23 results on '"Kim, Dennis Dong Hwan"'
Search Results
2. Cardiovascular Events After Exposure to Nilotinib in Chronic Myeloid Leukemia: Long-term Follow-up.
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Aghel, Nazanin, Lipton, Jeffrey Howard, Atenafu, Eshetu G., Kim, Dennis Dong Hwan, and Delgado, Diego Hernan
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- 2017
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3. Less Is More: Superior Graft-versus-Host Disease-Free/Relapse-Free Survival with Reduced-Intensity Conditioning and Dual T Cell Depletion in Acute Myelogenous Leukemia.
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Salas, Maria Queralt, Chen, Shiyi, Lam, Wilson, Pasic, Ivan, Gerbitz, Armin, Michelis, Fotios V., Kim, Dennis (Dong Hwan), Al-Shaibani, Zeyad, Lipton, Jeffrey Howard, Mattsson, Jonas, Kumar, Rajat, Viswabandya, Auro, and Law, Arjun Datt
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ACUTE myeloid leukemia , *ALEMTUZUMAB , *T cells , *HEMATOPOIETIC stem cell transplantation , *ANTIBIOTIC prophylaxis - Abstract
• Dual T cell depletion for graft-versus-host disease (GVHD) prophylaxis in reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation reduces clinically significant GVHD, thereby improving GVHD-free/relapse-free survival (GRFS) in patients with acute myelogenous leukemia (AML). • The intensity of the conditioning regimen was not a significant predictor for better post-transplantation outcomes (overall survival, GRFS) in patients with AML. In this study, we compared the outcomes of patients with acute myelogenous leukemia (AML) in complete remission treated with myeloablative conditioning (MAC) and those treated with reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HCT). In addition, we explored the efficacy of dual T cell depletion using anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) for the prevention of graft-versus-host disease (GVHD) in patients undergoing RIC allo-HCT. Our study cohort comprised 356 adults with AML in complete remission who underwent allo-HCT between 2013 and 2018. One hundred eleven patients (31.2%) received a MAC regimen, and 245 (68.8%) received an RIC regimen. One hundred seventy-one of the patients who received an RIC regimen (68.4%) received ATG, PTCy, and cyclosporine (ATG-PTCY-CsA) for GVHD prophylaxis in accordance with our institutional protocol. Data were collected retrospectively and updated in July 2019. With a median follow-up of 14.5 months (range, 0 to 76 months), 161 patients (45.2%) died, and 66 (18.5%) relapsed. Two-year overall survival (OS), relapse-free survival (RFS), and GVHD-free/RFS (GRFS) were 55%, 52.6%, and 35%, respectively. The intensity of the conditioning regimen, with or without ATG-PTCY-CsA, did not have a significant impact on OS and RFS. However, RIC in combination with ATG-PTCY-CsA was associated with a significantly lower cumulative incidence of acute GVHD and chronic GVHD. The use of RIC with ATG-PTCy-CsA was a significant predictor for higher GRFS secondary to the reduction of clinically relevant GVHD (P =.0001). In patients with AML, RIC allografts and dual T cell modulation with ATG and PTCy led to superior GRFS. The use of this GVHD prophylaxis strategy, along with mitigation of conditioning toxicity using RIC, may result in better long-term quality of life for allo-HCT recipients. [ABSTRACT FROM AUTHOR]
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- 2020
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4. Single centre retrospective analysis of extracorporeal photopheresis (ECP) therapy in patients heavily pre-treated for chronic graft-versus-host disease (cGvHD) with steroid failure.
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Linn, Swe Mar, Novitzky-Basso, Igor, Patriquin, Christopher, Pasic, Ivan, Lam, Wilson, Law, Arjun, Michelis, Fotios V., Gerbitz, Armin, Viswabandya, Auro, Lipton, Jeffrey, Kumar, Rajat, Mattsson, Jonas, Barth, David, and Kim, Dennis Dong Hwan
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GRAFT versus host disease , *CHRONIC diseases , *RETROSPECTIVE studies , *OPPORTUNISTIC infections - Abstract
Extracorporeal photopheresis (ECP) is recommended as a second- or later-line therapy for chronic GvHD (cGvHD). Benefits include reasonable response with avoidance of intense systemic immunosuppression, which can translate into lowering the risk of systemic toxicity and opportunistic infection. We evaluated 75 patients treated with ECP for cGvHD from 2007 to 2021 at Princess Margaret Cancer Centre, and analyzed overall response rate (ORR) and clinical benefit (CB) at 3, 6 and 12 months plus other long-term treatment outcomes. With a median follow-up of 72 months, a gradual increase in ORR was noted over time: 21% (16 out of 75 patients), 57% (36/63) and 70% (32/46) at month 3, 6 and 12, respectively. Gradual increase in CB was also observed over time with CB rate of 23% (17/75), 62% (39/63), and 76% (35/46) at months 3, 6 and 12, respectively. A total of 27 failures (36%) were noted, due to: 1) ECP resistance requiring switch to other therapy (n = 14, 19%), 2) non-relapse mortality (n = 10, 13%), 3) relapse of primary disease (n = 1, 1%) or 4) ECP procedure-related complication (n = 1, 1%, line infection), with 20 deaths (27%) observed. Failure-free survival (FFS) and overall survival (OS) rates were 68.3% and 85.9% at 12 months, respectively. After starting ECP, the proportions of patients who completely discontinued steroids were 17%, 32%, and 64% at months 3, 6 and 12, respectively. ECP is an effective treatment option for heavily pre-treated cGvHD patients. • ECP is a highly effective treatment in cGvHD, even in patients who had been heavily pre-treated and failed other GVHD therapy. • ECP induce durable responses and clinical benefit in cGvHD. • Steroid-sparing efficacy of ECP reduced systemic toxicity from prolonged use of corticosteroids. • Failure free survival of ECP comparable with ruxolitinib treatment in cGvHD. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Combination of the Centre for International Blood and Marrow Transplant Registry Risk Score and the Global Severity Score Enhances Prognostic Risk Stratification in Patients Receiving Frontline Therapy for Chronic Graft-versus-Host Disease.
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Shapiro, Roman M., Shin, Elizabeth, Law, Arjun Datt, Lam, Wilson, Michelis, Fotios V., Viswabandya, Auro, Kumar, Rajat, Lipton, Jeffrey H., Messner, Hans, Mattsson, Jonas, and Kim, Dennis Dong Hwan
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GRAFT versus host disease , *BONE marrow , *CHRONIC diseases , *CHRONICALLY ill , *TRANSPLANTATION of organs, tissues, etc. - Abstract
• The Centre for International Blood and Marrow Transplant Registry (CIBMTR) score classifies most patients with chronic graft-versus-host disease (GVHD) into low-risk groups. • A novel prognostic risk score further refines the CIBMTR low-risk groups. • The novel risk score improves on the CIBMTR in identifying high-risk chronic GVHD. • The novel risk score classifies patients with respect to failure-free survival. • The novel risk score groups patients according to other relevant clinical outcomes. The Centre for International Blood and Marrow Transplant Registry (CIBMTR) score has been shown to be prognostic for overall survival (OS) and nonrelapse mortality (NRM) but has been shown in several single-center studies to classify a large proportion of patients with chronic graft-versus-host disease (cGVHD) in the lower risk groups (RG1 to RG2), thereby limiting its prognostic utility for those patients. We evaluate the CIBMTR score, the Global Severity Score (GSS), and a novel risk score developed to improve on the limitations of the CIBMTR with respect to clinically relevant outcomes, including failure-free survival (FFS), in patients receiving frontline systemic treatment for cGVHD. We identified 277 patients between 2002 and 2012 at the Princess Margaret Cancer Centre in Toronto, Canada, who developed cGVHD and were treated with at least 1 line of systemic therapy. cGVHD was graded by GSS, and patients were stratified by CIBMTR. We evaluated OS, NRM, relapse, and FFS within GSS grade groups, as well as CIBMTR RGs, and used a novel prognostic risk score. The median FFS duration was 164 days in the severe GSS group versus 238 days in the moderate-grade group and 304 days in mild-grade group (P =.001). The median FFS duration was 501 days in CIBMTR RG1 versus 291 days in RG2 and 166 days in RG3 to RG6 (P =.003). A novel risk score combining the GSS and CIBMTR scores was prognostic of OS, NRM, and FFS and was able to subdivide patients with cGVHD in CIBMTR RG1 to RG2 into distinct prognostic risk categories. The CIBMTR risk score and the GSS are well correlated with FFS, OS, and NRM following frontline systemic treatment for cGVHD. A new risk score model combining the CIBMTR risk score and the GSS could enhance risk stratification in the lower CIBMTR risk groups. [ABSTRACT FROM AUTHOR]
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- 2019
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6. Remission clone in acute myeloid leukemia shows growth advantage after chemotherapy but is distinct from leukemic clone.
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Ahn, Jae-Sook, Kim, TaeHyung, Kim, Yeo-Kyeoung, Cho, Young-Chang, Cho, SaYeon, Jung, Sung-Hoon, Ahn, Seo-Yeon, Jung, Seung-Yeon, Yang, Deok-Hwan, Lee, Je-Jung, Choi, SeungHyun, Lee, Ja-Yeon, Shin, Myung-Geun, Yoshida, Kenichi, Ogawa, Seishi, Kim, Il-Chul, Zhang, Zhaolei, Kim, Hyeoung-Joon, and Kim, Dennis Dong Hwan
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ACUTE myeloid leukemia , *BONE marrow , *SOMATIC mutation , *B cells - Abstract
• A population with the same set of mutations was found in sequential remissions in the bone marrow of a patient with AML. • This "remission clone" contained mutations in NDC80, RBM5, GAS2L3, NR2C2 , and SF3B2. • At relapse, the contribution of the remission clone to the myeloid lineage was markedly reduced. • NR2C2 -A93V transfected into HEK-293 cells caused a significant increase in viability. In a previously published case study of acute myeloid leukemia, we tracked the dynamics of somatic mutations over 9 years. Interestingly, we observed a group of mutations that expanded during remission, which we named the "remission clone." To determine the nature of the remission clones, we performed flow cytometry-based cell sorting followed by ultradeep sequencing. The remission clone repeatedly expanded after chemotherapeutic cycles and was suppressed during relapse in the myeloid lineage (multipotent hematopoietic stem, progenitor, and myeloid cells). On the other hand, the remission clone was consistently observed in lymphoid lineages (B and T cells) regardless of the disease state. When transfected into the HEK-293 cell line, the NR2C2 (A93V) mutant exhibited a growth advantage (all p values < 0.05). The results indicate that the remission clone seems to be another form of clonal hematopoiesis, but without a clear association with leukemia. As the remission clone is present in both myeloid and lymphoid lineages, it likely originates from ancestral hematopoietic cell lineages. More importantly, the remission clone is distinct from the leukemic clone; therefore, mutations expanded during remission require special interpretation when performing next-generation sequencing-based measurable residual disease assessment. [ABSTRACT FROM AUTHOR]
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- 2019
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7. Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies
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Law, Arjun Datt, Salas, Maria Queralt, Lam, Wilson, Michelis, Fotios V., Thyagu, Santhosh, Kim, Dennis (Dong Hwan), Lipton, Jeffrey Howard, Kumar, Rajat, Messner, Hans, and Viswabandya, Auro
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CYCLOPHOSPHAMIDE , *GRAFT versus host disease , *HEMATOPOIETIC stem cell transplantation , *CYCLOSPORINE , *EPSTEIN-Barr virus - Abstract
Highlights • HaploHSCT after RIC with ATG, PTCy, and cyclosporine is a feasible transplant regimen. • Low rates of grade II to IV acute GVHD were observed. • ATG use leads to higher rates of viral reactivation, particularly CMV and EBV. Abstract Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018. RIC included fludarabine (30 mg/m2/day on days –5 to –2), busulfan (3.2 mg/m2/day on days –3 and –2), and total body irradiation (200 cGy) on day –1. Unmanipulated PBSCs were infused on day 0. GVHD prophylaxis included ATG (4.5 mg/kg over days –3 to –1), PTCy (50 mg/kg/day on days +3 and +4), and cyclosporine from day +5. Median age was 56 years (range, 22 to 70 years); 25 (73.5%) patients were in first complete remission (CR1), 5 (14.7%) were in second complete remission (CR2), and 8 (23.5%) had active disease. Median time to neutrophil engraftment was 16 days (range, 8 to 43 days). At day +100, the cumulative incidence of acute GVHD of any grade, and grades III to IV was 38.3% and 5.2%, respectively. Mild chronic GVHD was seen in 15.5%. Cytomegalovirus (CMV) reactivation occurred in 37 (74%) cases and CMV disease occurred in 4 (11.5%) cases. Epstein-Barr virus (EBV) reactivation occurred in 21 (61.8%) patients. The incidence of histologically confirmed post-transplantation lymphoproliferative disorder (PTLD) was 5.8%. Four patients received rituximab. There were no CMV, EBV, or PTLD-related deaths. Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD. [ABSTRACT FROM AUTHOR]
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- 2018
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8. Canadian chronic myeloid leukemia outcomes post-transplant in the tyrosine kinase inhibitor era.
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Savoie, Mary Lynn, Bence-Bruckler, Isabelle, Huebsch, Lothar B., Lalancette, Marc, Hillis, Chris, Walker, Irwin, Lipton, Jeffrey H., Forrest, Donna L., and Kim, Dennis (Dong Hwan)
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TREATMENT of chronic myeloid leukemia , *DRUG resistance in cancer cells , *CANCER relapse , *STEM cell transplantation - Abstract
Highlights • A 1.3 log reduction in BCR-ABL levels within 3 months post HCT is prognostic in TKI resistance or intolerance. • HCT remains a potential cure for patients with CML resistant or intolerant of TKI therapy. • Advanced phase disease remains a poor prognostic factor post HCT even in the TKI era. Abstract The majority of patients with TKI failure respond to HCT. However, the relapse risk remains high. This study has evaluated transplant outcomes in 223 CML patients with TKI failure due to resistance (n = 132) or intolerance (n = 29), as well as those that were TKI naïve/responding with advanced disease (n = 35) or with chronic phase (CP, n = 27). We studied outcomes according to post-transplant BCR-ABL transcript level within 3 months. With respect to transplant outcomes according to the post-transplant BCR/ ABLtranscript level within 3 months, the group failing to achieve a 1.3 log reduction (n = 14, 12.4%) showed the highest relapse rate of 78.6% at 5 years, compared to 26.2% and 24.1% in the groups achieving 1.3–4.0 log reduction (n = 45, 39.8%), and ≥4.1 log reduction (n = 54, 47.8%) respectively (p < 0.001). Multivariate analysis confirmed that the group failing to achieve a 1.3 log reduction had a 2.3-fold higher risk of death and 6.6 times higher risk of relapse. Poor overall survival after HCT was associated with advanced disease at diagnosis, but not disease status prior to HCT. Of 61 patients who relapsed after HCT, 47 were treated with post-transplant TKI therapy; those receiving TKI after loss of MR2 or MMR showed higher rates of response and survival compared to those receiving TKI after hematologic relapse (p < 0.001). QPCR log reduction level within 3 months post transplantation is prognostic in this population. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Efficacy of Cidofovir in Treatment of BK Virus–Induced Hemorrhagic Cystitis in Allogeneic Hematopoietic Cell Transplant Recipients.
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Coomes, Eric A., Wolfe (Jacques), Amanda, Michelis, Fotios V., Kim, Dennis (Dong Hwan), Thyagu, Santhosh, Viswabandya, Auro, Lipton, Jeffrey H., Messner, Hans A., and Deotare, Uday
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HEMATOPOIETIC stem cell transplantation , *BK virus , *CYSTITIS , *GRAFT versus host disease , *VIREMIA , *HEMATURIA , *POLYOMAVIRUSES , *DYSURIA , *PATIENTS - Abstract
Highlights • Twelve transplant recipients received cidofovir for BK virus hemorrhagic cystitis. • Mean hemorrhagic cystitis severity decreased significantly after cidofovir. • Two-thirds achieved partial response, which was similar between intravenous and intravesical. • One-third experienced renal toxicity, including 2 receiving intravesical therapy. Abstract BK virus–associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidences up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC, a retrospective study was undertaken of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada. The primary outcome measure was a reduction in BK-HC severity (graded from 1 to 4); secondary outcomes included overall survival, BK virus titers, and the onset of acute kidney injury. Twelve allo-HCT patients received cidofovir for BK-HC, with pretreatment clinical severity of 3 (50%) or 4 (50%). Cidofovir was administered via intravenous (33%), intravesical (58%), or both modalities (8%). After a median cumulative dose of 10 mg/kg (range, 1 to 37), mean BK-HC grade decreased significantly by 1.8 (3.5 precidofovir, 1.7 postcidofovir, P <.01). Sixty-six percent of patients had at least partial response to cidofovir, with similar response rates between intravenous (66%) and intravesical (62%) administration. Sixty-seven percent of patients died, and 33% of patients experienced renal toxicity, including 2 patients receiving intravesical therapy. In this retrospective series, there was a significant reduction in BK-HC severity after cidofovir administration; most patients achieved at least partial response after cidofovir administration. Even with intravesical instillation, acute kidney injury remains a potential complication of cidofovir. Although cidofovir may be an efficacious therapy for BK-HC, albeit with potential demonstrated toxicities, further prospective trials are needed. [ABSTRACT FROM AUTHOR]
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- 2018
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10. Incidence and Risk Factors for Nontuberculous Mycobacterial Infection after Allogeneic Hematopoietic Cell Transplantation.
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Beswick, Jennifer, Shin, Elizabeth, Michelis, Fotios V., Thyagu, Santhosh, Viswabandya, Auro, Lipton, Jeffrey H., Messner, Hans, Marras, Theodore K., and Kim, Dennis (Dong Hwan)
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MYCOBACTERIAL disease treatment , *HEMATOPOIETIC stem cell transplantation , *MYCOBACTERIAL diseases , *DISEASE incidence , *MYCOBACTERIAL disease diagnosis , *MULTIVARIATE analysis , *DISEASE risk factors - Abstract
Allogenic hematopoietic stem cell transplant (HCT) recipients are at risk of many infections. Nontuberculous mycobacteria (NTM) are increasingly recognized as clinically significant pathogens in this population. We investigated the incidence and risk factors for NTM infection after allogeneic HCT. This retrospective cohort study included all patients with allogeneic HCT at our institution during 2001 to 2013. Patients who developed significant NTM infection (NTM disease) were identified. Multivariable modeling was used to identify risk factors for NTM disease, and a risk score model was constructed to identify high-risk patients. Of 1097 allogeneic HCT patients, 45 (4.1%) had NTM isolated and 30 (2.7%) had NTM disease (28 [93.3%] exclusively pulmonary, 2 [6.7%] pulmonary plus another site). Incidence of NTM infection by competing risk analysis was 2.8% at 5 years (95% CI, 1.9% to 4.0%). The median time to diagnosis was 343 days (range, 19 to 1967). In Fine-Gray proportional hazards modeling, only global severity of chronic graft-versus-host disease (cGVHD) (HR, 1.99; 95% CI, 1.12 to 3.53; P = .019,) and cytomegalovirus (CMV) viremia (HR, 5.77; 95% CI, 1.71 to 19.45; P = .004) were significantly associated with NTM disease. Using these variables a risk score was calculated: 1 point for CMV viremia or moderate cGVHD and 2 points for severe cGVHD. The score divided patients into low risk (0 to 1 points, n = 820 [77.3%], 3-year NTM risk 1.2%), intermediate risk (2 points, n = 161 [15.4%], 3-year NTM risk 7.1%), and high risk (3 points, n = 56 [5.4%], 3-year NTM risk 14.3%). NTM disease after allogeneic HCT is common. Severe cGVHD and CMV viremia are associated with increased risk, permitting risk stratification. [ABSTRACT FROM AUTHOR]
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- 2018
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11. 349 - A Critically Unnoticed Condition, Secondary Hemophagocytosis Post Allogeneic Bone Marrow Transplant in Adults.
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Alblooshi, Rehab Mohamed, Viswanandya, Auro, Kim, Dennis (Dong Hwan), Deotare, Uday, Michelis, Frank, Thyagu, Santhosh, Lipton, Jeffrey H., and Messner, Hans
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BONE marrow transplantation , *ACUTE myeloid leukemia treatment , *PHAGOCYTOSIS , *MEDICAL research , *SURVIVAL analysis (Biometry) ,DISEASES in adults - Published
- 2017
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12. Allogeneic Hematopoietic Cell Transplantation for Adult T Cell Acute Lymphoblastic Leukemia.
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Hamilton, Betty Ky, Rybicki, Lisa, Abounader, Donna, Adekola, Kehinde, Advani, Anjali, Aldoss, Ibrahim, Bachanova, Veronika, Bashey, Asad, Brown, Stacey, DeLima, Marcos, Devine, Steven, Flowers, Christopher R., Ganguly, Siddharth, Jagasia, Madan, Kennedy, Vanessa E., Kim, Dennis Dong Hwan, McGuirk, Joseph, Pullarkat, Vinod, Romee, Rizwan, and Sandhu, Karamjeet
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HEMATOPOIETIC stem cell transplantation , *LYMPHOBLASTIC leukemia , *T cells , *TOTAL body irradiation , *CORD blood , *PHYSIOLOGY - Abstract
Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P = .021), age >35 years (HR, 1.55; P = .025), and disease status at HCT (HR, 1.98; P = .005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Molecular genetic characterization of Philadelphia chromosome-positive acute myeloid leukemia.
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Zhou, Qianghua, Zhao, Davidson, Eladl, Entsar, Capo-Chichi, Jose-Mario, Kim, Dennis Dong Hwan, and Chang, Hong
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ACUTE myeloid leukemia , *BLAST injuries , *CHRONIC myeloid leukemia , *LEUKOCYTE count , *MYELOID leukemia , *GENETIC profile - Abstract
Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a provisional disease entity in the 2016 WHO classification, while its genetic profile of Ph+ AML remains poorly defined. In addition, the differentiating features of Ph+ AML and chronic myeloid leukemia in myeloid blast crisis (CML-MBC) remain controversial. We conducted a retrospective study of 15 Ph+ AML patients to compare their clinical and laboratory profiles with 27 CML-MBC patients. Compared to CML-MBC, Ph+ AML patients presented with significantly higher peripheral WBC count and bone marrow blast percentage. The immunophenotypic profiles were largely similar between Ph+ AML and CML-MBC, except for CD4 expression, which was significantly enriched in CML-MBC. Ph+ AML patients less frequently harboured co-occurring additional cytogenetic abnormalities (ACA) compared to CML-MBC, and trisomy 19 (23%) and IDH1/2 (46%) were the most common ACA and mutated genes in Ph+ AML, respectively. Overall survival (OS) did not significantly differ between Ph+ AML and CML-MBC. Ph+ AML without CML-like features appeared to have a better outcome compared to Ph+ AML with CML-like features; ACA in Ph+ AML may confer an even worse prognosis. Our results indicate that patients with Ph+ AML share similar genetic profiles and clinical outcomes with those with CML-MBC, thus should be classified as a high-risk entity. • Ph+ AML occurs in a predominantly older male population and exhibits higher white blood cell counts and bone marrow blast percentages. • Ph+ AML frequently harbors IDH1/2 mutations. • Ph+ AML has similar adverse overall survival compared with CML-MBC and the survival outcomes are even worse if presenting with additional cytogenetic abnormalities or CML-like features. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Myeloablative versus Reduced-Intensity Conditioning in Patients with Myeloid Malignancies: A Propensity Score-Matched Analysis.
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Sibai, Hassan, Falcone, Umberto, Deotare, Uday, Michelis, Fotios V., Uhm, Jieun, Gupta, Vikas, Kuruvilla, John, Lipton, Jeffrey H., Seftel, Matthew D., Messner, Hans A., and Kim, Dennis (Dong Hwan)
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MYELOID leukemia , *LEUKEMIA treatment , *HEMATOPOIETIC stem cell transplantation , *PROPENSITY score matching , *DISEASE incidence , *CASE-control method - Abstract
Reduced-intensity conditioning (RIC) has been shown to have similar overall survival (OS) but higher relapse rates compared with myeloablative (MAC) regimens in patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Using propensity score matching (PSM) analysis, well-balanced pairs of different variables can be compared effectively. We retrospectively compared allo-HSCT recipients with acute myeloid leukemia or myelodysplasia receiving a RIC regimen (FBT200; fludarabine 30 mg/m 2 /day for 4 days, busulfan 3.2 mg/kg/day for 2 days, and total body irradiation [TBI] 200 cGy) or MAC regimen (FBT400; fludarabine 50 mg/m 2 /day for 4 days, busulfan 3.2 mg/kg/day for 4 days, and TBI 400 cGy). A total of 248 patients (121 in the RIC group and 127 in the MAC group) were included in the analysis. No statistically significant difference was observed in 2-year OS (RIC group, 45.2 ± 5.0%; MAC group, 51.7 ± 5.2%; P = .541), nonrelapse mortality (NRM; RIC group, 28.7 ± 2.8% MAC group, 34.7 ± 4.6%; P = .368), and acute graft-versus-host disease (GVHD) ( P = .171) or chronic GVHD ( P = .605) at 1 year. The cumulative incidence of relapse (CIR) at 2 years was statistically significantly different between the 2 groups, however (RIC, 26.1 ± 2.6%; MAC, 14.2 ± 3.5%; P = .033). When PSM was applied to the study population, 42 case-control pairs were evenly matched. PSM analysis confirmed no statistically significant difference in 2-year OS (RIC, 49.0 ± 9.1%; MAC, 54.9 ± 7.7%; P = .718), NRM (RIC, 22.2 ± 2.3%; MAC, 33.3 ± 2.8%; P = .238), or CIR (RIC, 25.7 ± 2.6%; MAC, 9.5 ± 1.1%; P = .315) in the PSM pairs. Our findings demonstrate that after applying PSM, FBT 200 RIC conditioning has comparable OS, NRM, and CIR to FBT 400 MAC conditioning before allo-HSCT. [ABSTRACT FROM AUTHOR]
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- 2016
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15. DNMT3A R882 Mutation with FLT3-ITD Positivity Is an Extremely Poor Prognostic Factor in Patients with Normal-Karyotype Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation.
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Ahn, Jae-Sook, Kim, Hyeoung-Joon, Kim, Yeo-Kyeoung, Lee, Seun-Shin, Jung, Sung-Hoon, Yang, Deok-Hwan, Lee, Je-Jung, Kim, Nan Young, Choi, Seung Hyun, Jung, Chul Won, Jang, Jun-Ho, Kim, Hee Je, Moon, Joon Ho, Sohn, Sang Kyun, Won, Jong-Ho, Kim, Sung-Hyun, and Kim, Dennis Dong Hwan
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LEUKEMIA treatment , *MYELOID leukemia , *GENETIC mutation , *EPIGENETICS , *MULTIVARIATE analysis , *RETROSPECTIVE studies , *HEALTH outcome assessment - Abstract
The prognostic relevance of epigenetic modifying genes ( DNMT3A , TET2 , and IDH1/2 ) in patients with acute myeloid leukemia (AML) has been investigated extensively. However, the prognostic implications of these mutations after allogeneic hematopoietic cell transplantation (HCT) have not been evaluated comprehensively in patients with normal-karyotype (NK)-AML. A total of 115 patients who received allogeneic HCT for NK-AML were retrospectively evaluated for the FLT3 -ITD, NPM1 , CEBPA , DNMT3A , TET2 , IDH1/2 , WT1 , NRAS , ASXL2 , FAT1 , DNAH11 , and GATA2 mutations in diagnostic samples and analyzed for long-term outcomes after allogeneic HCT. The prevalence rates for the mutations were as follows: FLT3 -ITD positivity ( FLT3 -ITD pos ) (32.2%), NPM1 mutation (43.5%), CEBPA mutation (double) (24.6%), DNMT3A mutation ( DNMT3A mut ) (31.3%), DNMT3A R882 mut (18.3%), TET2 mutation (8.7%), and IDH1/2 mutation (16.5%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57.3% and 58.1%, respectively. A multivariate analysis revealed that FLT3 -ITD pos (hazard ratio, [HR], 2.23; P = .006) and DNMT3A R882 mut (HR, 2.74; P = .002) were unfavorable prognostic factors for OS. In addition, both mutations were significant risk factors for EFS and relapse. People with DNMT3A R882 mut accompanied by FLT3 -ITD pos had worse OS and EFS, and higher relapse rates than those with the other mutations, which were confirmed in a propensity score 1:2 matching analysis. These results suggest that DNMT3A R882 mut , particularly when accompanied by FLT3 -ITD pos , is a significant prognostic factor for inferior transplantation survival outcome by increasing relapse risk, even after allogeneic HCT. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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16. Genetic changes during leukemic transformation to secondary acute myeloid leukemia from myeloproliferative neoplasms.
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Kim, TaeHyung, Ahn, Jae-Sook, Son, Meong Hi, Novitzky-Basso, Igor, Yi, Seong Yoon, Ahn, Seo-Yeon, Jung, Sung-Hoon, Yang, Deok-Hwan, Lee, Je-Jung, Choi, Seung Hyun, Lee, Ja-yeon, Moon, Joon Ho, Sohn, Sang Kyun, Kim, Hyeoung-Joon, Zhang, Zhaolei, and Kim, Dennis Dong Hwan
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SOMATIC mutation , *ACUTE myeloid leukemia , *MYELOPROLIFERATIVE neoplasms , *MYELOFIBROSIS , *DNA methylation , *DISEASE progression , *GENE frequency - Abstract
Leukemic transformation (LT) is the main cause of death for patients with myeloproliferative neoplasms (MPNs). To study genetic changes associated with the LT, we performed targeted sequencing in 26 MPN patients including 21 with paired samples. We observed that, besides three driver genes, IDH2 (19%) and ASXL1 (14%) were also frequently mutated at MPN diagnosis. Although variant allele frequencies (VAFs) of mutations in DNA methylation and spliceosome did not expand during LT, they were enriched in patients with LT (the LT group). At follow-up, we also observed acquisition of mutations, mostly in the LT group. When considering dynamics of VAF from diagnosis to follow-up, VAFs in the LT group expanded (median VAF, 36.7–43.7%, p = 0.045). In contrast, mutations in patients with no clinical progression was stable (median VAF, 36.3–35.7%, p = 0.739). Overall, the present study demonstrates genetic changes during LT and provides the potential for prognostic application. • Mutations in DNA methylation/spliceosome genes are enriched in the LT group. • Newly detected mutations are common during leukemic transformation. • Allelic burdens of pre-existing mutations increase during leukemic transformation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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17. Incidence, Risk Factors, and Long-Term Outcomes of Sclerotic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.
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Uhm, Jieun, Hamad, Nada, Shin, Elizabeth M., Michelis, Fotios V., Shanavas, Mohamed, Gupta, Vikas, Kuruvilla, John, Lipton, Jeffrey H., Messner, Hans A., Seftel, Matthew, and Kim, Dennis (Dong Hwan)
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LONG-term care facilities , *HEALTH outcome assessment , *HEMATOPOIETIC stem cell transplantation , *GRAFT versus host disease , *SCLERA , *CHRONIC diseases - Abstract
Sclerotic chronic graft-versus-host disease (sclGVHD) is associated with significant morbidity and a poor quality of life. We reviewed 502 patients diagnosed with chronic GVHD and analyzed the incidence and risk factors of sclGVHD and long-term outcomes and immunosuppressive therapy (IST) cessation in patients with sclGVHD. With a median onset at 18 months the cumulative incidence of sclGVHD was estimated at 22.6% at 5 years (95% confidence interval, 18.6% to 26.8%). Univariate and multivariate analysis identified 2 risk factors for sclGVHD: non-T cell depletion (hazard ratio [HR] 9.09, P < .001) and peripheral blood stem cell (HR 3.87, P < .001). Overall survival (OS) at 5 years was significantly better in the sclGVHD group (88.1%) compared with the non-sclGVHD group (62.7%; P < .001), as were nonrelapse mortality (7.3% versus 21.5% at 5 years) and relapse rates (9.1% versus 19.3% at 5 years). There was no difference in the rate of IST cessation at 5 years (44.8% versus 49.9%, P = .312), but there was a trend of longer IST duration in the sclGVHD group compared with the non-sclGVHD group (median 71.6 months versus 62.9 months). In conclusion, T cell depletion and graft source affect the risk of sclGVHD. SclGVHD did not adversely affect long-term outcomes or IST duration. [ABSTRACT FROM AUTHOR]
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- 2014
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18. Allogeneic Peripheral Blood Stem Cell Transplantation Significantly Increases Risk of Chronic Graft-versus-Host Disease of Lung Compared with Bone Marrow Transplantation
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Alam, Naheed, Marras, Theodore K., Atenafu, Eshetu G., Gupta, Vikas, Kuruvilla, John, Lipton, Jeffrey H., Messner, Hans A., and Kim, Dennis (Dong Hwan)
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GRAFT versus host disease , *DISEASE risk factors , *HEMATOPOIETIC stem cell transplantation , *LUNG diseases , *BONE marrow transplantation , *MEDICAL statistics , *FOLLOW-up studies (Medicine) - Abstract
The risk factors for lung chronic graft-versus-host disease (cGVHD) are not fully elucidated. We attempted to identify clinical risk factors for lung cGVHD after allogeneic hematopoietic cell transplantation (HCT). A total of 401 patients who underwent allogeneic HCT between 2000 and 2007 at Princess Margaret Hospital, Toronto, Canada, were evaluated for lung cGVHD serially starting on day 120 and then annually therafter. The stem cell source for HCT was peripheral blood stem cells (PBSCs) in 280 patients (69.8%) and bone marrow (BM) in 121 patients (30.2%). With a median follow-up of 36.8 months, 68 patients (17%) had a diagnosis of lung cGVHD, with a median time of onset of 11.4 months after HCT. Stem cell source was the sole risk factor identified in univariate analyses. The incidence of lung cGVHD was significantly higher in the patients receiving PBSCs (14.2% at 1 year and 22.7% at 2 years) compared with those receiving BM (6.8 at 1 year and 14.9% at 2 years; hazard ratio, 1.937; P = .02). Multivariate analyses also confirmed the use of PBSCs as an independent risk factor for lung cGVHD (hazard ratio, 2.408; 95% confidence interval, 1.289-4.496; P = .0058). The use of PBSCs is associated with an increased risk of lung cGVHD compared with the use of BM for allogeneic HCT. [Copyright &y& Elsevier]
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- 2012
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19. 434 - Post Transplant Cyclophosphamide (PTCy) with Anti-Thymocyte Globulin (ATG) Effectively Reduces the Severe (Grade III-IV) Acute Graft-Versus-Host Disease (GVHD) When Compared to ATG Alone in Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplants
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Deotare, Uday, Loach, David, Michelis, Frank, Kim, Dennis (Dong Hwan), Thyagu, Santhosh, Lipton, Jeffrey H., Messner, Hans, and Viswabandya, Auro
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GRAFT versus host disease , *HEMATOPOIETIC stem cell transplantation , *CYCLOPHOSPHAMIDE , *THYMOCYTES , *PREVENTIVE medicine , *THERAPEUTICS - Published
- 2017
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20. Allogeneic Hematopoietic Cell Transplantation (HCT) for Adult T-Cell Acute Lymphoblastic Leukemia (T-ALL).
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Hamilton, Betty Ky, Rybicki, Lisa, Advani, Anjali S., Abounader, Donna, Vu, Khoan, Romee, Rizwan, Zeichner, Simon B., Flowers, Christopher, Brown, Stacey, Bashey, Asad, Viswabandya, Auro, Kim, Dennis (Dong Hwan), Wall, Sarah, Devine, Steven M., Sandhu, Karamjeet S., Bachanova, Veronika, McGuirk, Joseph, Ganguly, Siddhartha, Adekola, Kehinde, and Mehta, Jayesh
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HEMATOPOIETIC stem cell transplantation , *HOMOGRAFTS , *T-cell lymphoma , *LYMPHOBLASTIC leukemia treatment , *LYMPHOBLASTIC leukemia , *DISEASES in older people , *PATIENTS - Published
- 2016
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21. Fertility Recovery Following Allogeneic Bone Marrow Transplantation in Aplastic Anemia; A Study of 157 Patients.
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Alfraih, Feras, Aljurf, Mahmoud D., Al Mohareb, Fahad, Alsharif, Fahad, Chaudhri, Naeem, Hanbali, Amr, Shaheen, Marwan, Ahmed, Syed O., Rasheed, Walid K., Kim, Dennis (Dong Hwan), Aldawsari, Ghuzayel, Said, Mohamad, Ahmed, Shad, and Alzahrani, Hazzaa
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BONE marrow transplantation , *HOMOGRAFTS , *HUMAN fertility , *APLASTIC anemia treatment , *APLASTIC anemia , *MEDICAL centers , *ACQUISITION of data , *PATIENTS - Published
- 2016
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22. Moderate/Severe Grade of Chronic Graft Versus Host Disease and Younger Age (Less Than 45 Years Old) Are Risk Factors for Avascular Necrosis in Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.
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Bhella, Sita D., Uhm, Jieun, Alam, Naheed, Gupta, Vikas, Kuruvilla, John, Lipton, Jeffrey H., Messner, Hans, Seftel, Matthew, and Kim, Dennis (Dong Hwan)
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HEMATOPOIETIC stem cell transplantation , *DISEASE risk factors , *GRAFT versus host disease , *OSTEONECROSIS , *RETROSPECTIVE studies , *MULTIVARIATE analysis , *FOLLOW-up studies (Medicine) , *PATIENTS ,DISEASES in adults - Published
- 2015
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23. Alemtuzumab As Therapy for Steroid Refractory Acute Gvhd: Promising Efficacy but Higher Rate of Infectious Complications Based on Observational Study.
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Alam, Naheed, Atenafu, Eshetu, Gupta, Vikas, Kuruvilla, John, Lipton, Jeffrey H., Messner, Hans, Seftel, Matthew, and Kim, Dennis (Dong Hwan)
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- 2014
- Full Text
- View/download PDF
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