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  • 1
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5702-5702
    Abstract: Introduction: Peri-transplant radiation (XRT) in Hodgkin Lymphoma (HL) patients undergoing autologous stem cell transplant (ASCT) has been associated with improved local control. However, this has not been well established with increased use of novel agents in peri-transplant setting. Methods: This was a retrospective analysis of HL patients who underwent their first ASCT between 2000 and 2018 at Karmanos Cancer Institute in Detroit, Michigan. Peri-transplant radiation was defined as XRT within 3-month window of autologous transplant. Novel agents included brentuximab, check-point inhibitors (CIs), and other targeted agents. The primary endpoint was to compare overall survival (OS) based on utilization of peri-transplant XRT and novel agents with standard salvage chemotherapy. Secondary endpoint was to assess the OS benefit of novel agent use in the post-transplant setting. Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between OS and nine prior chosen predictors (bulky relapse, pulmonary or bone marrow relapse, extranodal disease, CT/PET response [CR vs less than CR] , novel salvage [anytime], peri-transplant XRT, site of relapse [local vs systemic] , maintenance brentuximab, relapse after initial diagnosis [ 〉 1 year vs ≤1 year]). Results: From 2000-2018, there were total of 220 patients who underwent ASCT for HL. Patients underwent ASCT median of 575 days after initial diagnosis. 65 (30%) patients had XRT during initial treatment and XRT was utilized less frequently in all patients (13% vs 35%) and stage I-II patients (29% vs 46%) who were diagnosed after 2010. Peri-transplant XRT was used in 30 (14%) patients and was utilized similarly in patients who had ASCT before or after 2010 (13% vs 14%) (Figure 1). There was no difference in baseline characteristics (bulky relapse, local vs systemic relapse, etc.) of patients who did or did not receive peri-transplant XRT (Table 1). Novel salvage was used in 32 (15%) patients at any time before transplant (Figure 1). Median OS of all the patients who had ASCT was 11 years [7.6-NR] and PFS was 4.3 years [2.3-7.4] . Median OS of patients who had peri-transplant XRT was not reached [9.4-NR] compared to 7.7 [5.3-NR] years for those without peri-transplant XRT [HR 0.38; 95% CI 0.15-0.96; p=0.033] (Figure 2); on the contrary, there was no difference in PFS between the two groups. Median OS of patients who had novel salvage at any time was not reached [4.3-NR] compared to 11 [7.6-NR] years for those without novel salvage [HR 1.08; 95% CI 0.43-2.72; p=0.877] . Median OS of patients who had either novel salvage (anytime) or peri-transplant XRT was not reached [9.4-NR] compared to 11 years [6.5-NR] for those who had chemotherapy salvage only [HR 0.64; 95% CI 0.32-1.26; p=0.193]. In the multivariable analysis, less than CR to salvage therapy and lack of peri-transplant XRT use were associated with worse OS. There were total of 85 (39%) patients who progressed after ASCT. Median OS for those patients was 3.5 years [2.3-8.8] and PFS was 1 year [0.8-1.5] after relapse from ASCT. The median OS for patients who received novel agents (brentuximab 61%, CI 14%) during first progression after ASCT was 6.9 years [2.3-NR] after relapse from ASCT compared to 2.9 years [2.3-NR] for those that did not [HR 1.47; 95% CI 0.72-3; p=. 288]. In addition, the median OS for patients who received novel agent at any time after transplant was 6.9 years [2.6-NR] after relapse from ASCT compared to 2.5 years [2.2-7] for those who did not [HR 1.96; 95% CI 1-3.86; p=0.048] (Figure 3). Lastly, OS after relapse from ASCT was better if patients progressing on novel agent post-transplant received another novel agent for their successive therapy rather than any other treatment [HR 4.87; 95% CI 1.14-20.8; p=0.018]. Conclusions: We show that there was a lack of standardized patient selection for utilization of peri-transplant XRT and its use was similar before and after the novel agent era. Peri-transplant XRT was possibly used in patients who had residual disease or other high -risk features that could not be identified due to retrospective nature of this study and, despite this, use of peri-transplant XRT was associated with modest survival benefit. Surprisingly, use of novel agent at any time during salvage was not associated with survival benefit. Utilization of novel agents at any time after post-transplant progression was associated with OS benefit. Disclosures Deol: Kite: Other: Advisory board; Novartis: Other: Advisory board; Agios: Other: Advisory board.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
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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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    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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  • 4
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 61, No. 8 ( 2020-07-02), p. 1877-1884
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2030637-4
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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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 7546-7546
    Abstract: 7546 Background: Haploidentical transplant (HIDT) with post-transplant cyclophosphamide (pCY) is being increasingly used because of the universal availability of donor and rapid graft acquisition time. Cytokine release syndrome (CRS) is one of the commonly occurring complications in this population. The information on the impact of CRS on the post-HIDT outcomes is limited. Methods: We retrospectively evaluated 91 patients who underwent HIDT between June 2012 and June 2019 for the onset and severity of CRS. CRS was graded per ASTCT guidelines. The primary objective was to compare RFS (relapse-free survival), NRM (non-relapse mortality), OS (overall survival) and GVHD in patients with no CRS, CRS grade 1-2 and 3-4. Results: All received peripheral blood stem cells and pCY/tacrolimus/mycophenolate as GVHD prophylaxis. Fifty-six (62%) received reduced intensity and 35 (38%) received full intensity conditioning regimen. Ten (10.9%) had no CRS, 74 (81.3%) developed grade 1-2 CRS and seven (7.7%) experienced grade 3-4 CRS. Median time to onset of CRS was one day post-transplant. The most common symptoms were fever (87%), fatigue (30%), nausea/vomiting (24%), rigors (24%), diarrhea (20%) and rash (11%). Fifteen (20%) with grade 1-2 and six (85%) with grade 3-4 CRS received tocilizumab. Day +100 cumulative incidence of grade III-IV acute GVHD for no CRS, grade 1-2 and grade 3-4 CRS was 0%, 2.7%, and 14.3%, respectively (P = 0.36). One-year cumulative incidence of chronic GVHD for no CRS, grade 1-2 and grade 3-4 CRS was 30%, 31.9% and 14.3%, respectively (P = 0.70). One-year NRM for no CRS, grade 1-2 and grade 3-4 CRS was 30%, 16.5%, and 57.1%, respectively (P = 0.002). One-year RFS for no CRS, grade 1-2 and grade 3-4 CRS was 48%, 63.4% and 28.6%, respectively (p = 0.03). OS at 1-year for no CRS, grade 1-2 and grade 3-4 CRS was 60%, 73.9%, and 28.6%, respectively (P = 0.008). Multivariable analysis revealed that grade 3-4 CRS was associated with significantly higher NRM (HR 5.54, P = 0.002), worse RFS (HR 3.41, P = 0.011) and worse OS (HR 4.91, P = 0.001). Conditioning regimen, degree of HLA match and disease risk index did not affect post-transplant outcomes and were not predictors for developing CRS. Conclusions: Our study showed that grade 3-4 CRS was associated with inferior post-transplant outcomes. However, no impact on acute or chronic GVHD was noted. Therefore, early recognition and prompt management of CRS may help improve outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 7
    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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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e19524-e19524
    Abstract: e19524 Background: Lenalidomide (len) is approved for treatment in Multiple Myeloma (MM) Use of len has been associated with an increase in venous thrombotic events (VTE) and aspirin prophylaxis is recommended for pts who are on active treatment with len. Autologous stem cell transplant (ASCT) is used during the treatmentof MM after initial induction therapy. The use of intravenous catheters and hospitalization increase the risk of VTE in peri-transplant period. We evaluated the incidence of VTE in peri-transplant period to determine if len use increased the risk of VTE. Methods: We performed a retrospective chart review of pts with MM who underwent first ASCT at our institution between 1/2011-1/2015.Data was collected on pt. demographics, len use, VTE prophylaxis, VTE incidence and VTE treatment. Chemical anticoagulation during the peri-transplant period was based on physician preference and chemical anticoagulation was stopped once platelet counts dropped below 50,000/ uL. All pts were encouraged to ambulate daily for mechanical prophylaxis. Associations with incidence of VTE were conducted by univariable and multivariable logistic regression analyses. Results: A total of 303 pts met the study criteria. 204 pts received Len as part of induction treatment while 99 did not. There was no significant difference in demographics of the 2 groups. 87% pts in the Len group and 81% in the non-Len group did not receive any chemical prophylaxis, respectively during hospitalization. 15 pts developed DVT within 100 days of transplant: 10 in len group and 5 in non-len group (p 〉 0.99). 14 of the 15 were catheter associated. Median time to DVT was 10.5 days post-transplant. Caucasians had a higher risk of DVT; adjusted OR 0.315 (95%CI 0.03-0.99; p = 0.046). Incidence of VTE was not affected by prophylaxis, or response to induction. Conclusions: Despite the fact that during the peri-transplant period most of the patients were not on prophylactic chemical anticoagulation due to chemotherapy associated thrombocytopenia len use during the induction treatment did not increase the risk of peri-transplant VTE.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 60, No. 11 ( 2019-09-19), p. 2762-2770
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2030637-4
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  • 10
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 62, No. 2 ( 2021-01-28), p. 446-453
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2030637-4
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