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  • 1
    In: American Journal of Hematology, Wiley, Vol. 94, No. 10 ( 2019-10), p. 1072-1080
    Abstract: Liver Graft‐versus‐host disease (GVHD) is common in patients with post‐transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post‐transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a “non‐liver GVHD” group, which consisted of other etiologies of post‐transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post‐transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the “non‐liver GVHD” group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time‐varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non‐relapse mortality, and adverse relapse‐free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 2
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 3102-3102
    Abstract: Introduction: Use of cytoreductive therapy pre-transplant has remained a debatable issue in the management of MDS. Induction chemotherapy has been attempted with no clear advantage. However, the information on pre-transplant hypomethylating agents (HMA) as a debulking/bridging therapy in MDS is unclear. This study evaluates the impact of pre-transplant HMA on post-transplant outcomes in MDS. Methods: We retrospectively evaluated clinical outcomes of adult MDS patients, who underwent allogeneic stem cell transplant (ASCT) at out institute. We divided patients who received pre-transplant HMA into 〈 5% blasts (group 1) and ≥ 5% blasts (group 2) at transplant and compared transplant outcomes of both these groups with untreated patients (group 3). The objectives were to determine rate of GVHD, non-relapse mortality (NRM), relapse rate, progression free survival (PFS) and OS. Results: Between January 2000 and December 2016, 174 patients with MDS underwent ASCT. Of these, 80 patients received pre-transplant HMA, and 42 had 〈 5% blast (group 1) and 38 had ≥ 5% blasts (group 2) at transplant. Ninety-four patients did not receive HMA (group 3). Monosomy 5, 7 or del 5q was noted in 10%, 8% and 15% of patients, in group 1, 2 and 3, respectively, whereas complex cytogenetics were noted in 26%, 26% and 28% of patients, in group 1, 2 and 3, respectively. Median number of blasts at transplant was 0%, 10% (range, 5-19), 3% (range, 0-40), in group 1, 2 and 3, respectively. Thirty-nine percent patients received matched related, and 61% received matched unrelated donor transplants. Bu-Flu-TBI (53%) was the most commonly used conditioning regimen followed by Bu-Flu (41%). With a median follow up of 4.08 years, the cumulative incidence of grade III-IV aGVHD at 6 months was 9.5% (95% CI, 3-20.7%), 28.9% (95% CI, 15.5-43.9%), and 27.7% (95% CI, 19-37%) for group 1, 2 and 3, respectively (p=0.05). The 1-year cumulative incidence of cGVHD was 54.9% (95% CI, 37.4-69.4%), 28.4% (95% CI, 14.4-44.3%), and 51.1% (95% CI, 40.4-60.7%) (p=0.04), for group 1, 2 and 3, respectively. The 1-year OS for group 1, 2 and 3 was 75% (95% CI, 62.6-89.7%), 40.2% (95% CI, 26.5-61%), and 59.3% (95% CI, 50.1-70.1%), respectively; whereas PFS was 67.5% (95% CI, 54.4-83.8%), 34.8% (95% CI, 22.2-54.7%), 55.1% (95% CI, 45.9-66.2%), respectively. The 1-year outcomes in group 1, 2 and 3 were 17.6% (95% CI, 7.6-31%), 26.6% (95% CI, 13.6-41.6%), and 9.6% (95% CI, 4.7-16.6%) (p=0.07), respectively, for relapse; 14.8% (95% CI, 5.9-27.6%), 38.2% (95% CI, 22.4-53.9%), and 35.2% (95% CI, 25.7-44.9%) (p=0.11), respectively, for NRM. Multivariable analysis demonstrated that ≥5% blast at transplant, complex karyotype and high R-IPSS were associated with poor PFS and OS, whereas Complex karyotype was associated with higher relapse rate, poor PFS and OS. Conclusion: Our study shows pre-transplant disease burden and complex karyotype as independent risk factors for poor outcomes. No survival benefit was noted with pre-transplant HMA in MDS. Disclosures Deol: Novartis: Consultancy; Kite Pharmaceuticals: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 3
    Online Resource
    Online Resource
    American Society of Hematology ; 2021
    In:  Blood Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3103-3103
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3103-3103
    Abstract: Background: Transfusional iron overload contributes to considerable morbidity and mortality in patients with sickle cell disease. Despite FDA (Food and Drug Administration) approval of voxelotor in 2019, it remains underutilized, and RBC (red blood cell) transfusions play a prominent role in managing these patients. Contemporary large-scale epidemiologic data on blood transfusions in sickle cell disease are lacking. This study reports demographics, readmission rate, and factors associated with blood transfusion in hospitalizations for sickle cell disease. Methods: We performed a retrospective cohort study using the Nationwide Readmissions Database (NRD) for 2017 & 2018 to identify hospitalizations with the primary diagnosis of sickle disease using appropriate ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) codes. These admissions were categorized into those who received blood transfusions and those without blood transfusions. We performed descriptive analysis to compare demographics, hospital characteristics, various comorbid conditions, and complications between the two groups. All-cause 30-day readmission rate was calculated after excluding index admissions from December, deaths during index admissions, and elective readmissions. Multivariable logistic regression was used to adjust for confounders and determine factors associated with RBC transfusion. The analysis was carried out to produce national estimates after applying weights, and the methodology provided by the HCUP (Healthcare Cost and Utilization Project) was utilized. Results: Out of 109,783 weighted index hospitalizations, 28,300 were transfused, and 81,483 were not transfused. The proportion of females and 40 years & older was higher in the transfused category than not transfused (59.49% vs. 53.52% and 28.86% vs. 21.27% respectively; p & lt;0.001 for both). The wealthiest population was more likely to be in the transfused category than the non-transfused (11.27% vs. 8.34%; p & lt;0.001). The proportion of admissions to teaching hospitals, large metropolitan hospitals, and highest volume hospitals was higher in the non-transfused category compared to the transfused (79.89% vs. 72.17%; p & lt;0.001, 69.26% vs. 65.35%; p 0.003 and 74.71% vs. 63.51%; p & lt;0.001 respectively). The comorbidity burden, mean length of stay, total hospital charges, and inpatient mortality were higher in the transfused category than those without transfusion (table 1). Most admissions were transfused once, with multiple transfusions (3 or more) being given more in the non-teaching hospitals than teaching (1.27% vs. 0.41%; p 0.01). Furthermore, more than half of all transfusions happened within the first two days of admission, with a higher proportion of early transfusions in the non-teaching hospitals compared to teaching hospitals (65.6% vs. 57.82% for admission days 1 and 2; p & lt;0.001) (table 2). Age group ≥40 years and 25-39 years were more likely to receive transfusion in the first two days of admission than the 18-24-year-olds (69.01% vs. 59.14% vs. 49.2%; p & lt;0.001 respectively). After adjusting for confounders, older age groups (age ≥40 years and 25-39 years) compared to 18-24-year-olds (aOR {adjusted odds ratio} 1.48; 95% CI {confidence interval} 1.36-1.62 and aOR 1.21; 95% CI 1.12-1.31 respectively), female sex (aOR 1.23; 95% CI 1.17-1.31), highest community-level income (aOR 1.52; 95% CI 1.31-1.75), admission to rural hospital (aOR 1.82; 95% CI 1.26-2.6), length of stay 4-7 vs. ≤3 days (aOR 1.56; 95% CI 1.46-1.66) and length of stay ≥8 vs. ≤3 days (aOR 2.28; 95% CI 2.05-2.53) were found to be associated with higher odds of blood transfusion. Admission to a teaching hospital was associated with lower blood transfusion odds than a non-teaching hospital (aOR 0.70; 95% CI 0.56-0.87) (table 3). Conclusion: A quarter of admissions for sickle cell disease receive a blood transfusion. In addition to performing more frequent and early transfusions, the odds of being transfused are higher in a non-teaching hospital. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 4
    In: Blood, American Society of Hematology, Vol. 138, No. 22 ( 2021-12-02), p. 2278-2289
    Abstract: Belumosudil, an investigational oral selective inhibitor of Rho-associated coiled-coil–containing protein kinase 2 (ROCK2), reduces type 17 and follicular T helper cells via downregulation of STAT3 and enhances regulatory T cells via upregulation of STAT5. Belumosudil may effectively treat patients with chronic graft-versus-host disease (cGVHD), a major cause of morbidity and late nonrelapse mortality after an allogeneic hematopoietic cell transplant. This phase 2 randomized multicenter registration study evaluated belumosudil 200 mg daily (n = 66) and 200 mg twice daily (n = 66) in subjects with cGVHD who had received 2 to 5 prior lines of therapy. The primary end point was best overall response rate (ORR). Duration of response (DOR), changes in Lee Symptom Scale score, failure-free survival, corticosteroid dose reductions, and overall survival were also evaluated. Overall median follow-up was 14 months. The best ORR for belumosudil 200 mg daily and 200 mg twice daily was 74% (95% confidence interval [CI], 62-84) and 77% (95% CI, 65-87), respectively, with high response rates observed in all subgroups. All affected organs demonstrated complete responses. The median DOR was 54 weeks; 44% of subjects have remained on therapy for ≥1 year. Symptom reduction with belumosudil 200 mg daily and 200 mg twice daily was reported in 59% and 62% of subjects, respectively. Adverse events (AEs) were consistent with those expected in patients with cGVHD receiving corticosteroids and other immunosuppressants. Sixteen subjects (12%) discontinued belumosudil because of possible drug-related AEs. Belumosudil, a promising therapy for cGVHD, was well tolerated with clinically meaningful responses. This trial was registered at www.clinicaltrials.gov as #NCT03640481.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5769-5769
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5769-5769
    Abstract: Introduction: About 40-45% of relapsed chemo-sensitive diffuse large B cell lymphoma (DLBCL) patients achieve long term survival with autologous transplant (autoSCT). However, the outcomes of patients who fail autoSCT are extremely poor. In addition, patients with high risk DLBCL and refractory disease have lower chances of response to autoSCT. Allogeneic stem cell transplant (alloSCT) could be a viable option in these circumstances, in part due to cytoreductive effect of conditioning regimen and graft-versus-lymphoma effect. Here we report outcomes of DLBCL patients who received alloSCT in upfront settings or following failed autoSCT. Methods: We retrospectively evaluated clinical outcomes of adult DLBCL patients at Karmanos Cancer institute. The objectives were to determine rate of GVHD, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following alloSCT. Results: Between January 2005 and December 2017, 81 patients underwent alloSCT. Of these, 73 patients had de novo, 7 had transformed DLBCL and one had testicular involvement. The median age at transplant was 52 years (range, 21-68). The median number of treatments prior to alloSCT was 3 (range, 1-6). Twenty-four patients (30%) had prior failed autoSCT, and 57 (70%) had upfront alloSCT. Disease status at transplant were: complete remission in 22 patients (27%), partial remission in 6 (7%), relapse in 31 (38%) and refractory in 22 (27%). Thirty-three patients (41%) underwent matched related and 48 (59%) had matched unrelated alloSCT. CNS and bone marrow involvement at the time of transplant were noted in 10% and 47% of patients, respectively. Patients received following conditioning regimens: R-BEAM (58%), BU-FLU-TBI (27%), BU-FLU (2%), CY-TBI (2%), BU-CY (2%), CY-FLU-TBI (2%), and others (5%). With a median follow-up of 5 years (95% CI, 4.01-9.89), the cumulative incidences of grade III-IV acute GVHD at 6-month and chronic GVHD at 1-year were 27.2% (95% CI, 18-37.2%) and 37% (95% CI, 26.5-47.6%), respectively. At 1-year, OS was 48% (95% CI, 38.4-60.3%), PFS was 43.2% (95% CI, 33.6-55.4%) and GRFS was 13.5% (95% CI, 7.8-23.5%). One-year relapse rate was 24.7% (95% CI, 15.9-34.5%), and NRM was 32.1% (95% CI, 22.2-42.4%). Sixteen patients (20%) patients were alive without chronic GVHD and relapse. Relapse disease at the time of transplant was associated with higher post-transplant relapse rate, and poor performance status was adversely associated with OS and PFS. No effect of prior autoSCT, conditioning regimen or type of donor was found in multivariable analysis on OS, PFS, relapse and NRM. Twenty-seven out of 81 patients (33%) were alive at the time of data analysis. Causes of death included relapse (37%), infection (31%), acute GVHD (13%) and multiorgan failure (11%). Conclusion: Our study indicates that alloSCT provides long-term survival in these high-risk patients with low relapse rate; although non-relapse mortality was high in this group where about a third had failed prior autoSCT. Disclosures Deol: Kite Pharmaceuticals: Consultancy; Novartis: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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    detail.hit.zdb_id: 80069-7
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  • 6
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 26, No. 4 ( 2020-04), p. 683-690
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 7
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 24, No. 3 ( 2018-03), p. S261-S262
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 8
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 23, No. 3 ( 2017-03), p. S258-
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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  • 9
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 17 ( 2017-09), p. S328-
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2540998-0
    detail.hit.zdb_id: 2193618-3
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  • 10
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 54, No. 1 ( 2019-1), p. 164-167
    Type of Medium: Online Resource
    ISSN: 0268-3369 , 1476-5365
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2004030-1
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