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431 results on '"Pawarode, Attaphol"'

101. Biomarkers Predict Graft-Vs-Host Disease Outcomes Better Than Clinical Response after One Week of Treatment

Author

Major-Monfried, Hannah, primary, Ozbek, Umut, additional, Renteria, Anne S., additional, Hartwell, Matthew J, additional, Pawarode, Attaphol, additional, Yanik, Gregory A., additional, Ayuk, Francis A, additional, Holler, Ernst, additional, Efebera, Yvonne A, additional, Hogan, William J, additional, Qayed, Muna, additional, Hexner, Elizabeth O., additional, Wudhikarn, Kitsada, additional, Wolfl, Matthias, additional, Ordemann, Rainer, additional, Mielke, Stephan, additional, Bunworasate, Udomsak, additional, Devine, Steven M., additional, Kroeger, Nicolaus, additional, Al-Malki, Monzr, additional, Chen, Yi-Bin, additional, Harris, Andrew C., additional, Jagasia, Madan H., additional, Kitko, Carrie L, additional, Litzow, Mark R, additional, Locatelli, Franco, additional, Nakamura, Ryotaro, additional, Reddy, Pavan R., additional, Reshef, Ran, additional, Roesler, Wolf, additional, Weber, Daniela, additional, Ferrara, James, additional, and Levine, John E., additional

Published
2016
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102. An Early Biomarker Algorithm Predicts Lethal Graft-Versus-Host Disease and Survival after Allogeneic Hematopoietic Cell Transplantation

Author

Hartwell, Matthew J, primary, Ozbek, Umut, additional, Holler, Ernst, additional, Renteria, Anne S., additional, Reddy, Pavan R., additional, Aziz, Mina, additional, Hogan, William J, additional, Ayuk, Francis A, additional, Efebera, Yvonne A, additional, Hexner, Elizabeth O., additional, Bunworasate, Udomsak, additional, Qayed, Muna, additional, Ordemann, Rainer, additional, Wolfl, Matthias, additional, Mielke, Stephan, additional, Pawarode, Attaphol, additional, Chen, Yi-Bin, additional, Devine, Steven M., additional, Harris, Andrew C., additional, Jagasia, Madan H., additional, Kitko, Carrie L, additional, Litzow, Mark R, additional, Kroeger, Nicolaus, additional, Locatelli, Franco, additional, Nakamura, Ryotaro, additional, Reshef, Ran, additional, Roesler, Wolf, additional, Weber, Daniela, additional, Wudhikarn, Kitsada, additional, Yanik, Gregory A, additional, Levine, John E., additional, and Ferrara, James L.M., additional

Published
2016
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103. Rational Modification of Human Gut Microbiome and Metabolites By Dietary Resistant Starch in Allogeneic Hematopoietic Stem Cell Transplantation: A Feasibility Study

Author

Riwes, Mary Mansour, Golob, Jonathan Louis, Magenau, John M., Lyssiotis, Costas, Shan, Mengrou, Dick, Gregory, Braun, Thomas, Schmidt, Thomas M, Pawarode, Attaphol, Anand, Sarah, Ghosh, Monalisa, Maciejewski, John, King, Darren, Choi, Sung W., Yanik, Gregory, Geer, Marcus Johannes, Hillman, Ethan, Tewari, Muneesh, and Reddy, Pavan

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is limited by acute graft versus host disease (GVHD). GVHD is the principal cause of non-relapse mortality (NRM) and a major cause of morbidity after allo-HCT. Recent published experimental data demonstrated that altering the microbiome-metabolite axis regulates acute GVHD severity. Specifically, short chain fatty acid (SCFA) butyrate was significantly decreased in the intestinal epithelial cells (IECs) of mice experiencing GVHD, while restoring butyrate levels by increasing intestinal butyrate-producing bacteria, reduced experimental acute GI GVHD severity and mortality. Prebiotics usually refer to indigestible carbohydrates that are metabolized by the intestinal microbiota to produce microbial metabolites, such as SCFAs, that serve as nutrients for IECs. Administration of defined quantities of resistant potato starch (RPS), as a prebiotic, to normal healthy human volunteers promoted increase in butyrogenic bacteria and increased intestinal levels of SCFA butyrate to a greater extent than other commercially available resistant starch preparations tested. These data form the rationale for this study and led to prospectively study the clinical feasibility and impact of the administration of RPS as a prebiotic dietary intervention on the intestinal microbiota and its dependent metabolites in allo-HCT recipients.

Published
2023
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104. Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation

Author

Fenske, Timothy S., primary, Ahn, Kwang W., additional, Graff, Tara M., additional, DiGilio, Alyssa, additional, Bashir, Qaiser, additional, Kamble, Rammurti T., additional, Ayala, Ernesto, additional, Bacher, Ulrike, additional, Brammer, Jonathan E., additional, Cairo, Mitchell, additional, Chen, Andy, additional, Chen, Yi‐Bin, additional, Chhabra, Saurabh, additional, D'Souza, Anita, additional, Farooq, Umar, additional, Freytes, Cesar, additional, Ganguly, Siddhartha, additional, Hertzberg, Mark, additional, Inwards, David, additional, Jaglowski, Samantha, additional, Kharfan‐Dabaja, Mohamed A., additional, Lazarus, Hillard M., additional, Nathan, Sunita, additional, Pawarode, Attaphol, additional, Perales, Miguel‐Angel, additional, Reddy, Nishitha, additional, Seo, Sachiko, additional, Sureda, Anna, additional, Smith, Sonali M., additional, and Hamadani, Mehdi, additional

Published
2016
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106. Alpha 1 Anti-Trypsin (AAT): Novel Strategy to Treat Steroid Refractory Acute Graft Versus Host Disease

Author

Goldstein, Steven C., primary, Koreth, John, additional, Magenau, John M., additional, Soiffer, Robert J., additional, Braun, Thomas, additional, Kennel, Maggi, additional, Goyetche, Reaha, additional, Pawarode, Attaphol, additional, Riwes, Mary M., additional, Antin, Joseph H., additional, Cutler, Corey S., additional, Ho, Vincent T., additional, Alyea, Edwin P., additional, Parkin, Brian L., additional, Yanik, Gregory A., additional, Choi, Sung Won, additional, Couriel, Daniel R., additional, Levine, John E., additional, Radojcic, Vedran, additional, Dinarello, Charles, additional, and Reddy, Pavan, additional

Published
2016
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108. Phase 1 Study of Carfilzomib for the Prevention of Relapse and Graft-Versus-Host Disease in Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

Author

Pawarode, Attaphol, primary, Goldstein, Steven, additional, Couriel, Daniel R., additional, Braun, Thomas, additional, Magenau, John M., additional, Riwes, Mary Mansour, additional, Parkin, Brian, additional, Radojcic, Vedran, additional, Frame, David, additional, Choi, Sung, additional, Connelly, James, additional, Levine, John E., additional, Yanik, Gregory A., additional, and Reddy, Pavan, additional

Published
2015
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109. 92 - Impact of Broncho-Alveolar Lavage on the Diagnosis and Management of Pulmonary Complications Following Hematopoietic Cell Transplantation

Author

Triebwasser, Michael, Duvall, Adam, Hoffman, Timothy, Bloye, Kiernan, Braun, Thomas, Kaul, Daniel, Magenau, John M., Riwes, Mary M., Pawarode, Attaphol, Choi, Sung, Lugt, Mark Vander, Bonifant, Challice, Abusin, Ghada, Sekerak, Kevin, Bulte, Camille, Paglia, Danny, O'Dwyer, David, Brisson, Joseph, and Yanik, Gregory A.

Published
2018
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113. Phase II Clinical Trial of Etanercept Plus Extracorporeal Photopheresis GVHD Prophylaxis Following Unrelated Donor Reduced Intensity Transplant

Author

Kitko, Carrie L., primary, Braun, Thomas, additional, Schuler, Charles, additional, Choi, Sung Won, additional, Yanik, Gregory, additional, Pawarode, Attaphol, additional, Magenau, John, additional, Taylor, Austin, additional, Ferrara, James L.M., additional, Couriel, Daniel R., additional, and Levine, John, additional

Published
2015
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114. The Graft-Versus-Lymphoma Effect in Diffuse Large B-Cell Lymphoma

Author

Smith, Christina A.M., primary, Churay, Tracey L., additional, Justman, Holly A., additional, Yu, Jessica K., additional, Pawarode, Attaphol, additional, Hanauer, David, additional, Magenau, John, additional, Goldstein, Steven C., additional, Riwes, Mary Mansour, additional, Parkin, Brian, additional, Levine, John, additional, and Couriel, Daniel R., additional

Published
2015
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122. A Prospective Study of Allogeneic Transplant for Older Patients with Acute Myelogenous Leukemia (AML) Indicates that Unrelated Donor Transplants are as Efficacious as Related Donor, with Favorable Outcomes for Intermediate Risk Disease

Author

Yanik, Gregory, primary, Magenau, John, additional, Goldstein, Steven C., additional, Pawarode, Attaphol, additional, Talpaz, Moshe, additional, Levine, John, additional, Choi, Sung, additional, Kitko, Carrie L., additional, and Couriel, Daniel R., additional

Published
2013
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124. A Combination of Clinical Characteristics and Day 7 Biomarker Concentrations Predicts Graft-Versus-Host Disease Following Hematopoietic Cell Transplantation From Related Donors

Author

Harris, Andrew C., primary, Ferrara, James L.M., additional, Braun, Thomas, additional, Couriel, Daniel R., additional, Choi, Sung, additional, Kitko, Carrie L., additional, Goldstein, Steven C., additional, Magenau, John, additional, Paczesny, Sophie, additional, Pawarode, Attaphol, additional, Reddy, Pavan, additional, Yanik, Gregory, additional, Taylor, Austin, additional, Connelly, James A., additional, Byersdorfer, Craig A., additional, and Levine, John E., additional

Published
2013
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125. Phase 2 Study of Allogeneic Hematopoietic Cell Transplant (HCT) Following Intermediate-Intensity Fludarabine and Busulfan x 4 (FluBu4) Conditioning for High-Risk or Advanced Multiple Myeloma

Author

Pawarode, Attaphol, primary, Mineishi, Shin, additional, Braun, Thomas, additional, Ferrara, James L.M., additional, Magenau, John, additional, Peres, Edward, additional, Yanik, Gregory, additional, Reddy, Pavan, additional, Levine, John E., additional, Choi, Sung Won, additional, Kitko, Carrie L., additional, Harris, Andrew C., additional, Connelly, James A., additional, Goldstein, Steven C., additional, and Couriel, Daniel R., additional

Published
2013
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126. Biomarkers of Extracellular Matrix Remodeling in Chronic GVHD

Author

Kitko, Carrie L., primary, Saliba, Rima, additional, Choi, Sung Won, additional, Reddy, Pavan, additional, Goldstein, Steven C., additional, Magenau, John, additional, Pawarode, Attaphol, additional, Kennel, Maggi, additional, Levine, John E., additional, White, Eric, additional, and Couriel, Daniel R., additional

Published
2013
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127. Impact of Dose Intensification of FluBu2 to FluBu4 on Transplant Related Mortality, Relapse, and Survival After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia in Remission

Author

Magenau, John, primary, Pawarode, Attaphol, additional, Couriel, Daniel R., additional, Yanik, Gregory, additional, Mineishi, Shin, additional, Braun, Thomas, additional, Reddy, Pavan, additional, Ferrara, James L.M., additional, Frame, David, additional, Choi, Sung Won, additional, Harris, Andrew C., additional, Kitko, Carrie L., additional, Connelly, James A., additional, Levine, John, additional, and Goldstein, Steven C., additional

Published
2013
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128. Unrelated Donor Transplants for Older AML Patients Using a Low Dose TBI Containing Regimen Are As Efficacious As Related Donor Transplants, and Exhibit Favorable Outcomes for Intermediate Risk Disease.

Author

Yanik, Gregory A., primary, Magenau, John M., additional, Mineishi, Shin, additional, Pawarode, Attaphol, additional, Alangaden, Keith, additional, Peres, Edward M., additional, Goldstein, Steven, additional, Levine, John E., additional, Choi, Sung, additional, Kitko, Carrie L, additional, Talpaz, Moshe, additional, and Couriel, Daniel, additional

Published
2012
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129. Targeting Histone Deacetylases As a New Strategy for Graft Versus Host Disease Prevention

Author

Choi, Sung W., primary, DiPersio, John F., additional, Braun, Thomas M., additional, Hou, Guoqing, additional, Stockerl-Goldstein, Keith, additional, Tawara, Isao, additional, Levine, John E., additional, Sun, Yaping, additional, Couriel, Daniel R., additional, Krijanovski, Oleg I., additional, Chang, Lawrence, additional, Magenau, John M., additional, Pawarode, Attaphol, additional, Kitko, Carrie, additional, Paczesny, Sophie, additional, Peres, Edward M., additional, Mineishi, Shin, additional, Yanik, Gregory A., additional, Lehmann, Michael, additional, Dinarello, Charles A., additional, Ferrara, James L.M., additional, and Reddy, Pavan, additional

Published
2012
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130. An Algorithm Combining Clinical Characteristics and Day 7 Biomarker Concentrations Predicts Future Graft-Versus-Host Disease Following Related Donor Hematopoietic Cell Transplantation

Author

Harris, Andrew C., primary, Ferrara, James L.M., additional, Braun, Thomas M., additional, Couriel, Daniel R., additional, Choi, Sung W., additional, Kitko, Carrie, additional, Goldstein, Steven, additional, Magenau, John M., additional, Paczesny, Sophie, additional, Pawarode, Attaphol, additional, Reddy, Pavan, additional, Yanik, Gregory A., additional, Taylor, Austin, additional, Connelly, James, additional, Byersdorfer, Craig A., additional, and Levine, John E., additional

Published
2012
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131. Clofarabine and busulfan conditioning facilitates engraftment and provides significant antitumor activity in nonremission hematologic malignancies

Author

Magenau, John, primary, Tobai, Hiromi, additional, Pawarode, Attaphol, additional, Braun, Thomas, additional, Peres, Edward, additional, Reddy, Pavan, additional, Kitko, Carrie, additional, Choi, Sung, additional, Yanik, Gregory, additional, Frame, David, additional, Harris, Andrew, additional, Erba, Harry, additional, Kujawski, Lisa, additional, Elenitoba-Johnson, Kojo, additional, Sanks, Jennifer, additional, Jones, Dawn, additional, Paczesny, Sophie, additional, Ferrara, James, additional, Levine, John, additional, and Mineishi, Shin, additional

Published
2011
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132. Three Biomarker Panel at Day 7 and 14 Can Predict Development of Grade II-IV Acute Graft-Versus-Host Disease

Author

Paczesny, Sophie, primary, Braun, Thomas, additional, Lugt, Mark Vander, additional, Harris, Andrew, additional, Fiema, Bryan, additional, Hernandez, James, additional, Choi, Sung, additional, Kitko, Carrie, additional, Magenau, John, additional, Yanik, Gregory, additional, Peres, Edward M., additional, Pawarode, Attaphol, additional, Mineishi, Shin, additional, Whitfield, Joel, additional, Jones, Dawn, additional, Couriel, Daniel, additional, Reddy, Pavan, additional, Hanash, Samir, additional, Ferrara, James L.M., additional, and Levine, John E., additional

Published
2010
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133. Allogeneic Hematopoietic Stem Cell Transplantation with Clofarabine/Busulfan × 4 (CloBu4) Conditioning Exhibits Significant Anti-Tumor Activity In Non - Remission Hematologic Malignancies, Especially In AML

Author

Mineishi, Shin, primary, Magenau, John, additional, Tobai, Hiromi, additional, Pawarode, Attaphol, additional, Peres, Edward M., additional, Reddy, Pavan, additional, Kitko, Carrie, additional, Choi, Sung, additional, Erba, Harry P, additional, Kujawski, Lisa, additional, Yanik, Gregory, additional, Ferrara, James, additional, and Levine, John E., additional

Published
2010
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135. Standard Gvhd Prophylaxis Augmented with TNF-Inhibition in Alternative Donor HCT: Lower TNFR1 Levels Correlate with Better Outcomes.

Author

Choi, Sung, primary, Stiff, Patrick, additional, Braun, Thomas, additional, Ferrara, James LM, additional, Cooke, Kenneth R., additional, Khaled, Yasser, additional, Kitko, Carrie, additional, Lay-Luskin, Jennifer, additional, Mineishi, Shin, additional, Nickoloff, Brian, additional, Paczesny, Sophie, additional, Pawarode, Attaphol, additional, Whitfield, Joel, additional, Peres, Edward M., additional, Reddy, Pavan, additional, Richardson, Julia, additional, Rodriguez, Tulio, additional, Smith, Scott E., additional, Yanik, Gregory A., additional, and Levine, John E., additional

Published
2009
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136. Myeloablative Conditioning with Clofarabine and Busulfan X 4 (CloBu4) Is Well Tolerated, Facilitates Secure Engraftment, and Exhibits Significant Anti-Tumor Activity against Non-Remission Hematologic Malignancies Including AML.

Author

Mineishi, Shin, primary, Magenau, John, primary, Pawarode, Attaphol, primary, Buck, Timothy, primary, Jones, Dawn, primary, Kato, Koji, primary, Frame, David, primary, Kujawski, Lisa, primary, Erba, Harry Paul, primary, Khaled, Yasser, primary, Peres, Edward M., primary, Krijanovski, Oleg I., primary, Reddy, Pavan, primary, Kitko, Carrie, primary, Choi, Sung, primary, Yanik, Gregory A., primary, Braun, Thomas, primary, Ferrara, James L.M., primary, and Levine, John E., primary

Published
2008
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137. Bronchoscopic Evaluation of Pulmonary Complications in Patients Undergoing Reduced-Intensity Versus Full-Intensity Transplants.

Author

Maslak, Joseph, primary, Kaul, Daniel, primary, Connelly, James, primary, Mineishi, Shin, primary, Levine, John E., primary, Peres, Edward M., primary, Kitko, Carrie, primary, Choi, Sung W., primary, Khaled, Yasser, primary, Krijanovski, Oleg I., primary, Digiandomenico, Stefanie, primary, White, Eric, primary, Braun, Thomas, primary, Reddy, Pavan, primary, Pawarode, Attaphol, primary, Ferrara, James L.M., primary, and Yanik, Gregory A., primary

Published
2008
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147. Type-1 Interferon to Prevent Leukemia Relapse after Allogeneic Transplantation

Author

Magenau, John M., Peltier, Dan, Riwes, Mary, Pawarode, Attaphol, Parkin, Brian, Braun, Thomas, Anand, Sarah, Ghosh, Monalisa, Maciejewski, John, Yanik, Gregory, Choi, Sung, Talpaz, Moshe, and Reddy, Pavan

Abstract

A potent graft-versus-leukemia (GVL) response is crucial in preventing relapse, the major impediment to successful allogeneic hematopoietic cell transplantation (HCT). In preclinical studies, Type-1 interferon (IFNα) enhanced cross-presentation of leukemia specific antigens by CD8α dendritic cells (DCs) and amplified GVL. This observation was translated into a proof-of-concept phase I/II clinical trial with long-acting IFNα (pegIFNα) in patients undergoing HCT for high-risk acute myeloid leukemia (AML). Patients with treatment resistant AML not in remission or poor risk leukemia were administered four dosages of pegIFNα every 14 days beginning at day -1 before HCT. Dose selection was established by adaptive design that continuously assessed the probability of dose limiting toxicities throughout the trial. Efficacy was evaluated by determining the six-month incidence of relapse at the maximum tolerated dose (MTD). Thirty-six patients (median age of 60 years) received pegIFNα treatment. Grade 3 or greater SAEs occurred in 25% of patients establishing 180mcg as the MTD. In phase II, the incidence of relapse was 39% at six-months, which was sustained through one-year post HCT. The incidence of transplant-related mortality was 13% and severe grade III-IV acute GVHD occurred in 11%. Paired blood samples from donors and recipients after HCT indicated elevated levels of Type-1 IFN with cellular response, persistence of cross-presenting DCs and circulating leukemia antigen specific T cells. These data suggest that prophylactic administration of pegIFNα is feasible in the peri-HCT period. In high-risk AML, increased toxicity was not observed with preliminary evidence for reduction in leukemia relapse after HCT. This trial was registered at www.clinicaltrials.govas NCT02328755.

Published
2021
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148. MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD.

Author

Major-Monfried, Hannah, Renteria, Anne S., Pawarode, Attaphol, Reddy, Pavan, Ayuk, Francis, Holler, Ernst, Efebera, Yvonne A., Hogan, William J., Wölfl, Matthias, Qayed, Muna, Hexner, Elizabeth O., Wudhikarn, Kitsada, Ordemann, Rainer, Young, Rachel, Shah, Jay, Hartwell, Matthew J., Chaudhry, Mohammed S., Aziz, Mina, Etra, Aaron, and Yanik, Gregory A.

Subjects
*GRAFT versus host disease, *BIOLOGICAL tags, *STEROIDS, *GRAFT versus host reaction, *BIOINDICATORS
Abstract

Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n = 236) and 2 validation cohorts separated in time (n = 142 and n = 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3a) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS (P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P = .004) and for Minnesota risk (0.72, P = .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies. [ABSTRACT FROM AUTHOR]

Published
2018
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149. A Phase 2 Study of Pembrolizumab during Lymphodepletion after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma.

Author

D'Souza, Anita, Hari, Parameswaran, Pasquini, Marcelo, Braun, Thomas, Johnson, Bryon, Lundy, Steven, Couriel, Daniel, Hamadani, Mehdi, Magenau, John, Dhakal, Binod, Shah, Nirav N., Riwes, Mary, Parkin, Brian, Reddy, Pavan, and Pawarode, Attaphol

Subjects
*CELL transplantation, *MULTIPLE myeloma, *PEMBROLIZUMAB, *BONE marrow, *FLOW cytometry, *PLASMACYTOMA, BONE marrow examination
Abstract

• Post-transplantation pembrolizumab therapy with or without lenalidomide was feasible for myeloma. • The study was terminated early after failing to meet its interim analysis endpoint. • This resulted in a conversion from non-complete remission (CR) to 31% CR at day 180 post-transplantation. • This treatment is associated with a very promising 75% bone marrow flow cytometry-based minimal residual disease-negative rate. The programmed death-1 (PD-1) axis can suppress immune surveillance against multiple myeloma (MM). We tested the safety and efficacy of pembrolizumab, an anti-PD-1 antibody, in MM after autologous hematopoietic cell transplantation (AHCT). We enrolled patients with MM who did not achieve a complete response (CR) to induction therapy. The study intervention involved a total of 9 doses of i.v. pembrolizumab, with 1 dose given every 21 days starting on day +14 post-AHCT. The primary endpoint was the rate of CR at end of treatment (EOT) in patients receiving ≥2 pembrolizumab doses. Thirty-two patients were enrolled, but 3 withdrew consent before receiving the first dose. The study was terminated early after failing to meet its interim analysis endpoint to detect a 20% difference in EOT CR rate conversion. The median patient age was 59 years. All but 1 patient received triplet induction for a median of 4 cycles (range, 2 to 7 cycles), with 69% partial response (PR) and 31% very good PR (VGPR). No grade 4/5 toxicities or graft failures occurred. Among 26 evaluable patients, 23 had an EOT evaluation, and 7 of these 23 (31%) achieved CR. Two patients had EOT serologic CR but no bone marrow confirmation (CRu), and 1 patient had no EOT evaluation. Bone marrow was minimal residual disease-negative by flow cytometry in 12 of 16 patients (75%) at day +180. With a median follow-up of 23.7 months (range, 15.1 to 33.5 months), no patient achieving EOT CR/CRu had relapsed, whereas 3 patients progressed before EOT and 1 patient progressed at 8 months after EOT VGPR. The estimated 2-year progression-free rate was 83% (95% confidence interval, 68% to 100%). Our data show that early post-AHCT pembrolizumab with lenalidomide maintenance is feasible; however, the efficacy is uncertain and requires further study. This trial was registered at C l inical T rials.gov (NCT02331368). Image, graphical abstract [ABSTRACT FROM AUTHOR]

Published
2019
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150. Assessment of Individual versus Composite Endpoints of Acute Graft-versus-Host Disease in Determining Long-Term Survival after Allogeneic Transplantation.

Author

Magenau, John, Braun, Thomas, Gatza, Erin, Churay, Tracey, Mazzoli, Amanda, Chappell, Grant, Brisson, Joseph, Runaas, Lyndsey, Anand, Sarah, Ghosh, Monalisa, Riwes, Mary, Pawarode, Attaphol, Yanik, Gregory, Reddy, Pavan, and Choi, Sung Won

Subjects
*MONTE Carlo method, *GRAFT versus host disease, *ACUTE diseases, *ALEMTUZUMAB, *CELL transplantation, *TRANSPLANTATION of organs, tissues, etc., *LEUKAPHERESIS
Abstract

• The novel endpoint of graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) is achieved in a minority of allogeneic hematopoietic cell transplantation HCT recipients but is found to be highly prognostic for long term survival with major differences in the contribution of individual components. • Using statistical simulations, a modified form of GRFS (excluding death and chronic GVHD) that focuses on early severe events (grade III-IV acute GVHD and relapse) may serve as a useful surrogate endpoint in GVHD prevention studies given its strong associations with long-term overall survival. • Refinement of composite endpoints will necessarily occur depend on a priori assumptions of the study population as well as the intervention. The overall composite of graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS), defined as survival free of grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic immunosuppressive therapy (IST), or relapse, has emerged as a useful composite in clinical trials and to capture clinically meaningful events that impact quantity and quality of survival after allogeneic hematopoietic cell transplantation (HCT). We reviewed 565 consecutive patients aged ≥18 years undergoing HCT for hematologic malignancy to analyze how baseline incidence, specifics of clinical definitions, and proposed reductions in any one individual event may dynamically alter the overall performance of the composite To determine the relative impact of each GRFS event (excluding death), we accounted for competing risks using Fine and Gray methods, and correlated each event with overall survival (OS) using Kaplan-Meier methods. The consequences of modulating individual or composite endpoints on OS, such as hypothesized reductions of events of an HCT interventional trial, were examined using Monte Carlo simulations. The median age of the cohort was 54 years (range, 18 to 73 years). The majority of patients received HLA-matched unrelated donor HCT (53%), consisting of peripheral blood stem cell grafts (90%) after myeloablative conditioning (68%). Relapse conferred the greatest risk for death (hazard ratio [HR], 7.89; 95% confidence interval [CI], 5.83 to 10.69), followed by grade III-IV aGVHD (HR, 6.16; 95% CI, 4.42 to 8.56) and cGVHD requiring IST (HR, 1.69; 95% CI, 1.16 to 2.46). The overall GRFS composite correlated with an HR of 4.81 (95% CI, 3.61 to 6.41), which was lower compared with either relapse or grade III-IV aGVHD. Statistical simulations found that modulating the combined risk of both relapse and grade III-IV aGVHD predicted the greatest change in 5-year OS. These simulations suggest that GRFS as currently defined may be less optimal for correlating with OS, and further refinement of composite endpoints is needed. Nonetheless, composite endpoints may be particularly helpful in mitigating potential difficulties in interpretation when competing risks are present, most commonly seen in HCT studies. [ABSTRACT FROM AUTHOR]

Published
2019
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