10 results on '"Nakamura, Ryotaro"'
Search Results
2. Treatment of relapsed or refractory FLT-3 acute myelogenous leukemia with a triplet regimen of hypomethylating agent, venetoclax, and gilteritinib.
- Author
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Ngo, Dat, Tinajero, Jose, Li, Shanpeng, Palmer, Joycelynne, Pourhassan, Hoda, Aribi, Ahmed, Nakamura, Ryotaro, Stein, Anthony, Marcucci, Guido, Salhotra, Amandeep, Sandhu, Karamjeet, Pullarkat, Vinod, Ball, Brian, and Koller, Paul
- Subjects
ACUTE myeloid leukemia ,VENETOCLAX ,HEMATOPOIETIC stem cells ,STEM cell transplantation ,PROTEIN-tyrosine kinases - Abstract
Relapsed or refractory (R/R) acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3) mutations remains a difficult and hard to treat entity. Gilteritinib is a potent oral FLT-3 inhibitor that improves overall survival in R/R AML, but studies are limited in combining gilteritinib with a hypomethylating agent and venetoclax treatment backbone (HMA-VEN-GILT). Here we report our experience with HMA-VEN-GILT for 22 R/R FLT3 AML patients. HMA-VEN-GILT yielded an ORR of 77.3% (17/22), CR 4.5% (1/22), CRi 13.6% (3/22), MLFS 59.1% (13/22). Median follow-up was 10.4 months with a relapse rate of 29.4% (5/17), median time to relapse of 69 days (range 35–298 days), 6-month overall survival of 84%, and median OS of 10.1 months. Additionally, 36.4% (8/22) of patients proceeded to hematopoietic stem cell transplant. In conclusion, HMA-VEN-GILT for the treatment of R/R FLT3 AML is feasible and can be used as a bridge to allogeneic transplantation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. A review of low dose interleukin-2 therapy in management of chronic graft-versus-host-disease.
- Author
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Salhotra, Amandeep, Falk, Leah, Park, Gabriel, Sandhu, Karamjeet, Ali, Haris, Modi, Badri, Hui, Susanta, and Nakamura, Ryotaro
- Subjects
INTERLEUKIN-2 ,REGULATORY T cells ,GRAFT versus host disease ,PATIENT compliance - Abstract
Patients with chronic graft versus host disease (cGVHD) have low circulating regulatory T cells (Tregs). Interleukin-2(IL-2) is a growth factor for Tregs, and clinical trials have explored its use in cGVHD patients. Here we will discuss the biology of IL-2, its rationale for use and results of clinical trials in cGVHD. We also describe its mechanisms of action and alteration in gene expression in T-cell subsets after treatment with low dose IL-2 and photopheresis. Clinical trials using Low dose IL-2 have been done at single centers in small patient series. The majority of the clinical responses seen with IL-2 in cGVHD are classified as partial responses and efficacy as a single agent is limited. Compared to currently approved oral therapies, it has to be administered subcutaneously and requires specialized processing for compounding and storage limiting its widespread use. Its use is associated with constitutional symptoms and local injection site reactions. Local reactions can be easily managed by supportive care practices like rotation of injection sites and premeditations, constitutional symptoms resolve with, dose reduction (25–50%) allowing for continued therapy. Additional studies are needed to define optimal combination strategies with approved agents. Longer acting formulations of IL-2 that require less frequent dosing may also improve patient compliance. [ABSTRACT FROM AUTHOR]
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- 2024
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4. WT1-mutated acute myeloid leukemia is sensitive to fludarabine-based chemotherapy and conditioning regimens.
- Author
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Aribi, Ahmed, Salhotra, Amandeep, Afkhami, Michelle, Munteanu, Anamaria, Ali, Haris, Aldoss, Ibrahim, Otoukesh, Salman, Al Malki, Monzr M., Sandhu, Karamjeet S., Koller, Paul, Arslan, Shukaib, Stewart, Forrest, Artz, Andrew, Curtin, Peter, Ball, Brian, O'Hearn, James, Spielberger, Ricardo, Smith, Eileen, Budde, Elizabeth, and Nakamura, Ryotaro
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ACUTE myeloid leukemia ,STEM cell transplantation ,CANCER chemotherapy ,FLUDARABINE - Abstract
We conducted a retrospective analysis of WT1-mutated acute myeloid leukemia (AML) patients who underwent allogeneic stem cell transplant. Thirty-seven patients with WT1-mutated AML were identified. Primary induction failure (40%) and early relapse rate (18%) after idarubicin/cytarabine (7 + 3) chemotherapy were observed. All patients with induction failure subsequently achieved CR with additional chemotherapy. There was no significant difference between outcomes after myeloablative vs. reduced intensity (Fludarabine/Melphalan [Flu/Mel]) conditioning regimens. RFS but not OS was significantly better in patients who received FLAG-IDA prior to transplant and/or a fludarabine-containing conditioning. In an independent ex vivo study, WT1-mutated AML samples exhibited greater sensitivity to fludarabine (p = 0.026) and melphalan (p = 0.0005) than non-WT1-mutated AML samples while there was no difference between sensitivity to cytarabine. Our data favor using a fludarabine-based induction for AML with WT1 mutation instead of 7 + 3. Fludarabine conditioning regimens for alloHCT showed better RFS but not OS. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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5. A critical review of belumosudil in adult and pediatric patients with chronic graft-versus-host disease.
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Salhotra, Amandeep, Sandhu, Karamjeet, O'Hearn, James, Ali, Haris, Nakamura, Ryotaro, and Modi, Badri G
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GRAFT versus host disease ,CHILD patients ,CHRONICALLY ill ,HEMATOPOIETIC stem cell transplantation ,T helper cells - Abstract
Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is the main cause of late non-relapse mortality (NRM). Three new agents are now approved to treat cGVHD, of which belumosudil has a unique and dual mechanism of action of i) targeting the Rho-GTPase-associated coiled-coil kinase 2 (ROCK2) in T helper follicular cells (TFH) and TH17 cells, this results in downregulation of proinflammatory cytokines (interleukin −21 and 17), the former in a STAT3-dependent mechanism, ii) inhibition of tissue fibrosis by targeting stress-induced polymerization of G-actin fibrils by inhibiting the Rho-ROCK-MRTF pathway. In this review we describe the epidemiology of cGVHD, its cardinal symptoms, preventive and therapeutic options, including second-line approved therapies in the United States (US). Clinical trial data that led to approval of belumosudil is discussed, in addition to the clinical scenarios in which the approved drugs may be most applicable. Belumosudil is approved for treatment of adult and pediatric patients ≥ 12 years with cGVHD after failing two lines of therapy based on results of the ROCKstar study that showed high overall response rates (ORR), favorable adverse effect profiles, and low rates of severe infections. With the availability of three new agents for treatment of cGVHD, treating physicians have more therapeutic options for patients and have additional options of development new clinical trials using a combination of recently approved drugs. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Clinical experience with venetoclax and hypomethylating agents (HMA) in patients with newly diagnosed and relapsed or refractory KMT2A-Rearranged acute myeloid leukemia (AML).
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Ball, Brian J., Arslan, Shukaib, Koller, Paul, Ngo, Dat, Afkhami, Michelle, Salhotra, Amandeep, Al-Malki, Monzr, Aribi, Ahmed, Ali, Haris, Sandhu, Karamjeet, Otoukesh, Salman, Amanam, Idoroenyi, Pourhassan, Hoda, Artz, Andrew, Curtin, Peter, Stein, Anthony, Nakamura, Ryotaro, Marcucci, Guido, Smith, Eileen, and Pullarkat, Vinod
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ACUTE myeloid leukemia ,VENETOCLAX - Abstract
Rearrangements of I lysine [K] methyltransferase 2 A i ( I KMT2A i ) gene, previously known as the I MLL i gene, occur in 3 to 7% of adult patients with de novo AML and are enriched in therapy-related disease, particularly after treatment with topoisomerase II inhibitors [[1]]. Response and survival of patients with KMT2A rearranged acute myeloid leukemia (AML) receiving venetoclax in combination with hypomethylating agent therapy (HMA). The inferior prognosis of KMT2A rearranged AML patients undergoing alloSCT presents an opportunity for post-transplant maintenance trials with therapies targeting KMT2A. [Extracted from the article]
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- 2022
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7. Long-term follow-up of patients with poor-risk acute leukemia treated on a phase 2 trial undergoing intensified conditioning regimen prior to allogeneic hematopoietic cell transplantation.
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Salhotra, Amandeep, Yang, Dongyun, Mokhtari, Sally, Hui, Susanta, Al Malki, Monzr M., Armenian, Saro, Sigala, Brianna, Aldoss, Ibrahim, Pullarkat, Vinod, Forman, Stephen, Marcucci, Guido, Nakamura, Ryotaro, Artz, Andrew, Wong, Jeffery, and Stein, Anthony
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HEMATOPOIETIC stem cell transplantation ,ACUTE leukemia ,TOTAL body irradiation ,PROGRESSION-free survival - Abstract
Patients with acute leukemia who undergo allogenic hematopoietic cell transplantation with active disease have high rates of relapse and poor overall survival (OS) post-transplant compared to patients undergoing HCT in remission. Here, we report the long-term outcomes in 32 patients who received a high-intensity conditioning regimen comprising fractionated total body irradiation (FTBI; 1200 cGy) with pharmacokinetic (PK) dosing of intravenous Busulfan (IV BU) targeted to first dose area under curve (AUC) of 700–900 µM/min and etoposide (30 mg/kg) in a prospective phase 2 clinical trial. The median age of the patients at the time of HCT was 37 years (range: 18–50) presenting with high-risk (n = 6) and relapsed/refractory(r/r) acute leukemias (n = 26). All but one patient underwent HCT using peripheral blood stem cells from matched sibling donors. At a median follow-up of 17.3 years (range 14.4–19.0), 11 patients remained alive. The disease-free survival and OS at 15 years was 34% (versus 40% at 5-years post-HCT). The 15-year cumulative incidence of relapse was 26% and non-relapse mortality (NRM) was 38% (95% CI: 21–54%) and the cumulative incidence of chronic GVHD at 15 years was 33% using a prophylactic regimen of cyclosporine A and mycophenolate mofetil. The most common life-threatening late effects were secondary malignancies, metabolic, or cardiac complications with a cumulative incidence of 6.6%, 6.6%, and 13.3%, respectively. No unusual late effects or patterns of relapse were noted on longer followed on patients treated with intensified myeloablative condition regimen. Results from this study supports continued development of intensive conditioning regimens in patients with r/r acute leukemias to improve leukemia free (LFS) and OS in this high-risk population. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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8. The efficacy of venetoclax and hypomethylating agents in acute myeloid leukemia with extramedullary involvement.
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Otoukesh, Salman, Zhang, Jianying, Nakamura, Ryotaro, Stein, Anthony S., Forman, Stephen J., Marcucci, Guido, Pullarkat, Vinod, and Aldoss, Ibrahim
- Subjects
ACUTE myeloid leukemia ,CHRONIC leukemia - Published
- 2020
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9. Ruxolitinib for the treatment of graft-versus-host disease.
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Ali, Haris, Salhotra, Amandeep, Modi, Badri, and Nakamura, Ryotaro
- Abstract
Introduction: Ruxolitinib is an oral selective JAK1/JAK2 inhibitor, initially approved by the FDA for the treatment of intermediate-2 or high-risk myelofibrosis and patients with polycythemia vera who have had an inadequate response or are intolerant to hydroxyurea. Areas covered: Accumulating evidence supports the role of JAK1/JAK2 pathways in the pathogenesis of graft-versus-host disease (GVHD), and preclinical studies have demonstrated promising efficacy of ruxolitinib in treatment/prevention of GVHD. Early clinical observations that ruxolitinib was effective in treatment of steroid-refractory (SR) acute and chronic GVHD led to the development of prospective clinical trials; Phase II REACH1 (NCT02953678), Phase III REACH2 (NCT02913261), and REACH3 (NCT03112603). Based on the data from the REACH1 trial, ruxolitinib was approved by the FDA in May 2019 for SR acute GVHD in adult and pediatric patients 12 years and older. Expert opinion: Ruxolitinib and other JAK1/JAK2 inhibitors hold promise in other treatment settings such as GVHD prevention and/or first-line therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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10. A fifty-year odyssey: prospects for a cytomegalovirus vaccine in transplant and congenital infection.
- Author
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Diamond, Don Jeffrey, La Rosa, Corinna, Chiuppesi, Flavia, Contreras, Heidi, Dadwal, Sanjeet, Wussow, Felix, Bautista, Supriya, Nakamura, Ryotaro, and Zaia, John A.
- Abstract
Introduction: It has been almost fifty years since the Towne strain was used by Plotkin and collaborators as the first vaccine candidate for cytomegalovirus (CMV). While that approach showed partial efficacy, there have been a multitude of challenges to improve on the promise of a CMV vaccine. Efforts have been dichotomized into a therapeutic vaccine for patients with CMV-infected allografts, either stem cells or solid organ, and a prophylactic vaccine for congenital infection. Areas covered: This review will evaluate research prospects for a therapeutic vaccine for transplant recipients that recognizes CMV utilizing primarily T cell responses. Similarly, we will provide an extensive discussion on attempts to develop a vaccine to prevent the manifestations of congenital infection, based on eliciting a humoral anti-CMV protective response. The review will also describe newer developments that have upended the efforts toward such a vaccine through the discovery of a second pathway of CMV infection that utilizes an alternative receptor for entry using a series of antigens that have been determined to be important for prevention of infection. Expert commentary: There is a concerted effort to unify separate therapeutic and prophylactic vaccine strategies into a single delivery agent that would be effective for both transplant-related and congenital infection. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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