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2. Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic leukemia

Author

Koury, Luísa Corrêa de Araújo, Kim, Haesook T., Undurraga, Maria Soledad, Navarro-Cabrera, Juan Ramon, Salinas, Victor, Muxi, Pablo, Melo, Raul A. M., Glória, Ana Beatriz, Pagnano, Katia, Nunes, Elenaide C., Bittencourt, Rosane I., Rojas, Ninoska, Quintana, Shirley, Ayala-Lugo, Ana, Oliver, Ana Carolina, Figueiredo-Pontes, Lorena, Traina, Fabiola, Moreira, Frederico, Fagundes, Evandro M., Duarte, Bruno K. L., Mora-Alferez, Analí Pamela, Ortiz, Percy, Untama, Jose, Tallman, Martin, Ribeiro, Raul, Ganser, Arnold, Dillon, Richard, Valk, Peter J. M., Sanz, Miguel, Löwenberg, Bob, Berliner, Nancy, and Rego, Eduardo M.

Published
2024
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3. Active infection at the time of CD34+ selected stem cell boost is associated with treatment failure and poor overall survival

Author

Shapiro, Roman M., Kim, Haesook T., Dulery, Remy, Liney, Deborah, Garrity, Heather M., Panaro, Kevin, Au, Chloe, Gervais, Casey, Little, Jessica S., Ho, Vincent T., Cutler, Corey S., Koreth, John, Gooptu, Mahasweta, Antin, Joseph H., Kelkar, Amar H., Romee, Rizwan, Wu, Catherine J., Ritz, Jerome, Soiffer, Robert J., and Nikiforow, Sarah

Published
2024
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4. Experiences of Sleep Problems Among Older Korean Immigrants.

Author

Song, Yeonsu, Ryan, Gery W, Lee, Diane, Kim, Haesook, Martin, Jennifer L, Kramer, B Josea, Hays, Ron D, and Choi, Sarah E

Subjects
Health Services and Systems, Health Sciences, Sleep Research, Aging, Basic Behavioral and Social Science, Behavioral and Social Science, Aged, Emigrants and Immigrants, Focus Groups, Humans, Qualitative Research, Republic of Korea, Sleep Wake Disorders, United States, Nursing
Abstract

Despite poor sleep among older adults, little is known about the sleep habits of older immigrants living in the United States. The current pragmatic qualitative descriptive study explored sleep among older Korean immigrants, using a focus group with six participants and individual phone interviews with 22 Korean immigrants aged ≥60 years. Transcripts were coded to identify underlying themes. Several thematic categories were identified under six domains: daytime function, getting ready for bed, falling asleep, awakenings during sleep, going back to sleep, and seeking advice from peers. Unhealthy sleep behaviors were found during daytime and bedtime, particularly among those who were retired/unemployed or living alone. Seeking advice from peers was common but none of the advice helped participants sleep. Sleep education programs in Korean-speaking communities can be used to target those who are socially isolated and may benefit older Korean immigrants with sleep difficulties. [Research in Gerontological Nursing, 15(4), 193-202.].

Published
2022

5. The MAGIC algorithm probability predicts treatment response and long-term outcomes to second-line therapy for acute GVHD

Author

DeFilipp, Zachariah, Kim, Haesook T., Spyrou, Nikolaos, Katsivelos, Nikolaos, Kowalyk, Steven, Eng, Gilbert, Kasikis, Stelios, Beheshti, Rahnuma, Baez, Janna, Akahoshi, Yu, Ayuk, Francis, Choe, Hannah, Etra, Aaron, Grupp, Stephan A., Hexner, Elizabeth O., Hogan, William J., Kitko, Carrie L., Qayed, Muna, Reshef, Ran, Vasova, Ingrid, Zeiser, Robert, Young, Rachel, Holler, Ernst, Ferrara, James L. M., Nakamura, Ryotaro, Levine, John E., and Chen, Yi-Bin

Published
2024
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6. Third-party fecal microbiota transplantation for high-risk treatment-naïve acute GVHD of the lower GI tract

Author

DeFilipp, Zachariah, Damania, Ashish V., Kim, Haesook T., Chang, Chia-Chi, El-Jawahri, Areej, McAfee, Steven L., Bottoms, AJ S., Toncheva, Vesselina, Smith, Melissa M., Dolaher, Maria, Perry, Lindsey, White, Meghan, Diana, Brittany, Connolly, Sheila, Dey, Bimalangshu R., Frigault, Matthew J., Newcomb, Richard A., O’Donnell, Paul V., Spitzer, Thomas R., Mansour, Michael K., Weber, Daniela, Ajami, Nadim J., Hohmann, Elizabeth, Jenq, Robert R., and Chen, Yi-Bin

Published
2024
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7. Prophylactic maintenance with venetoclax/azacitidine after reduced-intensity conditioning allogeneic transplant for high-risk MDS and AML

Author

Garcia, Jacqueline S., Kim, Haesook T., Murdock, H. Moses, Ansuinelli, Michela, Brock, Jennifer, Cutler, Corey S., Gooptu, Mahasweta, Ho, Vincent T., Koreth, John, Nikiforow, Sarah, Romee, Rizwan, Shapiro, Roman, DeAngelo, Daniel J., Stone, Richard M., Bat-Erdene, Denbaa, Ryan, Jeremy, Contreras, Manuel E., Fell, Geoffrey, Letai, Anthony, Ritz, Jerome, Lindsley, R. Coleman, Soiffer, Robert J., and Antin, Joseph H.

Published
2024
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13. Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease

Author

Koshy, Anita G., Kim, Haesook T., Liegel, Jessica, Arnason, Jon, Ho, Vincent T., Antin, Joseph H., Joyce, Robin, Cutler, Corey, Gooptu, Mahasweta, Nikiforow, Sarah, Logan, Emma K., Elavalakanar, Pavania, Narcis, Michele, Stroopinsky, Dina, Avigan, Zachary M., Boussi, Leora, Stephenson, Susan, El Banna, Hassan, Bindal, Poorva, Cheloni, Giulia, Avigan, David E., Soiffer, Robert J., and Rosenblatt, Jacalyn

Published
2023
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15. Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents.

Author

Roeker, Lindsey, Dreger, Peter, Brown, Jennifer, Lahoud, Oscar, Eyre, Toby, Brander, Danielle, Skarbnik, Alan, Coombs, Catherine, Kim, Haesook, Davids, Matthew, Manchini, Steven, George, Gemlyn, Shah, Nirav, Voorhees, Timothy, Orchard, Kim, Walter, Harriet, Arumainathan, Arvind, Sitlinger, Andrea, Park, Jae, Geyer, Mark, Zelenetz, Andrew, Sauter, Craig, Giralt, Sergio, Perales, Miguel-Angel, and Mato, Anthony

Subjects
Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Retrospective Studies
Abstract

Although novel agents (NAs) have improved outcomes for patients with chronic lymphocytic leukemia (CLL), a subset will progress through all available NAs. Understanding outcomes for potentially curative modalities including allogeneic hematopoietic stem cell transplantation (alloHCT) following NA therapy is critical while devising treatment sequences aimed at long-term disease control. In this multicenter, retrospective cohort study, we examined 65 patients with CLL who underwent alloHCT following exposure to ≥1 NA, including baseline disease and transplant characteristics, treatment preceding alloHCT, transplant outcomes, treatment following alloHCT, and survival outcomes. Univariable and multivariable analyses evaluated associations between pre-alloHCT factors and progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS), nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in 27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial remission, and transplant characteristics were not independently associated with PFS. Hematopoietic cell transplantation-specific comorbidity index independently predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease control strategy that overcomes adverse CLL characteristics. Prior NAs do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA immediately preceding alloHCT. Decisions about proceeding to alloHCT should consider comorbidities and anticipated response to remaining therapeutic options.

Published
2020

17. Efficacy results of a phase 2 trial of first-line idelalisib plus ofatumumab in chronic lymphocytic leukemia

Author

Lampson, Benjamin L, Kim, Haesook T, Davids, Matthew S, Abramson, Jeremy S, Freedman, Arnold S, Jacobson, Caron A, Armand, Philippe A, Joyce, Robin M, Arnason, Jon E, Rassenti, Laura Z, Kipps, Thomas J, Fein, Joshua, Fernandes, Stacey M, Hanna, John R, Fisher, David C, and Brown, Jennifer R

Subjects
Hematology, Lymphoma, Clinical Research, Rare Diseases, Clinical Trials and Supportive Activities, Patient Safety, Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Purines, Quinazolinones, Safety-Based Drug Withdrawals, Survival Analysis, Treatment Outcome
Abstract

PI3 kinase (PI3K) activity is critical for survival of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL). Blockade of PI3K signaling with idelalisib is effective for the treatment of relapsed CLL in combination with the anti-CD20 antibody ofatumumab. In this single-arm, open-label, nonrandomized phase 2 study, we investigated the efficacy and safety of idelalisib with ofatumumab in 27 patients with treatment-naïve CLL in need of therapy. Patients were planned to receive idelalisib for 2 monthly cycles, then idelalisib and ofatumumab for 6 cycles, followed by idelalisib indefinitely. The study was closed early and all patients ceased therapy when an increased rate of death as a result of infection was observed on other first-line idelalisib trials. Median time on therapy was 8.1 months, and median duration of follow-up was 39.7 months. We previously reported high rates of hepatotoxicity in a smaller cohort of patients in this trial; toxicities necessitated therapy discontinuation in 15 patients after a median of 7.7 months. The most frequent grade ≥3 adverse events were transaminitis (52% of patients), neutropenia (33%), and colitis/diarrhea (15%). The best overall response rate (ORR) was 88.9%, including 1 complete response. Median progression-free survival (PFS) was 23 months (95% confidence interval [CI], 18-36 months); 11 patients have not yet required second-line therapy. Idelalisib and ofatumumab demonstrated an unacceptable safety profile in the first-line setting, which resulted in a short PFS despite a high ORR. Future development of PI3K inhibitors for use in treatment-naïve CLL will require novel approaches to mitigate toxicities. This trial was registered at www.clinicaltrials.gov as #NCT02135133.

Published
2019

18. Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for IDH2-mutated myeloid malignancies

Author

Fathi, Amir T., Kim, Haesook T., Soiffer, Robert J., Levis, Mark J., Li, Shuli, Kim, Annette S., Mims, Alice S., DeFilipp, Zachariah, El-Jawahri, Areej, McAfee, Steven L., Brunner, Andrew M., Narayan, Rupa, Knight, Laura W., Kelley, Devon, Bottoms, AJ S., Perry, Lindsey H., Wahl, Jonathan L., Brock, Jennifer, Breton, Elayne, Ho, Vincent T., and Chen, Yi-Bin

Published
2022
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22. Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML

Author

Murdock, H. Moses, Kim, Haesook T., Denlinger, Nathan, Vachhani, Pankit, Hambley, Bryan, Manning, Bryan S., Gier, Shannon, Cho, Christina, Tsai, Harrison K., McCurdy, Shannon, Ho, Vincent T., Koreth, John, Soiffer, Robert J., Ritz, Jerome, Carroll, Martin P., Vasu, Sumithira, Perales, Miguel-Angel, Wang, Eunice S., Gondek, Lukasz P., Devine, Steven, Alyea, Edwin P., III, Lindsley, R. Coleman, and Gibson, Christopher J.

Published
2022
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23. GM-CSF secreting leukemia cell vaccination for MDS/AML after allogeneic HSCT: a randomized, double-blinded, phase 2 trial

Author

Ho, Vincent T., Kim, Haesook T., Brock, Jennifer, Galinsky, Ilene, Daley, Heather, Reynolds, Carol, Weber, Augustine, Pozdnyakova, Olga, Severgnini, Mariano, Nikiforow, Sarah, Cutler, Corey, Koreth, John, Alyea, Edwin P., III, Antin, Joseph H., Gooptu, Mahasweta, Romee, Rizwan, Shapiro, Roman, Chen, Yi-Bin, Rosenblatt, Jacalyn, Avigan, David, Hodi, F. Stephen, Dranoff, Glenn, Wu, Catherine J., Ritz, Jerome, and Soiffer, Robert J.

Published
2022
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25. Adding venetoclax to fludarabine/busulfan RIC transplant for high-risk MDS and AML is feasible, safe, and active

Author

Garcia, Jacqueline S., Kim, Haesook T., Murdock, H. Moses, Cutler, Corey S., Brock, Jennifer, Gooptu, Mahasweta, Ho, Vincent T., Koreth, John, Nikiforow, Sarah, Romee, Rizwan, Shapiro, Roman, Loschi, Fiona, Ryan, Jeremy, Fell, Geoffrey, Karp, Hannah Q., Lucas, Fabienne, Kim, Annette S., Potter, Danielle, Mashaka, Thelma, Stone, Richard M., DeAngelo, Daniel J., Letai, Anthony, Lindsley, R. Coleman, Soiffer, Robert J., and Antin, Joseph H.

Published
2021
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27. Active infection at the time of CD34+ selected stem cell boost is associated with treatment failure and poor survival

Author

Shapiro, Roman M, primary, Kim, Haesook T, additional, Dulery, Remy, additional, Liney, Deborah, additional, Garrity, Heather M, additional, Panaro, Kevin M., additional, Au, Chloe, additional, Gervais, Casey, additional, Little, Jessica S., additional, Ho, Vincent T., additional, Cutler, Corey S., additional, Koreth, John, additional, Gooptu, Mahasweta, additional, Antin, Joseph H., additional, Kelkar, Amar H., additional, Romee, Rizwan, additional, Wu, Catherine J., additional, Ritz, Jerome, additional, Soiffer, Robert J., additional, and Nikiforow, Sarah, additional

Published
2024
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28. Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy

Author

Bachireddy, Pavan, Azizi, Elham, Burdziak, Cassandra, Nguyen, Vinhkhang N., Ennis, Christina S., Maurer, Katie, Park, Cameron Y., Choo, Zi-Ning, Li, Shuqiang, Gohil, Satyen H., Ruthen, Neil G., Ge, Zhongqi, Keskin, Derin B., Cieri, Nicoletta, Livak, Kenneth J., Kim, Haesook T., Neuberg, Donna S., Soiffer, Robert J., Ritz, Jerome, Alyea, Edwin P., Pe’er, Dana, and Wu, Catherine J.

Published
2021
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30. Active infection at the time of CD34+selected stem cell boost is associated with treatment failure and poor overall survival

Author

Shapiro, Roman M., Kim, Haesook T., Dulery, Remy, Liney, Deborah, Garrity, Heather M., Panaro, Kevin, Au, Chloe, Gervais, Casey, Little, Jessica S., Ho, Vincent T., Cutler, Corey S., Koreth, John, Gooptu, Mahasweta, Antin, Joseph H., Kelkar, Amar H., Romee, Rizwan, Wu, Catherine J., Ritz, Jerome, Soiffer, Robert J., and Nikiforow, Sarah

Abstract

•CD34+selected SCB can restore hematopoiesis after PGF after allogeneic hematopoietic stem cell transplant.•An active infection at the time of CD34+selected SCB is the strongest predictor of treatment failure and poor overall survival.

Published
2024
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37. BK virus–specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation

Author

Espada, Eduardo, Cheng, Matthew P., Kim, Haesook T., Woolley, Ann E., Avigan, Jason I., Forcade, Edouard, Soares, Maria V.D., Lacerda, João F., Nikiforow, Sarah, Gooptu, Mahasweta, Romee, Rizwan, Alyea, Edwin P., Armand, Philippe, Cutler, Corey S., Ho, Vincent T., Koreth, John, Antin, Joseph H., Soiffer, Robert J., Marty, Francisco M., and Ritz, Jerome

Published
2020
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38. Incidence, Predictors, and Outcomes of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

Author

Lewis, Clinton, Kim, Haesook T., Roeker, Lindsey E., Cutler, Corey, Koreth, John, Nikiforow, Sarah, Armand, Philippe, Gootpu, Mahasweta, Romee, Rizwan, Glotzbecker, Brett, Nageshwar, Prashant, Antin, Joseph H., Alyea, Edwin P., Richardson, Paul, Soiffer, Robert J., and Ho, Vincent T.

Published
2020
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39. Effective Prevention of Steroid-Requiring Chronic Gvhd with B Cell Depletion: A Randomized, Placebo-Controlled Trial

Author

Cutler, Corey, primary, Kim, Haesook T, additional, Banna, Hassan El, additional, Halloran, Elizabeth, additional, Matozel, Emily, additional, Ho, Vincent, additional, Koreth, John, additional, Gooptu, Mahasweta, additional, Shapiro, Roman M., additional, Kelkar, Amar H., additional, Gibson, Chris J., additional, Reynolds, Carol, additional, Ansuinelli, Michela, additional, Tamada, Rayuko, additional, Au, Chloe, additional, DeFilipp, Zachariah, additional, El-Jawahri, Areej, additional, Chen, Dr. Yi-Bin, additional, Jurdi, Najla El, additional, Weisdorf, Daniel J., additional, Couriel, Daniel R., additional, Lee, Catherine J., additional, Sahaf, Bita, additional, Craig, Juliana, additional, Ji, Kathleen, additional, Soiffer, Robert, additional, Antin, Joseph H., additional, Miklos, David B., additional, and Ritz, Jerome, additional

Published
2024
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40. The MAGIC Algorithm Probability Predicts Treatment Response and Long-Term Outcomes to Second-Line Therapy for Acute Gvhd

Author

DeFilipp, Zachariah, primary, Kim, Haesook T, additional, Spyrou, Nikolaos, additional, Kasikis, Stelios, additional, Kowalyk, Steven, additional, Eng, Gilbert, additional, Beheshti, Rahnuma, additional, Baez, Janna, additional, Ayuk, Francis, additional, Bunworasate, Udomsak, additional, Choe, Hannah, additional, Etra, Aaron, additional, Grupp, Stephan A., additional, Hexner, Elizabeth O, additional, Hogan, William J., additional, Kitko, Carrie L., additional, Qayed, Muna, additional, Reshef, Ran, additional, Vasova, Ingrid, additional, Zeiser, Robert, additional, Young, Ms. Rachel, additional, Holler, Ernst, additional, Ferrara, James, additional, Nakamura, Ryotaro, additional, Levine, John E, additional, and Chen, Dr. Yi-Bin, additional

Published
2024
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41. Ipilimumab for Patients with Relapse after Allogeneic Transplantation

Author

Davids, Matthew S, Kim, Haesook T, Bachireddy, Pavan, Costello, Caitlin, Liguori, Rebecca, Savell, Alexandra, Lukez, Alexander P, Avigan, David, Chen, Yi-Bin, McSweeney, Peter, LeBoeuf, Nicole R, Rooney, Michael S, Bowden, Michaela, Zhou, Chensheng W, Granter, Scott R, Hornick, Jason L, Rodig, Scott J, Hirakawa, Masahiro, Severgnini, Mariano, Hodi, F Stephen, Wu, Catherine J, Ho, Vincent T, Cutler, Corey, Koreth, John, Alyea, Edwin P, Antin, Joseph H, Armand, Philippe, Streicher, Howard, Ball, Edward D, Ritz, Jerome, Bashey, Asad, and Soiffer, Robert J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Hematology, Regenerative Medicine, Pediatric, Patient Safety, Stem Cell Research - Nonembryonic - Non-Human, Cancer, Rare Diseases, Pediatric Cancer, Clinical Trials and Supportive Activities, Stem Cell Research, Transplantation, Stem Cell Research - Nonembryonic - Human, 6.2 Cellular and gene therapies, 5.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Evaluation of treatments and therapeutic interventions, Adult, Aged, Antibodies, Monoclonal, CD4 Lymphocyte Count, Female, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Induction Chemotherapy, Ipilimumab, Leukemia, Lymphoma, Male, Middle Aged, Myeloproliferative Disorders, Recurrence, T-Lymphocytes, Regulatory, Transplantation Immunology, Transplantation, Homologous, Leukemia and Lymphoma Society Blood Cancer Research Partnership, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundLoss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect.MethodsWe conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit.ResultsA total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood.ConclusionsOur early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.).

Published
2016

43. Clinical Features of Acute Kidney Injury in the Early Post-Transplantation Period Following Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation

Author

Vergara-Cadavid, Juliana, Johnson, P. Connor, Kim, Haesook T., Yi, Alisha, Sise, Meghan E., Leaf, David E., Hanna, Paul E., Ho, Vincent T., Cutler, Corey S., Antin, Joseph H., Gooptu, Mahasweta, Kelkar, Amar H., Wells, Sophia L., Nikiforow, Sarah, Koreth, John, Romee, Rizwan, Soiffer, Robert J., Shapiro, Roman M., and Gupta, Shruti

Published
2023
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44. Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease

Author

Divito, Sherrie J., Aasebo, Anders T., Matos, Tiago R., Hsieh, Pei-Chen, Collin, Matthew, Elco, Christopher P., O'Malley, John T., Baekkevold, Espen S., Reims, Henrik, Gedde-Dahl, Tobias, Hagerstrom, Michael, Hilaire, Jude, Lian, John W., Milford, Edgar L., Pinkus, Geraldine S., Ho, Vincent T., Soiffer, Robert J., Kim, Haesook T., Mihm, Martin C., Ritz, Jerome, Guleria, Indira, Cutler, Corey S., Clark, Rachael A., Jahnsen, Frode L., and Kupper, Thomas S.

Subjects
Thermo Fisher Scientific Inc., Medical research -- Health aspects, Skin -- Health aspects, Hematopoietic stem cell transplantation -- Health aspects, Stem cells -- Health aspects, Scientific equipment industry -- Health aspects, T cells -- Health aspects, Health care industry
Abstract

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD. While blood contained primarily donor-derived T cells, most T cells in the skin were host derived. We next examined patient skin, colon, and blood during acute GVHD. Host T cells were present in all skin and colon acute GVHD specimens studied, yet were largely absent in blood. We observed acute skin GVHD in the presence of 100% host T cells. Analysis demonstrated that a subset of host T cells in peripheral tissues were proliferating ([Ki67.sup.+]) and producing the proinflammatory cytokines IFN-[gamma] and IL-17 in situ. Comparatively, the majority of antigen-presenting cells (APCs) in tissue in acute GVHD were donor derived, and donor-derived APCs were observed directly adjacent to host T cells. A humanized mouse model demonstrated that host skin-resident T cells could be activated by donor monocytes to generate a GVHD-like dermatitis. Thus, host tissue-resident T cells may play a previously unappreciated pathogenic role in acute GVHD., Introduction Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) (1-6). Current dogma holds that donor T cells, either transferred with or [...]

Published
2020
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47. Dose-escalated interleukin-2 therapy for refractory chronic graft-versus-host disease in adults and children

Author

Whangbo, Jennifer S., Kim, Haesook T., Mirkovic, Nikola, Leonard, Lauren, Poryanda, Samuel, Silverstein, Sophie, Kim, Soomin, Reynolds, Carol G., Rai, Sharmila C., Verrill, Kelly, Lee, Michelle A., Margossian, Steven, Duncan, Christine, Lehmann, Leslie, Huang, Jennifer, Nikiforow, Sarah, Alyea, Edwin P., III, Armand, Philippe, Cutler, Corey S., Ho, Vincent T., Blazar, Bruce R., Antin, Joseph H., Soiffer, Robert J., Ritz, Jerome, and Koreth, John

Published
2019
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48. Ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial treatment for younger patients with chronic lymphocytic leukaemia: a single-arm, multicentre, phase 2 trial

Author

Davids, Matthew S, Brander, Danielle M, Kim, Haesook T, Tyekucheva, Svitlana, Bsat, Jad, Savell, Alexandra, Hellman, Jeffrey M, Bazemore, Josie, Francoeur, Karen, Alencar, Alvaro, Shune, Leyla, Omaira, Mohammad, Jacobson, Caron A, Armand, Philippe, Ng, Samuel, Crombie, Jennifer, LaCasce, Ann S, Arnason, Jon, Hochberg, Ephraim P, Takvorian, Ronald W, Abramson, Jeremy S, Fisher, David C, and Brown, Jennifer R

Published
2019
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49. Umbralisib in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: a multicentre phase 1–1b study

Author

Davids, Matthew S, Kim, Haesook T, Nicotra, Alyssa, Savell, Alexandra, Francoeur, Karen, Hellman, Jeffrey M, Bazemore, Josie, Miskin, Hari P, Sportelli, Peter, Stampleman, Laura, Maegawa, Rodrigo, Rueter, Jens, Boruchov, Adam M, Arnason, Jon E, Jacobson, Caron A, Jacobsen, Eric D, Fisher, David C, and Brown, Jennifer R

Published
2019
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50. Expansion, persistence, and efficacy of donor memory-like NK cells infused for posttransplant relapse

Author

Shapiro, Roman M., Birch, Grace C., Hu, Guangan, Cadavid, Juliana Vergara, Nikiforow, Sarah, Baginska, Joanna, Ali, Alaa K., Tarannum, Mubin, Sheffer, Michal, Abdulhamid, Yasmin Z., Rambaldi, Benedetta, Arihara, Yohei, Reynolds, Carol, Halpern, Max S., Rodig, Scott J., Cullen, Nicole, Wolff, Jacquelyn O., Pfaff, Kathleen L., Lane, Andrew A., Lindsley, R. Coleman, Cutler, Corey S., Antin, Joseph H., Ho, Vincent T., Koreth, John, Gooptu, Mahasweta, Kim, Haesook T., Malmberg, Karl-Johan, Wu, Catherine J., Chen, Jianzhu, Soiffer, Robert J., Ritz, Jerome, and Romee, Rizwan

Subjects
Diseases -- Relapse, Killer cells -- Physiological aspects -- Usage -- Health aspects, Hematopoietic stem cells -- Transplantation, Health care industry
Abstract

BACKGROUND. Responses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell-based therapy is a promising modality to treat post-HCT relapse. METHODS. We initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. Highresolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion. RESULTS. In the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires. CONCLUSION. Given their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies. TRIAL REGISTRATION. ClinicalTrials.gov NCT04024761. FUNDING. Dunkin' Donuts, NIH/National Cancer Institute, and the Leukemia and Lymphoma Society., Introduction Relapse of acute myeloid leukemia (AML) occurs in up to 50% of patients after allogeneic hematopoietic stem cell transplant (HCT) and heralds an extremely poor prognosis (1). In several [...]

Published
2022
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