scholarly journals Minorities Do Not Have Worse Outcomes for Diffuse Large B Cell Lymphoma (DLBCL) If Optimally Managed

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 425-425
Author(s):  
Bei Hu ◽  
Tommy Chen ◽  
Danielle Boselli ◽  
Rupali Bose ◽  
James T. Symanowski ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
De Novo ◽  
Private Insurance ◽  
Insurance Coverage ◽  
Cancer Center ◽  
Advisory Committees

BACKGROUND: DLBCL is the most common and a potentially curable non-Hodgkin lymphoma. Multiple previous studies have shown that minority populations have worse outcomes compared to Caucasians (Tao L, Blood 2014; Griffiths R, BMC Cancer 2010; Koroukian et al, Cancer, 2010, Shenoy PJ Cancer 2010). Moreover, it has been reported that uninsured and Medicaid insured patients with DLBCL have inferior survival compared to privately insured patients (Han X, Cancer 2014; Koroukian et al, Cancer 2010;). It has also been well established that minorities are underrepresented in clinical trials (Gerrero S, Sci Rep 2018; Kwiatkowski K, Cancer 2013). We present the baseline characteristics, treatment paradigms and outcomes of Caucasian (C) and non-Caucasian (NC) patients with de novo DLBCL treated at a single academic hybrid cancer center. METHODS: We collected demographic, disease, insurance coverage, treatment characteristics, and treatment outcomes for patients with de novo DLBCL who presented between January 2016 and January 2019 at Levine Cancer Institute, Charlotte, North Carolina. Patient race, C or NC were self-reported. Insurance was categorized as Government (Medicaid or Medicare), Private, or Uninsured. We used the Revised International Prognostic Index (R-IPI) to risk stratify patients. Double-hit lymphomas (DHL) were defined as having the MYC translocation with either BCL2 or BCL6 translocation on fluorescent in situ hybridization. Treatments included standard chemoimmunotherapies, stem cell transplantation and clinical trials including chimeric antigen receptor therapies (CART). Outcomes of overall survival (OS) and progression free survival (PFS) were calculated using the Kaplan Meier method and compared with log rank test. Demographic data was compared using Fisher's Exact tests. RESULTS: One hundred and ninety-six consecutive patients with de novo DLBCL were included in the analysis [155 (79%) = C, 41 (21%) = NC] (Table). The NC group was predominantly African American (71%) followed by Hispanic (15%). Prognostic scores (R-IPI) and the incidence of DHL were similar between C and NC. The median age at diagnosis in the NC group was lower than in C. There were significant differences in insurance coverage between the 2 groups (p=0.012). The C group did not have any uninsured patients and had more patients with private insurance (33%) compared to the NC group (7% uninsured and 27% with private insurance). The most common frontline treatment was RCHOP (C=66%, NC=70%) followed by dose adjusted REPOCH (C=12%, NC=15%). Median follow up was 31.6 months. There was no difference in OS and PFS between the 2 groups (Figure 1). OS at 2 years from date of diagnosis was 81% for C and 84% for NC, p=0.852. Two-year PFS from time of diagnosis were similar for both groups: 61% for C and 63% for NC, p=0.999. Similar numbers of patients in both groups developed relapsed or refractory (R/R) disease after frontline therapy. Median number of treatments was 2 for both groups, p=0.582. For patients who developed R/R DLBCL, the 2-year OS was 60% for C and 63% for NC, p=0.590. Similar proportions underwent stem cell transplantation: 11% for C and 20% for NC, p= 0.186. Clinical trial enrollment was comparable: 11% for C and 12% for NC, p=0.785. CONCLUSION: Unlike previous population-based studies that have shown racial disparities with superior outcomes for Caucasians and for patients with private insurance, our single center experience demonstrates similar survival outcomes between Caucasians and non-Caucasians diagnosed with de novo DLBCL, despite differences in insurance coverage favoring Caucasians. In the R/R setting, similar proportions of both groups underwent stem cell transplantation and enrolled on clinical trials. The likely explanation is that our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported. Disclosures Symanowski: Immatics: Consultancy; Eli Lilly: Consultancy; Carsgen Therapeutics: Consultancy; Boston Biomedical: Consultancy. Park:Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Research Funding; Gilead: Speakers Bureau; Teva: Consultancy, Research Funding; G1 Therapeutics: Consultancy; Seattle Genetics: Research Funding, Speakers Bureau. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees; Best Practice-Br Med J: Patents & Royalties: receives royalties from a coauthored article on evaluation of neutropenia. Jacobs:Genentech: Speakers Bureau; AstraZeneca: Speakers Bureau; TG Therapeutics: Honoraria, Research Funding; AbbVie: Consultancy, Speakers Bureau; JUNO: Consultancy; Gilead: Consultancy; Pharmacyclics LLC, an AbbVie Company: Research Funding, Speakers Bureau. Ghosh:TG Therapeutics: Consultancy, Honoraria, Research Funding; SGN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Genentech: Research Funding; AstraZeneca: Honoraria, Speakers Bureau; Forty Seven Inc: Research Funding.

scholarly journals Patterns of Utilization and Outcome of Hematopoietic Stem Cell Transplantation Among Various Cancers: A Nationwide Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4749-4749
Author(s):  
Prabhjot Singh Bedi ◽  
Manoj P Rai ◽  
Justin D. Kaner ◽  
Samanjit Kaur Kandola ◽  
Varunsiri Atti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Private Insurance ◽  
Lymphocytic Leukemia ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Hematological Cancers

Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) is performed to treat hematologic malignancies such as acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS), lymphomas (HL and NHL) and hemophagocytic lymphohistiocytosis (HLH). Inpatient data on the characteristics of patients receiving BMT, the distribution of BMT among the above mentioned hematological cancers and their outcomes is lacking. This study analyzes patient and hospital characteristics of patients undergoing BMT, in addition the study describes resource utilization and outcomes of BMT among various hematological cancers. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a procedure diagnosis of BMT and a medical diagnosis of acute or chronic leukemia (ALL, AML, CLL, CML), lymphoma (HL and NHL), MM, MDS or HLH. HSCT or BMT includes both Allogeneic and Autologous Stem Cell Transplant however we did not differentiate one from the other since BMT in MM is almost universally auto stem cell transplantation. We performed descriptive statistics to characterize the cohort in terms of personal demographic factors (age, race, sex, insurance type, community level income level), indication for HSCT, hospital characteristics (size, region, teaching status, and urban or rural location), and timing of admission (weekend or weekday). We performed univariate analyses using these variables to determine the associations with LOS and mortality. All analyses apply the HCUP-NIS weights. Results: The cohort comprised of 18,275 patients who underwent HSCT. Most patients were male (59.1%), white (70.4%), aged 51-70 years (53.9%), and covered by private insurance (57.0%). Nearly a third (31.3%) lived in communities with the highest quartile of household incomes. The most common diagnosis associated with HSCT was MM (27.6%), followed by AML (15.6%). Most HSCT was performed at large hospitals (74.5%); only 0.1% were performed in rural and 1.1% at non-teaching hospitals. Average length of stay (ALOS) was 25.54 days (95% CI 24.19 to 26.89) and the mean total charges (per hospitalization) were $346,555 (95% CI $310,465 to $382,645) and net charge was $6.33 billion. Several factors were associated with lower ALOS: age (AMD -0.31, 95% CI -0.37 to -0.24), Charlson index (AMD -0.85, 95% CI -1.60 to -0.12), private insurance coverage (AMD -3.65, 95% CI -5.25 to -2.067) and self pay status (AMD -13.56, 95%CI -17.13 to -10.00). Urban (AMD 6.74, 95% CI 1.01 to 12.48), and teaching hospitals (AMD 8.31 95% CI 2.88 to 13.72) had longer ALOS. Only Hispanic race (OR 0.23 95% CI 0.068 to 0.77) and Charlson index (OR 1.2 95% CI 1.04 to 1.39) were associated with mortality. Multivariate analysis did not show any significant associations of mortality with age, race, geographic region, hospital size, median household income, type of insurance, timing of admission, or teaching or location status of hospitals. Discussion: MM accounted for the most significant portion of HSCT in 2014, although its incidence is lower than that for leukemia and lymphoma. This may partly be because autologous stem cell transplantation (ASCT) after high dose chemotherapy is the mainstay of MM treatment. In contrast to other hematological malignancies, some MM patients may also undergo tandem transplantation. Most HSCT recipients were covered under private insurance, and a significant proportion of them came from communities with the highest quartile of median household incomes. This suggests that socioeconomic status influences access to HSCT therapy, likely related to out of pocket costs. In addition, social determinants of health including health literacy, access to health care may play a role. Surprisingly, ALOS decreased with increasing age and Charlson comorbidity index. Reasons are unclear but may be related to increased or earlier mortality. Additional studies could help to elucidate this relationship. Figure. Figure. Disclosures Bussel: Rigel: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Momenta: Consultancy; Uptodate: Honoraria; Protalex: Consultancy; Amgen Inc.: Consultancy, Research Funding; Prophylix: Consultancy, Research Funding. Marks:Odonate: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Equity Ownership; Lilly: Membership on an entity's Board of Directors or advisory committees; Heron: Membership on an entity's Board of Directors or advisory committees; UPMC: Employment.

scholarly journals Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2149-2149
Author(s):  
Romil Patel ◽  
Neeraj Y Saini ◽  
Ankur Varma ◽  
Omar Hasan ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
First Remission ◽  
Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

scholarly journals The Prognostic Impact of the Diagnostic CD34+/CD38- Cell Burden and Expression of the Stem Cell Marker GPR56 after Stem Cell Transplantation Depends on the AML Origin

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 323-323
Author(s):  
Madlen Jentzsch ◽  
Marius Bill ◽  
Juliane Grimm ◽  
Dominic Brauer ◽  
Julia Schulz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Solid Tumors ◽  
Cell Transplantation ◽  
Research Funding ◽  
De Novo ◽  
Prognostic Impact ◽  
Expression Levels ◽  
Rheumatologic Diseases ◽  
De Novo Aml

Introduction: Acute myeloid leukemia (AML) developing secondary after other hematologic diseases, or therapy related after cytotoxic treatment for solid tumors or rheumatologic diseases (s/tAML) is clinically, genetically & prognostically distinct from de novo diseases. Data indicate that s/tAML patients (pts) have inferior outcome compared to de novo cases after chemotherapy & therefore often require consolidation therapy using allogeneic stem cell transplantation (HSCT). Leukemic stem cells (LSC) initiate & maintain AML. They are also believed to exist within the CD34+/CD38- &/or high GPR56 expressing bone marrow (BM) population, which have been shown to impact adversely on outcome. The prognostic impact of LSC markers in de novovs s/tAML after HSCT with non-myeloablative conditioning intensity - where the therapeutic approach also relies on immunological graft-versus-leukemia effects - is unknown. Methods: We analyzed 379 AML pts who received an allogeneic peripheral blood HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) between 1999 & 2018 after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning. At diagnosis, cytogenetic & flow cytometric analyses were performed centrally. For pts with pre-treatment BM available the mutation status of CEBPA, NPM1 & presence of FLT3-ITD by fragment analyses as well as expression levels of GPR56 by qPCR were assessed. Using a next-generation targeted amplicon sequencing approach we analyzed a panel comprising 54 recurrently mutated (mut) genes in myeloid malignancies on the MiSeq platform (Illumina). Median follow up after HSCT was 3.7 years. Results: 229 pts (60%) had de novo & 150 pts (40%) had AML secondary to myelodysplastic syndrome (MDS, n=82), myeloproliferative neoplasm (MPN, n=22) or MDS/MPN (n=10), or therapy related after Non-Hodgkin lymphoma (n=9), solid tumors (n=25) or rheumatologic diseases (n=2). At diagnosis, s/tAML pts had lower white blood counts (P=.03), lower blasts in BM (P<.001) or blood (P=.007) & a higher BM CD34+/CD38- cell burden (P=.01) & GPR56 expression (P=.04). They also had worse European LeukemiaNet risk (P=.007), were less likely to have a normal karyotype by trend (P=.06), to have a core binding factor AML (P=.02), to be NPM1mut (P=.003), DNMT3Amut (P=.03) & to harbor a FLT3-ITD (P=.002) but more likely to be JAK2mut (P<.001). Comparing pts with s/tAML vsde novo AML, there was no significant different cumulative incidence of relapse (CIR, P=.85) or overall survival (OS, P=.29). Next, we evaluated the prognostic impact of the LSC-associated populations in pts with de novo or s/tAML separately. In pts with de novo AML, we observed a significantly higher CIR & shorter OS for pts harboring a high CD34+/CD38- cell burden (high vs low, 6% cut, P=.006 [Fig. 1A] & P=.003) & a higher CIR but not significantly different OS for pts with a low GPR56 expression (high vs low, median cut, P=.03 [Fig. 1B] & P=.95). Combining both parameters, we observed a stepwise higher CIR & shorter OS for pts with low expression of both variables vs pts with a low CD34+/CD38- cell burden but high GPR56 expression vs pts with a high CD34+/CD38-cell burden (P=.003 [Fig. 1C] & P=.05). In contrast, in pts with s/tAML, there was no prognostic significance of the CD34+/CD38- cell burden (CIR P=.38 [Fig. 1D] & OS P=.95), the GPR56 expression (CIR P=.64 [Fig. 1E] & OS P=.82) & both markers combined (CIR P=.57 [Fig. 1F] & OS P=.98). Also in multivariate analyses, the combination of both markers significantly impacted CIR (Hazard ratio 2.49, P<.001 after adjustment for donor type) & was the only significant factor for OS (Odds Ratio 0.68, P=.04) in de novo AML but not in s/tAML. Conclusion: While there was no significantly different CIR or OS in s/tAML compared to de novo AML pts undergoing non-myeloablative HSCT we observed a significant impact on outcome for the known LSC-associated prognosticators CD34+/CD38- cell burden & GPR56 expression levels at diagnosis only in de novo AML pts. Different underlying disease biology & possibly different LSC-associated populations may be relevant for disease reoccurrence in s/tAML. Figure Disclosures Jentzsch: Novartis: Honoraria; Jazz Pharmaceuticals: Honoraria. Niederwieser:Daichii: Speakers Bureau; Cellectis: Consultancy. Platzbecker:Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Schwind:Daiichi Sankyo: Honoraria; Novartis: Honoraria, Research Funding.

Stem Cell Transplantation Can Provide Durable Disease Control in Blastic Plasmacytoid Dendritic Cell Neoplasia (BPDC): A Retrospective Study From the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3077-3077
Author(s):  
Sascha Dietrich ◽  
Damien Roos-Weil ◽  
Ariane Boumendil ◽  
Emanuelle Polge ◽  
Jian-Jian Luan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Nk Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Advisory Committees

Abstract Abstract 3077 Blastic plasmacytoid dendritic cell neoplasm (BPDC), formerly known as blastic NK cell lymphoma, is a rare hematopoietic malignancy preferentially involving the skin, bone marrow and lymph nodes. The overall prognosis of BPDC is dismal. Most patients show an initial response to acute leukemia-like chemotherapy, but relapses with subsequent drug resistance occur in virtually all patients resulting in a median overall survival of only 9–13 months. However, anecdotal long-term remissions have been reported in young patients who received early myeloablative allogeneic stem cell transplantation (alloSCT). We therefore performed a retrospective analysis of patients identified in the EBMT registry in order to evaluate the outcome of autologous stem cell transplantation (autoSCT) or alloSCT for BPDC. Eligible were all patients who had been registered with a diagnosis of BPDC or Blastic NK cell lymphoma and had received autologous stem cell transplantation (autoSCT) or alloSCT in 2000–2009. Centres were contacted to provide a written histopathology and immunophenotyping report and information about treatment and follow-up details. Patients who did not have a diagnostic score ≥ 2 as proposed by Garnache-Ottou et al. (BJH 2009) were excluded. RESULTS: Overall, 139 patients could be identified in the database who fulfilled the inclusion criteria (alloSCT 100, autoSCT 39). Of 74 patients for whom the requested additional information could be obtained, central review confirmed the diagnosis of BPDC in 39 patients (34 alloSCT, 5 autoSCT). The 34 patients who had undergone alloSCT had a median age of 41 years (range: 10–70 years), were transplanted from a related (n=11) or unrelated donor (n=23); received peripheral blood stem cells (n=9), bone marrow stem cells (n=19) or cord blood (n=6); and had been treated with a reduced intensity conditioning regimen (RIC, n=9) or myeloablative conditioning (MAC, n=25). Nineteen of 34 patients were transplanted in CR1. After a median follow up time of 28 months (range: 4–77+ months), 11 patients relapsed (median time to relapse: 8 months, range: 2–27 months) of whom 8 died due to disease progression. 9 patients died in the absence of relapse. No relapse occurred later than 27 months after transplant. Median disease free survival (DFS) was 15 months (range: 4–77+ months) and median overall survival (OS) was 22 months (range: 8–77+ months; Figure 1a). However, long-term remissions of up to 77 months after alloSCT could be observed. Patients allografted in CR1 tended to have a superior DFS (p=0.119) and OS (p=0.057; Figure 1b). MAC was associated with a better OS (p=0.001) which was attributable to the significantly higher non-relapse mortality (NRM) rate of patients after RIC (p=0.014), who had been significantly older (age RIC: 56 years, age MAC: 36 years, p=0.0014). The relapse rate was not different in patients after RIC and MAC, respectively. However, there was no survivor after RIC. Median age in the autoSCT group was 47 years (range: 14–62 years). Three of 5 patients were transplanted in CR1 of whom 1 patient relapsed after 8 months, 1 patient experienced treatment related mortality and 1 patient remained in CR for 28 months. The 2 remaining patients had more advanced disease at autoSCT and relapsed 4 and 8 months thereafter. CONCLUSION: AlloSCT is effective in BPDC and might provide curative potential in this otherwise incurable disease, especially when performed in CR1. However, it remains to be shown by prospective studies if the potential benefit of alloSCT in BPDC is largely due to conditioning intensity, or if there is a relevant contribution of graft-versus-leukemia activity. Disclosures: Tilly: Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel/accommodations/meeting expenses; Genentech: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Janssen Cilag: Speakers Bureau.

Survey of Treatment of 1021 Patients with Myelodysplastic Syndromes in a Tertiary Referal Center 2007-2013

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4647-4647
Author(s):  
Jennifer Schemenau ◽  
Kathrin Nachtkamp ◽  
Blanca Xicoy ◽  
Andrea Kuendgen ◽  
Corinna Strupp ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Allogeneic Stem Cell Transplantation ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Iron Chelation ◽  
Transfusion Therapy

Abstract Introduction: Clinical course, prognosis, and therapy are heterogeneous in patients with myelodysplastic syndromes (MDS). Iron chelation, epigenetic treatment, lenalidomide, and allogeneic stem cell transplantation are the only approved therapies. As these treatments are successful only in a minority of patients, other approaches, which do not always meet the criteria of evidence-based medicine, are also used in an individualized manner. In order to get a comprehensive picture of MDS treatment we analysed 1021 patients who were treated between 2007 and 2013. We included patients with RAEB-T (5%) and CMML (10%). Treatment regimens were inititated at our department. Methods: Diagnoses were established within the Düsseldorf MDS Registry. All treatments were documented until 31 Dec 2013. Prognostic risk assessment was performed according to the International Prognostic Scoring System (IPSS) and its revised version (IPSS-R). Results: Median age was 68 years (18-93 years), 13.5 % of patients were >80 years of age. 41% were diagnosed as RCMD, 12% as RAEB I, 15% as RAEB II, 4% as MDSdel(5q), 5% as RARS, and 9% as RCUD. Anemia was present at first diagnosis in 62.5%, hemorrhagic diathesis in 10%, and at least one comorbidity in 51%. Transfusion therapy was the only treatment in 57% of the patients. 43% (n=441) received at least one specific treatment during the course of the disease. The median number of different therapies was 2 (range 1-9). Of these, 29.9% received cytokines (Epo, G-CSF), 14.4% iron chelation, 11.0% immunomodulation (lenalidomide, thalidomide), 8.7% immuno­suppressive treatment (ATG, CSA, AntiCD52), 16.4% cytoreduction (Ara-C, hydroxyurea), and 16.4% valproic acid as a histone-deacetylating agent (HDAC), partly in combination with all-trans retinoic acid. 28.3% were treated with hypomethylating agents (5-azacytidine, decitabine), 14.6% with induction chemotherapy, and 31.1% underwent allogeneic stem cell transplantation. 5,2 % of the patients were treated within clinical trials. Treatment approaches were distributed among IPSS risk groups as follows: cytokines (low: 55.6%/ intermediate-1: 32.8% /intermediate-2: 24.1%/ high: 9.1%), chelation (18.1%/20.9%/8.9%/4.5%), epigenetic treatment (HMA) (6.9%/19.4%/48.1%/54.5%), immunmodulation (19.4%/13.4%/7.6%/2.3%), immunosuppressive treatment (5.6%/17.2%/2.5%/0.0%), HDA (26.4%/16.4% /11.4%/13.6%), induction chemotherapy (5.6%/9.7%/20.3%/34.1%), cyto-reduction (9.7%/13.4%/20.3%/13.6%), and allogeneic stem cell transplantation (13.9%/32.8%/48.1%/54.5%). Using the IPSS-R, results were similar: cytokines (very low: 62.5%/low: 38.0%/intermediate:25.3%/high: 29.6%/very high:11.5%), chelation (15.6%/26.0%/10.1%/14.8%/5.8%), epigenetic treatment (HMA)(6.3%/8.0%/ 30.4%/40.7%/44.2%), immunmodulation (9.4%/18.0%/7.6%/7.4%/5.8%), immunosuppression (9.4%/11.0%/16.5%/3.7%/3.8%), HDA (21.9%/26.0% /13.9 %/11.1%/15.4%), induction chemotherapy (6.3%/7.0%/17.7%/20.4%/26.9%), cytoreduction (12.5%/11.0%/20.3%/14.8%/15.4%) and allogeneic transplan-tation (15.6%/22.0%/36.7%/48.1%/50.0%). More than 96% of the patients who were treated with HMA, induction chemotherapy or allogeneic transplantation had high-risk MDS (at least IPSS intermediate II) either at diagnosis or during the course of the disease. Conclusions: Our survey shows that off-label treatment is frequent in MDS because there is still a lack of efficient therapies for many patients. During the observation period several treatment modalities were employed, varying in number and type according to IPSS and IPSS-R risk groups.Although numerous clinical trials with new compounds were initiated over the last few years, only a minority of MDS patients were eligible to participate. In the future, a further increase in clinical trial activity will hopefully allow a greater proportion of MDS patients to get access to effective treatment. Disclosures Xicoy: Celgene: Honoraria. Kuendgen:Celgene: Honoraria, Research Funding. Kobbe:Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Medac: Other; Astellas: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Other. Gattermann:Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding. Germing:Novartis: Research Funding; Celgene: Honoraria, Research Funding; AMGEN: Research Funding; Janssen-Cilag: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria.

scholarly journals Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia: Why Do Adolescents and Young Adults Outcomes Differ from Those of Children? a Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2921-2921
Author(s):  
Audrey Grain ◽  
Fanny Rialland ◽  
Patrice Chevallier ◽  
Nicolas Blin ◽  
Jean-Hugues Dalle ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Cellular Therapy ◽  
Lymphoblastic Leukemia ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Support Research

Abstract Introduction: Adolescents and Young Adults (AYA) represent a specific population in the Acute Lymphoblastic Leukemia (ALL) landscape, often presenting high-risk diseases and increased chemotherapy-related toxicities. Indications of Hematopoietic Stem Cell Transplantation for pediatric patients (HSCT) have been restricted to those with early poor response to chemotherapy. The same trend has led to a decrease of HSCT indications in AYAs, which are nevertheless still more frequent than in younger counterpart. Outcomes of AYAs after HSCT seemed to be worse than the ones of children in two previous studies published in 2013 and 2014. In Minneapolis, the decrease of overall survival in AYA was attributed to an excess of Treatment Related mortality (TRM) (28% versus 14%; p=0.04), but because of small numbers, factors influencing TRM were not identified. Our study aimed to compare, in a large cohort, the outcomes of children and AYA with ALL after HSCT and to determine factors influencing potential differences. Material and Methods: All patients aged between 1 and 25 years, reported in the SFGM-TC (Francophone Society of bone marrow transplantation and cellular therapy) registry, who received a first HSCT in treatment for ALL between 2005 and 2012 were included. The AYA group was defined by age range between 15 and 25 years old, according to European studies and the SFGM-TC. Data about diagnosis and transplantation procedure were prospectively collected in the registry. Before transplant procedure, patients or their parents/guardians provide a signed consent in order to be included in the registry. Results: 891 patients were included, 494 children and 397 AYA. Median time of follow up was 45.6 months (0 to 114). HSCT was performed in first CR for 56.8% of the AYAs, whereas 57.5% of children received HSCT in second CR or more advanced phase (p<0.001). HSCT procedures mainly included a Myelo-Ablative Conditioning (MAC) regimen. TBI was used more frequently in AYAs than in children (90.1% versus 83.1%, p=0.003). Bone Marrow (BM) or Cord-Blood (CB) were often used in children 60.2% and 29.4% versus 55.6% and 16.4% in AYA group respectively (p < 0.0001) . Peripheral Blood Stem Cells (PBSC) were more frequently used for AYA (28%) than for children 10.3% (p < 0.0001). Moreover, when being transplanted in an adult center, PBSC were more commonly used for AYA (30% of AYA's HSCT in adult centers versus 21.2% of AYA's HSCT in pediatric centers, p=0.051). BM and PBSC cells were provided by a match sibling donor (MSD) in 40.2% of children and 43.4% of AYAs and from a MUD in 57.2% and 55.1% of cases respectively (p = 0.474). Anti-thymoglobulins (ATG) were used for 336 patients (48% of children and 26% of AYA patients, p<0.001). See patient's characteristics in Table. Five-year OS was lower in AYA 53.1% versus 64% (p = 0.0012) and we confirmed higher 5-years TRM in AYA 19% versus 13% (p=0.04). TRM incidence markedly rose after 10 years of age (from 9% before 10 years old to 20% between 10 and 15 years, and 17% after 15 years). Graft versus host disease and Relapse Free Survival probability (GRFS) was lower in AYA: 36% versus 47% (p=0.007), while Cumulative Incidence of Relapse (CIR) and acute Graft versus Host Disease (GvHD) incidence were both similar in our two groups: 32% and 61% in AYAs versus 27% and 59% in children, (p=0.19 and p=0.62), respectively. Thus, chronic GvHD, which occurred more frequently in AYA than in children (32% versus 19%, p<0.001), mainly impact post-HSCT morbi-mortality in AYA (Figure 1 and 2). In our multivariate analysis, two factors were associated with higher risk of cGvHD: use of PBSC as stem cell source (HR 1.41 [0.96-2.07], p=0.083), and absence of ATG use (HR associated with use of ATG: 0.62 [0.42-0.92], p=0.017) (Figure 3). Of note a subgroup analysis in patients who received a bone marrow transplant after a MAC, showed no TRM difference between AYA and children. Conclusion: AYA or patients aged more than 10 years, compared to ones aged less than 10 years have a worse outcome after HSCT for ALL. Excess of death in this specific population is mainly due cGvHD. Transplantation practices in those patients, particularly choice of stem cells source and GvHD prophylaxis, should be discussed. Their treatment adherence should also be questioned and reinforced by development of multidisciplinary teams. Figure 1 Figure 1. Disclosures Peffault De Latour: Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Other, Research Funding; Jazz Pharmaceuticals: Honoraria; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Forcade: Novartis: Other: travel grant.

scholarly journals The Effect of JAK 1/2 Inhibitors on Outcomes of Allogeneic Stem Cell Transplantation for Patients with Myelofibrosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5784-5784
Author(s):  
Guido Lancman ◽  
Kathleen Miller ◽  
Shuli Li ◽  
Vincent T. Ho ◽  
Amir T. Fathi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Advisory Committees ◽  
Free Survival ◽  
Donor Type

Abstract Introduction: Ruxolitinib was the first JAK 1/2 inhibitor (JAKi) approved for myelofibrosis (MF), with several other JAKi in development. Ruxolitinib was approved on the basis of reducing splenomegaly and improving constitutional symptoms, but its effect on subsequent allogeneic stem cell transplantation (SCT) is not well understood. Retrospective studies to date have reported mixed outcomes after SCT for MF patients with previous exposure to JAKi. In this multicenter retrospective study, we report on outcomes of patients with MF treated with SCT at our institutions. Methods: We analyzed outcomes for 184 consecutive patients at three institutions who underwent SCT for primary or secondary MF. Primary outcomes included overall survival (OS), progression free survival (PFS), and graft-versus-host-disease (GVHD)-free and relapse-free survival (GRFS), all measured from the time of SCT. Cox proportional hazard regressions were fit to estimate the association between the use of JAK 1/2 inhibitors prior to SCT and OS, PFS, and GRFS, adjusting for donor type and DIPSS-plus status. p<0.05 was considered statistically significant. Results: 72 patients received a JAKi prior to SCT, while 112 did not. Patients in these two groups were well-matched with respect to age, sex, DIPSS plus score, conditioning, and donor type (Table 1). Median follow-up was 31.2 months (range: 0.8-146.3 months). In univariate analysis, there was no difference in OS (JAKi: 4-yr OS 56.7% [95% CI 40.9-69.8%] vs. no JAKi: 43.6% [95% CI 32.9-53.9%], p=0.49), PFS (JAKi: 4 yr PFS 54.1% [95% CI 40.8-65.7%] vs. no JAKi: 43.9% [95% CI 33.4-53.9%], p=0.77), or GRFS (JAKi: 8-month GRFS 56.6% [95% CI 44.1-67.4%] vs. no JAKi: 50.4% [95% CI 40.4-59.5%], p=0.62) in the overall population; there was similarly no difference when comparing only intermediate-risk or only high-risk patients. In multivariate analysis, there was no difference in these outcomes for patients based on previous JAKi exposure when accounting for DIPSS plus score and donor type (related vs unrelated). Rates of acute GVHD were similar between the two groups (JAKi: 53.5% vs. no JAKi: 55.0%, p=0.88), including grade 3 or 4 acute GVHD (JAKi: 16.9% vs no JAKi: 19.8%, p=0.70). Conclusions: Our data suggest that there is no statistically significant difference in OS, PFS, GRFS, or rates of acute GVHD after SCT for MF patients based on previous JAKi treatment. This was true overall and after adjusting for DIPSS plus risk score or donor type. Given the retrospective design of our study, we were not able to assess prior response to JAKi or splenomegaly at SCT, which may influence outcomes. Given mixed results in the literature to date, we eagerly await the results of ongoing phase 2 trials of JAKi prior to SCT for MF. Disclosures Ho: Jazz Pharmaceuticals: Consultancy. Fathi:Astellas: Honoraria; Jazz: Honoraria; Boston Biomedical: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Agios: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria. Chen:Takeda Pharmaceuticals: Consultancy; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Consultancy; REGiMMUNE: Consultancy. Hoffman:Formation Biologics: Research Funding; Incyte: Research Funding; Janssen: Research Funding; Merus: Research Funding; Summer Road: Research Funding. Mascarenhas:Novartis: Research Funding; Merck: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Promedior: Research Funding; Janssen: Research Funding; Roche: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Feasibility and Outcomes of T-Cell Depleted Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory AML and High Risk MDS

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3324-3324
Author(s):  
Satyajit Kosuri ◽  
Sang Mee Lee ◽  
Hongtao Liu ◽  
Mylove Mortel ◽  
Lucy A Godley ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees

Background: Survival in patients (pts) with relapsed/refractory (R/R) acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) is dismal. Treatment options are limited; however, a proportion of these individuals can be rescued by allogeneic stem cell transplantation (allo-SCT). Historically, allo-SCT, especially for R/R myeloid diseases, has used myeloablative regimens and no T-cell depletion (TCD) to maximize graft-versus-leukemia effect, often restricting this approach to younger and fit pts with matched donors. The aim of this study was to investigate outcomes of in vivo T-cell depleted stem cell transplantation (TCD-SCT) in a high-risk AML and MDS population. Methods: We performed a retrospective analysis of 141 patients with R/R AML (n=108)/high risk MDS (RAEB or CMML, n=33) who received TCD-SCT at our center from 2002-2015. Median age was 55 years (18-71) with 37 (26%) pts older than 60. Patients underwent in vivo TCD with alemtuzumab or ATG and 117 (88%) received reduced-intensity conditioning (RIC). Alemtuzumab was generally given as 100 mg total divided over 5 days whereas rabbit ATG dosing included days -1, - 3, -5 (+/- on day -7). Alemtuzumab usually partnered with matched related (n=65; 46%) or unrelated (n=53; 38%) peripheral blood stem cell (PBSC) grafts whereas ATG mostly was a component of umbilical cord grafts combined with a CD34 selected haploidentical donor (haplo-cord) (n=23; 16%). Prognostic factors such as age, HCT-CI, CIBMTR score (Duval 2010), revised disease risk index (R-DRI), donor type and pre-transplant disease status were analyzed. Multivariate cox regression models were considered from forward selection for factors with a p value <0.1 in univariate analysis. Results: Table 1 summarizes baseline characteristics. Among the 141 R/R AML or high risk MDS pts, AML predominated (77%). Sixty six (47%) pts had primary induction failure (PIF), 42 (37%) had relapse and 33 (23%) had high risk MDS. Eighty three pts (59%) had peripheral blasts at time of TCD-SCT. Cumulative incidence (CI) of relapse for all pts was 53% and non-relapse mortality was 28% at 2 yrs. Two and 5 yr PFS rates for the group were 19% and 11%, respectively. Two and 5 yr OS rates for the group were 30% and 18%, respectively. Figure 1 shows OS by disease type. Day 100 mortality was 18%. Twenty one percent developed Grade 2-4 acute GVHD (aGVHD) (6% Grade 3-4), and only 5% developed chronic GVHD (cGVHD) requiring therapy. Figure 2 shows CI of cGVHD amongst disease types. Differences in 2yr survival outcomes were not significant among prognostic factors. Specifically, age 60+ vs younger was not prognostic (PFS 24% vs 17% p=0.4, OS 29% vs 29% p=0.7). Likewise, haplo-cord did not differ relative to matched donors in outcomes (PFS 18% vs 26% p=0.2, OS 35% vs 29% p=0.5). Conclusions: Although novel therapeutic approaches are emerging for R/R AML and high risk MDS, allo-SCT remains an established option for long-term disease control. In our analysis, outcomes after in vivo TCD-SCT in R/R AML and high-risk MDS pts treated with RIC mirror published historical results (Duval 2010, Schlenk 2010) but with low rates of cGVHD. The lack of significant difference in survival outcomes amongst age groups and donor sources suggests RIC with in vivo TCD can also be utilized as a platform in older individuals and those with alternative donors. With high relapse rates in this population, better pre-transplant disease reduction, minimal residual disease monitoring and post-transplant maintenance will be critical to increase long-term cures. Disclosures Liu: Agios: Honoraria; Arog: Other: PI of clinical trial; BMS: Research Funding; Karyopharm: Research Funding; Novartis: Other: PI of clinical trial. Larson:Novartis: Honoraria, Other: Contracts for clinical trials; Agios: Consultancy; Celgene: Consultancy. Odenike:Oncotherapy: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Astra Zeneca: Research Funding; Astex Pharmaceuticals: Research Funding; NS Pharma: Research Funding; Gilead Sciences: Research Funding; Janssen Oncology: Research Funding; Agios: Research Funding; CTI/Baxalta: Research Funding. Stock:Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria; Research to Practice: Honoraria. Kline:Merck: Honoraria; Merck: Research Funding. Riedell:Bayer: Honoraria, Speakers Bureau; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Van Besien:Miltenyi Biotec: Research Funding. Bishop:Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Artz:Miltenyi: Research Funding.

scholarly journals Letermovir Is Effective for Prevention of Cytomegalovirus Reactivation in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2858-2858
Author(s):  
Takahide Ara ◽  
Yuta Hasegawa ◽  
Hiroyuki Ohigashi ◽  
Souichi Shiratori ◽  
Atsushi Yasumoto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Cmv Infection ◽  
Advisory Committees ◽  
Cmv Disease ◽  
Cmv Reactivation

Abstract [Introduction] Cytomegalovirus (CMV) infection is a common viral infection in recipients of allogeneic hematopoietic stem cell transplantation (allo-SCT). Early CMV reactivation after allo-SCT is associated with worse non-relapse mortality (NRM) and overall survival (OS). Recently, T-cell replete HLA-haploidentical SCT using post-transplant cyclophosphamide (PTCy-haplo SCT) has been developed and spread rapidly worldwide. Rationale of this strategy is assumed to be selective and cytotoxic depletion of alloreactive T cells which are responsible for graft-versus-host disease (GVHD), while preserving non-alloreactive T cells which can contribute to fight infections. However, recent studies showed that PTCy-haplo SCT was associated with the increased incidence of CMV infection. Letermovir (LET), a novel anti-CMV agent, which inhibits the CMV DNA terminase complex, was approved for the prevention of CMV reactivation in allo-SCT recipients in 2018 in some countries including Japan based on the result of a phase 3 trial. Our facility performs LET prophylaxis in allo-SCT recipient if either donor or recipient is seropositive CMV. Although LET is effective for the prevention of CMV reactivation in allo-SCT recipients, the clinical effectiveness of LET prophylaxis in PTCy-haplo SCT is not well elucidated. Based on these things, we retrospectively evaluated the efficacy of LET prophylaxis in PTCy-haplo SCT. [Methods] We retrospectively analyzed consecutive 99 recipients who received PTCy-haplo SCT at Hokkaido University Hospital from March 2013 to March 2021. We compared the cumulative incidence of CMV reactivation between the LET prophylaxis group (LET group, 33 patients) and LET non-prophylaxis group (non-LET group, 66 patients). LET was initiated on the day 0 at a dosage of 480mg daily. All patients were monitored for CMV reactivation by using the anti-CMV pp65 monoclonal antibody HRP-C7 assay at least once a week from the time of engraftment. CMV reactivation was defined as the detection of CMV antigen positive cells per 50000 white blood cells, whereas CMV disease was defined by organ dysfunction attributable to CMV. [Results] As baseline patient's characteristics were summarized in Table1, there were no difference between LET and non-LET group in terms of age, sex, underlying disease, disease risk at transplantation, prior transplantation, conditioning intensity, and CMV serostatus. All patients received peripheral blood stem cell transplantation. GVHD prophylaxis consisted of Cy (40-50 mg/kg on day 3 and 4), tacrolimus (from day 5), and mycophenolate mofetil (from day 5). The cumulative incidence of CMV reactivation at 150 days after transplantation in LET group was significantly lower than that in non-LET group (30.3% versus 69.7%; P &lt;.001, Figure1A). Importantly, CMV disease were occurred in three patients without LET prophylaxis (gastritis, enteritis, and retinitis), but not in the patients with LET prophylaxis. The cumulative incidence of NRM at 1 year was similar between the patients with and without LET prophylaxis (17.6% versus 9.2%; P=0.366, Figure1B), as was OS at 1 year (71.5% versus 69.4%; P=0.801, Figure1C). Neutrophil engraftment was achieved in 32 patients (97%) at a median of 15 days in LET group and 64 patients (97%) at a median of 14.5 days in non-LET group (P=0.243). Furthermore, platelet engraftment was achieved in 26 patients (79%) at a median of 34 days in LET group and 57 patients (86%) at a median of 31 days in non-LET group (P=0.282). These findings suggest that LET does not affect engraftment. Interestingly, the length of hospitalization in the LET group was significantly shorter than that in non-LET group (the median, 59.5 days versus 71 days; P=0.0488), suggesting that LET suppresses CMV reactivation leading to early discharge. [Conclusion] To our best knowledge, this is the largest retrospective study about the efficacy of LET in PTCy-Haplo SCT. LET is effective for prevention of CMV reactivation in PTCy-haplo SCT. Further studies focused on the long term effect of LET prophylaxis in PTCy-haplo SCT, such as the incidence of relapse and chronic GVHD, is warranted. Figure 1 Figure 1. Disclosures Nakagawa: AbbVie GK: Research Funding; Takeda Pharmaceutical Company: Research Funding. Teshima: Gentium/Jazz Pharmaceuticals: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Honoraria; Nippon Shinyaku Co., Ltd.: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Fuji pharma CO.,Ltd: Research Funding; Takeda Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis International AG: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; TEIJIN PHARMA Limited: Research Funding; Astellas Pharma Inc.: Research Funding; Bristol Myers Squibb: Honoraria; Janssen Pharmaceutical K.K.: Other; Kyowa Kirin Co.,Ltd.: Honoraria, Research Funding; Sanofi S.A.: Research Funding.

scholarly journals Autologous Stem Cell Transplantation for Multiple Myeloma Patients Aged ≥ 75 Treated with Novel Agents

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Iuliana Vaxman ◽  
Alissa Visram ◽  
Shaji K. Kumar ◽  
Angela Dispenzieri ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Mayo Clinic ◽  
Research Funding ◽  
Advisory Board ◽  
Novel Agents

Introduction Autologous stem cell transplantation (ASCT) has been used for treating multiple myeloma (MM) for over three decades and is generally reserved for patients younger than 65 years of age. The definition of transplant eligible is ill-defined and different centers have different policies to determine which patients are transplant eligible. Some centers have an age cut-off, others use clinical judgment, and some use various frailty scores (a scoring system based on comorbidities and physical and cognitive assessments) aiming to objectively assess transplant eligibility. There are limited data about outcomes in patients ≥ 75 years. Aim To report on outcomes of ASCT in a cohort of patients with MM aged 75 years or older. Methods Retrospective study of all consecutive MM patients aged ≥ 75 years that underwent ASCT at Mayo Clinic, Rochester, Minnesota. Stem cell transplantation at our center is routinely performed as an outpatient, with patients being hospitalized when deemed clinically necessary upon physician review. Results Between October 2005 and March 2020, 46 patients aged 75 years or older, received an ASCT at Mayo Clinic, Rochester. The median hematopoietic stem cell transplantation specific comorbidity index (HCT-CI) was 0 (range 0-6) with 8 patients having HCT-CI of 5 or 6. Median time from diagnosis to ASCT was 6.45 months (IQR 5.2-10.52) and 54% received reduced intensity conditioning with melphalan 140 mg/m2. All patients except one (that was treated with dexamethasone only) received induction with novel agents (listed in table 1) and 6 patients (13%) received doublet induction. All others received triplet induction. 46% of patients completed the ASCT without requiring hospitalization and 54% (n=25) of patients required hospitalization with a median duration of hospital admission of 9 days (IQR 5-13). Reasons for hospitalization included fever or infection (32%), cardiac arrhythmia (36%) and dehydration (32%). Overall response rate was 100% with a complete response seen in 57% of patients and 16 patients achieving MRD negative sCR. Median overall survival and progression free survival for the cohort were 82 months and 33 months, respectively. One patient died within 100 days of transplant representing a 2% 100-day mortality rate. Univariable cox regression model that evaluated the effect of gender, high risk cytogenetics, hemoglobin, renal function and melphalan dose did not detect any variable that was predictive of OS or PFS (Table 3). Conclusions ASCT is efficacious and can be safely delivered in the outpatient setting in carefully screened patients aged 75 or above. An arbitrary cutoff for age should not be used to exclude patients from ASCT, rather a careful assessment of "physiological age" including performance status and co-morbidities is required by an experienced treating team. Disclosures Kumar: Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Cellectar: Other; Carsgen: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; MedImmune: Research Funding; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Karyopharm: Consultancy; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Adaptive Biotechnologies: Consultancy. Dispenzieri:Pfizer: Research Funding; Janssen: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Dingli:Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Karyopharm Therapeutics: Research Funding; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy. Kapoor:Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding. Gertz:Prothena: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Appellis: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Janssen: Other: personal fee; Research to Practice: Other; Sanofi: Other; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Proclara: Other; Springer Publishing: Patents & Royalties; Celgene: Other; Physicians Education Resource: Other: personal fee; Aurora Bio: Other; Amgen: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Abbvie: Other.

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