dean, R., additional, Sobecks, R., additional, Andresen, S., additional, Pohlman, B., additional, Copelan, E., additional, and Kalaycio, M., additional
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- 2012
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14. The Slope of Circulating Blast Clearance Does Not Predict Disease Relapse After Allogeneic Stem Cell Transplantation
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Lazaryan, A., primary, Bejanyan, N., additional, Rybicki, L., additional, Tench, S., additional, Andresen, S., additional, Sobecks, R., additional, Dean, R., additional, Pohlman, B., additional, Kalaycio, M., additional, Bolwell, B., additional, and Copelan, E., additional
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- 2011
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15. Sustained High-Dose Corticosteroid Use Does Not Independently Diminish Survival After Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
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Bejanyan, N., primary, Lazaryan, A., additional, Rybicki, L., additional, Tench, S., additional, Andresen, S., additional, Sobecks, R., additional, Dean, R., additional, Pohlman, B., additional, Kalaycio, M., additional, Bolwell, B., additional, and Copelan, E., additional
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- 2011
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16. Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8+ large granular lymphocyte leukemia
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Mohan, S. R., primary, Clemente, M. J., additional, Afable, M., additional, Cazzolli, H. N., additional, Bejanyan, N., additional, Wlodarski, M. W., additional, Lichtin, A. E., additional, and Maciejewski, J. P., additional
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- 2009
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17. TP53 mutations in myeloid malignancies are either homozygous or hemizygous due to copy number-neutral loss of heterozygosity or deletion of 17p
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Jasek, M, primary, Gondek, L P, additional, Bejanyan, N, additional, Tiu, R, additional, Huh, J, additional, Theil, K S, additional, O'Keefe, C, additional, McDevitt, M A, additional, and Maciejewski, J P, additional
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- 2009
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18. 515 - Immunotherapy: ZEDENOLEUCEL (MT-401, MUTLI-TUMOR ASSOCIATED ANTIGEN-SPECIFIC T CELLS) UTILIZED FOR TREATMENT FOR MRD+ AML PATIENTS.
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Arslan, S., Liu, H., silverman, M., Bejanyan, N., McCallum, R., Quintero, S., Garrett, G., Wang, K., Smith, E., Hoang, T., Shahim, T., Crisostomo, J., Wilga-Savitski, A., Pickering, J., Angelo, L., Smith, A., Vera, J., and Koneru, M.
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- *
ACUTE myeloid leukemia , *IMMUNOTHERAPY , *T cells , *CYTOTOXIC T cells - Published
- 2022
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19. Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation
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Amado J Karduss-Urueta, Francesca Ferraro, Dongyun Yang, Stefan O. Ciurea, Mohamad Mohty, Ryotaro Nakamura, Gérard Socié, Armin Ghobadi, Yener Koc, Boris V. Afanasyev, Myriam Labopin, Martin Bornhäuser, Stephen J. Forman, Partow Kebriaei, Richard E. Champlin, Monzr M. Al Malki, Arnon Nagler, Grzegorz Helbig, Sally Mokhtari, Asad Bashey, Arne Brecht, Fabio Ciceri, Arnold Ganser, Emanuele Angelucci, Nelli Bejanyan, Riitta Niittyvuopio, Al Malki, M. M., Yang, D., Labopin, M., Afanasyev, B., Angelucci, E., Bashey, A., Socie, G., Karduss-Urueta, A., Helbig, G., Bornhauser, M., Niittyvuopio, R., Ganser, A., Ciceri, F., Brecht, A., Koc, Y., Bejanyan, N., Ferraro, F., Kebriaei, P., Mokhtari, S., Ghobadi, A., Nakamura, R., Forman, S. J., Champlin, R., Mohty, M., Ciurea, S. O., and Nagler, A.
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Adult ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Retrospective Studies ,Lymphoid Neoplasia ,business.industry ,Incidence (epidemiology) ,Hematology ,Matched Unrelated Donor ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Minimal residual disease ,3. Good health ,Calcineurin ,Transplantation ,Graft-versus-host disease ,030220 oncology & carcinogenesis ,Methotrexate ,business ,Unrelated Donors ,030215 immunology ,medicine.drug - Abstract
We compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.
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- 2020
20. Allogeneic Hematopoietic Cell Transplantation for the Treatment of Severe Aplastic Anemia: Evidence-Based Guidelines from the American Society for Transplantation and Cellular Therapy.
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Iftikhar R, DeFilipp Z, DeZern AE, Pulsipher MA, Bejanyan N, Burroughs LM, Kharfan-Dabaja MA, Arai S, Kassim A, Nakamura R, Saldaña BJD, Aljurf M, Hamadani M, Carpenter PA, and Antin JH
- Abstract
Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe aplastic anemia (SAA). Existing guidance about HCT in SAA is primarily derived from expert reviews, registry data and societal guidelines; however, transplant-specific guidelines for SAA are lacking. A panel of SAA experts, both pediatric and adult transplant physicians, developed consensus recommendations using Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology employing a GRADE guideline development tool. The panel agrees with previous recommendations for the preferential use of bone marrow as a graft source and the use of rabbit over horse antithymocyte globulin (ATG) for HCT conditioning. Fludarabine containing regimens are preferred for patients at high risk of graft failure and those receiving matched unrelated or haploidentical donor transplant. Given advancements in HCT, the panel does not endorse the historical 40-year age cut-off for considering upfront HCT in adults, acknowledging that fit older patients may also benefit from HCT. The panel also endorses increased utilization of HCT by prioritizing matched unrelated or haploidentical donor HCT over immunosuppressive therapy in children and adults who lack a matched related donor. Finally, the panel suggests either calcineurin inhibitor plus methotrexate or post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis for matched related or matched unrelated donor recipients. These recommendations reflect a significant advancement in transplant strategies for SAA and highlight the importance of ongoing and further research to revisit current evidence in terms of donor choice, conditioning chemotherapy, GVHD prophylaxis and post-transplant immunosuppression., Competing Interests: Declaration of competing interest 1. Kharfan A Dabaja: Research/grant from pharmacyclics, Bristol Myers Squibb and Novartis. Lecture/honoraria from Kite Pharma. 2. Mehdi Hamadani reports research support/Funding: Takeda Pharmaceutical Company; ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite, AbbVie, Caribou, Genmab, Autolus. Speaker's Bureau: ADC Therapeutics, AstraZeneca, Bei Gene, Kite. DMC: Inc, Genentech, Myeloid Therapeutics, CRISPR 3. Amy E DeZern participated in advisory boards, and/or had a consultancy with and received honoraria from Celgene/BMS, Agios, Regeneron, Sobi, Novartis, Astellas, Gilead. AED served on clinical trial committees and DSMB for Novartis, Abbvie, Kura, Geron and Celgene/BMS. 3. Paul A. Carpenter participated in advisory boards, and/or had a consultancy with and received honoraria from Abbvie, Sanofi, Incyte, Johnson and Johnson. 4. Michael A. Pulsipher participated in advisory boards, and/or had a consultancy with and received honoraria from Vertex, Novartis, Bluebird, Gentibio, Cargo, and Pfizer. He is on a study steering committee for Autolous and Novartis. He has received research support from Miltenyi and Adaptive. 5. Lauri M. Burroughs received research support from Medac, is a member of the DSMB for Jasper Therapeutics, and served on an advisory board for Horizon Therapeutics USA., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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21. ASTCT Consensus Recommendations on Testing and Treatment of Patients with Donor-specific Anti-HLA Antibodies.
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Kongtim P, Vittayawacharin P, Zou J, Srour S, Shaffer B, Shapiro RM, Varma A, McGuirk J, Dholaria BR, McCurdy SR, DeZern AE, Bejanyan N, Bashey A, Furst S, Castagna L, Mariotti J, Ruggeri A, Bailen R, Teshima T, Xiao-Jun H, Bonfim C, Aung F, Cao K, Carpenter PA, Hamadani M, Askar M, Fernandez-Vina M, Girnita A, and Ciurea SO
- Abstract
Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients., Competing Interests: Declaration of competing interest PK - none for this work; other COI - consulting for CareDx and reseach funding from Eurofins Viracor PV - none declared JZ - none declared SS - none declared BS - none declared RMS - none declared AV - none declared JM - none for this work; other COI - honoraria from Kite, AlloVir, Bristol Myers Squibb, Novartis, CRISPR, Nektar Therapeutics, Caribou Bio, Sana Technologies, Legend Biotech and Cargo Therapeutics. BRD - none declared SRM – none declared AED - none for this work; participated in advisory boards, and/or had a consultancy with and received honoraria from Celgene/BMS, Agios, Regeneron, Sobi, Novartis, Astellas, Gilead. AED served on clinical trial steering committees or DSMB for Novartis, Abbvie, Kura, Geron and Celgene/BMS. NB – none for this work; consulting, advisory role or research funding with Magenta Therapeutics, Medexus Pharmaceuticals, CTI BioPharma, CareDx Pharma, Orca Bio, Allovir and CRISPR Therapeutics. AB – none declared SF – none declared LC – none declared JM – none declared AR - none declared RB - none for this work; travel & accommodation: Pfizer, Jazz Pharmaceuticals, Gilead Sciences, Sanofi. Research Funding: Jazz Pharmaceuticals. Speaker: Pfizer, Gilead Sciences. TT – none declared XH - none declared CB – none declared FA – none declared KC – none declared PAC – none for this work; consulting or advisory roles and/or research funding with Incyte, AbbVie and Sanofi MH - none for this work; research support/funding from ADC Therapeutics; Spectrum, Pharmaceuticals; Astellas Pharma, consultancy for ADC Therapeutics, Omeros, BMS, Kite, Abbvie, Genmab, Allovir, CRISPR, Caribou, Autolus, Forte Biosciences, and speaker's bureau for ADC Therapeutics, AstraZeneca, Kite, Beigene MA – none for this work; director clinical services, Be The Match/National Marro Donor Program (NMDP), Minneapolis, MN MFV – none declared AG – none declared SOC – none for this work; reports participation is advisory board for Hansa Therapeutics, CardDx, Spetrum/Achrotech, Kiadis Pharma, Magenta, Allogene, Cellularity, MolMed, Pharmacyclics and received research funds from Miltenyi and Kiadis Pharma., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
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22. Donor types and outcomes of transplantation in myelofibrosis: a CIBMTR study.
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Jain T, Estrada-Merly N, Salas MQ, Kim S, DeVos J, Chen M, Fang X, Kumar R, Andrade-Campos M, Elmariah H, Agrawal V, Aljurf M, Bacher U, Badar T, Badawy SM, Ballen K, Beitinjaneh A, Bhatt VR, Bredeson C, DeFilipp Z, Dholaria B, Farhadfar N, Farhan S, Gandhi AP, Ganguly S, Gergis U, Grunwald MR, Hamad N, Hamilton BK, Inamoto Y, Iqbal M, Jamy O, Juckett M, Kharfan-Dabaja MA, Krem MM, Lad DP, Liesveld J, Al Malki MM, Malone AK, Murthy HS, Ortí G, Patel SS, Pawarode A, Perales MA, van der Poel M, Ringden O, Rizzieri DA, Rovó A, Savani BN, Savoie ML, Seo S, Solh M, Ustun C, Verdonck LF, Wingard JR, Wirk B, Bejanyan N, Jones RJ, Nishihori T, Oran B, Nakamura R, Scott B, Saber W, and Gupta V
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- Humans, Male, Female, Middle Aged, Adult, Treatment Outcome, Transplantation Conditioning methods, Aged, Graft vs Host Disease etiology, Tissue Donors, Registries, Unrelated Donors, Primary Myelofibrosis therapy, Primary Myelofibrosis mortality, Hematopoietic Stem Cell Transplantation methods
- Abstract
Abstract: We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)-HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched unrelated (MUD) HR, 4.50 [95% CI, 2.24-9.03]; mismatched unrelated HR, 5.13 [95% CI, 1.44-18.31]; P < .001). This difference in OS aligns with lower graft failure with MSD (haploidentical HR, 6.11 [95% CI, 2.98-12.54]; matched unrelated HR, 2.33 [95% CI, 1.20-4.51]; mismatched unrelated HR, 1.82 [95% CI, 0.58-5.72]). There was no significant difference in OS among haploidentical, MUD, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months after HCT, relapse, disease-free survival, or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. Although MSD-HCTs were superior, there is no significant difference in HCT outcomes from haploidentical and MUDs. These results establish haploidentical HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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23. Melphalan Dose in Combination With Fludarabine Affects Gastrointestinal Toxicity and Graft-Versus-Host Disease After Allogeneic Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndromes.
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Albanyan O, Elmariah H, Kalos D, Kim J, Faramand R, Sallman D, Mishra A, Sweet K, Perez L, Ochoa-Bayona J, Nieder M, Komrokji R, Lancet J, Fernandez H, Nishihori T, Pidala J, Anasetti C, and Bejanyan N
- Abstract
Fludarabine (Flu) and melphalan (Mel) reduced-intensity conditioning is frequently used for allogenic hematopoietic cell transplant (allo-HCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, there is limited evidence on the impact of Mel dosing on toxicities and clinical outcomes of allo-HCT. We retrospectively compared 8/8 HLA-matched donor allo-HCT outcomes of 345 patients with AML or MDS receiving total Mel dose of 100 mg/m
2 (Mel-100, n = 62) versus 140 mg/m2 (Mel-140, n = 283) in combination with Flu. Median age at allo-HCT was 66 years and median follow-up was 36.5 months. For Mel-100 versus Mel-140 groups, any grade gastrointestinal (GI) toxicity rates were 40.3% versus 67.8% (P < .001), day 100 grade II to IV acute graft-versus-host disease (GVHD) rates were 21.0% versus 43.1% (P = .001) and 2-year chronic GVHD rates were 17.4% versus 27.1% (P = .033). In multivariable analysis, Mel-140 resulted in higher risks of GI toxicity (HR = 1.83, P = .013), grade II to IV acute GVHD (HR=2.35, P = .003), and moderate/severe chronic GVHD (HR = 3.13, P = .007). Total Mel dose had no independent impact on oral mucositis, nonrelapse mortality, relapse, relapse-free survival, and overall survival. While independent validation of our observation is warranted, our findings support using Mel-100 in combination with Flu to minimize allo-HCT toxicities and morbidities related to GVHD., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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24. JAK2/mTOR Inhibition Fails to Prevent Acute GVHD Despite Reduced Th1/Th17 cells: Final Phase II Trial Results.
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Pidala JA, Holtan SG, Walton K, Kim J, Cao B, Elmariah H, Mishra A, Bejanyan N, Nishihori T, Khimani F, Perez LE, Faramand RG, Davila ML, McSain S, Pleskow J, Baron J, Anasetti C, Moran Segura CM, Weisdorf DJ, Blazar BR, Miller JS, Bachanova V, El Jurdi N, and Betts BC
- Abstract
Our phase I graft-versus-host disease (GVHD) prevention trial of JAK2 inhibitor, pacritinib, (recommended phase II dose: 100mg po BID day 0 to +70) plus sirolimus and tacrolimus (PAC/SIR/TAC) demonstrated the regimen was safe and free of pan-JAK myelosuppression after allogeneic hematopoietic cell transplantation (alloHCT). PAC inhibits IL-6 receptor activity and pathogenic Th1/Th17 differentiation in preclinical models and the phase I trial. Herein we report on our completed phase II trial of PAC/SIR/TAC after 8/8-HLA matched alloHCT. This single-arm phase II trial (NCT02891603) was powered to determine if PAC/SIR/TAC suppressed %pSTAT3+ CD4+ T cells at day +21 (primary endpoint: %pSTAT3+ CD4+ T cells ≤ 35%) and estimated grade II-IV acute GVHD by day +100. The impact of PAC/SIR/TAC on T cell subsets, CD28 (pS6 and pH3ser10), and IL-2 receptor (pSTAT5) signal transduction was also evaluated. Eligible patients (n=28) received alloHCT for hematologic malignancies or myeloproliferative neoplasms. Reduced or myeloablative intensity conditioning was permitted. PAC/SIR/TAC met the primary endpoint, reducing %pSTAT3+ CD4+ T cells to 9.62% at day +21. Th1/Th17 cells were decreased at day +21, increasing the ratio of Tregs to Th1 and Th17 cells with PAC/SIR/TAC at RP2D PAC compared to dose level 1 PAC. The cumulative incidence of grade II-IV acute GVHD by day +100 with PAC/SIR/TAC was similar to historic SIR/TAC values (46 v 43%). While PAC/SIR/TAC suppressed pSTAT3 and Th1/Th17 cells, the regimen did not improve acute GVHD prevention., (Copyright © 2024 American Society of Hematology.)
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- 2024
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25. Lower Weight-Based Mycophenolate Mofetil Dosing is Associated with Superior Outcomes after Haploidentical Hematopoietic Cell Transplant with Post-transplant Cyclophosphamide.
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Elmariah H, Otoukesh S, Kumar A, Haris Ali, Shukaib Arslan, Dimaggio E, Gonzalez R, Shouse G, Pourhassan H, Taiga Nishihori, Faramand R, Mishra A, Khimani F, Fernandez H, Lazaryan A, Nieder M, Perez L, Liu H, Ryotaro Nakamura, Pidala J, Guido Marcucci, Stephen J Forman, Anasetti C, Bejanyan N, and Monzr M Al Malki
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Transplantation, Haploidentical, Body Weight, Immunosuppressive Agents therapeutic use, Immunosuppressive Agents administration & dosage, Hematologic Neoplasms therapy, Treatment Outcome, Aged, Tacrolimus therapeutic use, Tacrolimus administration & dosage, Young Adult, Mycophenolic Acid therapeutic use, Mycophenolic Acid administration & dosage, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease prevention & control
- Abstract
Mycophenolate mofetil (MMF) is commonly included in post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prophylaxis after haploidentical (haplo) hematopoietic cell transplant (HCT). In the non-PTCy setting, higher MMF dose/kg has been shown to reduce rates of acute graft-versus-host disease (GVHD). When used in conjunction with PTCy, MMF is dosed at 15 mg/kg three times daily up to a maximum dose of 3 g/day. Thus, patients who weigh ≥67 kg receive 3 g/day and a variable dose/kg of MMF. We investigated the impact of MMF dose/kg on clinical outcomes following haploidentical PBSCT with PTCy-based GVHD prophylaxis. All consecutive adult patients with hematologic malignancies receiving haploidentical T cell replete peripheral blood stem cell transplant (PBSCT) with PTCy/MMF and either tacrolimus or sirolimus at the Moffitt Cancer Center or City of Hope between April 2014-August 2020 were included. For analyses, MMF dose relative to patient actual body weight (mg/kg/day), was stratified into categories of low (<29 mg/kg/day), low intermediate (29-34 mg/kg/day), high intermediate (35-41 mg/kg/day), and high (>41 mg/kg/day). Three hundred eighty-six patients were included. Of these, 54 patients received low dose, 73 low intermediate, 137 high intermediate and 122 high dose MMF by relative weight exposure. In multivariate analysis, low MMF dose exposure was associated with reduced rates of relapse in comparison to the high dose group (HR = 0.45, 95% CI: 0.21 to 0.94, P = .03). This led to superior PFS among patients with low compared to high MMF dose exposure (HR = 0.58, 95% CI: 0.34 to 0.99, P = .045). MMF relative dose exposure was not associated with engraftment, GVHD, nonrelapse mortality, or OS. In this study of patients receiving haploidentical PBSCT with PTCy based GVHD prophylaxis, low MMF dose/kg was associated with improved rates of relapse and PFS. Future prospective studies should investigate optimal dosing strategies of MMF when given with the PTCy regimen., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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26. Hypomethylating Agents and Venetoclax for Acute Myeloid Leukemia Relapsed After Hematopoietic Stem Cell Transplant.
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Ionescu F, David JC, Ravichandran A, Sallman DA, Sweet K, Komrokji RS, Chan O, Kuykendall A, Padron E, Faramand R, Bejanyan N, Khimani F, Elmariah H, Pidala J, Mishra A, Perez L, Nishihori T, and Lancet JE
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Aged, Retrospective Studies, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols adverse effects, Recurrence, Hematopoietic Stem Cell Transplantation methods, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Bridged Bicyclo Compounds, Heterocyclic pharmacology, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Sulfonamides pharmacology, Sulfonamides therapeutic use, Nucleophosmin
- Abstract
Background: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment., Patients and Methods: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival. We leveraged our larger sample to analyze the impact of cytogenetic/molecular features on the odds of CR/CRi., Results: CR/CRi was achieved among 32 of 67 (48%) patients, and MRD negativity was recorded among 10 of 12. NPM1 and IDH 1 or 2 mutations increased the odds of CR/CRi, as did increasing time from alloHCT to relapse. Fourteen patients subsequently received donor lymphocyte infusions or a second alloHCT. Responses lasted a median of 17.8 months (95% CI, 7.2 months to not reached), and responders had a greater median overall survival of 19.7 months (95% CI, 7.6-51.5 months) compared to 2.9 months among nonresponders (95% CI, 1.8-4.4 months; log-rank P < .01). Treatment was well tolerated, but prolonged cytopenias were common and most patients required reduction in the number of venetoclax days per cycle., Conclusion: These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases. These responses can be durable and profound as evidenced by conversion to MRD negativity., Competing Interests: Disclosures Authors reports no conflicts of interest. The study received no external funding., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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27. Mismatched donor allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide achieves comparable outcomes between racially and ethnically diverse patient populations.
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Caprice T, Fan W, Kim J, Faramand R, Mishra A, Perez L, Khimani F, Lazaryan A, Ochoa-Bayona JL, Liu H, Jain MD, Nieder M, Anasetti C, Nishihori T, Pidala JA, Bejanyan N, and Elmariah H
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Ethnicity, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Immunosuppressive Agents therapeutic use, Transplantation, Homologous, Treatment Outcome, Racial Groups, Histocompatibility Testing, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Hematopoietic Stem Cell Transplantation
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- 2024
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28. Sirolimus Is an Acceptable Alternative to Tacrolimus for Graft-versus-Host Disease Prophylaxis after Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide.
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Elmariah H, Otoukesh S, Kumar A, Ali H, Arslan S, Shouse G, Pourhassan H, Nishihori T, Faramand R, Mishra A, Khimani F, Fernandez H, Lazaryan A, Nieder M, Perez L, Liu H, Nakamura R, Pidala J, Marcucci G, Forman SJ, Anasetti C, Locke F, Bejanyan N, and Al Malki MM
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- Humans, Adolescent, Young Adult, Adult, Middle Aged, Aged, Tacrolimus therapeutic use, Sirolimus therapeutic use, Retrospective Studies, Neoplasm Recurrence, Local drug therapy, Cyclophosphamide therapeutic use, Mycophenolic Acid therapeutic use, Peripheral Blood Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cell Transplantation methods, Graft vs Host Disease prevention & control
- Abstract
Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor HCT. A phase II study from the Moffitt Cancer Center substituting sirolimus (Siro) for Tac in this prophylactic regimen reported comparable rates of grade II-IV acute GVHD (aGVHD). Many centers have substituted Siro for Tac in this setting based on a preferable side effect profile, although comparative data are limited. In this study, we retrospectively compared outcomes in haplo-HCT with PTCy/Siro/MMF versus haplo-HCT with PTCy/Tac/MMF. The study cohort included all consecutive patients receiving haploidentical donor T cell-replete peripheral blood stem cell (PBSC) HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. A total of 423 patients were included, of whom 84 (20%) received PTCy/Siro/MMF and 339 (80%) received PTCy/Tac/MMF. The median age for the entire cohort was 54 years (range, 18 to 78 years), and the median follow-up was 30 months. The Siro group had a higher proportion of patients age ≥60 years (58% versus 34%; P < .01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV aGVHD (45% versus 47%; P = .6) at day +100 or chronic GVHD (cGVHD) (47% versus 54%; P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better in the Tac group (odds ratio, .30; 95% confidence interval, .1 to .83; P = .02), with a median time to engraftment of 17 days versus 18 days in the Siro group, but platelet engraftment was similar in the 2 groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on aGVHD or cGVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease-free survival, or overall survival after PBSC haplo-HCT. These findings suggest that Siro is a comparable alternative to Tac in combination with PTCy/MMF for GVHD prophylaxis, with overall similar clinical outcomes despite delayed engraftment after peripheral blood stem cell haplo-HCT. Although Tac remains the standard of care, Siro may be substituted based on the side effect profile of these medications, with consideration of patient medical comorbidities at HCT., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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29. Association between CYP3A4 , CYP3A5 and ABCB1 genotype and tacrolimus treatment outcomes among allogeneic HSCT patients.
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Ho TT, Perkins JB, Gonzalez R, Hicks JK, Martinez RA, Duranceau K, North B, Kim J, Teer JK, Yao J, Yoder SJ, Nishihori T, Bejanyan N, Pidala J, and Elmariah H
- Subjects
- Humans, Tacrolimus, Cytochrome P-450 CYP3A genetics, Cytochrome P-450 CYP3A metabolism, Immunosuppressive Agents, Retrospective Studies, Treatment Outcome, Genotype, ATP Binding Cassette Transporter, Subfamily B genetics, Graft vs Host Disease drug therapy, Graft vs Host Disease genetics, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation methods
- Abstract
Aim: Successful treatment with tacrolimus to prevent graft versus host disease (GVHD) and minimize tacrolimus-related toxicities among allogeneic hematopoietic cell transplantation (alloHCT) recipients is contingent upon quickly achieving and maintaining concentrations within a narrow therapeutic range. The primary objective was to investigate associations between CYP3A4, CYP3A5 or ABCB1 genotype and the proportion of patients that attained an initial tacrolimus goal concentration following initiation of intravenous (iv.) and conversion to oral administration. Materials & methods: We retrospectively evaluated 86 patients who underwent HLA-matched (8/8) related donor alloHCT and were prescribed a tacrolimus-based regimen for GVHD prophylaxis. Results & conclusion: The findings of the present study suggests that CYP3A5 genotype may impact attainment of initial therapeutic tacrolimus concentrations with oral administration in alloHCT recipients.
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- 2024
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30. Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis.
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Murthy HS, Zhang MJ, Chen K, Ahmed S, Deotare U, Ganguly S, Kansagra A, Michelis FV, Nishihori T, Patnaik M, Abid MB, Aljurf M, Arai Y, Bacher U, Badar T, Badawy SM, Ballen K, Battiwalla M, Beitinjaneh A, Bejanyan N, Bhatt VR, Brown VI, Martino R, Cahn JY, Castillo P, Cerny J, Chhabra S, Copelan E, Daly A, Dholaria B, Diaz Perez MA, Freytes CO, Grunwald MR, Hashmi S, Hildebrandt GC, Jamy O, Joseph J, Kanakry CG, Khera N, Krem MM, Kuwatsuka Y, Lazarus HM, Lekakis LJ, Liu H, Modi D, Munshi PN, Mussetti A, Palmisiano N, Patel SS, Rizzieri DA, Seo S, Shah MV, Sharma A, Sohl M, Solomon SR, Ulrickson M, Ustun C, van der Poel M, Verdonck LF, Wagner JL, Wang T, Wirk B, Zeidan A, Litzow M, Kebriaei P, Hourigan CS, Weisdorf DJ, Saber W, and Kharfan-Dabaja MA
- Subjects
- Humans, Middle Aged, Transplantation, Homologous, Neoplasm Recurrence, Local, Acute Disease, Chronic Disease, Recurrence, Dendritic Cells pathology, Hematopoietic Stem Cell Transplantation adverse effects, Myeloproliferative Disorders pathology
- Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
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31. Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients.
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Boyiadzis M, Zhang MJ, Chen K, Abdel-Azim H, Abid MB, Aljurf M, Bacher U, Badar T, Badawy SM, Battiwalla M, Bejanyan N, Bhatt VR, Brown VI, Castillo P, Cerny J, Copelan EA, Craddock C, Dholaria B, Perez MAD, Ebens CL, Gale RP, Ganguly S, Gowda L, Grunwald MR, Hashmi S, Hildebrandt GC, Iqbal M, Jamy O, Kharfan-Dabaja MA, Khera N, Lazarus HM, Lin R, Modi D, Nathan S, Nishihori T, Patel SS, Pawarode A, Saber W, Sharma A, Solh M, Wagner JL, Wang T, Williams KM, Winestone LE, Wirk B, Zeidan A, Hourigan CS, Litzow M, Kebriaei P, de Lima M, Page K, and Weisdorf DJ
- Subjects
- Adult, Humans, Transplantation, Homologous, Transplantation Conditioning, Neoplasm Recurrence, Local etiology, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute
- Abstract
We investigated the impact of the number of induction/consolidation cycles on outcomes of 3113 adult AML patients who received allogeneic hematopoietic cell transplantation (allo-HCT) between 2008 and 2019. Patients received allo-HCT using myeloablative (MAC) or reduced-intensity (RIC) conditioning in first complete remission (CR) or with primary induction failure (PIF). Patients who received MAC allo-HCT in CR after 1 induction cycle had 1.3-fold better overall survival (OS) than 2 cycles to CR and 1.47-fold better than ≥3 cycles. OS after CR in 2 or ≥3 cycles was similar. Relapse risk was 1.65-fold greater in patients receiving ≥3 cycles to achieve CR. After RIC allo-HCT, the number of induction cycles to CR did not affect OS. Compared to CR in 1 cycle, relapse risk was 1.24-1.41-fold greater in patients receiving 2 or ≥3 cycles. For patients receiving only 1 cycle to CR, consolidation therapy prior to MAC allo-HCT was associated with improved OS vs. no consolidation therapy. Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1-3 cycles., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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32. Correction to: Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113AML patients.
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Boyiadzis M, Zhang MJ, Chen K, Abdel-Azim H, Abid MB, Aljurf M, Bacher U, Badar T, Badawy SM, Battiwalla M, Bejanyan N, Bhatt VR, Brown VI, Castillo P, Cerny J, Copelan EA, Craddock C, Dholaria B, Perez MAD, Ebens CL, Gale RP, Ganguly S, Gowda L, Grunwald MR, Hashmi S, Hildebrandt GC, Iqbal M, Jamy O, Kharfan-Dabaja MA, Khera N, Lazarus HM, Lin R, Modi D, Nathan S, Nishihori T, Patel SS, Pawarode A, Saber W, Sharma A, Solh M, Wagner JL, Wang T, Williams KM, Winestone LE, Wirk B, Zeidan A, Hourigan CS, Litzow M, Kebriaei P, de Lima M, Page K, and Weisdorf DJ
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- 2023
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33. Hematopoietic Cell Transplantation in the Management of Myelodysplastic Syndrome: An Evidence-Based Review from the American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines.
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DeFilipp Z, Ciurea SO, Cutler C, Robin M, Warlick ED, Nakamura R, Brunner AM, Dholaria B, Walker AR, Kröger N, Bejanyan N, Atallah E, Tamari R, Solh MM, Percival ME, de Lima M, Scott B, Oran B, Garcia-Manero G, Hamadani M, Carpenter P, and DeZern AE
- Subjects
- Humans, United States, Aged, Transplantation Conditioning, Transplantation, Homologous, Recurrence, Hematopoietic Stem Cell Transplantation, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes genetics
- Abstract
The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and critically evaluated in the context of the evidence. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of MDS experts comprising transplantation and nontransplantation physicians developed consensus treatment recommendations. This review summarizes the standard MDS indications for HCT and addresses areas of controversy. Recent prospective trials have confirmed that allogeneic HCT confers survival benefits in patients with advanced or high-risk MDS compared with nontransplantation approaches, and the use of HCT is increasing in older patients with good performance status. However, patients with high-risk cytogenetic or molecular mutations remain at high risk for relapse. It is unknown whether administration of novel therapies before or after transplantation may decrease the risk of disease relapse in selected populations. Ongoing and future studies will investigate revised approaches to disease risk stratification, patient selection, and post-transplantation approaches to optimize allogeneic HCT outcomes for patients with MDS., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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34. Large Scale Ex Vivo Expansion of γδ T cells Using Artificial Antigen-presenting Cells.
- Author
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Boucher JC, Yu B, Li G, Shrestha B, Sallman D, Landin AM, Cox C, Karyampudi K, Anasetti C, Davila ML, and Bejanyan N
- Subjects
- T-Lymphocytes, Interleukin-2 pharmacology, Antigen-Presenting Cells
- Abstract
Higher γδ T cell counts in patients with malignancies are associated with better survival. However, γδ T cells are rare in the blood and functionally impaired in patients with malignancies. Promising results are reported on the treatment of various malignancies with in vivo expansion of autologous γδ T cells using zoledronic acid (zol) and interleukin-2 (IL-2). Here we demonstrated that zol and IL-2, in combination with a novel genetically engineered K-562 CD3scFv/CD137L/CD28scFv/IL15RA quadruplet artificial antigen-presenting cell (aAPC), efficiently expand allogeneic donor-derived γδ T cells using a Good Manufacturing Practice (GMP) compliant protocol sufficient to achieve cell doses for future clinical use. We achieved a 633-fold expansion of γδ T cells after day 10 of coculture with aAPC, which exhibited central (47%) and effector (43%) memory phenotypes. In addition, >90% of the expanded γδ T cells expressed NKG2D, although they have low cell surface expression of PD1 and LAG3 inhibitory checkpoint receptors. In vitro real-time cytotoxicity analysis showed that expanded γδ T cells were effective in killing target cells. Our results demonstrate that large-scale ex vivo expansion of donor-derived γδ T cells in a GMP-like setting can be achieved with the use of quadruplet aAPC and zol/IL-2 for clinical application., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2023
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35. Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma.
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Logue JM, Peres LC, Hashmi H, Colin-Leitzinger CM, Shrewsbury AM, Hosoya H, Gonzalez RM, Copponex C, Kottra KH, Hovanky V, Sahaf B, Patil S, Lazaryan A, Jain MD, Baluch A, Klinkova OV, Bejanyan N, Faramand RG, Elmariah H, Khimani F, Davila ML, Mishra A, Blue BJ, Grajales-Cruz AF, Castaneda Puglianini OA, Liu HD, Nishihori T, Freeman CL, Brayer JB, Shain KH, Baz RC, Locke FL, Alsina M, Sidana S, and Hansen DK
- Subjects
- Humans, Retrospective Studies, Standard of Care, Granulocyte Colony-Stimulating Factor, Multiple Myeloma therapy, Receptors, Chimeric Antigen, Thrombocytopenia, Anemia
- Abstract
Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On the KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard-of-care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day-90 follow-up. Data were censored at day 100. Grade ≥ 3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥ 3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 and 100 were 50% bacterial and 42% viral; only 13% were grade ≥ 3. On univariate analysis, high pre-CAR-T marrow myeloma burden (≥ 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥ 3 anemia at pre-LD were associated with grade ≥ 3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2022
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36. A gut-graft axis mediated by microbiota.
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Bejanyan N and Rashidi A
- Subjects
- CD4-Positive T-Lymphocytes, Gastrointestinal Microbiome, Hematopoietic Stem Cell Transplantation, Microbiota
- Published
- 2022
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37. Correction to: An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis.
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Jimenez Jimenez AM, De Lima M, Komanduri KV, Wang TP, Zhang MJ, Chen K, Abdel-Azim H, Abid MB, Aljurf M, Alkhateeb H, Assal A, Bacher U, Baron F, Battiwalla M, Beitinjaneh A, Bejanyan N, Bhatt VR, Byrne M, Cahn JY, Cairo M, Castillo P, Copelan E, DeFilipp Z, Perez MAD, Elsawy M, Gale RP, George B, Grunwald MR, Hildebrandt GC, Hogan WJ, Kanakry CG, Kansagra A, Kharfan-Dabaja MA, Khera N, Krem MM, Lazaryan A, Maakaron J, Martino R, McGuirk J, Michelis FV, Milone G, Mishra A, Murthy HS, Mussetti A, Nathan S, Nishihori T, Olsson RF, Palmisiano N, Patel S, Saad A, Seo S, Sharma A, Solh M, Verdonck LF, Wirk B, Yared JA, Litzow M, Kebriaei P, Hourigan CS, Saber W, and Weisdorf D
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- 2022
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38. Outcomes Following Intolerance to Tacrolimus/Sirolimus Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation.
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Mirza AS, Tandon A, Jenneman D, Cao S, Brimer T, Kumar A, Kidd M, Khimani F, Faramand R, Mishra A, Liu H, Nishihori T, Perez L, Lazaryan A, Bejanyan N, Nieder M, Anasetti C, Pidala J, and Elmariah H
- Subjects
- Adult, Humans, Retrospective Studies, Sirolimus adverse effects, Tacrolimus adverse effects, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation
- Abstract
Although tacrolimus and sirolimus (TAC/SIR) is an accepted graft-versus-host disease (GVHD) prophylaxis regimen following allogeneic hematopoietic cell transplantation (HCT), toxicity from this regimen can lead to premature discontinuation of immunosuppression. There are limited studies reporting outcomes and subsequent treatment of patients with TAC/SIR intolerance. This study was conducted to assess the outcomes of patients with TAC/SIR intolerance and guide their subsequent management. We retrospectively analyzed transplantation outcomes of consecutive adult patients at Moffitt Cancer Center who underwent allogeneic HCT with TAC/SIR as GVHD prophylaxis between 2009 and 2018. TAC/SIR intolerance was defined as discontinuation of either TAC or SIR due to toxicity before post-transplantation day +100. A total of 777 patients met the inclusion criteria. The median duration of follow-up was 22 months (range, 0.2 to 125 months). Intolerance occurred in 13% (n = 104) of the patients at a median of 30 days (range, 5 to 90 days). The most common causes of intolerance were acute kidney injury (n = 53; 51%), thrombotic microangiopathy (n = 31; 28%), and veno-occlusive disease (n = 23; 22%). The cumulative incidence of grade II-IV acute GVHD at 100 days was 50% (95% CI, 39% to 64%) in the TAC/SIR-intolerant patients and 25% (95% CI, 22% to 29%) in patients tolerant to this regimen (P < .0001). In multivariate analyses, the incidence of grade II-IV 4 acute GVHD was significantly higher in the TAC/SIR-intolerant patients (hazard ratio [HR], 2.40; 95% CI, 1.59 to 3.61; P < .0001). Similarly, in multivariate analyses, the TAC/SIR-intolerant patients had a higher incidence of chronic GVHD (HR, 1.48; 95% CI, 1.03 to 2.12; P = .03). The nonrelapse mortality (NRM) at 1 year was 47% (95% CI, 38% to 59%) in the TAC/SIR-intolerant patients and 12% (95% CI, 10% to 15%) in those tolerant to the regimen (P < .0001). The 2-year relapse-free survival was 35% (95% CI, 25% to 44%) in the TAC/SIR-intolerant patients and 60% (95% CI, 57% to 65%) in the TAC/SIR-tolerant patients (HR, 2.30; 95% CI, 1.61 to 3.28; P < .0001). Intolerance stratified by early (≤30 days) versus late (31 to 100 days) significantly affected the cumulative incidence of acute GVHD at 75% (early; 95% CI, 59% to 94%) versus 33% (late; 95% CI, 21% to 50%) (P = .001), as well as the cumulative incidence of NRM at 61% (early; 95% CI, 48% to 77%) versus 35% (late; 95% CI, 24% to 51%) (P = .006). Most patients who developed TAC/SIR intolerance were switched to an alternative 2-drug regimen (71 of 104; 68%), most commonly mycophenolate mofetil in addition to continuing TAC or SIR (68 of 71; 96%). Overall, TAC/SIR intolerance was associated with poorer outcomes. Early intolerance contributed to a higher risk of acute GVHD, increased NRM, and inferior survival. Patients with early intolerance were often switched to an alternative agent, and patients with late intolerance tended to be continued on single-drug therapy without substitution. The use of single-drug versus 2-drug regimens after intolerance did not appear to affect outcomes. Management strategies to mitigate the risks of intolerance are warranted., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report. Financial disclosure: No disclosures relevant to this work., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2022
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39. Cytokine Release Syndrome Following Peripheral Blood Stem Cell Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide.
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Otoukesh S, Elmariah H, Yang D, Clark MC, Siraj M, Ali H, Mogili K, Arslan S, Nishihori T, Nakamura R, Pidala J, Marcucci G, Forman SJ, Anasetti C, Al Malki MM, and Bejanyan N
- Subjects
- Cyclophosphamide therapeutic use, Cytokine Release Syndrome, Humans, Neoplasm Recurrence, Local complications, Graft vs Host Disease epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cells
- Abstract
Post-transplantation cyclophosphamide (PTCy) is a safe and efficacious graft-versus-host-disease (GVHD) prophylaxis following hematopoietic cell transplantation (HCT) from a haploidentical (haplo) donor. Cytokine release syndrome (CRS) is a common complication of this platform. Early fever post-haplo-HCT using bone marrow grafts is associated with higher CD3
+ cell dose and CRS. However, the impact of CD3+ and CD34+ cell dose on CRS post-haplo-HCT using peripheral blood stem cell (PBSC) grafts is unknown. Our goals were to evaluate the incidence of CRS following PBSC transplantation (PBSCT) and to identify factors that can be modified to prevent the development of severe CRS in this setting. In 271 patients, we investigated factors associated with the development of CRS following haplo-PBSCT and examined the impact of CRS on clinical outcomes. Ninety-three percent of the patients developed CRS of any grade post-haplo-PBSCT. In multivariate analysis, severe CRS (grade 3-4 versus grade 0-1) was associated with higher nonrelapse mortality (hazard ratio [HR], 6.42; 95% confidence interval [CI], 2.68 to 15.39; P < .001), worse 1-year overall survival (HR, 3.40; 95% CI, 1.63 to 7.08; P = .005), and worse disease-free survival (HR, 4.02; 95% CI, 1.99 to 8.08; P < .001). Moderate to severe CRS (grade 2-4) did not impact 1-year relapse or acute GVHD (grade II-IV and III-IV) at 100 days (P = .71 and .19, respectively). Importantly, higher CD3+ cell dose, but not CD34+ cell dose, predicted a higher incidence of grade 2-4 CRS (HR, 1.20; 95% CI,1.07 to 1.36; P = .003) and grade 3-4 CRS (HR, 1.40; 95% CI, 1.05 to 1.86; P = .022). Both older age (HR, 8.57; 95% CI, 1.73 to 42.36; P < .001) and non-total body irradiation-based reduced-intensity conditioning with fludarabine/melphalan (HR, 15.38; 955 CI, 2.06 to 114.67; P < .001) were predictive of grade 3-4 CRS. Overall, we observed that severe CRS (grade 3-4) negatively affected transplantation outcome, and that higher CD3 cell dose was associated with the development of any grade CRS and severe CRS., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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40. A phase 2 multicenter trial of ofatumumab and prednisone as initial therapy for chronic graft-versus-host disease.
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Lazaryan A, Lee S, Arora M, Kim J, Betts BC, Khimani F, Nishihori T, Bejanyan N, Liu H, Kharfan-Dabaja MA, Locke FL, Gonzalez R, Jain MD, Davila ML, Perez LE, Mishra A, Perez Perez A, Balke K, Ayala E, Ochoa L, Castaneda Puglianini O, Faramand R, Alsina M, Elmariah H, Nieder ML, Fernandez H, Anasetti C, and Pidala JA
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- Antibodies, Monoclonal, Humanized therapeutic use, Drug Therapy, Combination adverse effects, Humans, Immunosuppression Therapy, Prednisone therapeutic use, Graft vs Host Disease drug therapy
- Abstract
Standard initial therapy of chronic graft vs. host disease (cGVHD) with glucocorticoids results in suboptimal response. Safety and feasibility of therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) was previously established in our phase I trial (n = 12). We now report the mature results of the phase II expansion of the trial (n = 38). The overall NIH severity of cGVHD was moderate (63%) or severe (37%) with 74% of all patients affected by the overlap subtype of cGVHD and 82% by prior acute cGVHD. The observed 6 month clinician-reported and 2014 NIH-defined overall response rates (ORR = complete + partial response [CR/PR]) of 62.5% (1-sided lower 90% confidence interval=51.5%) were not superior to pre-specified historic benchmark of 60%. Post-hoc comparison of 6 month NIH response suggested benefit compared to more contemporaneous NIH-based benchmark of 48.6% with frontline sirolimus/prednisone (CTN 0801 trial). Baseline cGVHD features (organ involvement, severity, initial immune suppression agents) were not significantly associated with 6-month ORR. The median time to initiation of second-line therapy was 5.4 months (range 0.9-15.1 months). Failure-free survival (FFS) was 64.2% (95% CI 46.5-77.4%) at 6 months and 53.1% (95% CI 35.8-67.7%) at 12 months, whereas FFS with CR/PR at 12 months of 33.5% exceeded a benchmark of 15% in post-hoc analysis, and was associated with greater success in steroid discontinuation by 24 months (odds ratio 8 (95% CI 1.21-52.7). This single-arm phase II trial demonstrated acceptable safety and potential efficacy of the upfront use of ofatumumab in combination with prednisone in cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01680965., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
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41. Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.
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Menghrajani K, Gomez-Arteaga A, Madero-Marroquin R, Zhang MJ, Bo-Subait K, Sanchez J, Wang HL, Aljurf M, Assal A, Bacher VU, Badawy SM, Bejanyan N, Bhatt VR, Bredeson C, Byrne M, Castillo P, Cerny J, Chhabra S, Ciurea SO, DeFilipp Z, Farhadfar N, Gadalla S, Gale RP, Ganguly S, Gowda L, Grunwald MR, Hashmi S, Hildebrandt G, Kanakry CG, Kansagra A, Khimani F, Krem M, Lazarus H, Liu H, Martino R, Michelis FV, Nathan S, Nishihori T, Olsson R, Reshef R, Rizzieri D, Rowe JM, Savani BN, Seo S, Sharma A, Solh M, Ustun C, Verdonck LF, Hourigan C, Sandmaier B, Litzow M, Kebriaei P, Weisdorf D, Zhang Y, Tallman MS, and Saber W
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- Humans, Recurrence, Remission Induction, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
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42. An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis.
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Jimenez Jimenez AM, De Lima M, Komanduri KV, Wang TP, Zhang MJ, Chen K, Abdel-Azim H, Abid MB, Aljurf M, Alkhateeb H, Assal A, Bacher U, Baron F, Battiwalla M, Beitinjaneh A, Bejanyan N, Bhatt VR, Byrne M, Cahn JY, Cairo M, Castillo P, Copelan E, DeFilipp Z, Perez MAD, Elsawy M, Gale RP, George B, Grunwald MR, Hildebrandt GC, Hogan WJ, Kanakry CG, Kansagra A, Kharfan-Dabaja MA, Khera N, Krem MM, Lazaryan A, Maakaron J, Martino R, McGuirk J, Michelis FV, Milone G, Mishra A, Murthy HS, Mussetti A, Nathan S, Nishihori T, Olsson RF, Palmisiano N, Patel S, Saad A, Seo S, Sharma A, Solh M, Verdonck LF, Wirk B, Yared JA, Litzow M, Kebriaei P, Hourigan CS, Saber W, and Weisdorf D
- Subjects
- Humans, Retrospective Studies, Risk Assessment, Transplantation Conditioning, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N = 181), intermediate (IM, N = 1185), and adverse (Adv, N = 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p < 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p < 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p < 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p ≤ 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p < 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2021
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43. Allogeneic Transplantation to Treat Therapy-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Adults.
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Metheny L, Callander NS, Hall AC, Zhang MJ, Bo-Subait K, Wang HL, Agrawal V, Al-Homsi AS, Assal A, Bacher U, Beitinjaneh A, Bejanyan N, Bhatt VR, Bredeson C, Byrne M, Cairo M, Cerny J, DeFilipp Z, Perez MAD, Freytes CO, Ganguly S, Grunwald MR, Hashmi S, Hildebrandt GC, Inamoto Y, Kanakry CG, Kharfan-Dabaja MA, Lazarus HM, Lee JW, Nathan S, Nishihori T, Olsson RF, Ringdén O, Rizzieri D, Savani BN, Savoie ML, Seo S, van der Poel M, Verdonck LF, Wagner JL, Yared JA, Hourigan CS, Kebriaei P, Litzow M, Sandmaier BM, Saber W, Weisdorf D, and de Lima M
- Subjects
- Humans, Middle Aged, Retrospective Studies, Transplantation Conditioning, Transplantation, Homologous, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy
- Abstract
Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with t-AML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT., (Copyright © 2021. Published by Elsevier Inc.)
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- 2021
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44. Increased Infections and Delayed CD4 + T Cell but Faster B Cell Immune Reconstitution after Post-Transplantation Cyclophosphamide Compared to Conventional GVHD Prophylaxis in Allogeneic Transplantation.
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Khimani F, Ranspach P, Elmariah H, Kim J, Whiting J, Nishihori T, Locke FL, Perez Perez A, Dean E, Mishra A, Perez L, Lazaryan A, Jain MD, Nieder M, Liu H, Faramand R, Hansen D, Alsina M, Ochoa L, Davila M, Anasetti C, Pidala J, and Bejanyan N
- Subjects
- CD4-Positive T-Lymphocytes, Cyclophosphamide therapeutic use, Humans, T-Lymphocytes, Transplantation, Homologous, Graft vs Host Disease prevention & control, Immune Reconstitution
- Abstract
Post-transplantation cyclophosphamide (PTCy) is being increasingly used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation (allo-HCT) across various donor types. However, immune reconstitution and infection incidence after PTCy-based versus conventional GVHD prophylaxis has not been well studied. We evaluated the infection density and immune reconstitution (ie, absolute CD4
+ T cell, CD8+ T cell, natural killer cell, and B cell counts) at 3 months, 6 months, and 1 year post-HCT in 583 consecutive adult patients undergoing allo-HCT with myeloablative (n = 223) or reduced-intensity (n = 360) conditioning between 2012 and 2018. Haploidentical (haplo; n = 75) and 8/8 HLA-matched unrelated (MUD; n = 08) donor types were included. GVHD prophylaxis was PTCy-based in all haplo (n = 75) and in 38 MUD allo-HCT recipients, whereas tacrolimus/methotrexate (Tac/MTX) was used in 89 and Tac/Sirolimus (Tac/Sir) was used in 381 MUD allo-HCT recipients. Clinical outcomes, including infections, nonrelapse mortality (NRM), relapse, and overall survival (OS), were compared across the 4 treatment groups. The recovery of absolute total CD4+ T-cell count was significantly lower in the haplo-PTCy and MUD-PTCy groups compared with the Tac/MTX and Tac/Sir groups throughout 1 year post-allo-HCT (P = .025). In contrast, CD19+ B-cell counts at 6 months and thereafter were higher in the haplo-PTCy and MUD-PTCy groups compared with the Tac/MTX and Tac/Sir groups (P < .001). Total CD8+ T cell and NK cell recovery was not significantly different among the groups. Infection density analysis showed a significantly higher frequency of total infections in the haplo-PTCy and MUD-PTCy groups compared with the Tac/MTX and Tac/Sir groups (5.0 and 5.0 vs 1.8 and 2.6 per 1000-person days; P < .01) within 1 year of allo-HCT. The cumulative incidence of cytomegalovirus reactivation/infection at 1 year post-allo-HCT was higher in the haplo-PTCy group (51%) compared with the MUD-PTCy (26%), Tac/MTX (26%), or Tac/Sir (13%) groups (P < .001). The incidence of BK, human herpesvirus 6, and other viruses were also higher in the PTCy-based groups. Overall, the treatment groups had similar 2 year NRM (P = .27) and OS (P = .78) outcomes. Our data show that PTCy-based GVHD prophylaxis is associated with delayed CD4+ T cell but faster B cell immune reconstitution and a higher frequency of infections compared with conventional GVHD prophylaxis but has no impact on nonrelapse mortality or overall survival., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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45. Expansion and Enrichment of Gamma-Delta (γδ) T Cells from Apheresed Human Product.
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Landin AM, Cox C, Yu B, Bejanyan N, Davila M, and Kelley L
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- Humans, Interleukin-2, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Blood Component Removal, Receptors, Antigen, T-Cell, gamma-delta
- Abstract
Although Vγ9Vδ2 T cells are a minor subset of T lymphocytes, this population is sought after for its ability to recognize antigens in a major histocompatibility complex (MHC)-independent manner and develop strong cytolytic effector function that makes it an ideal candidate for cancer immunotherapy. Due to the low frequency of Gamma-Delta (γδ) T cells in the peripheral blood, we developed an effective protocol to greatly expand a highly pure γδ T cells drug product for first-in-human use of allogeneic γδ T cells in patients with acute myeloid leukemia (AML). Using healthy donor apheresis as an allogenic cell source, the lymphocytes are isolated using a validated device for a counterflow centrifugation method of separating cells by size and density. The lymphocyte-rich fraction is utilized, and the γδ T cells are preferentially activated with zoledronic acid (FDA-approved) and interleukin (IL)-2 for 7 days. Following the preferential expansion of γδ T cells, a clinical-grade magnetic cell-separation device and TCRαβ beads are used to deplete contaminating T-cell receptor (TCR)αβ T cells. The highly enriched γδ T cells then undergo a second expansion using engineered artificial antigen-presenting cells (aAPCs) derived from K562 cells-genetically engineered to express single-chain variable fragment (scFv) for CD3 and CD28, 41BBL (CD137L) and IL15-RA-together with zoledronic acid and IL-2. Seeding all day-7 enriched γδ T cells in co-culture with the aAPCs facilitates the manufacture of highly pure γδ T cells with an average fold expansion of >229,000-fold from healthy donor blood.
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- 2021
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46. Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation.
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Percival ME, Wang HL, Zhang MJ, Saber W, de Lima M, Litzow M, Kebriaei P, Abdel-Azim H, Adekola K, Aljurf M, Bacher U, Badawy SM, Beitinjaneh A, Bejanyan N, Bhatt V, Byrne M, Cahn JY, Castillo P, Chao N, Chhabra S, Copelan E, Cutler C, DeFilipp Z, Dias A, Diaz MA, Estey E, Farhadfar N, Frangoul HA, Freytes CO, Gale RP, Ganguly S, Gowda L, Grunwald M, Hossain N, Kamble RT, Kanakry CG, Kansagra A, Kharfan-Dabaja MA, Krem M, Lazarus HM, Lee JW, Liesveld JL, Lin R, Liu H, McGuirk J, Munker R, Murthy HS, Nathan S, Nishihori T, Olsson RF, Palmisiano N, Passweg JR, Prestidge T, Ringdén O, Rizzieri DA, Rybka WB, Savoie ML, Schultz KR, Seo S, Sharma A, Solh M, Strair R, van der Poel M, Verdonck LF, Yared JA, Weisdorf D, and Sandmaier BM
- Subjects
- Humans, Neoplasm, Residual, Prognosis, Remission Induction, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Abstract
Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2021
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47. Prognostic factors for clinical outcomes of patients with central nervous system leukemia.
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Bharucha J, Cao Q, Sachs Z, Smith A, Williams S, Amin K, Bachanova V, Warlick E, Brunstein C, Weisdorf D, and Bejanyan N
- Subjects
- Adolescent, Adult, Age Factors, Aged, Allografts, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Infant, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Central Nervous System Neoplasms diagnosis, Central Nervous System Neoplasms mortality, Central Nervous System Neoplasms therapy, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Stem Cell Transplantation
- Abstract
Prognostic factors associated with clinical outcomes of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients with central nervous system (CNS) involvement are unknown. We retrospectively studied the characteristics and outcomes of 66 (18 pediatric and 48 adult) patients with CNS leukemia with ALL (n = 41) or AML (n = 25). The median age of patients at diagnosis of CNS leukemia was 30 (range, 1-69) years. Nearly two-third patients had CNS involvement at the initial diagnosis of leukemia. Complete remission of CNS leukemia was attained in 58 (88%) patients, and probability of overall survival at 36 months after the diagnosis of CNS leukemia was 43% for the entire cohort. We identified that achieving remission of systemic leukemia and having CNS leukemia diagnosed and treated before allogeneic transplantation were the factors associated with CNS leukemia remission. Prognostic factors associated with better overall survival in patients with CNS leukemia included pediatric age, diagnosis of CNS leukemia before receiving allogenic transplantation, achieving clearance of systemic or CNS leukemia, receiving no cranial radiation in conjunction with intrathecal chemotherapy (IT), and receiving IT consolidation after achieving remission of CNS leukemia. Our findings show that patients with CNS leukemia are at considerable risk of mortality. Awareness of modifiable prognostic factors such as avoidance of cranial radiation whenever possible and use of IT consolidation can result in improved outcomes in subset of patients with CNS leukemia., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)
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- 2021
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48. Correction to: Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation.
- Author
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Percival ME, Wang HL, Zhang MJ, Saber W, de Lima M, Litzow M, Kebriaei P, Abdel-Azim H, Adekola K, Aljurf M, Bacher U, Badawy SM, Beitinjaneh A, Bejanyan N, Bhatt V, Byrne M, Cahn JY, Castillo P, Chao N, Chhabra S, Copelan E, Cutler C, DeFilipp Z, Dias A, Diaz MA, Estey E, Farhadfar N, Frangoul HA, Freytes CO, Gale RP, Ganguly S, Gowda L, Grunwald M, Hossain N, Kamble RT, Kanakry CG, Kansagra A, Kharfan-Dabaja MA, Krem M, Lazarus HM, Lee JW, Liesveld JL, Lin R, Liu H, McGuirk J, Munker R, Murthy HS, Nathan S, Nishihori T, Olsson RF, Palmisiano N, Passweg JR, Prestidge T, Ringdén O, Rizzieri DA, Rybka WB, Savoie ML, Schultz KR, Seo S, Sharma A, Solh M, Strair R, van der Poel M, Verdonck LF, Yared JA, Weisdorf D, and Sandmaier BM
- Published
- 2021
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49. Return to Work Among Young Adult Survivors of Allogeneic Hematopoietic Cell Transplantation in the United States.
- Author
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Bhatt NS, Brazauskas R, Salit RB, Syrjala K, Bo-Subait S, Tecca H, Badawy SM, Baker KS, Beitinjaneh A, Bejanyan N, Byrne M, Dias A, Farhadfar N, Freytes CO, Ganguly S, Hashmi S, Hayashi RJ, Hong S, Inamoto Y, Jamani K, Kasow KA, Khera N, Krem MM, Lazarus HM, Lee CJ, Lee S, Majhail NS, Malone AK, Marks DI, Mau LW, Mayo SJ, Muffly LS, Nathan S, Nishihori T, Page KM, Preussler J, Rangarajan HG, Rotz SJ, Salooja N, Savani BN, Schears R, Schechter-Finkelstein T, Schiller G, Shah AJ, Sharma A, Wang T, Wirk B, Battiwalla M, Schoemans H, Hamilton B, Buchbinder D, Phelan R, and Shaw B
- Subjects
- Female, Humans, Neoplasm Recurrence, Local, Survivors, Transplantation, Homologous, United States, Young Adult, Hematopoietic Stem Cell Transplantation, Return to Work
- Abstract
Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. All rights reserved.)
- Published
- 2021
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50. Managing multiple myeloma in a resource-limited region: Diagnosis and treatment in Armenia.
- Author
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Oganesyan A, Ghahramanyan N, Mekinian A, Bejanyan N, Kazandjian D, and Hakobyan Y
- Subjects
- Adult, Armenia, Humans, Quality of Life, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Multiple Myeloma drug therapy, Multiple Myeloma therapy
- Abstract
Multiple myeloma (MM) is the second most common blood cancer in adults leading to 117,000 deaths every year. Major breakthroughs in clinical research of the past decades transformed the diagnosis and treatment of MM improving the survival rates and overall quality of life of patients. Unfortunately, scientific advancements are not distributed equally around the globe leading to disparities in the treatment outcomes between different regions of the world. Management of MM in low- and middle-income countries represents a big challenge for healthcare providers considering the economic, technological, and infrastructural restraints in comparison to developed countries. Many standards of practice, including diagnostic tools and therapeutic regimens, are not available in developing regions of the world. As an example of an upper-middle-income country, Armenia has been witnessing considerable progress in the diagnosis and treatment of MM, including but not limited to the establishment of autologous stem cell transplant (ASCT), accessibility to modern anti-myeloma medications, and improved diagnostic and monitoring workup. Despite significant improvements, there is still a need for refinement in the management of MM. The aim of this review article is to discuss the latest developments and the current diagnosis and treatment of MM in Armenia as an example of a resource-limited region., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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