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Browsing by Author "Kebriaei, Partow"
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Item Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis(Springer Nature, 2022) Maakaron, Joseph E.; Zhang, Mei-Jie; Chen, Karen; Abhyankar, Sunil; Bhatt, Vijaya Raj; Chhabra, Saurabh; El Jurdi, Najla; Farag, Sherif S.; He, Fiona; Juckett, Mark; de Lima, Marcos; Majhail, Navneet; van der Poel, Marjolein; Saad, Ayman; Savani, Bipin; Ustun, Celalettin; Waller, Edmund K.; Litzow, Mark; Kebriaei, Partow; Hourigan, Christopher S.; Saber, Wael; Weisdorf, Daniel; Medicine, School of MedicineAcute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60-64; 65-69; 70+). With median follow-up of nearly 3 years, patients aged 60-64 had modestly, though significantly better OS, DFS and lower TRM than those either 65-69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.Item Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer(Springer Nature, 2021) Ragoonanan, Dristhi; Khazal, Sajad J.; Abdel-Azim, Hisham; McCall, David; Cuglievan, Branko; Tambaro, Francesco Paolo; Ahmad, Ali Haider; Rowan, Courtney M.; Gutierrez, Cristina; Schadler, Keri; Li, Shulin; Di Nardo, Matteo; Chi, Linda; Gulbis, Alison; Shoberu, Basirate; Mireles, Maria E.; McArthur, Jennifer; Kapoor, Neena; Miller, Jeffrey; Fitzgerald, Julie C.; Tewari, Priti; Petropoulos, Demetrios; Gill, Jonathan B.; Duncan, Christine N.; Lehmann, Leslie E.; Hingorani, Sangeeta; Angelo, Joseph R.; Swinford, Rita D.; Steiner, Marie E.; Hernandez Tejada, Fiorela N.; Martin, Paul L.; Auletta, Jeffery; Choi, Sung Won; Bajwa, Rajinder; Garnes, Natalie Dailey; Kebriaei, Partow; Rezvani, Katavoun; Wierda, Willian G.; Neelapu, Sattva S.; Shpall, Elizabeth J.; Corbacioglu, Selim; Mahadeo, Kris M.; Pediatrics, School of MedicineCancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.Item Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research(Ferrata Storti Foundation, 2019-09-26) Lazaryan, Aleksandr; Dolan, Michelle; Zhang, Mei-Jie; Wang, Hai-Lin; Kharfan-Dabaja, Mohamed A.; Marks, David I.; Bejanyan, Nelli; Copelan, Edward; Majhail, Navneet S.; Waller, Edmund K.; Chao, Nelson; Prestidge, Tim; Nishihori, Taiga; Kebriaei, Partow; Inamoto, Yoshihiro; Hamilton, Betty; Hashmi, Shahrukh K.; Kamble, Rammurti T.; Bacher, Ulrike; Hildebrandt, Gerhard C.; Stiff, Patrick J.; McGuirk, Joseph; Aldoss, Ibrahim; Beitinjaneh, Amer M.; Muffly, Lori; Vij, Ravi; Olsson, Richard F.; Byrne, Michael; Schultz, Kirk R.; Aljurf, Mahmoud; Seftel, Matthew; Savoie, Mary Lynn; Savani, Bipin N.; Verdonck, Leo F.; Cairo, Mitchell S.; Hossain, Nasheed; Bhatt, Vijaya Raj; Frangoul, Haydar A.; Abdel-Azim, Hisham; Al Malki, Monzr; Munker, Reinhold; Rizzieri, David; Khera, Nandita; Nakamura, Ryotaro; Ringdén, Olle; van der Poel, Marjolein; Murthy, Hemant S.; Liu, Hongtao; Mori, Shahram; De Oliveira, Satiro; Bolaños-Meade, Javier; Elsawy, Mahmoud; Barba, Pere; Nathan, Sunita; George, Biju; Pawarode, Attaphol; Grunwald, Michael; Agrawal, Vaibhav; Wang, Youjin; Assal, Amer; Castillo Caro, Paul; Kuwatsuka, Yachiyo; Seo, Sachiko; Ustun, Celalettin; Politikos, Ioannis; Lazarus, Hillard M.; Saber, Wael; Sandmaier, Brenda M.; De Lima, Marcos; Litzow, Mark; Bachanova, Veronika; Weisdorf, Daniel; Acute Leukemia Committee of the CIBMTR; Medicine, School of MedicineCytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.Item Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report(SAGE, 2020-07-14) Zhou, Zheng; Nath, Rajneesh; Cerny, Jan; Wang, Hai-Lin; Zhang, Mei-Jie; Abdel-Azim, Hisham; Agrawal, Vaibhav; Ahmed, Gulrayz; Al-Homsi, A. Samer; Aljurf, Mahmoud; Alkhateeb, Hassan B.; Assal, Amer; Bacher, Ulrike; Bajel, Ashish; Bashir, Qaiser; Battiwalla, Minocher; Bhatt, Vijaya Raj; Byrne, Michael; Cahn, Jean-Yves; Cairo, Mitchell; Choe, Hannah; Copelan, Edward; Cutler, Corey; Damlaj, Moussab B.; DeFilipp, Zachariah; De Lima, Marcos; Diaz, Miguel Angel; Farhadfar, Nosha; Foran, James; Freytes, César O.; Gerds, Aaron T.; Gergis, Usama; Grunwald, Michael R.; Gul, Zartash; Hamadani, Mehdi; Hashmi, Shahrukh; Hertzberg, Mark; Hildebrandt, Gerhard C.; Hossain, Nasheed; Inamoto, Yoshihiro; Isola, Luis; Jain, Tania; Kamble, Rammurti T.; Khan, Muhammad Waqas; Kharfan-Dabaja, Mohamed A.; Kebriaei, Partow; Kekre, Natasha; Khera, Nandita; Lazarus, Hillard M.; Liesveld, Jane L.; Litzow, Mark; Liu, Hongtao; Marks, David I.; Martino, Rodrigo; Mathews, Vikram; Mishra, Asmita; Murthy, Hemant S.; Nagler, Arnon; Nakamura, Ryotaro; Nathan, Sunita; Nishihori, Taiga; Olin, Rebecca; Olsson, Richard F.; Palmisiano, Neil; Patel, Sagar S.; Patnaik, Mrinal M.; Pawarode, Attaphol; Perales, Miguel-Angel; Politikos, Ioannis; Popat, Uday; Rizzieri, David; Sandmaier, Brenda M.; Savani, Bipin N.; Seo, Sachiko; Shah, Nirav N.; Uy, Geoffrey L.; Valcárcel, David; Verdonck, Leo F.; Waller, Edmund K.; Wang, Youjin; Weisdorf, Daniel; Wirk, Baldeep; Wong, Eric; Yared, Jean A.; Saber, Wael; Medicine, School of MedicineThere is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.