Browsing by Author "Arora, Mukta"

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    Biomarker Panel for Chronic Graft-Versus-Host Disease
    (American Society of Clinical Oncology, 2016-08-01) Yu, Jeffrey; Storer, Barry E.; Kushekhar, Kushi; Zaid, Mohammad Abu; Zhang, Qing; Gafken, Philip R.; Ogata, Yuko; Martin, Paul J.; Flowers, Mary E.; Hansen, John A.; Arora, Mukta; Cutler, Corey; Jagasia, Madan; Pidala, Joseph; Hamilton, Betty K.; Chen, George L.; Pusic, Iskra; Lee, Stephanie J.; Paczesny, Sophie; Medicine, School of Medicine
    PURPOSE: To identify diagnostic and prognostic markers of chronic graft-versus-host disease (cGVHD), the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). PATIENTS AND METHODS: Using a quantitative proteomics approach, we compared pooled plasma samples obtained at matched time points after HCT (median, 103 days) from 35 patients with cGVHD and 18 without cGVHD (data are available via ProteomeXchange with identifier PXD002762). Of 105 proteins showing at least a 1.25-fold difference in expression, 22 were selected on the basis of involvement in relevant pathways and enzyme-linked immunosorbent assay availability. Chemokine (C-X-C motif) ligand 9 (CXCL9) and suppression of tumorigenicity 2 (ST2) also were measured on the basis of previously determined associations with GVHD. Concentrations of the four lead biomarkers were measured at or after diagnosis in plasma from two independent verification cohorts (n = 391) to determine their association with cGVHD. Their prognostic ability when measured at approximately day +100 after HCT was evaluated in plasma of a second verification cohort (n = 172). RESULTS: Of 24 proteins measured in the first verification cohort, nine proteins were associated with cGVHD, and only four (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) were necessary to compose a four-biomarker panel with an area under the receiver operating characteristic curve (AUC) of 0.89 and significant correlation with cGVHD diagnosis, cGVHD severity, and nonrelapse mortality. In a second verification cohort, this panel distinguished patients with cGVHD (AUC, 0.75), and finally, the panel measured at day +100 could predict cGVHD occurring within the next 3 months with an AUC of 0.67 and 0.79 without and with known clinical risk factors, respectively. CONCLUSION: We conclude that the biomarker panel measured at diagnosis or day +100 after HCT may allow patient stratification according to risk of cGVHD.
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    Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT
    (American Society of Clinical Oncology, 2020-06-20) Mehta, Rohtesh S.; Holtan, Shernan G.; Wang, Tao; Hemmer, Michael T.; Spellman, Stephen R.; Arora, Mukta; Couriel, Daniel R.; Alousi, Amin M.; Pidala, Joseph; Abdel-Azim, Hisham; Agrawal, Vaibhav; Ahmed, Ibrahim A.; Al-Homsi, Samer; Aljurf, Mahmoud; Antin, Joseph H.; Askar, Medhat; Auletta, Jeffery J.; Bhatt, Vijaya Raj; Chee, Lynette; Chhabra, Saurabh; Daly, Andrew; DeFilipp, Zachariah; Gajewski, James; Gale, Robert Peter; Gergis, Usama; Hematti, Peiman; Hildebrandt, Gerhard C.; Hogan, William J.; Inamoto, Yoshihiro; Martino, Rodrigo; Majhail, Navneet S.; Marks, David I.; Nishihori, Taiga; Olsson, Richard F.; Pawarode, Attaphol; Diaz, Miguel Angel; Prestidge, Tim; Rangarajan, Hemalatha G.; Ringden, Olle; Saad, Ayman; Savani, Bipin N.; Schoemans, Hélène; Seo, Sachiko; Schultz, Kirk R.; Solh, Melhem; Spitzer, Thomas; Storek, Jan; Teshima, Takanori; Verdonck, Leo F.; Wirk, Baldeep; Yared, Jean A.; Cahn, Jean-Yves; Weisdorf, Daniel J.; Medicine, School of Medicine
    Purpose: There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. Methods: We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. Results: In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. Conclusion: Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
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    Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation
    (Elsevier, 2019) Saad, Ayman; Lamb, Lawrence; Wang, Tao; Hemmer, Michael T.; Spellman, Stephen; Couriel, Daniel; Alousi, Amin; Pidala, Joseph; Abdel-Azim, Hisham; Agrawal, Vaibhav; Aljurf, Mahmoud; Beitinjaneh, Amer M.; Bhatt, Vijaya Raj; Buchbinder, David; Byrne, Michael; Cahn, Jean-Yves; Cairo, Mitchell; Castillo, Paul; Chhabra, Saurabh; Diaz, Miguel Angel; Farhan, Shatha; Floisand, Yngvar; Frangoul, Hadar A.; Gadalla, Shahinaz M.; Gajewski, James; Gale, Robert Peter; Gandhi, Manish; Gergis, Usama; Hamilton, Betty Ky; Hematti, Peiman; Hildebrandt, Gerhard C.; Kamble, Rammurti T.; Kanate, Abraham S.; Khandelwal, Pooja; Lazaryn, Aleksandr; MacMillan, Margaret; Marks, David I.; Martino, Rodrigo; Mehta, Parinda A.; Nishihori, Taiga; Olsson, Richard F.; Patel, Sagar S.; Qayed, Muna; Rangarajan, Hemalatha G.; Reshef, Ran; Ringden, Olle; Savani, Bipin N.; Schouten, Harry C.; Schultz, Kirk R.; Seo, Sachiko; Shaffer, Brian C.; Solh, Melhem; Teshima, Takanori; Urbano-Ispizua, Alvaro; Verdonck, Leo F.; Vij, Ravi; Waller, Edmund K.; William, Basem; Wirk, Baldeep; Yared, Jean A.; Yu, Lolie C.; Arora, Mukta; Hashmi, Shahrukh; Medicine, School of Medicine
    Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.
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    Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
    (Elsevier, 2020-08) Im, Annie; Rashidi, Armin; Wang, Tao; Hemmer, Michael; MacMillan, Margaret L.; Pidala, Joseph; Jagasia, Madan; Pavletic, Steven; Majhail, Navneet S.; Weisdorf, Daniel; Abdel-Azim, Hisham; Agrawal, Vaibhav; Al-Homsi, A. Samer; Aljurf, Mahmoud; Askar, Medhat; Auletta, Jeffery J.; Bashey, Asad; Beitinjaneh, Amer; Bhatt, Vijaya Raj; Byrne, Michael; Cahn, Jean-Yves; Cairo, Mitchell; Castillo, Paul; Cerny, Jan; Chhabra, Saurabh; Choe, Hannah; Ciurea, Stefan; Daly, Andrew; Perez, Miguel Angel Diaz; Farhadfar, Nosha; Gadalla, Shahinaz M.; Gale, Robert; Ganguly, Siddhartha; Gergis, Usama; Hanna, Rabi; Hematti, Peiman; Herzig, Roger; Hildebrandt, Gerhard C.; Lad, Deepesh P.; Lee, Catherine; Lehmann, Leslie; Lekakis, Lazaros; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Khandelwal, Pooja; Martino, Rodrigo; Murthy, Hemant S.; Nishihori, Taiga; O'Brien, Tracey A.; Olsson, Richard F.; Patel, Sagar S.; Perales, Miguel-Angel; Prestidge, Tim; Qayed, Muna; Romee, Rizwan; Schoemans, Hélène; Seo, Sachiko; Sharma, Akshay; Solh, Melhem; Strair, Roger; Teshima, Takanori; Urbano-Ispizua, Alvaro; Van der Poel, Marjolein; Vij, Ravi; Wagner, John L.; William, Basem; Wirk, Baldeep; Yared, Jean A.; Spellman, Steve R.; Arora, Mukta; Hamilton, Betty K.; Medicine, School of Medicine
    Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.