28 results on '"J. Senapati"'
Search Results
2. P369: A PHASE II STUDY OF MINI-HYPER-CVD PLUS VENETOCLAX IN PATIENTS WITH PHILADELPHIA CHROMOSOME-NEGATIVE ACUTE LYMPHOBLASTIC LEUKEMIA
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J. Senapati, H. Kantarjian, N. Short, M. Konopleva, F. Ravandi, N. Jain, P. A. Thompson, N. Pemmaraju, W. G. Wierda, G. Borthakur, T. M. Kadia, G. Garcia-Manero, M. Yilmaz, J. Thankachan, M. Zhao, C. Loiselle, M. T. Talley, M. I. Kwari, R. S. Garris, and E. J. Jabbour
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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3. P367: LONG TERM OUTCOMES OF NEWLY DIAGNOSED CRLF2 REARRANGED B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
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J. Senapati, E. J. Jabbour, N. J. Short, F. Ravandi, P. Kebriaei, T. M. Kadia, G. Borthakur, N. Pemmaraju, R. S. Garris, D. Bansal, S. Konoplev, S. Wang, W. Wang, G. Tang, K. P. Patel, M. Konopleva, and N. Jain
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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4. P497: PROGNOSTIC IMPACT OF RAS AND C-KIT MUTATIONS (SINGLE VS. MULTIPLE) IN CORE-BINDING FACTOR ACUTE MYELOID LEUKEMIA TREATED WITH FLUDARABINE, CYTARABINE, G-CSF (FLAG) BASED REGIMEN
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T. Abuasab, J. Senapati, T. Kadia, F. Ravandi, C. DiNardo, N. Pemmaraju, M. Ohanion, Y. Alvarado, H. Kantarjian, and G. Borthakur
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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5. P541: OUTCOMES AND MANAGEMENT OF PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA PRESENTING WITH HYPERLEUKOCYTOSIS
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F. Haddad, K. Sasaki, T. Abuasab, S. Venugopal, D. Rivera Delgado, A. Bazinet, R. Babakhanlou, K. Kim, J. Senapati, F. Ong, S. Desikan, N. Short, N. Pemmaraju, G. Borthakur, C. DiNardo, N. Daver, E. Jabbour, G. Garcia-Manero, F. Ravandi, and T. Kadia
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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6. P575: IMPACT OF MOLECULAR RESPONSE AND CHEMOTHERAPY REGIMEN ON OUTCOMES IN CORE BINDING FACTOR AML
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J. Senapati, F. Haddad, F. Ravandi, T. Kadia, C. DiNardo, N. Daver, N. Pemmaraju, Y. Alvarado, M. A. Brandt, H. Kantarjian, and G. Borthakur
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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7. P576: A PHASE I/II STUDY OF MILADEMETAN (DS3032B) IN COMBINATION WITH LOW DOSE CYTARABINE WITH OR WITHOUT VENETOCLAX IN ACUTE MYELOID LEUKEMIA
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J. Senapati, J. Ishizawa, H. A. Abbas, S. Loghavi, G. Borthakur, G. C. Issa, S. I. Dara, R. Pourebrahim, N. Daver, E. J. Jabbour, S. M. Kornblau, N. Pemmaraju, G. Garcia-Manero, F. Ravandi, M. Muftuoglu, J. Khoury, C. DiNardo, and M. Andreeff
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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8. P1052: IMPACT OF SF3B1 MUTATION IN MYELOFIBROSIS
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J. Senapati, S. Verstovsek, L. Masarova, N. Pemmaraju, G. Montalban Bravo, S. Pierce, L. Zhou, G. Garcia-Manero, H. Kantarjian, and P. Bose
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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9. Liver elastography for risk-assessment of liver toxicity and risk factors for Sinusoidal obstruction syndrome in patients with acute lymphoblastic leukemia receiving inotuzumab ozogamicin.
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Senapati J, Jabbour E, Short NJ, Jain N, Haddad F, Bathala T, Kovalenko I, Bidikian A, Ravandi F, Khouri I, Kadia TM, Garris R, Montalban Bravo G, Chien K, Shpall E, Kebriaei P, and Kantarjian HM
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- Humans, Male, Female, Middle Aged, Risk Factors, Adult, Liver diagnostic imaging, Liver pathology, Liver drug effects, Risk Assessment, Aged, Chemical and Drug Induced Liver Injury etiology, Chemical and Drug Induced Liver Injury diagnosis, Antineoplastic Agents, Immunological adverse effects, Antineoplastic Agents, Immunological therapeutic use, Hepatic Veno-Occlusive Disease chemically induced, Hepatic Veno-Occlusive Disease diagnostic imaging, Hepatic Veno-Occlusive Disease diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Inotuzumab Ozogamicin adverse effects, Inotuzumab Ozogamicin therapeutic use, Elasticity Imaging Techniques
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- 2024
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10. Characteristics and outcomes of patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after failure of a frontline ponatinib-containing therapy.
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Short NJ, Jabbour E, Nasr LF, Jain N, Haddad FG, Issa GC, Sasaki K, Senapati J, Kebriaei P, Garris R, Konopleva M, Ravandi F, and Kantarjian H
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- Humans, Male, Female, Middle Aged, Aged, Adult, Antineoplastic Agents therapeutic use, Antineoplastic Agents adverse effects, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors adverse effects, Pyridazines therapeutic use, Pyridazines adverse effects, Pyridazines administration & dosage, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Imidazoles therapeutic use, Imidazoles adverse effects, Imidazoles administration & dosage, Philadelphia Chromosome, Recurrence
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- 2024
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11. A phase 1/2 study of mini-hyper-CVD plus venetoclax in patients with relapsed/refractory acute lymphoblastic leukemia.
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Short NJ, Jabbour E, Jain N, Senapati J, Nasr L, Haddad FG, Li Z, Hsiao YC, Yang JJ, Pemmaraju N, Ohanian M, Wierda WG, Montalban-Bravo G, Borthakur G, Han L, Xiao L, Huang X, Abramova R, Zhao M, Garris R, Konopleva M, Ravandi F, and Kantarjian H
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- Adult, Humans, Inotuzumab Ozogamicin therapeutic use, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Cardiovascular Diseases chemically induced, Sulfonamides
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Abstract: Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles. Twenty-two patients were treated. The median number of prior therapies was 2 (range, 1-6). Thirteen patients (59%) had undergone prior allogeneic stem cell transplant (allo-SCT), and 7 of 18 patients (39%) with B-cell ALL had previously received both inotuzumab ozogamicin and blinatumomab. The recommended phase 2 dose of venetoclax in the combination regimen was 400 mg daily. The composite complete remission (CR) and CR with incomplete hematologic recovery (CRi) rate was 57% (CR, 43%; CRi, 14%), and 45% of responders achieved measurable residual disease negativity by multiparameter flow cytometry. Four patients proceeded to allo-SCT. The median duration of response was 6.3 months. The median overall survival was 7.1 months, and the 1-year overall survival rate was 29%. The most common grade ≥3 nonhematologic adverse events were infection in 17 patients (77%) and febrile neutropenia in 4 patients (18%). Overall, the combination of mini-hyper-CVD plus venetoclax was active in heavily pretreated relapsed/refractory ALL. Further development of venetoclax-based combinations in ALL is warranted. This trial is registered at www.clinicaltrials.gov as #NCT03808610., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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12. Venetoclax abrogates the prognostic impact of splicing factor gene mutations in newly diagnosed acute myeloid leukemia.
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Senapati J, Urrutia S, Loghavi S, Short NJ, Issa GC, Maiti A, Abbas HA, Daver NG, Pemmaraju N, Pierce S, Chien KS, Sasaki K, Kadia TM, Hammond DE, Borthakur G, Patel K, Ravandi F, Kantarjian HM, Garcia-Manero G, and DiNardo CD
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- Humans, Aged, RNA Splicing Factors genetics, Prognosis, Serine-Arginine Splicing Factors genetics, Splicing Factor U2AF genetics, Mutation, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
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Mutations in splicing factor (SF) genes SRSF2, U2AF1, SF3B1, and ZRSR2 are now considered adverse risk in the European LeukemiaNet 2022 acute myeloid leukemia (AML) risk stratification. The prognostic impact of SF mutations in AML has been predominantly derived from younger patients treated with intensive (INT) therapy. We evaluated 994 patients with newly diagnosed AML, including 266 (27%) with a SFmut. Median age was 67 years overall, with patients with SFmut being older at 72 years. SRSF2 (n = 140, 53%) was the most common SFmut. In patients treated with INT, median relapse-free survival (RFS) (9.6 vs 21.4 months, P = .04) and overall survival (OS) (15.9 vs 26.7 months, P = .06) were shorter for patients with SFmut than without SFwt, however this significance abrogated when evaluating patients who received venetoclax with INT therapy (RFS 15.4 vs 20.3 months, P = .36; OS 19.6 vs 30.7 months, P = .98). In patients treated with LI, median RFS (9.3 vs 7.7 months, P = .35) and OS (12.3 vs 8.5 months, P = .14) were similar for patients with and without SFmut , and outcomes improved in all groups with venetoclax. On multivariate analysis, SFmut did not affect hazards of relapse and death for INT arm but reduced both these hazards in LI arm. In a large AML data set with >60% of patients receiving venetoclax with LI/INT therapy, SFmut had no independent negative prognostic impact. Newer prognostic models that consider LI therapy and use of venetoclax among other factors are warranted., (© 2023 by The American Society of Hematology.)
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- 2023
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13. Maintenance therapy in acute myeloid leukemia: advances and controversies.
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Senapati J, Kadia TM, and Ravandi F
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- Humans, Quality of Life, Recurrence, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation
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The last decade has seen steadfast progress in drug development in acute myeloid leukemia (AML) which has moved progressively towards genomic-based therapy. With these advances, outcomes in AML have improved but remains far from satisfactory. One approach towards preventing relapse in AML is to use maintenance therapy in patients, after attaining remission. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective post-remission therapy that has been proven to reduce the risk of relapse. However, in patients who are ineligible for HSCT or have a high risk of relapse, other effective measures to prevent relapse are needed. There is also a need for post-HSCT maintenance to reduce relapse in high-risk subsets. Over the last 3 decades maintenance therapy in AML has evolved from the use of chemotherapeutic agents to more targeted therapies and better modulation of the immune system. Unfortunately, improvements in survival outcomes as a result of using these agents have not been consistently demonstrated in clinical trials. To derive the optimum benefit from maintenance therapy the time points of therapy initiation need to be defined and therapy must be selected precisely with respect to the AML genetics and risk stratification, prior treatment exposure, transplant eligibility, expected toxicity and the patient's clinical profile and desires. The far-reaching goal is to facilitate patients with AML in remission to achieve a normal quality of life while improving remission duration and overall survival. The QUAZAR trial was a welcome step towards a safe maintenance drug that is easy to administer and showed survival benefit but leaves many open issues for discussion. In this review we will discuss these issues, highlighting the development of AML maintenance therapies over the last 3 decades.
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- 2023
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14. A Phase I study of Milademetan (DS3032b) in combination with low dose cytarabine with or without venetoclax in acute myeloid leukemia: Clinical safety, efficacy, and correlative analysis.
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Senapati J, Muftuoglu M, Ishizawa J, Abbas HA, Loghavi S, Borthakur G, Yilmaz M, Issa GC, Dara SI, Basyal M, Li L, Naqvi K, Pourebrahim R, Jabbour EJ, Kornblau SM, Short NJ, Pemmaraju N, Garcia-Manero G, Ravandi F, Khoury J, Daver N, Kantarjian HM, Andreeff M, and DiNardo CD
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- Adult, Humans, Young Adult, Middle Aged, Aged, Aged, 80 and over, Tumor Suppressor Protein p53, Myeloid Cell Leukemia Sequence 1 Protein, Proteomics, Cytarabine, Leukemia, Myeloid, Acute drug therapy
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In TP53 wild-type acute myeloid leukemia (AML), inhibition of MDM2 can enhance p53 protein expression and potentiate leukemic cell apoptosis. MDM2 inhibitor (MDM2i) monotherapy in AML has shown modest responses in clinical trials but combining options of MDM2i with other potent AML-directed agents like cytarabine and venetoclax could improve its efficacy. We conducted a phase I clinical trial (NCT03634228) to study the safety and efficacy of milademetan (an MDM2i) with low-dose cytarabine (LDAC)±venetoclax in adult patients with relapsed refractory (R/R) or newly diagnosed (ND; unfit) TP53 wild-type AML and performed comprehensive CyTOF analyses to interrogate multiple signaling pathways, the p53-MDM2 axis and the interplay between pro/anti-apoptotic molecules to identify factors that determine response and resistance to therapy. Sixteen patients (14 R/R, 2 N/D treated secondary AML) at a median age of 70 years (range, 23-80 years) were treated in this trial. Two patients (13%) achieved an overall response (complete remission with incomplete hematological recovery). Median cycles on trial were 1 (range 1-7) and at a median follow-up of 11 months, no patients remained on active therapy. Gastrointestinal toxicity was significant and dose-limiting (50% of patients ≥ grade 3). Single-cell proteomic analysis of the leukemia compartment revealed therapy-induced proteomic alterations and potential mechanisms of adaptive response to the MDM2i combination. The response was associated with immune cell abundance and induced the proteomic profiles of leukemia cells to disrupt survival pathways and significantly reduced MCL1 and YTHDF2 to potentiate leukemic cell death. The combination of milademetan, LDAC±venetoclax led to only modest responses with recognizable gastrointestinal toxicity. Treatment-induced reduction of MCL1 and YTHDF2 in an immune-rich milieu correlate with treatment response., (© 2023. The Author(s).)
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- 2023
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15. Outcomes of adult patients with relapsed/refractory CRLF2 rearranged B-cell acute lymphoblastic leukemia.
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Desikan SP, Senapati J, Jabbour E, Abuasab T, Short N, Tang G, Wang S, Kebriaei P, Kadia T, Borthakur G, Ravandi F, Roberts K, Mullighan C, Konopleva M, Kantarjian H, and Jain N
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- Humans, Adult, Receptors, Cytokine genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Burkitt Lymphoma
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- 2023
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16. A phase 2 study of nivolumab combined with ibrutinib in patients with diffuse large B-cell Richter transformation of CLL.
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Jain N, Senapati J, Thakral B, Ferrajoli A, Thompson P, Burger J, Basu S, Kadia T, Daver N, Borthakur G, Konopleva M, Pemmaraju N, Parry E, Wu CJ, Khoury J, Bueso-Ramos C, Garg N, Wang X, Lopez W, Ayala A, O'Brien S, Kantarjian H, Keating M, Allison J, Sharma P, and Wierda W
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- Humans, Middle Aged, Aged, Aged, 80 and over, Nivolumab therapeutic use, Programmed Cell Death 1 Receptor, B-Lymphocytes pathology, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse pathology
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Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of 24 cycles. A standard dose ibrutinib was initiated from cycle 2 onward and continued daily until progression. For patients who were already on ibrutinib at the time of study entry, the same was continued while nivolumab was initiated. A total of 24 patients with RT with a median age of 64.5 years (range, 47-88) were enrolled. Ten patients (42%) had received prior treatment for RT and 13 patients (54%) had received a prior BTKi. A total of 10 patients (42%) responded with a median duration of response of 15 months. The median overall survival was 13 months. Four of 24 (17%) patients had checkpoint inhibition-related immunological toxicities. In the CLL cohort, 10 patients were enrolled, of whom 3 patients converted from partial to complete remission; 1 patient had a grade 2 immunological toxicity. Combined nivolumab and ibrutinib is an active regimen for patients with DLBCL RT with an overall response rate of 42%. Given the limited treatment options for patients with RT, checkpoint inhibition provides a potential therapeutic option. This trial is registered at www.clinicaltrials.gov as #NCT02420912., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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17. Management of chronic myeloid leukemia in 2023 - common ground and common sense.
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Senapati J, Sasaki K, Issa GC, Lipton JH, Radich JP, Jabbour E, and Kantarjian HM
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- Humans, Dasatinib therapeutic use, Imatinib Mesylate therapeutic use, Protein Kinase Inhibitors adverse effects, Fusion Proteins, bcr-abl genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Antineoplastic Agents adverse effects
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With the improving knowledge of CML and its management, the goals of therapy need to be revisited to ensure an optimal use of the BCR::ABL1 TKIs in the frontline and later-line therapy of CML. In the frontline therapy of CML in the chronic phase (CML-CP), imatinib and the three second-generation TKIs (bosutinib, dasatinib and nilotinib) are associated with comparable survival results. The second-generation TKIs may produce earlier deep molecular responses, hence reducing the time to reaching a treatment-free remission (TFR). The choice of the second-generation TKI versus imatinib in frontline therapy is based on the treatment aims (survival, TFR), the CML risk, the drug cost, and the toxicity profile with respect to the patient's comorbidities. The TKI dosing is more flexible than has been described in the registration trials, and dose adjustments can be considered both in the frontline and later-line settings (e.g., dasatinib 50 mg frontline therapy; dose adjusted schedules of bosutinib and ponatinib), as well as during an ongoing TKI therapy to manage toxicities, before considering changing the TKI. In patients who are not candidates for TFR, BCR::ABL1 (International Scale) transcripts levels <1% are acceptable, result in virtually similar survival as with deeper molecular remissions, and need not warrant a change of TKI. For patients with true resistance to second-generation TKIs or with the T315I gatekeeper mutation, the third-generation TKIs are preferred. Ponatinib should be considered first because of the cumulative experience and results in the CML subsets, including in T315I-mutated CML. A response-based dosing of ponatinib is safe and leads to high TKI compliance. Asciminib is a third-generation TKI with possibly a better toxicity profile, but lesser activity in T315I-mutated CML. Olverembatinib is another potent third-generation TKI with early promising results., (© 2023. The Author(s).)
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- 2023
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18. Common kinase mutations do not impact optimal molecular responses in core binding factor acute myeloid leukemia treated with fludarabine, cytarabine, and G-CSF based regimens.
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Senapati J, Abuasab T, Haddad FG, Ravandi F, Kadia T, DiNardo C, Daver N, Pemmaraju N, Alvarado Y, Brandt MA, Kantarjian H, and Borthakur G
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- Humans, Granulocyte Colony-Stimulating Factor therapeutic use, Vidarabine therapeutic use, Mutation, Core Binding Factors, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cytarabine therapeutic use, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
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- 2023
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19. North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: position on standards of care and areas of need.
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Pemmaraju N, Kantarjian H, Sweet K, Wang E, Senapati J, Wilson NR, Konopleva M, Frankel AE, Gupta V, Mesa R, Ulrickson M, Gorak E, Bhatia S, Budak-Alpdogan T, Mason J, Garcia-Romero MT, Lopez-Santiago N, Cesarman-Maus G, Vachhani P, Lee S, Bhatt VR, Blum W, Walter RB, Bixby D, Gojo I, Duvic M, Rampal RK, de Lima M, Foran J, Fathi AT, Hall AC, Jacoby MA, Lancet J, Mannis G, Stein AS, Mims A, Rizzieri D, Olin R, Perl A, Schiller G, Shami P, Stone RM, Strickland S, Wieduwilt MJ, Daver N, Ravandi F, Vasu S, Guzman M, Roboz GJ, Khoury J, Qazilbash M, Aung PP, Cuglievan B, Madanat Y, Kharfan-Dabaja MA, Pawlowska A, Taylor J, Tallman M, Dhakal P, and Lane AA
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- Child, Humans, Aged, Standard of Care, Interleukin-3 Receptor alpha Subunit, Dendritic Cells pathology, Neoplasm Recurrence, Local pathology, Acute Disease, North America, Myeloproliferative Disorders pathology, Hematologic Neoplasms pathology, Skin Neoplasms pathology
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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC's inaugural meetings are presented herein., (© 2023 by The American Society of Hematology.)
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- 2023
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20. AbdomenNet: deep neural network for abdominal organ segmentation in epidemiologic imaging studies.
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Rickmann AM, Senapati J, Kovalenko O, Peters A, Bamberg F, and Wachinger C
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- Abdomen diagnostic imaging, Cohort Studies, Humans, Water, Magnetic Resonance Imaging methods, Neural Networks, Computer
- Abstract
Background: Whole-body imaging has recently been added to large-scale epidemiological studies providing novel opportunities for investigating abdominal organs. However, the segmentation of these organs is required beforehand, which is time consuming, particularly on such a large scale., Methods: We introduce AbdomentNet, a deep neural network for the automated segmentation of abdominal organs on two-point Dixon MRI scans. A pre-processing pipeline enables to process MRI scans from different imaging studies, namely the German National Cohort, UK Biobank, and Kohorte im Raum Augsburg. We chose a total of 61 MRI scans across the three studies for training an ensemble of segmentation networks, which segment eight abdominal organs. Our network presents a novel combination of octave convolutions and squeeze and excitation layers, as well as training with stochastic weight averaging., Results: Our experiments demonstrate that it is beneficial to combine data from different imaging studies to train deep neural networks in contrast to training separate networks. Combining the water and opposed-phase contrasts of the Dixon sequence as input channels, yields the highest segmentation accuracy, compared to single contrast inputs. The mean Dice similarity coefficient is above 0.9 for larger organs liver, spleen, and kidneys, and 0.71 and 0.74 for gallbladder and pancreas, respectively., Conclusions: Our fully automated pipeline provides high-quality segmentations of abdominal organs across population studies. In contrast, a network that is only trained on a single dataset does not generalize well to other datasets., (© 2022. The Author(s).)
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- 2022
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21. Chromosomal Instability in Chronic Myeloid Leukemia: Mechanistic Insights and Effects.
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Senapati J and Sasaki K
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The most recent two decades have seen tremendous progress in the understanding and treatment of chronic myeloid leukemia, a disease defined by the characteristic Philadelphia chromosome and the ensuing BCR::ABL fusion protein. However, the biology of the disease extends beyond the Philadelphia chromosome into a nebulous arena of chromosomal and genetic instability, which makes it a genetically heterogeneous disease. The BCR::ABL oncoprotein creates a fertile backdrop for oxidative damage to the DNA, along with impairment of genetic surveillance and the favoring of imprecise error-prone DNA repair pathways. These factors lead to growing chromosomal instability, manifested as additional chromosomal abnormalities along with other genetic aberrations. This worsens with disease progression to accelerated and blast phase, and modulates responses to tyrosine kinase inhibitors. Treatment options that target the genetic aberrations that mitigate chromosome instability might be a potential area for research in patients with advanced phase CML.
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- 2022
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22. Activity of decitabine as maintenance therapy in core binding factor acute myeloid leukemia.
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Senapati J, Shoukier M, Garcia-Manero G, Wang X, Patel K, Kadia T, Ravandi F, Pemmaraju N, Ohanian M, Daver N, DiNardo C, Alvarado Y, Aldrich J, and Borthakur G
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- Antineoplastic Combined Chemotherapy Protocols, Core Binding Factors genetics, Cytarabine, Decitabine therapeutic use, Humans, Neoplasm, Residual diagnosis, Prognosis, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
- Abstract
Background: Posttherapy measurable residual disease (MRD) positivity in core binding factor acute myeloid leukemia (CBF-AML) is associated with shorter relapse-free survival (RFS). Elimination of MRD measured via quantitative reverse transcription polymerase chain reaction (qRTPCR) for disease specific transcripts can potentially lead to better outcomes in CBF-AML., Methods: We prospectively monitored the MRD using qRTPCR and flow cytometry on bone marrow samples in patients with newly diagnosed CBF-AML who received decitabine (DAC) maintenance therapy after fludarabine/cytarabine/G-CSF (FLAG)-based induction/consolidation regimen. Negative qRTPCR (CMR) was defined as fusion transcript <0.01%., Results: Thirty-one patients with CBF-AML including 14 with t(8;21) and 17 with inv(16) received parenteral DAC as maintenance therapy. Fifteen patients (48.3%) had completed FLAG-based induction/consolidation but with positive MRD (0.35%, range = 0.01%-0.91%) (Group 1). Sixteen patients (51.7%) could not complete recommended consolidations with FLAG-based regimen (due to older age or complications) and were switched to DAC maintenance (Group 2). In Group 2, eight patients (50%) had undetectable MRD (Group 2A) (all had qRTPCR ≤ 0.01%) and the other eight patients (50%) had residual fusion product by qRTPCR (0.1%, range = 0.02%-0.36%) (Group 2B) prior to starting DAC. Amongst the 23 patients who had a PCR ≥ 0.01% before maintenance therapy (Groups 1 and 2B), 12 patients (52%) attained a CMR as their best response (responders). The median pre-DAC qRTPCR amongst responders were 0.03% compared to 0.14% in nonresponders (p = .002). The median estimated molecular RFS amongst responders were 93.9 months. At a median follow-up of 59.3 months (13.2-106 months) from DAC initiation, 16 patients (51.6%) had to be initiated on a second line of therapy (40%, 25%, and 100% patients, respectively, in Groups1, 2A, and 2B). The median estimated time to new treatment between responders was 112.4 versus 5.8 months in nonresponders (hazard ratio = 0.16, 95% confidence interval = 0.04-0.54); however, there were no difference in overall survival between these groups (p = .37)., Conclusion: DAC is an effective maintenance therapy for CBF-AML patients with persistent fusion transcript at a low level after FLAG-based regimen. Attainment of CMR with DAC maintenance can lead to long-term remission in patients who have persistent MRD positive after FLAG-based regimen or are unable to receive the full course of consolidation therapy., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
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23. Disease Status at Transplant has a Significant Impact on Outcomes of Autologous Transplantation (ASCT) in Patients with Hodgkin Lymphoma-A Single Center Experience.
- Author
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Senapati J, Devasia AJ, Korula A, Fouzia NA, Kulkarni U, Lakshmi KM, Lionel S, Abraham A, Srivastava A, Mathews V, and George B
- Abstract
High dose chemotherapy followed by autologous stem cell transplantation is the treatment of choice for relapsed Hodgkin lymphoma (HL). We analyzed 100 consecutive patients who underwent ASCT at our center between January 1999 and June 2019 for relapsed or refractory disease with a median age of 28 years (range: 9-65). At ASCT, 59 were in complete remission (CR) while 31 achieved partial remission (PR) and 10 had refractory disease (RD). Most had BEAM conditioning with a median infused cell dose of 4.84 × 10
6 CD 34 cells/kg. Prompt engraftment occurred in 97 patients at a median of 11 days. The day 100 transplant related mortality (TRM) was 5%. At a median of 37 months follow up, 79 patients are alive while 34 have relapsed. The 3-year event free survival (EFS) and overall survival (OS) are 62.3 ± 0.5% and 77.9 ± 4.4% respectively . The 3-year OS for patients in CR, PR and RD were 83.0 ± 5.2%, 78.4 ± 8.1% and 38.9 ± 1.7 respectively [ p = 0.007] while the 3-year EFS for CR, PR and RD were 73.1 ± 6.2%, 61.3 ± 9.2% and 25.0 ± 1.5 respectively [ p = 0.005] . Only disease status at time of ASCT was found to correlate with both OS and EFS. ASCT for HL is associated with good outcomes and low TRM. Disease status at ASCT impacted both OS and EFS and strategies to improve outcomes in patients with refractory disease needs to be explored., Competing Interests: Conflicts of interestNo conflict of interest for any of the authors., (© Indian Society of Hematology and Blood Transfusion 2021.)- Published
- 2022
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24. Prevention and management of carbapenem-resistant Enterobacteriaceae in haematopoietic cell transplantation.
- Author
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Sahitya DSK, Jandiyal A, Jain A, Senapati J, Nanda S, Aggarwal M, Kumar P, Mohapatra S, Ray P, Malhotra P, Mahapatra M, and Dhawan R
- Abstract
Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high morbidity and mortality rates in haematopoietic cell transplantation (HCT) recipients. Factors like mucositis, neutropenia, prolonged hospital stay, and frequent use of prophylactic antimicrobials make HCT recipients especially susceptible to CRE infections. Low culture positivity rates, delay in microbiological diagnosis, and resistance to empirical antimicrobial therapy for febrile neutropenia are responsible for high mortality rates in HCT recipients infected with CRE. In this review we discuss the epidemiology, diagnosis, and management of CRE infections with particular emphasis on patients undergoing HCT. We emphasise the need for preventive strategies like multidisciplinary antimicrobial stewardship, and pre-emptive screening for CRE colonisation in prospective HCT patients as measures to mitigate the adverse impact of CRE on HCT outcomes. Newer diagnostic tests like polymerase chain reaction and matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) assay that enable earlier and better identification of CRE isolates are discussed. Antimicrobial agents available against CRE, including newer agents like ceftazidime-avibactam and meropenem-vaborbactam, have been reviewed. We also discuss the data on promising experimental treatments against CRE: phage therapy and healthy donor faecal microbiota transplant. Finally, this review puts forth recommendations as per existing literature on diagnosis and management of CRE infections in blood and marrow transplant (BMT) unit., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s), 2021.)
- Published
- 2021
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25. Tele-Medicine Services in Hematological Practice During Covid Pandemic: Its Feasibility and Difficulties.
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Kumar P, Aggarwal M, Dhawan R, Dass J, Kumar G, Sharma V, Mirza S, Senapati J, Ganju N, Vaid T, Vijayran M, Panda T, Pragna GS, Krishna SS, Khandelwal A, Verghese R, Tyagi S, Seth T, and Mahapatra M
- Abstract
In COVID 19 pandemic, delivery and access of health care services have become challenging. Telemedicine services can be considered for management of patients with hematological diseases. This study included all patients who enrolled for telemedicine facility for hematology from May 15 to July 15, 2020. Patient's demographic and disease related parameters were recorded during the teleconsultation call. Overall satisfaction of attending doctor and patients were also recorded. A total of 1187 teleconsultation appointments were taken, of which 944 (79.6%) were successfully attended. Median age of patients was 38 years (range- 0.5-78 years), with 38% females. 55% of successful calls were from patients suffering a malignant hematological disorder. 24% had an active complaint pertaining to their disease or treatment. Of these, 162 (17%) were asked for a physical consultation. A significant association was found between the requirement of physical consultation and diagnosis ( p < 0.001), absence of active complaint (< 0.0001) and education level of responder ( p = 0.008). Patients understand that teleconsultation is helpful in preventing COVID-19 infection (71.4%) and avoids outpatient department rush (14.5%) associated with physical appointments; and around 80% patients were satisfied with the teleconsult. With the emergence of COVID 19, many localities under partial lockdown with constant fear of contacting virus amongst patients and health care providers, we can clearly see the advantages as well as feasibility of telemedicine services for our patients. The acute surge in telemedicine could be harnessed in the future to provide comprehensive and integrated care to patients of hematological disorders., (© Indian Society of Hematology and Blood Transfusion 2020.)
- Published
- 2021
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26. Early T cell precursor lymphoid blast crisis of chronic myeloid leukemia - a novel transformation.
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Senapati J, Devasia AJ, Alex AA, and George B
- Subjects
- Adult, Humans, Male, Blast Crisis pathology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Precursor Cells, T-Lymphoid pathology
- Published
- 2015
- Full Text
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27. Diffuse large B cell lymphoma in wiskott-Aldrich syndrome: a case report and review of literature.
- Author
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Senapati J, Devasia AJ, David S, Manipadam MT, Nair S, Jayandharan GR, and George B
- Abstract
Wiskott-Aldrich syndrome (WAS) is an X linked rare primary immunodeficiency syndrome with an increased propensity for infection, autoimmunity and malignancy. Here we report a male child, who was diagnosed with WAS at 1 year of age following evaluation for symptomatic thrombocytopenia and eczematous skin lesions. He presented later with lymphadenopathy, which was consistent with diffuse large B cell lymphoma on histopathology. He received 6 cycles of R-CHOP chemotherapy for the same and is presently in remission after 6 months. We review the major publications of lymphoma in WAS and discuss the pathological findings, treatment and prognosis of lymphoma in WAS.
- Published
- 2014
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28. Sorafenib Induced Hand Foot Skin Rash in FLT3 ITD Mutated Acute Myeloid Leukemia-A Case Report and Review of Literature.
- Author
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Senapati J, Devasia AJ, Ganapule A, George L, and Viswabandya A
- Abstract
Sorafenib is a novel small molecule multiple kinase inhibitor which has been used for metastatic renal cancer, hepatocellular cancer. Sorafenib induced skin rash has been discussed as a side effect in trials in both, FLT3 wild type and mutated acute myeloid leukemia (AML), as monotherapy or as combination with other chemotherapeutic agents. We describe a patient with FLT 3 ITD mutated AML, who was started on adjunctive Sorafenib therapy. Skin reactions manifested as NCI Grade III palmoplantar erythrodysesthesia (PPE), requiring drug discontinuation. Several pathogenic mechanisms have been implicated in Sorafenib induced skin reactions, but none has been conclusively proven. While treatment options are varied for early stage skin reactions, drug discontinuation remains the only possible therapy presently for severe grade skin reaction.
- Published
- 2014
- Full Text
- View/download PDF
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