Browsing by Author "Lazarus, Hillard M."

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    Age no Bar – a CIBMTR analysis of Elderly Patients undergoing Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
    (Wiley, 2020) Munshi, Pashna N.; Vesole, David; Jurczyszyn, Artur; Zaucha, Jan Maciej; St. Martin, Andrew; Davila, Omar; Agrawal, Vaibhav; Badawy, Sherif M.; Battiwalla, Minoo; Chhabra, Saurabh; Copelan, Edward; Kharfan-Dabaja, Mohamed A.; Farhadfar, Nosha; Ganguly, Siddhartha; Hashmi, Shahrukh; Krem, Maxwell M.; Lazarus, Hillard M.; Malek, Ehsan; Meehan, Kenneth; Murthy, Hemant S.; Nishihori, Taiga; Olin, Rebecca L.; Olsson, Richard F.; Schriber, Jeffrey; Seo, Sachiko; Shah, Gunjan; Solh, Melhem; Tay, Jason; Kumar, Shaji; Qazilbash, Muzaffar H.; Shah, Nina; Hari, Parameswaran N.; D'Souza, Anita; Medicine, School of Medicine
    Background: Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. Methods: The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori. Results: An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2 . On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P = .02]) compared with the reference group (those aged 60-69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2 , including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%]; P = .003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%]; P = .003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%]; P = .01]), likely representing frailty. Conclusions: The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.
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    CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials
    (American Society of Hematology, 2021) Ganzel, Chezi; Lee, Ju-Whei; Fernandez, Hugo F.; Paietta, Elisabeth M.; Luger, Selina M.; Lazarus, Hillard M.; Cripe, Larry D.; Douer, Dan; Wiernik, Peter H.; Rowe, Jacob M.; Tallman, Martin S.; Litzow, Mark R.; Medicine, School of Medicine
    Central nervous system (CNS) involvement in patients with newly diagnosed acute myeloid leukemia (AML) is rare, and systematic data regarding outcome are scarce. This retrospective study summarized data from 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials for patients with newly diagnosed AML. In all, 3240 patients with AML were analyzed, and 36 (1.11%) were found to have CNS involvement at diagnosis. The incidence of CNS disease among the 5 studies with per protocol mandatory lumbar puncture (LP) was similar to the incidence among studies in which LP was performed at the discretion of the investigator (0.86% vs 1.41%; P = .18). There was no significant difference in the rate of complete remission (CR) among patients with CNS involvement and those with other extramedullary disease (EMD) sites or those with no EMD (52.8% vs 59.3%-60%). The median overall survival (OS) for patients who were CNS positive, who had other EMD, or who had no EMD was 11.4, 11.3, and 12.7 months, respectively. There was no difference in OS among patients with CNS involvement, those with other EMD (hazard ratio [HR], 0.96; adjusted P = .84), and those with no EMD (HR, 1.19; adjusted P = .44). In conclusion, the reported incidence of CNS involvement in patients with newly diagnosed AML is low (1.1%), irrespective of whether an LP is mandatory or not. The presence of CNS disease at diagnosis in and of itself does not seem to portend a poor prognosis for achieving an initial CR or for OS.
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    Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes
    (Elsevier, 2021) Oran, Betül; Ahn, Kwang Woo; Fretham, Caitrin; Beitinjaneh, Amer; Bashey, Asad; Pawarode, Attaphol; Wirk, Baldeep; Scott, Bart L.; Savani, Bipin N.; Bredeson, Christopher; Weisdorf, Daniel; Marks, David I.; Rizzieri, David; Copelan, Edward; Hildebrandt, Gerhard C.; Hale, Gregory A.; Murthy, Hemant S.; Lazarus, Hillard M.; Cerny, Jan; Liesveld, Jane L.; Yared, Jean A.; Yves-Cahn, Jean; Szer, Jeffrey; Verdonck, Leo F.; Aljur, Mahmoud; van der Poel, Marjolein; Litzow, Mark; Kalaycio, Matt; Grunwald, Michael R.; Diaz, Miguel Angel; Sabloff, Mitchell; Kharfan-Dabaja, Mohamed A.; Majhail, Navneet S.; Farhadfar, Nosha; Reshef, Ran; Olsson, Richard F.; Gale, Robert Peter; Nakamura, Ryotaro; Seo, Sachiko; Chhabra, Saurabh; Hashmi, Shahrukh; Farhan, Shatha; Ganguly, Siddhartha; Nathan, Sunita; Nishihori, Taiga; Jain, Tania; Agrawal, Vaibhav; Bacher, Ulrike; Popat, Uday; Saber, Wael; Medicine, School of Medicine
    Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m2. The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.
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    Human Mesenchymal Stem Cell (hMSC)Donor Potency Selection for the “First in Cystic Fibrosis” Phase I Clinical Trial (CEASE-CF)
    (MDPI, 2023-02-01) Bonfield, Tracey L.; Sutton, Morgan T.; Fletcher, David R.; Reese-Koc, Jane; Roesch, Erica A.; Lazarus, Hillard M.; Chmiel, James F.; Caplan, Arnold I.; Pediatrics, School of Medicine
    Human Mesenchymal Stem Cell (hMSC) immunotherapy has been shown to provide both anti-inflammatory and anti-microbial effectiveness in a variety of diseases. The clinical potency of hMSCs is based upon an initial direct hMSC effect on the pro-inflammatory and anti-microbial pathophysiology as well as sustained potency through orchestrating the host immunity to optimize the resolution of infection and tissue damage. Cystic fibrosis (CF) patients suffer from a lung disease characterized by excessive inflammation and chronic infection as well as a variety of other systemic anomalies associated with the consequences of abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function. The application of hMSC immunotherapy to the CF clinical armamentarium is important even in the era of modulators when patients with an established disease still need anti-inflammatory and anti-microbial therapies. Additionally, people with CF mutations not addressed by current modulator resources need anti-inflammation and anti-infection management. Furthermore, hMSCs possess dynamic therapeutic properties, but the potency of their products is highly variable with respect to their anti-inflammatory and anti-microbial effects. Due to the variability of hMSC products, we utilized standardized in vitro and in vivo models to select hMSC donor preparations with the greatest potential for clinical efficacy. The models that were used recapitulate many of the pathophysiologic outcomes associated with CF. We applied this strategy in pursuit of identifying the optimal donor to utilize for the “First in CF” Phase I clinical trial of hMSCs as an immunotherapy and anti-microbial therapy for people with cystic fibrosis. The hMSCs screened in this study demonstrated significant diversity in antimicrobial and anti-inflammatory function using models which mimic some aspects of CF infection and inflammation. However, the variability in activity between in vitro potency and in vivo effectiveness continues to be refined. Future studies require and in-depth pursuit of hMSC molecular signatures that ultimately predict the capacity of hMSCs to function in the clinical setting.
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    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 Medicine
    Cytogenetic 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.
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    Independent Prognostic Significance of Monosomy 17 and Impact of Karyotype Complexity in Monosomal Karyotype/Complex Karyotype Acute Myeloid Leukemia: Results from Four ECOG-ACRIN Prospective Therapeutic Trials
    (Elsevier, 2017-08) Strickland, Stephen A.; Sun, Zhuoxin; Ketterling, Rhett P.; Cherry, Athena M.; Cripe, Larry D.; Dewald, Gordon; Fernandez, Hugo; Hicks, Gary A.; Higgins, Rodney R.; Lazarus, Hillard M.; Litzow, Mark R.; Luger, Selina M.; Paietta, Elisabeth M.; Rowe, Jacob M.; Vance, Gail H.; Wiernik, Peter; Wiktor, Anne E.; Zhang, Yanming; Tallman, Martin S.; Department of Medicine, IU School of Medicine
    The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥ 5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CK≥ 5 (p = 0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥ 5 (p = 0.39) or CK ≤ 4 (p = 0.44). Monosomy 17 appeared in 43% (68/158) of CK≥ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML.
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    Prognostic effect of gender on outcome of treatment for adults with acute myeloid leukaemia
    (Wiley, 2021) Wiernik, Peter H.; Sun, Zhuoxin; Cripe, Larry D.; Rowe, Jacob M.; Fernandez, Hugo F.; Luger, Selina M.; Lazarus, Hillard M.; Paietta, Elisabeth M.; Tallman, Martin S.; Litzow, Mark R.; Medicine, School of Medicine
    There are conflicting reports in the literature suggesting that one gender or the other has a better survival with acute myeloid leukaemia (AML). This study was done in an attempt to resolve the issue. The effect of gender was examined on 3,546 newly diagnosed patients with AML, including 548 patients with acute promyelocytic leukaemia (APL) enrolled in 10 multi-institutional treatment studies from March 1984 to November 2008. Kaplan-Meier estimates were used to estimate event-time distributions for survival and multivariate models were used to examine the gender effect after adjusting for multiple risk factors. P values were based on 2-sided tests. Non-APL female patients had a significantly better overall but not disease-free survival than males, irrespective of age, initial WBC count, or dose of daunorubicin. No differences were observed for obese or FLT3-ITD + patients. Female APL patients had a significantly better overall and disease-free survival than male APL patients, and differences in survival were greater for patients with t(15;17) + other cytogenetic abnormalities compared with those with t(15;17) only. Gender is an independent prognostic variable in patients with AML. Whether these survival differences are due to hormonal, genetic or pharmacokinetic differences between the sexes, or differential toxin exposure such as smoking is unknown. However, the former seems less likely since patient age did not influence the survival advantage for female patients.
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    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 Medicine
    There 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.
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    The Role of Donor Lymphocyte Infusion (DLI) in Post Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era
    (Elsevier, 2020-06) Schmidt, Sarah; Liu, Ying; Hu, Zhen-Huan; Williams, Kirsten M.; Lazarus, Hillard M.; Vij, Ravi; Kharfan-Dabaja, Mohamed A.; Ortí, Guillermo; Wiernik, Peter H.; Weisdorf, Daniel; Kamble, Rammurti T.; Herzig, Roger; Wirk, Baldeep; Cerny, Jan; Bacher, Ulrike; Chaudhri, Naeem A.; Nathan, Sunita; Farhadfar, Nosha; Aljurf, Mahmoud; Gergis, Usama; Szer, Jeffrey; Seo, Sachiko; Hsu, Jack W.; Olsson, Richard F.; Maharaj, Dipnarine; George, Biju; Hildebrandt, Gerhard C.; Agrawal, Vaibhav; Nishihori, Taiga; Abdel-Azim, Hisham; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Scott, Bart L.; Holter Chakrabarty, Jennifer; Saber, Wael; Medicine, School of Medicine
    Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKIs) with or without donor lymphocyte infusions (DLIs), but the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups: (1) TKI alone (n = 128), (2) TKI with DLI (n = 48), and (3) DLI without TKI (n = 39). In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients who received a DLI alone compared with a TKI with a DLI had inferior survival (hazard ratio, 2.28; 95% confidence interval, 1.23 to 4.24; P= .009). Those who received a TKI alone had similar survival compared with those who received a TKI with a DLI (P = .81). These data support that despite use of TKIs pretransplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data do not suggest that adding a DLI to a TKI adds an improvement in OS.
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    Survival following allogeneic transplant in patients with myelofibrosis
    (American Society of Hematology, 2020-05-08) Gowin, Krisstina; Ballen, Karen; Ahn, Kwang Woo; Hu, Zhen-Huan; Ali, Haris; Arcasoy, Murat O.; Devlin, Rebecca; Coakley, Maria; Gerds, Aaron T.; Green, Michael; Gupta, Vikas; Hobbs, Gabriela; Jain, Tania; Kandarpa, Malathi; Komrokji, Rami; Kuykendall, Andrew T.; Luber, Kierstin; Masarova, Lucia; Michaelis, Laura C.; Patches, Sarah; Pariser, Ashley C.; Rampal, Raajit; Stein, Brady; Talpaz, Moshe; Verstovsek, Srdan; Wadleigh, Martha; Agrawal, Vaibhav; Aljurf, Mahmoud; Diaz, Miguel Angel; Avalos, Belinda R.; Bacher, Ulrike; Bashey, Asad; Beitinjaneh, Amer M.; Cerny, Jan; Chhabra, Saurabh; Copelan, Edward; Cutler, Corey S.; DeFilipp, Zachariah; Gadalla, Shahinaz M.; Ganguly, Siddhartha; Grunwald, Michael R.; Hashmi, Shahrukh K.; Kharfan-Dabaja, Mohamed A.; Kindwall-Keller, Tamila; Kröger, Nicolaus; Lazarus, Hillard M.; Liesveld, Jane L.; Litzow, Mark R.; Marks, David I.; Nathan, Sunita; Nishihori, Taiga; Olsson, Richard F.; Pawarod, Attaphol; Rowe, Jacob M.; Savani, Bipin N.; Savoie, Mary Lynn; Seo, Sachiko; Solh, Melhem; Tamari, Roni; Verdonck, Leo F.; Yared, Jean A.; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Scott, Bart L.; Nakamura, Ryotaro; Mesa, Ruben; Saber, Wael; Medicine, School of Medicine
    Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.