27 results on '"Hogan, William J."'
Search Results
2. Genetic landscape and clinical outcomes of patients with BCOR mutated myeloid neoplasms.
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Baranwal A, Gurney M, Basmaci R, Katamesh B, He R, Viswanatha DS, Greipp P, Foran J, Badar T, Murthy H, Yi CA, Palmer J, Mangaonkar AA, Patnaik MM, Litzow MR, Hogan WJ, Begna K, Gangat N, Tefferi A, Al-Kali A, Shah MV, and Alkhateeb HB
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- Humans, Male, Female, Middle Aged, Aged, Adult, Aged, 80 and over, Core Binding Factor Alpha 2 Subunit genetics, Prognosis, Young Adult, Hematopoietic Stem Cell Transplantation, Adolescent, Repressor Proteins genetics, Mutation, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute diagnosis, Proto-Oncogene Proteins genetics
- Abstract
The BCL6-corepressor (BCOR) is a tumor-suppressor gene located on the short arm of chromosome X. Data are limited regarding factors predicting survival in BCOR-mutated (mBCOR) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We evaluated 138 patients with mBCOR myeloid disorders, of which 36 (26.1%) had AML and 63 (45.6%) had MDS. Sixty-six (47.8%) patients had a normal karyotype while 18 (13%) patients had complex karyotype. BCOR-mutated MDS/AML were highly associated with RUNX1 and U2AF1 co-mutations. In contrast, TP53 mutation was infrequently seen with mBCOR MDS. Patients with an isolated BCOR mutation had similar survival compared to those with high-risk co-mutations by European LeukemiaNet (ELN) 2022 criteria (median OS 1.16 vs. 1.27 years, P=0.46). Complex karyotype adversely impacted survival among mBCOR AML/MDS (HR 4.12, P<0.001), while allogeneic stem cell transplant (alloSCT) improved survival (HR 0.38, P=0.04). However, RUNX1 co-mutation was associated with an increased risk of post-alloSCT relapse (HR 88.0, P=0.02), whereas melphalan-based conditioning was associated with a decreased relapse risk (HR 0.02, P=0.01). We conclude that mBCOR is a high-risk feature across MDS/AML, and that alloSCT improves survival in this population.
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- 2024
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3. Cardiac events in newly diagnosed acute myeloid leukaemia during treatment with venetoclax + hypomethylating agents.
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Johnson IM, Karrar O, Rana M, Iftikhar M, Chen S, McCullough K, Saliba AN, Al-Kali A, Alkhateeb H, Begna K, Litzow M, Hogan WJ, Shah M, Patnaik MM, Pardanani A, Hermann J, Tefferi A, and Gangat N
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- Male, Humans, Female, Retrospective Studies, Treatment Outcome, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Myeloid, Acute, Cardiomyopathies etiology, Sulfonamides
- Abstract
Among 301 newly diagnosed patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent, 23 (7.6%) experienced major cardiac complications: 15 cardiomyopathy, 5 non-ST elevation myocardial infarction and/or 7 pericarditis/effusions. Four patients had more than one cardiac complication. Baseline characteristics included median age ± interquartile range; 73 ± 5 years; 87% males; 96% with cardiovascular risk factors; and 90% with preserved baseline ejection fraction. In multivariate analysis, males were more likely (p = 0.02) and DNMT3A-mutated cases less likely (p < 0.01) to be affected. Treatment-emergent cardiac events were associated with a trend towards lower composite remission rates (43% vs. 62%; p = 0.09) and shorter survival (median 7.7 vs. 13.2 months; p < 0.01). These observations were retrospectively retrieved and warrant further prospective examination., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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4. Venetoclax plus hypomethylating agents in DDX41-mutated acute myeloid leukaemia and myelodysplastic syndrome: Mayo Clinic series on 12 patients.
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Nanaa A, He R, Foran JM, Badar T, Gangat N, Pardanani A, Hogan WJ, Litzow MR, Patnaik M, Al-Kali A, and Alkhateeb HB
- Subjects
- Humans, Aged, Bridged Bicyclo Compounds, Heterocyclic, Sulfonamides, Antineoplastic Combined Chemotherapy Protocols adverse effects, DEAD-box RNA Helicases, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes chemically induced, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute chemically induced
- Abstract
Venetoclax (VEN) is an FDA-approved selective inhibitor of B-cell leukaemia/lymphoma-2 (BCL-2), used for treating elderly or unfit acute myeloid leukaemia (AML) patients unable to undergo intensive chemotherapy. Combining VEN with hypomethylating agents (HMAs) has shown impressive response rates in high-risk myelodysplastic syndromes (MDS) and relapsed/refractory AML. However, the efficacy of VEN and HMAs in treating DDX41-mutated (mDDX41) MDS/AML patients remains uncertain. Despite the favourable prognostic nature of mDDX41 MDS/AML patients, there is a lack of clinical experience regarding their response to different treatment regimens, leading to an unknown optimal therapeutic approach., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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5. Factors predicting survival following alloSCT in patients with therapy-related AML and MDS: a multicenter study.
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Baranwal A, Chhetri R, Yeung D, Clark M, Shah S, Litzow MR, Hogan WJ, Mangaonkar A, Alkhateeb HB, Singhal D, Cibich A, Bardy P, Kok CH, Hiwase DK, and Shah MV
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- Humans, Transplantation, Homologous, Retrospective Studies, Neoplasm Recurrence, Local, Monosomy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Therapy-related myeloid neoplasms (t-MN) are aggressive myeloid neoplasms. Factors predicting post-allogeneic stem cell transplant (alloSCT) survival are not well-known. We studied the prognostic utility of factors at: t-MN diagnosis, pre-alloSCT, and post-alloSCT. Primary endpoints were 3-year overall survival (OS), relapse incidence (RI), and non-relapse mortality (NRM). Post-alloSCT OS did not differ between t-MDS and t-AML (20.1 vs. 19.6 months, P = 1), though t-MDS had a significantly higher 3-year RI compared to t-AML (45.1% vs. 26.9%, P = 0.03). In t-MDS, the presence of monosomy 5 (HR 3.63, P = 0.006) or monosomy 17 (HR 11.81, P = 0.01) pre-alloSCT were associated with higher RI. Complex karyotype was the only factor adversely influencing survival at all the timepoints. The inclusion of genetic information yielded 2 risk-categories: high-risk defined by the presence of pathogenic variants (PV) in (TP53/BCOR/IDH1/GATA2/BCORL1) and standard-risk (remainder of the patients) with 3-year post-alloSCT OS of 0% and 64.6%, respectively (P = 0.001). We concluded that while alloSCT was curative in a subset of t-MN patients, outcomes remained poor, specifically in the high-risk category. t-MDS patients, especially those with persistent disease pre-alloSCT were at increased risk of relapse. Disease-related factors at t-MN diagnosis were the most prognostic of post-alloSCT survival; utility of factors available later in the course, was incremental., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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6. Predictors of response to venetoclax plus hypomethylating agent therapy and survival in blastphase myeloproliferative neoplasm.
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Gangat N, Ilyas R, McCullough K, Begna KH, Al-Kali A, Patnaik MM, Litzow MR, Hogan WJ, Mangaonkar A, Alkhateeb H, Shah MV, Elliott MA, Foran JM, Badar T, Palmer JM, Hanson CA, Pardanani A, and Tefferi A
- Subjects
- Humans, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Sulfonamides therapeutic use, Antineoplastic Combined Chemotherapy Protocols, Myeloproliferative Disorders drug therapy, Neoplasms, Leukemia, Myeloid, Acute
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- 2023
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7. Adverse karyotype subcategories in acute myeloid leukemia display significant differences in mutation composition and transplant-augmented survival.
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Tefferi A, Singh A, Gangat N, Al-Kali A, Alkhateeb H, Shah M, Patnaik MS, Elliott MA, Hogan WJ, Litzow MR, Wolanskyj-Spinner A, Hook CC, Mangaonkar A, Viswanatha D, Chen D, Pardanani A, Begna KH, and Ketterling RP
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- Humans, Mutation, Karyotyping, Karyotype, Prognosis, Leukemia, Myeloid, Acute genetics
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- 2023
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8. Outcomes of allogeneic transplant in patients with DDX41 mutated myelodysplastic syndrome and acute myeloid leukemia.
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Baranwal A, Nanaa A, Viswanatha D, He R, Foran J, Badar T, Hogan WJ, Litzow MR, Shah MV, Patnaik MM, Al-Kali A, and Alkhateeb HB
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- Humans, Allografts, DEAD-box RNA Helicases genetics, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
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- 2022
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9. Daunorubicin-60 versus daunorubicin-90 versus idarubicin-12 for induction chemotherapy in acute myeloid leukemia: a retrospective analysis of the Mayo Clinic experience.
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Tefferi A, Gangat N, Shah M, Alkhateeb H, Patnaik MS, Al-Kali A, Elliott MA, Hogan WJ, Litzow MR, Hook CC, Mangaonkar A, Viswanatha D, Chen D, Pardanani A, Ketterling RP, and Begna KH
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Cytarabine therapeutic use, Daunorubicin therapeutic use, Humans, Induction Chemotherapy, Remission Induction, Retrospective Studies, Idarubicin therapeutic use, Leukemia, Myeloid, Acute drug therapy
- Published
- 2022
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10. Cardiac events in patients with acute myeloid leukemia treated with venetoclax combined with hypomethylating agents.
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Johnson IM, Bezerra ED, Farrukh F, McCullough K, Al-Kali A, Alkhateeb HB, Begna K, Litzow MR, Hogan WJ, Shah MV, Patnaik MM, Tefferi A, and Gangat N
- Subjects
- Humans, Sulfonamides adverse effects, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Leukemia, Myeloid, Acute chemically induced, Leukemia, Myeloid, Acute drug therapy
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- 2022
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11. A dynamic 3-factor survival model for acute myeloid leukemia that accounts for response to induction chemotherapy.
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Tefferi A, Gangat N, Al-Kali A, Alkhateeb H, Shah M, Patnaik MS, Elliott MA, Hogan WJ, Litzow MR, Hook CC, Mangaonkar A, Viswanatha D, Chen D, Pardanani A, Ketterling RP, DiNardo CD, Kadia TM, Ravandi F, Sasaki K, and Begna KH
- Subjects
- Abnormal Karyotype, Humans, Induction Chemotherapy, Middle Aged, Mutation, Prognosis, Remission Induction, Retrospective Studies, fms-Like Tyrosine Kinase 3 genetics, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
- Abstract
The current study was approached with the assumption that response to induction chemotherapy, in acute myeloid leukemia (AML), overshadows pre-treatment risk variables in predicting survival and therefore be used as an anchor for a simplified risk model. We considered 759 intensively-treated patients with AML, not promyelocytic: median age 60 years; primary 66%, secondary 25%, and therapy-related 9%; European LeukemiaNet cytogenetic risk category favorable 8%, intermediate 61%, and adverse 31%. Complete remission with (CR) or without (CRi) count recovery was achieved in 608 (80%) patients. After a median follow-up of 22 months, 503 deaths, 272 relapses, and 257 allogeneic hematopoietic stem cell transplants (AHSCTs) were recorded. Multivariable analysis identified failure to achieve CR/CRi (HR 3.8, 95% CI 3.1-4.8), adverse karyotype (2.2, 1.8-2.8), and age >55 years (2.1, 1.6-2.7) as main risk factors for survival. HR-weighted scoring resulted in four-tiered risk stratification: low (0 points; N = 183), intermediate-1 (1 point; N = 331), intermediate-2 (2 points; N = 117), and high (≥3 points; N = 128), with respective median survival (5-year rate) not reached (68%), 34 (37%), 13 (20%), and 5 (5%) months (p < .001). FLT3-ITD mutation was associated with inferior survival in intermediate-1 (p = .004) and TP53 in intermediate-2 (p = .06) and high (p = .02) risk disease; the latter was fully accounted for by the close association between TP53 mutation and complex/monosomal karyotype while the observations regarding FLT3-ITD were not affected by treatment with midostaurin. AHSCT had a favorable impact on survival, most apparent in intermediate-1 (p < .001), intermediate-2 (p = .03), and high (p = .01) risk disease. The proposed 3-factor survival model offers a novel prototype that is amenable to further enhancement by molecular information and was validated in an external cohort of 1032 intensively-treated AML patients., (© 2022 Wiley Periodicals LLC.)
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- 2022
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12. Therapy-related clonal cytopenia as a precursor to therapy-related myeloid neoplasms.
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Shah MV, Mangaonkar AA, Begna KH, Alkhateeb HB, Greipp P, Nanaa A, Elliott MA, Hogan WJ, Litzow MR, McCullough K, Tefferi A, Gangat N, Patnaik MM, Al-Kali A, He R, and Chen D
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- Clonal Evolution genetics, Cytogenetics, Humans, Mutation, Leukemia, Myeloid, Acute genetics, Myeloproliferative Disorders genetics, Neoplasms, Second Primary genetics, Neoplasms, Second Primary pathology
- Abstract
Therapy-related myeloid neoplasms (t-MN) are aggressive leukemia that develops as a complication of prior exposure to DNA-damaging agents. Clonal cytopenia of undetermined significance (CCUS) is a precursor of de novo myeloid neoplasms. Characteristics of CCUS that develop following cytotoxic therapies (therapy-related clonal cytopenia, t-CC) and outcomes following t-CC have not been described. We identified 33 patients with t-CC and compared to a cohort of the WHO-defined t-MN (n = 309). t-CC had a distinct genetic and cytogenetic profile: pathogenic variants (PV) in TET2 and SRSF2 were enriched in t-CC, whereas TP53 PV was more common in t-MN. Ten (30%) t-CC patients developed a subsequent t-MN, with a cumulative incidence of 13%, 23%, and 50% at 6 months, 1, and 5 years, respectively. At t-MN progression, 44% of evaluable patients had identifiable clonal evolution. The median survival following t-CC was significantly superior compared all t-MN phenotype including t-MDS with <5% bone marrow blasts (124.5 vs. 16.3 months, P < 0.001) respectively. The presence of cytogenetic abnormality and the absence of variants in DNMT3A, TET2, or ASXL1 (DTA-genes) were associated with a higher likelihood of developing a subsequent t-MN and an inferior survival. We describe a putative precursor entity of t-MN with distinct features and outcomes., (© 2022. The Author(s).)
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- 2022
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13. An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis.
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Jimenez Jimenez AM, De Lima M, Komanduri KV, Wang TP, Zhang MJ, Chen K, Abdel-Azim H, Abid MB, Aljurf M, Alkhateeb H, Assal A, Bacher U, Baron F, Battiwalla M, Beitinjaneh A, Bejanyan N, Bhatt VR, Byrne M, Cahn JY, Cairo M, Castillo P, Copelan E, DeFilipp Z, Perez MAD, Elsawy M, Gale RP, George B, Grunwald MR, Hildebrandt GC, Hogan WJ, Kanakry CG, Kansagra A, Kharfan-Dabaja MA, Khera N, Krem MM, Lazaryan A, Maakaron J, Martino R, McGuirk J, Michelis FV, Milone G, Mishra A, Murthy HS, Mussetti A, Nathan S, Nishihori T, Olsson RF, Palmisiano N, Patel S, Saad A, Seo S, Sharma A, Solh M, Verdonck LF, Wirk B, Yared JA, Litzow M, Kebriaei P, Hourigan CS, Saber W, and Weisdorf D
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- Humans, Retrospective Studies, Risk Assessment, Transplantation Conditioning, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N = 181), intermediate (IM, N = 1185), and adverse (Adv, N = 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p < 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p < 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p < 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p ≤ 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p < 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2021
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14. Acute myeloid leukemia after age 70 years: A retrospective comparison of survival following treatment with intensive versus HMA ± venetoclax chemotherapy.
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Begna KH, Gangat N, Al-Kali A, Litzow MR, Hogan WJ, Patnaik MM, Pardanani A, Hook CC, Wolanskyj AP, Elliott MA, Hanson CA, Ketterling RP, and Tefferi A
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- Abnormal Karyotype, Age of Onset, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic pharmacology, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, CCAAT-Enhancer-Binding Proteins genetics, DNA Methylation drug effects, Female, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Myelodysplastic Syndromes epidemiology, Myeloproliferative Disorders epidemiology, Neoplasm Proteins genetics, Prognosis, Proportional Hazards Models, Remission Induction, Sulfonamides administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Acute drug therapy
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- 2021
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15. Salvage use of venetoclax-based therapy for relapsed AML post allogeneic hematopoietic cell transplantation.
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Joshi M, Cook J, McCullough K, Nanaa A, Gangat N, Foran JM, Murthy HS, Kharfan-Dabaja MA, Sproat L, Palmer J, Pardanani A, Tefferi A, Begna K, Elliot M, Al-Kali A, Patnaik M, Shah MV, Hogan WJ, Litzow MR, and Alkhateeb HB
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Salvage Therapy, Young Adult, Antineoplastic Agents therapeutic use, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Neoplasm Recurrence, Local therapy, Sulfonamides therapeutic use
- Published
- 2021
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16. Mayo Clinic experience with 1123 adults with acute myeloid leukemia.
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Begna KH, Ali W, Naseema Gangat, Elliott MA, Al-Kali A, Litzow MR, Christopher Hook C, Wolanskyj-Spinner AP, Hogan WJ, Patnaik MM, Pardanani A, Zblewski DL, Chen D, He R, Viswanatha D, Hanson CA, Ketterling RP, and Tefferi A
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- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Female, Hematopoietic Stem Cell Transplantation, Humans, Karyotype, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Male, Middle Aged, Prognosis, Remission Induction, Survival Analysis, Transplantation, Homologous, Young Adult, Leukemia, Myeloid, Acute therapy
- Abstract
Between 2004 and 2017, a total of 1123 adult patients (median age 65 years; 61% males) with newly diagnosed acute myeloid leukemia (AML), not including acute promyelocytic leukemia, were seen at the Mayo Clinic. Treatment included intensive (n = 766) or lower intensity (n = 144) chemotherapy or supportive care (n = 213), with respective median survivals of 22, 9, and 2 months (p < 0.01). Intensive chemotherapy resulted in complete remission (CR) and CR with incomplete count recovery (CRi) rates of 44 and 33%, respectively, with no difference in survival outcome between the two (p = 0.4). Allogeneic hematopoietic stem cell transplant (AHSCT) was documented in 259 patients and provided the best survival rate (median 55 months; p < 0.01). After a median follow-up of 13 months, 841 (75%) deaths were recorded. Multivariate analysis identified age >60 years (HR 2.2, 1.9-2.6), adverse karyotype (HR 2.9, 1.9-4.9), intermediate-risk karyotype (HR 1.6, 1.02-2.6), post-myeloproliferative neoplasm AML (HR 1.9, 1.5-2.4), and other secondary AML (HR 1.3 (1.1-1.6) as risk factors for shortened survival. These risk factors retained their significance after inclusion of FLT3/NPM1 mutational status in 392 informative cases: FLT3+NPM1- (HR 2.8, 1.4-5.6), FLT3+/NPM+ (HR 2.6 (1.3-5.2), and FLT3-NPM1- (HR 1.8, 1.0-3.0).
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- 2021
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17. PD-1/PD-L1 expression in extramedullary lesions of acute myeloid leukemia.
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Meleveedu KS, Chen D, Nadiminti K, Sidiqi H, Khan S, Alkhateeb H, Shah MV, Patnaik M, Hogan WJ, Begna K, and Litzow M
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- B7-H1 Antigen genetics, Humans, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Programmed Cell Death 1 Receptor genetics
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- 2021
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18. Cardiovascular outcomes in patients receiving myeloablative vs. reduced intensity conditioning prior to allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.
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El-Harasis MA, Hefazi M, Julakanti R, Hogan WJ, Litzow MR, Patnaik MM, and Herrmann J
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- Humans, Myeloablative Agonists, Retrospective Studies, Transplantation Conditioning adverse effects, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
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- 2021
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19. Safety and tolerability of lurbinectedin (PM01183) in patients with acute myeloid leukemia and myelodysplastic syndrome.
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Benton CB, Chien KS, Tefferi A, Rodriguez J, Ravandi F, Daver N, Jabbour E, Jain N, Alvarado Y, Kwari M, Pierce S, Maiti A, Hornbaker M, Santos MA, Martinez S, Siguero M, Zblewski D, Al-Kali A, Hogan WJ, Kantarjian H, Pardanani A, and Garcia-Manero G
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Bone Marrow Cells metabolism, Bone Marrow Cells pathology, Carbolines administration & dosage, Carbolines therapeutic use, Chromosome Aberrations, Female, Heterocyclic Compounds, 4 or More Rings administration & dosage, Heterocyclic Compounds, 4 or More Rings therapeutic use, Humans, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute etiology, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes etiology, Myelodysplastic Syndromes mortality, Treatment Outcome, Young Adult, Antineoplastic Agents adverse effects, Carbolines adverse effects, Heterocyclic Compounds, 4 or More Rings adverse effects, Leukemia, Myeloid, Acute drug therapy, Myelodysplastic Syndromes drug therapy
- Abstract
Trabectedin is an FDA-approved DNA minor groove binder that has activity against translocation-associated sarcomas. Lurbinectedin is a next-generation minor groove binder with preclinical activity against myeloid leukemia cells. A dose-finding phase 1 clinical trial was performed in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with further assessment of safety and tolerability. Forty-two patients with relapsed/refractory AML/MDS received lurbinectedin administered as a 1-hour intravenous infusion in a 3 + 3 study design. Two dosing schedules were used: 3.5, 5, 7, or 6 mg on days 1 and 8 or 2, 3, 1, or 1.5 mg for 3 consecutive days on days 1 to 3. Three patients experienced dose-limiting toxicities of rhabdomyolysis (grade 4), hyperbilirubinemia (grade 3), and oral herpes (grade 3) with the day 1 and 8 schedule. Otherwise, adverse events mainly consisted of gastrointestinal manifestations (n = 11), febrile neutropenia/infections (n = 4), pulmonary toxicity (n = 2), and renal failure (n = 2). The most common laboratory abnormalities observed were an increase in creatinine (93%) and anemia, neutropenia, and thrombocytopenia (100%). Overall, 33 of 42 patients (79%) had reduction in blasts in peripheral blood or bone marrow. One patient achieved a partial response and 2 patients a morphologic leukemia-free state. Most (n = 30, 71%) were discontinued due to progressive disease. Early deaths occurred from disease-related causes that were not attributable to lurbinectedin. Four patients with a chromosome 11q21-23 abnormality had significantly greater bone marrow blast reduction than those without such abnormality, with decrease of 31 ± 14% (n = 4) vs 8 ± 8% (n = 16), respectively (P = .04). Overall, lurbinectedin was safe and tolerated using the schedules and dose levels tested. While no sustained remissions were observed, single-agent lurbinectedin was transiently leukemia suppressive for some patients., (© 2018 John Wiley & Sons, Ltd.)
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- 2019
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20. A novel predictive model of outcome in acute myeloid leukemia without favorable karyotype based on treatment strategy, karyotype and FLT3-ITD mutational status.
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Begna KH, Ali W, Gangat N, Elliott MA, Al-Kali A, Litzow MR, Hook CC, Wolanskyj AP, Hogan WJ, Patnaik MM, Pardanani A, Zblewski DL, Chen D, He R, Viswanatha D, Hanson CA, Ketterling RP, and Tefferi A
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Mutation, Prognosis, Remission Induction, Stem Cell Transplantation, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Young Adult, Karyotype, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy, fms-Like Tyrosine Kinase 3 genetics
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- 2018
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21. Acute leukemia in pregnancy: a single institution experience with 23 patients.
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Farhadfar N, Cerquozzi S, Hessenauer MR, Litzow MR, Hogan WJ, Letendre L, Patnaik MM, Tefferi A, and Gangat N
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- Adolescent, Adult, Biomarkers, Tumor, Combined Modality Therapy, Consolidation Chemotherapy, Female, Gestational Age, Humans, Infant, Newborn, Male, Pregnancy, Pregnancy Outcome, Remission Induction, Treatment Outcome, Young Adult, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Pregnancy Complications, Neoplastic diagnosis, Pregnancy Complications, Neoplastic therapy
- Abstract
Management of acute leukemia during pregnancy presents a considerable challenge. Herein, we review our experience of 23 patients diagnosed with acute leukemia; during pregnancy at the Mayo Clinic between 1962 and 2016. Ten (43.4%), seven (30.4%), and six (26.2%) patients were diagnosed in first, second, and third trimester, respectively. In approximately, 50% (n = 11) therapeutic terminations or spontaneous abortions occurred. Fifty percent (2/4) of patients diagnosed during either first or second trimester who delayed chemotherapy by greater than one week died during induction therapy. Eleven patients received chemotherapy while pregnant which led to four fetal losses and seven deliveries (five full-term and two preterm deliveries). No congenital malformations were reported. Eighteen patients (78%) achieved complete remission. At a median follow up of 55 months, seven patients (30%) remain alive. In summary, we provide a comprehensive description of maternal and fetal outcomes and insight into management of acute leukemia during pregnancy.
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- 2017
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22. Vancomycin-resistant Enterococcus colonization and bloodstream infection: prevalence, risk factors, and the impact on early outcomes after allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia.
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Hefazi M, Damlaj M, Alkhateeb HB, Partain DK, Patel R, Razonable RR, Gastineau DA, Al-Kali A, Hashmi SK, Hogan WJ, Litzow MR, and Patnaik MM
- Subjects
- Adolescent, Adult, Aged, Anti-Bacterial Agents therapeutic use, Bacteremia microbiology, Bacterial Proteins isolation & purification, Carbon-Oxygen Ligases isolation & purification, Female, Gram-Positive Bacterial Infections blood, Gram-Positive Bacterial Infections microbiology, Humans, Male, Middle Aged, Polymerase Chain Reaction, Prevalence, Prognosis, Retrospective Studies, Risk Factors, Survival Analysis, Transplantation, Homologous adverse effects, Vancomycin therapeutic use, Vancomycin Resistance genetics, Vancomycin-Resistant Enterococci physiology, Young Adult, Bacteremia epidemiology, Gram-Positive Bacterial Infections epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute surgery, Vancomycin-Resistant Enterococci isolation & purification
- Abstract
Background: Screening for vancomycin-resistant Enterococcus (VRE) is performed at many transplant centers, but data on the impact of VRE colonization and bloodstream infection (BSI) on hematopoietic cell transplantation (HCT) outcomes remain conflicting., Methods: Consecutive adults with acute myeloid leukemia who underwent allogeneic HCT between 2004 and 2014 were retrospectively reviewed. Patients were screened by perirectal PCR swabs targeting vanA and vanB twice weekly while inpatient., Results: Of a total of 203 patients (median age 54 years), 73 (36%) were VRE colonized prior to HCT, 23 (11%) became colonized within the first 100 days, and 107 (53%) remained non-colonized through day 100 post HCT. A landmark analysis on HCT day 0 revealed no significant difference in overall survival according to pre-transplant colonization status (P=.20). However, patients with subsequent VRE colonization within the first 100 days of HCT had a significantly worse survival on both univariable (P=.04) and multivariable (P=.03) analyses. During the first 30 days post HCT, 11 (5% of total and 11% of the VRE colonized) patients developed VRE BSI. Ten (91%) of these had screened positive for VRE colonization before the bacteremia. Age ≥60 years, HCT-comorbidity index ≥3, and VRE colonization were independent risk factors for VRE BSI on multivariable analysis (P=.04, .03, .003, respectively). Only 1 (9%) patient with VRE BSI died within the first 100 days post HCT., Conclusion: VRE colonization is a surrogate marker and not an independent predictor of worse outcomes post HCT. VRE BSI is associated with increased morbidity, but does not impact post-HCT survival., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2016
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23. Comparison of complication rates of Hickman(®) catheters versus peripherally inserted central catheters in patients with acute myeloid leukemia undergoing induction chemotherapy.
- Author
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Lim MY, Al-Kali A, Ashrani AA, Begna KH, Elliott MA, Hogan WJ, Hook CC, Kaufmann SH, Letendre L, Litzow MR, Patnaik MS, Pardanani A, Tefferi A, Wolanskyj AP, Grill DE, and Pruthi RK
- Subjects
- Adult, Aged, Aged, 80 and over, Catheters, Indwelling, Female, Humans, Induction Chemotherapy, Leukemia, Myeloid, Acute drug therapy, Male, Middle Aged, Young Adult, Catheterization, Central Venous adverse effects, Catheterization, Peripheral adverse effects, Leukemia, Myeloid, Acute complications, Postoperative Complications etiology
- Abstract
Central venous access devices (CVADs) are used for intravenous therapy in patients with hematological malignancies. There are limited data comparing catheter outcomes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy. A retrospective review comparing the incidence of early and late CVAD-associated complications and their effect on CVAD removal was performed in patients with AML undergoing induction chemotherapy between 2007 and 2011. Overall, 64 Hickman(®) catheters and 84 peripherally inserted central catheters (PICCs) were inserted. There was a trend toward increasing use of PICCs. The rate of CVAD occlusion was higher in PICCs compared to Hickman catheters (48.2% vs. 3.2%), for a rate of 20.43 vs. 1.25 per 1000 CVAD-days (p = 0.0001). There was no significant difference in the rates of CVAD-associated thrombosis, premature removal, blood stream infection (BSI) and CVAD-related BSI. Importantly, there was no significant difference in the rate of CVAD removal between Hickman catheters and PICCs for the duration that the CVADs were in place. The choice of type of CVAD inserted into patients with newly diagnosed AML will depend on ease of catheter placement, cost, perception of frequency and severity of complications, and clinician preference.
- Published
- 2013
- Full Text
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24. The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole.
- Author
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Barreto JN, Beach CL, Wolf RC, Merten JA, Tosh PK, Wilson JW, Hogan WJ, and Litzow MR
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Aspergillus isolation & purification, Female, Humans, Incidence, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute microbiology, Male, Middle Aged, Mycoses etiology, Mycoses microbiology, Mycoses prevention & control, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes microbiology, Neutropenia drug therapy, Neutropenia etiology, Neutropenia microbiology, Recurrence, Remission Induction, Retrospective Studies, Rhizopus isolation & purification, Voriconazole, Antifungal Agents therapeutic use, Leukemia, Myeloid, Acute epidemiology, Mycoses epidemiology, Myelodysplastic Syndromes epidemiology, Neutropenia epidemiology, Pyrimidines therapeutic use, Triazoles therapeutic use
- Abstract
The objective of this study is to characterize the outcomes of primary antifungal prophylaxis with voriconazole in patients receiving intensive chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). We conducted a single center, retrospective, cohort study of consecutive adult patients with AML or MDS at Mayo Clinic between January 1, 2006 and July 1, 2010. The study included patients undergoing induction or first relapse combination chemotherapy who received voriconazole 200 mg orally twice daily as prophylaxis during the neutropenic phase. Patient records were evaluated until 30 days after neutrophil recovery for development of invasive fungal infection (IFI) as defined per EORTC/MSG 2008 criteria with computed tomography scans independently reviewed by a radiologist. Therapeutic drug monitoring and reasons for voriconazole discontinuation were documented. Twenty four episodes of IFI were detected among 165 consecutive patients for an overall incidence of 145 per 1000 patients. The incidence of IFI was 24, 42, and 78 per 1000 patients for proven, probable, and possible infection, respectively. Four patients developed proven IFI (n = 2 Aspergillus spp., n = 2 Rhizopus spp.). Serum voriconazole trough concentrations were available in 39 patients, and no statistically significant difference in voriconazole trough level was observed between those with versus without an IFI. Voriconazole prophylaxis was discontinued in 81 patients due to suspected IFI (n = 24), fever of unknown origin (n = 19), adverse events (n = 23), and other causes (n = 17). Voriconazole as primary IFI prophylaxis is safe and may be beneficial in AML/MDS patients receiving intensive chemotherapy., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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25. Peripheral blood lymphocyte and monocyte recovery and survival in acute leukemia postmyeloablative allogeneic hematopoietic stem cell transplant.
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Thoma MD, Huneke TJ, DeCook LJ, Johnson ND, Wiegand RA, Litzow MR, Hogan WJ, Porrata LF, and Holtan SG
- Subjects
- Adolescent, Adult, Cell Count, Cluster Analysis, Disease-Free Survival, Female, Graft vs Host Disease immunology, Graft vs Host Disease pathology, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Longitudinal Studies, Lymphocytes immunology, Male, Middle Aged, Monocytes immunology, Myeloablative Agonists administration & dosage, Myeloablative Agonists therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Prognosis, Time Factors, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute pathology, Lymphocytes pathology, Monocytes pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Transplantation Conditioning
- Abstract
Many previous studies of immune reconstitution (IR) postallogeneic hematopoietic stem cell transplantation (HSCT) have focused on lymphocyte recovery. Recognizing that IR involves complex interactions between innate and adaptive immune networks, we hypothesized that patterns of both monocyte and lymphocyte recovery could provide additional prognostic information. To test our hypothesis, we analyzed data from 135 consecutive patients undergoing myeloablative allogeneic HSCT for acute myeloid (AML) and lymphoblastic leukemia (ALL) from 2001 to 2010. The absolute lymphocyte and monocyte counts (ALC and AMC, respectively) were determined longitudinally at days +15, +30, +60, and +100, and correlated with clinical outcomes. At the day +30 time point, both ALC and AMC >0.3 × 10(9) cells/L were strongly associated with improved survival (overall survival [OS] 29.6 months versus 5.4 months, P = .006 and 25.3 months versus 5.1 months, P = .01 respectively), a pattern that generally continued through the day +100 evaluation. Multivariate analysis revealed the following independent prognostic factors: early disease status at transplantation, the development of chronic GVHD, the day +30 AMC, day +100 AMC, and day +100 ALC. To further explore whether any inherent patterns in the timing of lymphocyte and monocyte recovery had prognostic value post-HSCT, we performed unsupervised hierarchical clustering on the longitudinal hematopoietic parameters studied in this cohort. Four clusters of patients were identified: clusters A-D. Patient clusters B and D both demonstrated improved ALC and AMC recovery at the day +60 and day +100 time points and had significantly improved OS compared with clusters A and C (57.8 months versus 19.7 and 4.4 months, respectively, P < .001). Our data suggest that patients with poor lymphocyte and monocyte recovery beyond the day +60 time points may be at risk for poorer outcomes, and that further investigation into lymphoid/myeloid interactions in developing individualized immunotherapy is warranted., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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26. Neutropenic colitis after treatment of acute myelogenous leukemia with idarubicin and cytosine arabinoside.
- Author
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Hogan WJ, Letendre L, Litzow MR, Tefferi A, Hoagland HC, Pruthi RK, and Kaufmann SH
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colitis epidemiology, Cytarabine administration & dosage, Female, Humans, Idarubicin administration & dosage, Incidence, Male, Middle Aged, Neutropenia chemically induced, Retrospective Studies, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Colitis chemically induced, Cytarabine adverse effects, Idarubicin adverse effects, Leukemia, Myeloid, Acute drug therapy
- Abstract
Objective: To determine the gastrointestinal toxic effects of idarubicin and cytosine arabinoside combination therapy in patients with newly diagnosed acute myelogenous leukemia (AML)., Patients and Methods: We performed a single-institution retrospective analysis of the incidence of neutropenic colitis in patients with newly diagnosed AML receiving idarubicin and cytosine arabinoside combination therapy. Using pharmacy records, we identified 78 patients who received idarubicin during the study period of January 1997 to September 1998 and who agreed to a review of their medical records. Patients with preexisting bowel conditions were excluded from this analysis. We used a strict definition of neutropenic colitis that included clinical findings (severe abdominal pain, diarrhea, hematochezia, and/or peritoneal signs) plus radiographic evidence of bowel inflammation in the absence of an identified bacterial pathogen., Results: Of the 78 patients receiving idarubicin and cytosine arabinoside for treatment of AML, 65 were included in this study. We observed neutropenic colitis in 10 of these 65 AML patients. This complication was followed by sepsis in 3 patients and was the major cause of death in 4 of the 8 patients who died., Conclusion: This analysis suggests that neutropenic colitis is a frequent and serious complication of idarubicin and cytosine arabinoside treatment.
- Published
- 2002
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27. The impact of smoking on outcomes among patients undergoing hematopoietic stem cell transplant for the treatment of acute leukemia
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Ehlers, Shawna L., Gastineau, Dennis A., Patten, Christi A., Decker, Paul A., Rausch, Sarah M., Cerhan, James R., Hogan, William J., Ebbert, Jon O., and Porrata, Luis F.
- Subjects
Adult ,Male ,transplants ,Smoking ,neoplasms ,leukemia ,Hematopoietic Stem Cell Transplantation ,life style ,Length of Stay ,Middle Aged ,tobacco ,Leukemia, Lymphocytic, Chronic, B-Cell ,Article ,Cohort Studies ,Leukemia, Myeloid, Acute ,Treatment Outcome ,health behavior ,Humans ,Female ,Aged ,Retrospective Studies - Abstract
A paucity of research exists examining the potential impact of tobacco use on cancer treatment outcomes, especially among patients treated with hematopoietic stem cell transplantation (HSCT). A retrospective cohort study design was utilized to examine the impact of smoking on duration of hospitalization and overall survival among 148 consecutive patients undergoing HSCT for treatment of acute leukemia from 1999 to 2005. Of the 148 patients, 15% reported current smoking, 30% former smoking, and 55% never used tobacco. Patients were followed for a median 3.5 years (Interquartile Range= 2.1-5.5). Compared to no history of smoking, current smoking was associated with worse pre-HSCT pulmonary function tests (p< .02 in each case), more days hospitalized (46.2 versus 25.7 days, p = 0.025, and poorer overall survival (HR=1.88; 95% CI 1.09-3.25). Results were similar after multivariate adjustment, although the association with overall survival attenuated slightly (HR=1.75, 95% CI 1.00-3.06). Current smoking appears to adversely affect the number of days hospitalized post-HSCT and overall survival. Translational research focused on interventions to promote tobacco cessation may lead to improved HSCT outcomes.
- Published
- 2010
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