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  1. Article ; Online: Differential Association between Blood Glucose Levels and Nonrelapse Mortality after Allogeneic Hematopoietic Cell Transplantation Based on Presence or Absence of Preexisting Diabetes.

    Rashid, Nahid / Gooley, Ted / Boeckh, Michael / Oshima, Masumi Ueda / Chao, Jing H / Hirsch, Irl B / Mielcarek, Marco

    Transplantation and cellular therapy

    2024  Volume 30, Issue 4, Page(s) 417.e1–417.e9

    Abstract: Malglycemia, defined as hyperglycemia, hypoglycemia, or increased glycemic variability, has been associated with increased mortality after allogeneic hematopoietic cell transplantation (HCT). Among critically ill non-HCT recipients with diabetes and poor ...

    Abstract Malglycemia, defined as hyperglycemia, hypoglycemia, or increased glycemic variability, has been associated with increased mortality after allogeneic hematopoietic cell transplantation (HCT). Among critically ill non-HCT recipients with diabetes and poor glycemic control, compared to those without diabetes, stringent blood glucose control has been associated with increased mortality. This study investigated whether a pre-HCT diagnosis of diabetes and the type of pre-HCT diabetes treatment modulate the previously reported negative impact of malglycemia on post-HCT nonrelapse mortality (NRM). We performed a single-institution retrospective analysis of mortality outcomes after allogeneic HCT as a function of post-HCT blood glucose levels, pre-HCT diagnosis of diabetes, and type of pre-HCT diabetes treatment (insulin, no insulin). A total of 1062 patients who underwent allogeneic HCT between 2015 and 2020 were included in this study. Among these patients, 84 (8%) had a pre-HCT diagnosis of diabetes, of whom 38 (4%) used insulin and 46 (4%) used a noninsulin antiglycemic agent. Post-HCT blood glucose values measured within 100 days from HCT, modeled as a continuous nonlinear time-varying covariate, were associated with day-200 NRM, with both lower and higher glycemic values associated with higher NRM compared to normoglycemic values (adjusted P < .0001). The association between post-HCT blood glucose and NRM varied, however, depending on the presence or absence of a pre-HCT diagnosis of diabetes; that is, there was evidence of a statistical interaction between blood glucose levels and diabetes (adjusted P = .008). In particular, the detrimental impact of hyperglycemic values was more pronounced in patients without a pre-HCT diagnosis of diabetes compared to those with a pre-HCT diagnosis of diabetes. As reported previously, higher and lower blood glucose levels measured within 100 days after allogeneic HCT were associated with an increased risk of NRM; however, this association was more pronounced among patients without a pre-HCT diagnosis of diabetes compared to those with a pre-HCT diagnosis of diabetes, suggesting that patients with diabetes are relatively protected from the downstream effects of hyperglycemia. These data support the notion that patients with pre-HCT diabetes may need a different approach to blood glucose management after transplantation compared to those without diabetes. © 2024 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
    MeSH term(s) Humans ; Blood Glucose ; Retrospective Studies ; Prognosis ; Hematopoietic Stem Cell Transplantation/adverse effects ; Diabetes Mellitus/etiology ; Hyperglycemia/etiology ; Insulins
    Chemical Substances Blood Glucose ; Insulins
    Language English
    Publishing date 2024-01-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2024.01.065
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Impact of Donor Statin Treatment on Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.

    Rashid, Nahid / Gooley, Ted / Furlong, Terry / Lee, Stephanie J / Martin, Paul J / Storb, Rainer / Mielcarek, Marco

    Transplantation and cellular therapy

    2023  Volume 29, Issue 11, Page(s) 701.e1–701.e8

    Abstract: Some retrospective studies have suggested that long-term donor statin use may protect against graft-versus-host disease (GVHD) in patients receiving cyclosporine (CSP)-based immunosuppression after allogeneic hematopoietic cell transplantation (HCT), but ...

    Abstract Some retrospective studies have suggested that long-term donor statin use may protect against graft-versus-host disease (GVHD) in patients receiving cyclosporine (CSP)-based immunosuppression after allogeneic hematopoietic cell transplantation (HCT), but prospective studies of short-term treatment of donors with statin have shown conflicting results. We conducted 2 consecutive prospective clinical trials to assess whether donor statin treatment was associated with protection against severe acute GVHD (aGVHD). In a single-arm phase II trial (study 1), we evaluated whether short-term statin treatment of HLA-matched related donors for 14 days before HCT prevented grade III-IV aGVHD. In a prospective observational cohort study (study 2), we evaluated whether longer-term (>14 days) donor statin use was required for GVHD-protective effects. Study 1 was terminated after 6 of the 35 recipients (17%) developed grade III-IV GVHD. For study 2, we identified 135 patients whose unrelated donors had received long-term treatment with statins up to the time of HCT and 4942 patients whose donors had not received long-term statin treatment. The adjusted odds ratio for grade III-IV aGVHD (statin versus no statin) was .83 (95% confidence interval [CI], .46 to 1.50; P = .54). Multivariable analysis showed no statistically significant differences between the 2 groups in the risk of grade II-IV aGVHD, chronic GVHD, nonrelapse mortality, recurrent malignancy, or overall mortality. Among patients receiving CSP-based immunosuppression, including 35 with donors receiving long-term statin treatment and 973 with donors who did not receive statins, the adjusted odds ratio of grade III-IV aGVHD was .30 (95% CI, .07 to 1.35; P = .12). In study 1, short-term statin treatment of donors was ineffective in preventing grade III-IV GVHD. In study 2, in the prespecified subgroup of recipients given CSP-based immunosuppression, nondefinitive evidence suggested that donor statin use was associated with a reduced risk of severe aGVHD.
    MeSH term(s) Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Prospective Studies ; Retrospective Studies ; Neoplasm Recurrence, Local/drug therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/methods ; Graft vs Host Disease/drug therapy ; Graft vs Host Disease/prevention & control ; Cyclosporine/therapeutic use ; Unrelated Donors
    Chemical Substances Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Cyclosporine (83HN0GTJ6D)
    Language English
    Publishing date 2023-08-30
    Publishing country United States
    Document type Observational Study ; Journal Article
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2023.08.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Frailty in Patients with Chronic Graft-versus-Host Disease.

    Rashid, Nahid / Arora, Mukta / Jurdi, Najla El / Onstad, Lynn / Pidala, Joseph A / Flowers, Mary E / Lee, Stephanie J

    Transplantation and cellular therapy

    2023  Volume 29, Issue 6, Page(s) 367–374

    Abstract: Frailty is an increasingly recognized clinical diagnosis associated with high risk of disability and mortality. Frailty in patients after hematopoietic cell transplantation (HCT) is associated with increased nonrelapse mortality (NRM) and decreased ... ...

    Abstract Frailty is an increasingly recognized clinical diagnosis associated with high risk of disability and mortality. Frailty in patients after hematopoietic cell transplantation (HCT) is associated with increased nonrelapse mortality (NRM) and decreased overall survival (OS). Frailty has not been studied extensively in patients with chronic graft-versus-host disease (cGVHD). The objectives of the present study were to assess the prevalence and clinical correlates of frailty and the association of frailty with NRM and OS in patients enrolled in the Chronic GVHD Consortium. Patients were characterized as frail if they met the Fried definition of ≥3 of the following criteria at enrollment: unintentional weight loss, exhaustion, slow walking speed, low physical activity, and weakness. Frailty was assessed retrospectively using surrogate measures for the 5 domains of frailty. Frailty, cGVHD organ scores, and patient-reported outcomes were measured at the time of enrollment. The study included 399 patients from 9 centers in the United States, with 32% characterized as frail and 68% as not frail. The median duration of follow-up from enrollment was 9 years (interquartile range, 7 to 11 years). Frail patients were more likely to be older (P = .004), to have a lower Karnofsky Performance Status (P < .001), to have severe cGVHD (P < .001), and to have gastrointestinal (P < .001), liver (P = .04), or lung cGVHD (P = .002). In a multivariable analysis, older age, increased cGVHD global severity, and thrombocytopenia were statistically significantly associated with frailty when cGVHD organ involvement was excluded. A separate analysis excluding cGVHD severity and including organ involvement showed that lung and liver cGVHD and older age were associated with frailty. Neither corticosteroid use at the time of enrollment nor the maximum recorded dose of corticosteroids before enrollment was associated with frailty. Frail patients had higher NRM than nonfrail patients (P < .001), with a 10-year cumulative incidence of 41% (95% confidence interval [CI], 32% to 49%) versus 22% (95% CI, 17% to 28%). Reciprocally, frailty also was associated with a significantly lower OS (P < .001), with a 10-year OS of 43% (95% CI, 35% to 53%) in frail patients versus 63% (95% CI, 57% to 69%) in nonfrail patients. In multivariable analysis that included the individual domains of frailty, weakness, low physical activity, and slow walking speed were associated with survival. Frail patients also had worse scores on various measures of patient-reported outcomes, including the Short Form (SF)-36, the Lee Symptom Scale, and the trial outcome of the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) index score. Frail patients with cGVHD have significantly worse outcomes than nonfrail patients. Such clinical features as older age and lung and liver cGVHD are associated with frailty. Earlier clinical recognition of frailty in patients with cGVHD may prompt interventions to counteract frailty that could be beneficial for this population.
    MeSH term(s) Humans ; United States ; Frailty/epidemiology ; Frailty/etiology ; Bronchiolitis Obliterans Syndrome ; Retrospective Studies ; Bone Marrow Transplantation ; Hematopoietic Stem Cell Transplantation/adverse effects
    Language English
    Publishing date 2023-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2023.03.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Late Effects of Severe Acute Graft-versus-Host Disease on Quality of Life, Medical Comorbidities, and Survival.

    Rashid, Nahid / Krakow, Elizabeth F / Yeh, Albert C / Oshima, Masumi Ueda / Onstad, Lynn / Connelly-Smith, Laura / Vo, Phuong / Mielcarek, Marco / Lee, Stephanie J

    Transplantation and cellular therapy

    2022  Volume 28, Issue 12, Page(s) 844.e1–844.e8

    Abstract: Grade III-IV acute graft-versus-host disease (aGVHD) is associated with high short-term morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). The long-term effects after recovery from grade III-IV aGVHD are unknown. This ... ...

    Abstract Grade III-IV acute graft-versus-host disease (aGVHD) is associated with high short-term morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). The long-term effects after recovery from grade III-IV aGVHD are unknown. This study aimed to analyze late medical comorbidities, quality of life, nonrelapse mortality, and survival in patients treated for grade III-IV aGVHD. Chart review identified late effects, and patients were asked to complete annual surveys to collect patient-reported outcomes. Outcomes were compared between patients with grade 0-I aGVHD and grade III-IV aGVHD who underwent HCT between 2001 and 2019 and survived for at least 1 year post-transplantation. Patients with a history of grade III-IV aGVHD (n = 192) had significantly higher rates of late medical comorbidities (P < .001) and worse physical (P = .01) and mental (P = .04) functioning compared with patients with grade 0-I aGVHD (n = 615). Patients who survived for >1 year post-transplantation and had prior grade III-IV aGVHD also had worse 5-year overall survival (77.5% versus 83.6%; P = .006) and higher nonrelapse mortality (19.2% versus 10.6%; P < .001) compared with those with a history of grade 0-I aGVHD. No between-group difference was found in cumulative incidence of chronic GVHD. Patients who recover from severe aGVHD remain vulnerable to developing late comorbidities. These patients would likely benefit from continued monitoring and supportive care in an attempt to prevent late effects and improve survival.
    MeSH term(s) Humans ; Graft vs Host Disease/epidemiology ; Quality of Life ; Hematopoietic Stem Cell Transplantation/adverse effects ; Incidence ; Disease Progression
    Language English
    Publishing date 2022-08-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2022.08.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The effect of donor type on outcomes in adults with acute myeloid leukemia after reduced-intensity hematopoietic peripheral blood cell transplant - a retrospective study.

    Rashid, Nahid / Slade, Michael / Abboud, Ramzi / Gao, Feng / DiPersio, John F / Westervelt, Peter / Uy, Geoffrey / Stockerl-Goldstein, Keith / Romee, Rizwan / Schroeder, Mark A

    Transplant international : official journal of the European Society for Organ Transplantation

    2020  Volume 33, Issue 9, Page(s) 1089–1098

    Abstract: We retrospectively analyzed outcomes in patients with acute myeloid leukemia (AML) receiving reduced-intensity conditioning (RIC) hematopoietic stem cell transplants (HCT) from a peripheral blood (PB) source. We identified 46 haploidentical HCT (haplo), ... ...

    Abstract We retrospectively analyzed outcomes in patients with acute myeloid leukemia (AML) receiving reduced-intensity conditioning (RIC) hematopoietic stem cell transplants (HCT) from a peripheral blood (PB) source. We identified 46 haploidentical HCT (haplo), 59 matched unrelated donor HCT (MUD), and 40 matched related donor HCT (SIB) patients at a single institution. Haplo had improved overall survival (OS) when compared to MUD, HR 2.03 (P = 0.01) but not SIB, HR 1.17 (P = 0.61). There were no differences in relapse rates or treatment-related mortality (TRM). Haplo had higher rates of acute graft-versus-host disease (GVHD) grade II-IV at day 180 than MUD (44% vs. 25%, P = 0.03) and SIB (44% vs. 13% P < 0.01). Rates of acute GVHD III-IV and chronic GVHD were similar among the groups. Haplo had slower engraftment rates compared to MUD with neutrophil engraftment at 87% vs. 93%, (P < 0.01) and platelet engraftment at 59% vs. 86%, (P < 0.01) at 28 days. Although patients receiving haplo had higher acute GVHD II-IV and slower engraftment, they did not have increased TRM. These data may suggest that patients receiving haplo have improved OS compared to MUD for AML patients receiving RIC transplants. This should be confirmed using a larger cohort.
    MeSH term(s) Adult ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy ; Retrospective Studies ; Transplantation Conditioning ; Unrelated Donors
    Language English
    Publishing date 2020-06-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 639435-8
    ISSN 1432-2277 ; 0934-0874
    ISSN (online) 1432-2277
    ISSN 0934-0874
    DOI 10.1111/tri.13659
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Ruxolitinib resistance or intolerance in steroid-refractory acute graft-versus-host disease - a real-world outcomes analysis.

    Abedin, Sameem / Rashid, Nahid / Schroeder, Mark / Romee, Rizwan / Nauffal, Mary / Alhaj Moustafa, Muhamad / Kharfan-Dabaja, Mohamed A / Palmer, Jeanne / Hogan, William / Hefazi, Mehrdad / Larson, Samantha / Holtan, Shernan / DeFilipp, Zachariah / Jayani, Reena / Dholaria, Bhagirathbhai / Pidala, Joseph / Khimani, Farhad / Grunwald, Michael R / Butler, Candace /
    Hamadani, Mehdi

    British journal of haematology

    2021  Volume 195, Issue 3, Page(s) 429–432

    Abstract: Ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) results in resistance or intolerance in 1/5 of patients. Outcomes of such patients are undefined. We identified these patients in a multicentre review and reported outcomes. ... ...

    Abstract Ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) results in resistance or intolerance in 1/5 of patients. Outcomes of such patients are undefined. We identified these patients in a multicentre review and reported outcomes. Ruxolitinib-resistant aGVHD was identified in 48/307 patients. Among patients receiving additional therapy, the overall response rate to next therapy was 36%. Median survival was 21 days. Ruxolitinib intolerance led to treatment discontinuation in 16/307 patients. Ten intolerant patients received additional therapy with 50% experiencing continued improvement of aGVHD. Median survival was 50 days in these patients. These data serve as a baseline for future SR-aGVHD studies.
    MeSH term(s) Acute Disease ; Adult ; Aged ; Allografts ; Bone Marrow Transplantation/adverse effects ; Cord Blood Stem Cell Transplantation/adverse effects ; Drug Resistance ; Female ; Graft vs Host Disease/drug therapy ; Graft vs Host Disease/mortality ; Graft vs Host Disease/prevention & control ; Humans ; Immunosuppressive Agents/therapeutic use ; Male ; Middle Aged ; Nitriles/adverse effects ; Nitriles/pharmacology ; Nitriles/therapeutic use ; Peripheral Blood Stem Cell Transplantation/adverse effects ; Pyrazoles/adverse effects ; Pyrazoles/pharmacology ; Pyrazoles/therapeutic use ; Pyrimidines/adverse effects ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use ; Retrospective Studies ; Salvage Therapy ; Young Adult
    Chemical Substances Immunosuppressive Agents ; Nitriles ; Pyrazoles ; Pyrimidines ; ruxolitinib (82S8X8XX8H)
    Language English
    Publishing date 2021-07-12
    Publishing country England
    Document type Journal Article ; Multicenter Study
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.17700
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