scholarly journals Impact of Chronic Graft-Versus-Host Disease on Non-Relapse Mortality

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-42
Author(s):  
Justin Jiang ◽  
Qiuhong Zhao ◽  
Audrey M. Sigmund ◽  
Patrick Elder ◽  
Don M. Benson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Older Patients ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Ohio State University ◽  
State University ◽  
Research Support ◽  
Advisory Committees ◽  
Hematopoietic Stem

Introduction-Chronic graft-versus-host disease (cGVHD) poses as a major late complication of hematopoietic stem cell transplantation. The role of cGVHD as a determinant in transplant-related morbidity and mortality, infectious complications, prolonged immune suppression, and impaired patient-reported quality of life has been extensively studied. Nonetheless, numerous advances in allogeneic hematopoietic stem cell transplant (allo-SCT) in recent years have expanded the indications for allo-SCT to a broader range of patients, including previously excluded older patients. However, long-term health status of older transplant recipients is poorly studied. Notably, the incidence of cGVHD may increase with age. Therefore, the development of cGVHD and the use of immunosuppressive therapy may lead to a higher degree of non-relapse mortality (NRM) in older patients. The objective of this study was to compare the NRM in both younger and older transplant recipients with and without cGVHD. Methods-We performed a retrospective cohort study of patients that underwent allo-SCT at the Ohio State University from 1999 to 2018. Data was analyzed from 1194 patients who survived or have been followed up with by at least day (d) 180 post-transplantation, among which 373 patients had developed cGVHD. Patients were grouped based on their age into a younger and older population. The older population was defined as ≥60 (N=373, 31%) with the younger population defined as <60 (N=821, 69%) years (yr) of age. NRM was defined as death unrelated to relapse, with relapsed mortality as a competing risk. A landmark analysis approach was used to study the association between the age groups to NRM, stratified by whether or not patients had developed cGVHD by d180. Fine and Gray competing risk model was used to build the multivariable regression model controlling for confounding variables, such as gender, donor type, donor source, conditioning regimen, and diagnosis. Results-The median age at allo-SCT was 53.0 yr (range: 18-76) and 61.1% were male. Acute myeloid leukemia accounted for 36.7% of transplants, followed by non-Hodgkin's lymphoma (14.8%), acute lymphoid leukemia (12.7%), and myelodysplastic syndrome (11.0%). Additionally, 58.0% received reduced-intensity conditioning regimen. The majority of stem cell donor types were match unrelated (45.3%) and match related (39.8%). Patients who had developed cGVHD by d180, regardless of age, were at higher risk of NRM compared to patients with no cGVHD (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.16-1.99; p=0.002). To examine the influence of age with NRM, we stratified the analysis by cGVHD status by d180. Among patients developed cGVHD by d180, in both univariable (HR 1.22, 95% CI 0.79-1.9, p=0.373) and multivariable analysis (HR: 1.17, 95% CI: 0.74-1.87; p=0.501), there was no statistically significant difference in NRM between patients ≥60 and <60 yr of age. Among patients without cGVHD by day 180, age ≥60 yr was a significant factor for increased NRM in both univariable (HR: 1.52, 95% CI 1.08-2.15; p=0.017) and multivariable (HR: 1.55, 95% CI: 1.04-2.30; p=0.031) analysis. Conclusion-This study showed that patients with cGVHD by day 180 were at higher risk for higher NRM compared to patients without cGVHD. Among cGVHD patients, there was no difference on the outcome of older patients (≥60 years old) compared to younger ones (<60 years old). This suggests that cGVHD therapy is equally tolerable among different age groups. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy. William:Celgene: Consultancy, Honoraria; Dova: Research Funding; Guidepoint Global: Consultancy; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Seattle Genetics: Research Funding; Incyte: Research Funding. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Novartis: Speakers Bureau; Agios: Consultancy. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Magenta Therapeutics: Other: Personal Fees; Incyte Pharmaceuticals: Other: Personal Fees; Amgen: Other: research support; Kadmon: Other: research support; Orcabio: Other: research support. Efebera:Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Celgene: Research Funding; Ohio State University: Current Employment.

scholarly journals Optimal Conditioning for Older Patients with Acute Myeloid Leukemia (AML) Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Propensity Score Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 42-42 ◽  
Author(s):  
Stefan O. Ciurea ◽  
Ankur Varma ◽  
Piyanuch Kongtim ◽  
Samer Srour ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Board Of Directors ◽  
Hematopoietic Stem Cell ◽  
Older Patients ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Secondary Aml

Introduction Allogeneic hematopoietic stem cell transplantation (AHSCT) is increasingly performed for older patients with AML; however, the optimal conditioning regimen for these patients remains unclear. Methods: We retrospectively evaluated outcomes of 404 patients with AML, ≥60 years receiving AHSCT at our institution between 01/2005-08/2018 who received 4 conditioning regimens: 1) fludarabine+melphalan 100mg/m2 (FM100, N=78), 2) fludarabine+melphalan 140mg/m2 (FM140, N=89), 3) fludarabine+IV busulfan x 4 days with Bu AUC≥5,000/day (equivalent dose 130mg/m2/day) (Bu≥5,000, N=131), 4) fludarabine+IV busulfan x 4 days with Bu AUC 4,000/day (equivalent dose 110mg/m2/day) (Bu4,000, N=106). To adjust for potential selection bias in choices of conditioning regimen, propensity score was calculated and used as a stratifying variable in a multivariable Cox regression model. Factors included in the propensity score calculation were age, secondary AML, ELN2017 genetic risk, remission status before transplant, induction failure, donor type, stem cell source and KPS. Results are presented for the FM100, FM140, Bu≥5,000 and Bu4000, respectively. Median follow-up survivors were 40, 74, 30 and 44 months, respectively (p=0.06). Donors are matched sibling, matched unrelated, haploidentical and mismatched unrelated donor in 126 (31%), 218 (54%), 40 (10%) and 20 (5%) patients, respectively. Patients in the FM100 group were significantly older and had lower KPS. The median age was 67, 64, 64 and 65 years, respectively (p=0.001), while 51%, 32%, 27% and 27% had KPS<90%, respectively (p<0.001). The HCT-CI of ≥3 was present in 57%, 62%, 56% and 70%, respectively (p=0.33), while 42%, 78%, 47% and 51% had high and very high-risk DRI, respectively (p<0.001), and 12%, 46%, 18% and 32% of the patients were transplanted in active disease (p<0.001). No significant differences were seen in both cytogenetic and ELN2017 genetic risk. More patients in FM100 group were treated using a standard of care protocol (73%, 64%, 25% and 31%, respectively, p<0.001). Grade 2-4 aGVHD at day 100 were 26% vs. 26%, 36% and 40% (p=0.04), and extensive cGVHD at 3 years 14% vs. 42%, 36% and 37%, respectively (p=0.07). The NRM at 3 years were 19%, 29%, 25% and 21% (p=0.06), and 3-year relapse rates were 32% vs. 32%, 30% and 55%, respectively (p=0.003). Among 4 groups, FM100 group had a significantly better PFS and GRFS with 5-year PFS for these 4 groups were 44%, 30%, 33% and 22% (p=0.02) and 5-year GRFS were 28%, 20%, 18% and 9% (p=0.006), respectively (Figure 1). For subgroup of patients with KPS <90%, 5-year PFS were 41%, 27%, 28%, 22%, respectively (p=0.007), while there was no significant difference between 4 conditioning groups in patients with high-risk AML defined as either secondary AML, induction failure or high-risk cytogenetics/high ELN2017 risk, suggesting that a more intense conditioning is not beneficial in this group of patients. The survival benefit of FM100 persisted after adjusted for baseline factors, transplant characteristics as well as propensity scores in a multivariable analysis (MVA). In MVA for PFS, HR was 0.57 (p=0.013) for FM100, 0.68 (p=0.056) for FM140 and 0.77 (p=0.137) for Bu> 5000 as compared with Bu 4,000 group (Figure 1). In the MVA for GRFS, HR for FM100, FM140 and Bu> 5000 was 0.53 (p=0.005), 0.78 (p=0.196), and 0.81 (p=0.178), respectively as compared with Bu 4,000 group. Other factors that independently predicted PFS were secondary AML (HR 1.68, p=0.001), remission status before transplant (HR 1.82, p=0.048 for CR with MRD positive, HR 1.87, p=0.043 for CR with unknown MRD status and HR 2.86, p=0.001 for active disease at transplant as compared with CR with MRD negative), KPS (HR 0.98, p=0.005) and use of a mismatched unrelated donor (HR 2.46, p=0.001 compared with matched related donor transplant). Conclusions: Older patients with AML benefit from a reduced-intensity conditioning with FM100 conditioning regimen, which was associated with better survival despite the fact that patients who could not receive more intense conditioning preferentially received this regimen. Higher intensity conditioning does not appear to improve survival in older patients. Alternative approaches to increase in conditioning intensity are needed to improve survival in patients with AML receiving allogeneic hematopoietic stem cell transplantation. Disclosures Ciurea: Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder; Miltenyi: Research Funding; Spectrum: Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Acrotech: Research Funding; StemLine: Research Funding; Spectrum: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Oran:Astex pharmaceuticals: Research Funding; AROG pharmaceuticals: Research Funding. Popat:Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Konopleva:Stemline Therapeutics: Consultancy, Honoraria, Research Funding; Reata Pharmaceuticals: Equity Ownership, Patents & Royalties; Ablynx: Research Funding; Astra Zeneca: Research Funding; Agios: Research Funding; Ascentage: Research Funding; Calithera: Research Funding; Forty-Seven: Consultancy, Honoraria; Kisoji: Consultancy, Honoraria; Eli Lilly: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Cellectis: Research Funding; Amgen: Consultancy, Honoraria; F. Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Genentech: Honoraria, Research Funding.

Outcomes in Allogeneic Hematopoietic Stem Cell Transplant Patients ≥ 60 Years of Age with a Novel Reduced Intensity Conditioning Regimen Incorporating Extracorporeal Photopheresis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4153-4153
Author(s):  
Furha I. Cossor ◽  
Sandy Wong ◽  
Kenneth B Miller ◽  
Deborah Black ◽  
Raymond L. Comenzo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Extracorporeal Photopheresis ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Blood Stem Cells ◽  
Grade Ii

Abstract Abstract 4153 The optimal preparative regimen for older patients undergoing hematopoietic stem cell transplantation (HSCT) is unclear. We routinely employ a reduced intensity conditioning regimen consisting of extracorporeal photopheresis (ECP) on days −6 and −5, Pentostatin 4 mg/m2/day by continuous infusion on days −4 and −3, and 600 cGy total body irradiation in 3 divided fractions on days −2 and −1 (“PPT regimen”) for patients greater than 60 years of age (Bone Marrow Transp 2004; 33:881). We now report outcomes of 38 consecutive patients ≥ 60 years old (median 62, range 60–70) (M 22, F 16) transplanted at our center between 1/1/00 and 4/1/11 for hematologic malignancies: AML (n=23), MDS (n=10), ALL (n=1), CLL (n=1), NHL (n=2) and MM (n=1). Twenty-six (68.4%) received matched related and 12 (31.6%) 6/6 matched unrelated donor (MUD) grafts. Twenty-five (65.8%) received marrow and 13 (34.2%) peripheral blood stem cell grafts. Median time to neutrophil engraftment was 16 days (3–25). Survival at day 100 was 84% (32/38), with a 13% TRM (5/38) and 3% (1/38) incidence of relapse-related death. Actuarial 1-year overall survival (OS) for all patients was 45% (95% CI 28 – 61%), and median OS in all patients was 10.6 months (95% CI 4.6 – 25.7 months). Estimated 1-year event-free survival, defined as freedom from relapse, progression, or death from any cause, was 44% (95% CI 27 – 59%). Median event-free survival for the entire cohort was 7 months (95% CI 3.6 – 25.6 months). Grade II and grades III/IV acute GvHD (aGvHD) occurred in 8 (21%) and 2 (5%) patients respectively within 1 to 8 weeks of HSCT (median 16 days). After day 100, 6 patients had died, 1 was missing data, and 23 (74% of remaining patients and 60% of the original cohort) had symptoms of GvHD. Fourteen met NIH consensus criteria for chronic GvHD (cGvHD) including 6 with severe classic or overlap cGvHD while 6 had recurrent, 2 persistent and 1 delayed aGvHD. Of those with aGvHD after day 100, 2 patients exhibited ≥ grade III disease. Median time to onset of cGvHD was 4.1 months (3.3 – 11.7). Among patients who received marrow as their stem cell source (n=25), incidence of grades II-IV aGvHD was 32% (24% grade II, 8% grade III/IV), and incidence of any GvHD from day 100 up to date of death or last follow-up was 68%. Among those who received blood stem cells (n=13) incidence of grades II-IV aGvHD was 15% (all grade II) and incidence of GvHD from day 100 until date of death or last follow-up was 83%. There was no statistically significant difference between those who received marrow versus blood stem cells with respect to incidence of either grade II-IV aGvHD or GvHD after day 100 (P =0.27 and 0.36). For those who received MUD transplants (n=12), incidence of grades II-IV aGvHD and of any post-day 100 GvHD were 42% (33% grade II, 8% grade IV) and 75% respectively, and in those who received related donor transplants (n=26) were 19% (15% grade II, 4% grade IV) and 74%, respectively. There was no statistically significant difference between MUD HSCT versus related donor HSCT patients with regard to grade II-IV aGvHD or GvHD after day 100 (P =0.14 and 0.94). In conclusion, our approach was well tolerated by HSCT patients > 60 years old, provided prompt myeloid recovery and had an acceptable incidence of post-day 100 severe chronic (19%) or > grade II late acute GvHD (6%). Disclosures: Off Label Use: Pentostatin and Extracorporeal photopheresis are not FDA approved for conditioning prior to allogeneic transplant. Comenzo:Elan: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Neotope: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adults with Chronic Granulomatous Disease (CGD): A Study of the Inborn Errors Working Party (IEWP) of the EBMT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 970-970 ◽  
Author(s):  
Robert Chiesa ◽  
Junfeng Wang ◽  
Henric-Jan Blok ◽  
Benedicte Neven ◽  
Despina Moshous ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Graft Failure ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Engraftment Failure

Abstract Introduction: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by impairment of the phagocyte NADPH-oxidase complex, resulting in deficient microbial killing and life-threatening bacterial and fungal infections. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative approach, but it can be complicated by graft failure, graft versus-host disease (GvHD) and transplant-related mortality (TRM). In order to define prognostic risk factors in this setting, the IEWP of the EBMT performed a large retrospective registry study on 600 pediatric and adult patients with CGD undergoing allo-HSCT. Patients and Methods: We analyzed the outcome of patients with CGD who received allo-HSCT in EBMT centers between 1993 and 2017. The main end-points of the study were overall survival (OS) and event-free survival (EFS; events were death and primary or secondary engraftment failure) according to patient's age, donor type, stem cell source and conditioning regimen. One patient died before allo-HSCT and was excluded from analysis. Results: We studied 536 children (aged < 18 years) and 63 adults (aged ≥ 18 years) affected by CGD. The median follow-up was 45.37 months (IQR 15.8-81.8). Genetic results were available for 307 patients: inheritance was X-linked (75%) or autosomal recessive (25%). Median age at transplant was 7.2 years (range: 0.12-48.56). Conditioning regimen was Busulfan/Fludarabine (n=244; 41%), Busulfan/Cyclophosphamide (n=104; 17%), Treosulfan/Fludarabine (n=76; 13%), Treosulfan/Fludarabine/Thiotepa (n=52; 9%) or other drug combinations (n=123; 20%). Donors were human leukocyte antigen (HLA) matched related (MFD, 10/10; n=211, 40%), matched unrelated (MUD, 10/10 or 6/6 in UCB; n=201; 38%), mismatched related (MMFD, ≥ 9/10; n= 27; 5%) or mismatched unrelated (MMUD, ≥ 9/10 or 5/6 in UCB; n= 83; 16%). Stem cell source was bone marrow (BM; n=408; 69%), peripheral blood (PB; n=153; 26%) or umbilical cord blood (UCB; n=27; 5%). Donor engraftment occurred in 516 evaluable patients (88%), while primary or secondary engraftment failure occurred in 68 patients (12%). Seventy-nine patients (13%) died after allo-HSCT. The 2 year Kaplan-Meier estimate of OS and EFS were 87.1% (95% CI, 84.2-89.9) and 77.8% (95% CI, 74.2-81.4), respectively (Fig A). The 2-year cumulative incidence of grade II-IV acute GvHD, chronic GvHD and extensive chronic GvHD was 18.6% (95%, 15.1-22.2), 16.2 % (95%, 18.8-19.7) and 5.5% (95%, 3.4-7.7), respectively. A univariate cox model with spline term demonstrated that older age at transplant was associated with an increased risk of death (p=0.002). Children undergoing allo-HSCT had a superior 2y OS (88.1%; 95% CI 85.2-91.0), compared to adults (78.2%; 95% CI, 67.7-88.7), p=0.03 (Fig B). Patients undergoing allo-HSCT from a MFD had a superior EFS (86.5%; 95% CI 81.5-91.4) compared to MUD (73.3%; 95% CI 66.7-79.9), MMUD (78.2%; 95% CI 69-87.5) and MMFD (59.7; 95% CI 40.4-79.1), p< 0.001 (Fig C). Patients receiving BM grafts had superior 2y EFS (81.0%; 95% CI 76.9-85.1) compared to PB (72.5%; 95% CI 64.7-80.4) and UCB (66.7%; 95% CI 48.9-84.4), p=0.04. The pattern of disease inheritance and the choice of conditioning regimen didn't have an impact on outcome (Fig D). Fifty-three patients with graft failure underwent a second allo-HSCT and the 2y OS in this group was 82.1% (95% CI, 71.5-92.7). Year of transplantation didn't have an influence on outcome. Conclusion: This is the largest study describing the outcome of allo-HSCT in children and adults affected by CGD. We demonstrate an excellent outcome, with a low incidence of graft failure, TRM and GvHD. Older patients with CGD have reduced survival after allo-HSCT, indicating that transplant should be considered at a younger age. The use of a MMFD is associated with poorer outcome; indication to transplant in this setting should be carefully evaluated by the treating physicians. Disclosures Chiesa: Bluebird Bio: Consultancy; Gilead: Consultancy. Kalwak:medac: Other: travel grants; Sanofi: Other: travel grants. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Locatelli:Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; bluebird bio: Consultancy; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wynn:Orchard SAB: Membership on an entity's Board of Directors or advisory committees; Orchard Therapeutics: Equity Ownership; Chimerix: Research Funding; Genzyme: Honoraria; Bluebird Bio: Consultancy; Orchard Therapeutics: Consultancy; Chimerix: Consultancy. Zecca:Chimerix: Honoraria. Veys:Pfizer: Honoraria; Servier: Research Funding; Novartis: Honoraria. Slatter:Medac: Other: Travel assistance.

scholarly journals Impact of Race and Geographic Location on Outcomes in Allogeneic Transplant

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Audrey M. Sigmund ◽  
Qiuhong Zhao ◽  
Justin Jiang ◽  
Patrick Elder ◽  
Don M. Benson ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Ohio State University ◽  
Cell Transplant ◽  
State University ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
The Ohio State University ◽  
The Impact

Introduction: Allogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of both malignant and nonmalignant hematologic disorders. However, allo-HCT is costly and requires highly specialized, technologically advanced care that is only available in select healthcare centers across the country. Due to its cost and limited availability, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Prior studies have focused on the impact of health disparities, including race, and geographic residence at time of transplant, on allo-HCT outcomes with variable results. The aim of this study was to evaluate the impact of race and location of residence on outcomes of allo-HCT at one major referral institution. Methods: We performed a retrospective cohort study of patients that underwent allo-HCT at the Ohio State University from 1984 to 2018. The impact of demographic factors including race and place of primary residence were assessed. Patients were divided into race defined as Caucasian, African American (AA), and other. They were also grouped by zip code into rural, suburban, and urban groups. Rural was defined as less than 1000 people per square mile, suburban between 1000-3000 people per square mile, and urban greater than 3000 people per square mile. 2018 population estimates were used. Patients were then stratified into 7 groups based on year (yr) of transplant for analysis. Group (gp) 1 included 1984-1988, gp 2 1989-1993, gp 3 1994-1998, gp 4 1999-2003, gp 5 2004-2008, gp 6 2009-2013, and gp 7 2014-2018. Primary endpoints were progression free survival (PFS) and overall survival (OS). PFS and OS were calculated using Kaplan Meier Curves and compared using log-rank test between race and residence groups. Results: A total of 1,943 patients were included in the study. Of these patients, median age at time of transplant was 50 years old (range 18-76), and 59.6% were male. AML/MDS patients made up the majority of the cohort at 46.3%, with the other most common diagnoses being non-Hodgkin's lymphoma (14.2%), acute lymphocytic leukemia (11.8%), and chronic myeloid leukemia (10.1%). Most patients (94.3%) identified as Caucasian, while 4.6% identified as AA, and 1.1% other. The majority of patients lived in a rural area at the time of transplant with 63.4% rural, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS between Caucasian and AA patients (Figure 1A and B; p=0.15, 0.21). Median OS for AA was 1.9 yrs [95% confidence interval (CI): 0.8-3.6] as compared to 2.3 yrs (95% CI: 1.9-2.9) for Caucasians, with 5 -yr OS of 33 vs. 42% and 10-yr OS of 21 vs. 36% for AA and Caucasian, respectively. Median PFS was 0.9 (95% CI: 0.5-2.7) and 1.3 yrs (95% CI 1.1-1.6), with 5 -yr PFS of 30 vs. 37% and 10-yr PFS of 21 vs. 32% for AA and Caucasian, respectively. There also was no significant difference in OS or PFS between rural, urban, and suburban patients (Figure 2A and 2B; p=0.39, 0.17), with median OS in the three groups 2.2 (95%CI: 1.7-2.9), 2.9 (95%CI: 1.6-4.5), and 2.2 (95% CI: 1.6-3.6) yrs, and 5-yr OS of 40 vs. 43 vs. 43% and 10-yr OS of 33 vs. 39 vs. 39%, respectively. Median PFS were 2.2 (95%CI: 1.7-2.9), 2.9 (95%CI: 1.6-4.5), and 2.2 yrs [95% CI: 1.6-3.6], with 5-yr PFS of 36 vs. 40 vs. 38% and 10-yr PFS of 30 vs. 37 vs. 35%, respectively. Conclusion: Our study suggests that once patients undergo allo-HCT, there is no significant difference in outcomes between patients based on race or residence. This finding suggests that while these underserved populations may initially have less access to specialized care for HCT, if they ultimately undergo allo-HCT, outcomes are similar to their counterparts. Our study did show a significantly lower rates of allo-HCT performed in non-Caucasian races (94% Caucasians vs 4.6% AA and 1% other), which may reflect disparities in access to care in these groups as well as a lack of donors. Further research is needed to assess the barriers for these underserved patients to undergo transplant and to help ameliorate these barriers. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees; Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University. Jaglowski:Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy; Novartis: Consultancy, Research Funding; CRISPR: Consultancy. William:Merck: Research Funding; Celgene: Consultancy, Honoraria; Dova: Research Funding; Seattle Genetics: Research Funding; Incyte: Research Funding; Guidepoint Global: Consultancy; Kyowa Kirin: Consultancy, Honoraria. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Novartis: Speakers Bureau; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board. Brammer:Seattle Genetics, Inc.: Speakers Bureau; Celgene Corporation: Research Funding. Efebera:Celgene: Research Funding; Pharmacyclics: Research Funding; Takeda: Honoraria, Speakers Bureau; Ohio State University: Current Employment.

scholarly journals Trend in Survival in Patients Undergoing Allogeneic Stem Cell Transplantation: An Institutional Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-15
Author(s):  
Justin Jiang ◽  
Audrey M. Sigmund ◽  
Qiuhong Zhao ◽  
Patrick Elder ◽  
Don M. Benson ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Progression Free Survival ◽  
Ohio State University ◽  
State University ◽  
Research Support ◽  
Advisory Committees ◽  
Grade Ii ◽  
The Ohio State University ◽  
Grade Iii

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for many hematological malignancies and disorders. However, this potential is often impeded by several factors including relapse of the underlying disease, graft-vs-host disease (GVHD) and infectious complications. Specifically, acute GVHD continues to be a major factor in the morbidity and mortality of patients. Hence, the practice of allo-SCT is continuously evolving to mitigate these factors. In particular, advances in the conditioning regimens, GVHD prophylaxis, infectious disease monitoring and prophylaxis and supportive care not only have resulted in improved outcomes, but also have expanded potential indications for allo-HSCT. Therefore, we conducted a retrospective analysis on patients who underwent allo-SCT at The Ohio State University from 1986-2018 to better understand how survival has changed longitudinally in accordance with these therapeutic advancements. Method: We analyzed data from 1943 consecutive patients who received an allo-SCT. Patients were divided into seven groups based on the year of transplant: groups (gp) 1: 1984-1988, 2: 1989-1993, 3: 1994-1998, 4: 1999-2003, 5: 2004-2008, 6: 2009-2013, and 7: 2014-2018. The primary endpoints were overall survival (OS) and progression free survival (PFS), and log-rank test was used to compare across transplant years. The Kaplan-Meier method was used to estimate OS and PFS. The secondary endpoints were the cumulative incidences of grade II-IV and grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD), and non-relapse mortality (NRM). Cumulative incidence rates were estimated and compared using Gray's test accounting for competing risks. Results: Across the years (1984-2018), the median age was 50.0 (range: 18-76) with 59.6% of the patients being male. Acute myeloid leukemia accounted for 36.3% of transplants, followed by non-Hodgkin lymphoma (14.2%), acute lymphoid leukemia (11.8%), chronic myeloid leukemia (10.1%), and myelodysplastic syndrome (10.0%). Fifty-five percent of patients received myeloablative conditioning. Across the groups, statistically significant improvements in PFS and OS were observed (p&lt;0.001 and p&lt;0.001, respectively) (Figure 1a, 1b). The median PFS improved from 0.8 yrs. (95% confidence interval [CI]: 0.6-1.2) in gp 1 to 3.7 yrs. (95% CI: 2.3-NR) in gp 7. The median OS also improved from 1.0 yrs. (95% CI: 0.7-1.2) in gp1 to NR (95% CI: 4.2-NR) in gp7. The 5-yr PFS among the groups were 24, 25, 25, 28, 33, 41 and 48%, respectively, with a significant improvement seen since 2004. Similar improved trends were seen at 10 yrs. The 5-yr OS were 25, 28, 28, 28, 40, 47 and 53%, respectively, with similar significant improvement seen since 2004. Similar improved trends were seen at 10 yrs. Complete GVHD data was available since 1999 (gp 4-7). The cumulative incidence of grade II-IV aGVHD increased over the years: 36, 27, 38, and 52% at day 100 and 37, 31, 44, and 55%, respectively, at day 180 (Figure 1c). Grade III-IV aGVHD were 21, 10, 11, and 19% at day 100 and 22, 11, 13, and 21% by day 180, respectively, with the highest rate seen for groups 4 and 7. Overall cGVHD also increased over the 4 group years with day 365 cGVHD at 38, 40, 34, and 48% and extensive cGVHD at 27, 34, 31, and 44%, respectively (p&lt;0.001 and p&lt;0.001, respectively). The rate of NRM significantly improved across the years, with 1-yr NRM at 40, 38, 42, 46, 21, 15, and 15% and 5-yr NRM at 54, 51, 51, 57, 31, 22, and 24%, respectively, with a significant improvement seen since 2004 (Figure 1d). Conclusion: Our data shows improved overall and progression-free survival post allo-SCT over decades, which may be attributed to advances in supportive care, and GVHD and relapse mitigation therapy. The decline in NRM is also likely due to improved supportive measures such as infectious disease monitoring and prophylaxis. Nonetheless, post-transplant relapse and grade III-IV aGVHD remain prominent challenges. Therefore, future research should continue to investigate therapeutic strategies that can both reduce high grade GVHD while limiting post-transplant relapse. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:CRISPR: Consultancy; Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. William:Incyte: Research Funding; Guidepoint Global: Consultancy; Dova: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Mims:Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Incyte Pharmaceuticals: Other: Personal Fees; Amgen: Other: research support; Kadmon: Other: research support; Orcabio: Other: research support; Magenta Therapeutics: Other: Personal Fees. Efebera:Celgene: Research Funding; Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Ohio State University: Current Employment.

scholarly journals Outcome of Patients with Immunoglobulin Light-Chain Amyloidosis with t(11;14) Undergoing Autologous Hematopoietic Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Aimaz Afrough ◽  
Leonard C Alsfeld ◽  
Samer A. Srour ◽  
Qaiser Bashir ◽  
Neeraj Saini ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Board ◽  
Single Center ◽  
Research Support ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Free Survival

Background- In patients with light chain amyloidosis (AL), t(11;14) detected by fluorescence in situ hybridization (FISH) is the most common cytogenetic aberration. Several studies have shown that t(11;14) is associated with inferior outcomes in newly diagnosed AL patients [1, 2]. In contrast, at least one study in patients with t(11;14) who underwent high-dose therapy and autologous hematopoietic stem cell transplantation (auto-HCT) showed improved complete response (CR) rate and prolonged hematologic event-free survival[3]. In this single-center, retrospective analysis, we evaluated the outcome of patients with AL and t(11;14) who underwent auto-HCT at our institution. Method- We identified 122 consecutive patients with AL with cardiac or renal involvement who received an auto-HCT between 2011 and 2019. Baseline FISH data were available for 92 patients, 15 (16 %) of whom had t(11;14). Seventy-seven (84%) patients without t(11;14) were included as control . Hematologic and organ responses were evaluated according to the Consensus Guidelines for AL [4]. Revised Mayo staging system was utilized for Cardiac staging [5]. Result- The median age at auto-HCT was 60 years (range, 27 to 77). There were no significant differences in baseline characteristics between the two groups (Table 1). The median follow-up from auto-HCT was 28 months (range, 1 to 100). Overall, 40%, and 42% of patients with or without t(11;14), respectively (p=0.573), received post-auto-HCT maintenance therapy. One-year non-relapse mortality (NRM) was 2%. The 1-year NRM was 0 and 2.6% (n=2) in patients with or without t(11;14) (p=0.366). Hematologic CR after auto-HCT was seen in 7 (47%) and 33 (42%) patients with or without t(11;14), respectively (p=0.78). Organ response (OR) after auto-HCT was seen in 10 (71%) and 50 (67%) patients with or without t(11;14), respectively (p=0.586). The 2-year hematologic disease-free survival (Heme DFS) was 93% and 87% with or without t(11;14), respectively (p=0.422). The 2-year progression-free survival (PFS) was 92%, and 87% in patients with or without t(11;14) (p=0.6) (Figure 1A).The 2-year overall survival was 100%, ad 87% in patients with or without t(11;14) (p=0.2) (Figure 1B). Cardiac involvement with AL was associated with a shorter OS (p=0.012). Conclusion- In this single-center retrospective analysis, we showed that auto-HCT is safe and feasible in selected patients with AL and t(11;14), and these patients have comparable outcomes to patients without t(11;14). Disclosures Bashir: Celgene: Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Takeda: Other: Advisory Board, Research Funding; KITE: Other: Advisory Board; Purdue: Other: Advisory Board; Amgen: Other: Advisory Board. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Novartis: Other: Served on advisory board; Ziopharm: Other: Research Support; Jazz: Consultancy. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Manasanch:Adaptive Biotechnologies: Honoraria; Sanofi: Research Funding; Novartis: Research Funding; JW Pharma: Research Funding; Merck: Research Funding; Quest Diagnostics: Research Funding; Takeda: Honoraria; BMS: Honoraria; Sanofi: Honoraria; GSK: Honoraria. Lee:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy. Kaufman:Janssen: Research Funding; Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding. Patel:Oncopeptides: Consultancy; Celgene: Consultancy, Research Funding; Cellectis: Research Funding; Janssen: Consultancy, Research Funding; Nektar: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Precision Biosciences: Research Funding; Poseida: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Thomas:Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards; Genentech: Research Funding; BMS: Research Funding. Orlowski:STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding. Champlin:Actinium: Consultancy; Omeros: Consultancy; Takeda: Patents & Royalties; Cytonus: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Johnson and Johnson: Consultancy. Qazilbash:Janssen: Research Funding; Bioline: Research Funding; Angiocrine: Research Funding; Amgen: Research Funding; Bioclinica: Consultancy.

scholarly journals Comparison of Bone Marrow Versus Peripheral Blood in Haploidentical Transplantation Using Post-Transplant Cyclophosphamide- a Retrospective Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Nidhi Sharma ◽  
Justin Jiang ◽  
Qiuhong Zhao ◽  
Patrick Elder ◽  
Don M. Benson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Ohio State University ◽  
State University ◽  
Research Support ◽  
Advisory Committees

Background: Allogeneic transplantation (allo-HCT) is a potentially curative treatment for a variety of hematologic malignancies and nonmalignant hematologic disorders. Allo-HCT from a haploidentical (Haplo) related donor has emerged as a suitable alternative in the absence of matched related donor (MRD) and matched unrelated donor (MUD). Haplo HCT patients however have higher risk of graft rejection and graft versus-host disease (GVHD). Thus, patients often receive post-transplant cyclophosphamide (PTCy), which has proven to be highly effective in reducing GVHD. While the use of peripheral blood is an attractive option due to the ease of collection and rapid peripheral blood count recovery, not much information is available on the impact of graft sources using PTCy in Haplo-HCT. This study compares outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for Haplo-HCT in adult patients. Methods: We performed a retrospective study of 81 adult patients who underwent Haplo-HCT at The Ohio State University from 2009 to 2018. The study endpoints were overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse, engraftment, acute GVHD (grade II-IV), and chronic GVHD. All endpoints were measured from the time of transplantation. Patient, disease, and transplant-related characteristics were compared between the two groups (BM versus PB) using the Mann-Whitney U test for continuous variables, and chi-squared or Fisher's exact test for categorical variables. The probabilities of OS and PFS were calculated using the Kaplan-Meier (KM) method and compared using log-rank test. Cumulative incidence rates were estimated and compared using Gray's test accounting for competing risks. Results: We compared the outcomes of patients who received a BM graft (N=43) with those receiving a PB graft (N=38). The median age at transplant was 57 years (20-74). All patients received PTCy in addition to tacrolimus and mycophenolate in 91% of patients. Reduced intensity conditioning (RIC) was used in majority of patients (N=63, 78%). The two groups were comparable including age (median, 60 years for BM and 56 years for PB, p=0.60) and the type of conditioning regimen (79% RIC for BM, 76% RIC for PB, p=0.77). The number of CD34+ and CD3+ infused cells was higher in PB grafts (median, 8.6x106 CD34+ cells/Kg, 2.0 x108 CD3+ cells/Kg, respectively) than for BM (median, 3.7x106 CD34+cells/Kg, 0.4x108 CD3+cells/Kg, respectively). Time to neutrophil and platelet engraftment were significantly shorter in patients receiving PB versus those getting BM grafts: median 15 vs. 17.5 days, (p=0.02) and median 20 vs. 29 days (p&lt;0.01) respectively. In univariable analysis there was no difference in OS (p=0.30), PFS (p=0.29) or NRM (p=0.33) between the groups. The BM cohort showed a 3-year OS rate of 62% (95% confidence interval [CI]: 45-75), and 3-year PFS of 48% (95% CI: 32-62). For PB group, 3-year OS and PFS were 68% (95% CI: 50-80) and 60% (95% CI: 43-74), respectively. There were no differences in the incidence of acute GVHD (p=0.80) and chronic GVHD (p=0.53). For BM vs. PB, cumulative incidences of grade II-IV acute GVHD at day +180 were 57% (95% CI: 41-70) vs. 55% (95% CI: 69-38) and for chronic GVHD at day 365, they were 40% (95% CI 26-55) vs. 47% (95% CI: 31-62), respectively. There was a significant difference in the incidence of relapse (p=0.04, Figure 1) with 2-year relapse rate of 36% (95% CI: 22-50) for BM vs. 19% (95% CI: 8-32) for PB. After controlling for conditioning regimen, PB graft had a reduced risk of relapse compared to BM graft, HR=0.35 (95% CI: 0.13-0.93, p=0.03). Conclusion: Our study suggests peripheral blood for haploidentical transplant to be a good alternative to bone marrow. Similar PFS, OS and NRM were seen between the two graft sources. As expected, faster neutrophil and platelets engraftment were seen with PB due to more CD3+ and CD34+ infused, but without an increase in acute or chronic GVHD. A reduced relapse risk was observed with PB graft. Our study is small and is retrospective, but provide encouraging results. A prospective randomized controlled trial is required to confirm these results. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy. William:Seattle Genetics: Research Funding; Merck: Research Funding; Dova: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Guidepoint Global: Consultancy; Incyte: Research Funding; Celgene: Consultancy, Honoraria. Mims:Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Novartis: Speakers Bureau. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Amgen: Other: research support; Magenta Therapeutics: Other: Personal Fees; Incyte Pharmaceuticals: Other: Personal Fees; Orcabio: Other: research support; Kadmon: Other: research support. Efebera:Celgene: Research Funding; Ohio State University: Current Employment; Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding.

scholarly journals Outcome of Transformed Fanconi Anaemia Patients after Hematopoietic Stem Cell Transplantation: Analysis on Behalf of European Group for Blood and Marrow Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 646-646
Author(s):  
Stefano Giardino ◽  
Dirk-Jan Eikema ◽  
Regis Peffault De Latour ◽  
Yves Bertrand ◽  
Mahmoud Aljurf ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Related Donor

Abstract INTRODUCTION Fanconi anemia (FA) is an inherited bone marrow failure syndrome that carries a high risk of transformation to myelodysplasia (MDS) and acute leukemia. Hematopoietic stem cell transplantation (HSCT) is used to treat FA patients in clonal evolution. The roles of chemotherapy before HSCT and the intensity of conditioning regimens in transformed FA patients are controversial, because of the high sensitivity of FA patients to DNA-damaging agents increases the risk of severe toxicities, the duration of aplasia, the risk of infective complications thus limiting the possibility to administer full dose cytoreductive treatments. The sequence chemotherapy-HSCT has been reported by some groups (MehtaPA et al Pediatr Blood Cancer 2007, Talbot A et al Haematologica 2014, Mitchell R et al Br J Haematol 2014, Ayas M et al J Clin Oncol 2013), but conclusive information is lacking because of small number of patients described without a risk factors' analysis. The aim of this retrospective study is to report the outcome of a large cohort of transformed FA who underwent allo-HSCT and to define the factors that may impact on its outcome. PATIENTS AND METHODS The study was conducted on behalf of the Severe Aplastic Anemia (SAAWP) and Chronic Malignancies Working Parties (CMWP) of the EBMT and was based on data of patients who underwent allo-HSCT between 1999-2016 for transformed FA, defined as a diagnosis of FA in presence of any hematological malignancies or cytogenetic abnormalities, registered in the EBMT Data Base. Clinical and biological information of the disease and details on transplant procedures and outcome were collected by a specific form distributed to Centres participating in the study. RESULTS Data of 71 patients (35 males-36 females) affected by transformed FA (42 MDS, 25 AL, 4 with cytogenetic abnormalities but without blasts) undergoing allo-HSCT were collected from 25 Centres . A matched related donor (MRD) was used in 31% of cases, an unrelated donor (UD) in 56.3% and a mismatched related donor (MMRD) in 12.7%. Bone marrow was the main source of cells (54.3%) followed by cord blood (22.9%), peripheral blood (21.4%) and bone marrow plus peripheral blood (1.4%). The median age at allo-HSCT was 12.7 years (range 9.3-23.4). Thirty seven (52.1%) patients received a chemotherapy before HSCT. Pre-HSCT status of malignancy in available patients was complete remission (CR) in 24% (n = 12/50) and an active disease (no-CR) in 76 % patients (n = 38/50). The conditioning regimen included total body irradiation (TBI) in 37 (52.1%) (radiation dose: ≤ 4.0 Gy in 30; > 4.0 Gy in 7), busulphan (BUS) in 16 (22.6%), no-TBI nor BUS in 18 (25.3%). Median follow-up was 93.7 months (71-110.6). GvHD prophylaxis and transplants' details are summarized in Table 1. All patients engrafted. Median time for neutrophils was 17 days (14-23) and it was 25 days (23-42) for platelets. The 2-and 5-year overall survival (OS) probability were 54% (41-66%) and 45% (32-57%) respectively; the 2- and 5-year event-free survival (EFS) (events being death, relapse and graft loss) 52% (40-65%) and 45% (32-58%). The cumulative incidence of relapse were 15% (7-24%) and 21% (11-31%), , of non-relapse mortality (NRM) were 37% (25-49%) and 39% (27-51%) respectively at 2 and 5-year. Most frequent causes of death were GvHD (33.3%), infections (23.3%) and relapse of malignancy (16.7%). Patients transplanted in CR, (neither blasts, nor major dysplastic features) and from matched related donor had a significantly better outcome (5-year OS: CR 83% (62-100%) vs no-CR 36% (19-52%) [p 0.01], MRD 60% (37-83%) vs UD 47% (31-64%) vs MMRD 12% (0-35%) [p 0.03]; 5-year EFS: CR 83% (62-100%) vs no-CR 34% (17-51%) [p 0.01], MRD 61% (38-83%) vs UD 48% (31-64%) vs MMRD 12% (0-35%) [p 0.02]; 5-year NRM: CR 0% vs no-CR 44% (27-61%) [p 0.007]) vs those engrafted in no-CR and from no-MRD. (Fig 1 a, b, c). No other tested variable (therapy before transplant and conditioning regimen) significantly affected the outcome. CONCLUSION This study on large cohort of FA patients transplanted because of transformation shows that allo-HSCT from MRD has a better outcome and that CR from malignancy before transplant appears to be a major determinant for a favorable outcome. Disclosures Peffault De Latour: Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Pfizer Inc.: Consultancy, Honoraria, Research Funding. Ganser:Novartis: Membership on an entity's Board of Directors or advisory committees. Risitano:Pfizer Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Ra Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Amyndas Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Lower Hematopoietic Progenitor Cell Counts and Yields at Subsequent Donations Is Influenced By a Shorter Inter-Donation Interval between the First and Subsequent Mobilizations

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1962-1962
Author(s):  
Sandhya R. Panch ◽  
Brent R. Logan ◽  
Jennifer A. Sees ◽  
Bipin N. Savani ◽  
Nirali N. Shah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Peripheral Blood ◽  
Research Funding ◽  
Time Interval ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Peripheral Blood Cd34 ◽  
Cell Counts ◽  
Cd34 Cells

Introduction: Approximately 7% of unrelated hematopoietic stem cell (HSC) donors are asked to donate a subsequent time to the same or different recipient. In a recent large CIBMTR study of second time donors, Stroncek et al. incidentally found that second peripheral blood stem cell (PBSC) collections had lower total CD34+ cells, CD34+ cells per liter of whole blood processed, and CD34+ cells per kg donor weight. Based on smaller studies, the time between the two independent PBSC donations (inter-donation interval) as well as donor sex, race and baseline lymphocyte counts appear to influence CD34+ cell yields at subsequent donations. Our objective was to retrospectively evaluate factors contributory to CD34+ cell yields at subsequent PBSC donation amongst NMDP donors. Methods. The study population consisted of filgrastim (G-CSF) mobilized PBSC donors through the NMDP/CIBMTR between 2006 and 2017, with a subsequent donation of the same product. evaluated the impact of inter-donation interval, donor demographics (age, BMI, race, sex, G-CSF dose, year of procedure, need for central line) and changes in complete blood counts (CBC), on the CD34+ cell yields/liter (x106/L) of blood processed at second donation and pre-apheresis (Day 5) peripheral blood CD34+ cell counts/liter (x106/L) at second donation. Linear regression was used to model log cell yields as a function of donor and collection related variables, time between donations, and changes in baseline values from first to second donation. Stepwise model building, along with interactions among significant variables were assessed. The Pearson chi-square test or the Kruskal-Wallis test compared discrete variables or continuous variables, respectively. For multivariate analysis, a significance level of 0.01 was used due to the large number of variables considered. Results: Among 513 PBSC donors who subsequently donated a second PBSC product, clinically relevant decreases in values at the second donation were observed in pre-apheresis CD34+ cells (73.9 vs. 68.6; p=0.03), CD34+cells/L blood processed (32.2 vs. 30.1; p=0.06), and total final CD34+ cell count (x106) (608 vs. 556; p=0.02). Median time interval between first and second PBSC donations was 11.7 months (range: 0.3-128.1). Using the median pre-apheresis peripheral blood CD34+ cell counts from donation 1 as the cut-off for high versus low mobilizers, we found that individuals who were likely to be high or low mobilizers at first donation were also likely to be high or low mobilizers at second donation, respectively (Table 1). This was independent of the inter-donation interval. In multivariate analyses, those with an inter-donation interval of >12 months, demonstrated higher CD34+cells/L blood processed compared to donors donating within a year (mean ratio 1.15, p<0.0001). Change in donor BMI was also a predictor for PBSC yields. If donor BMI decreased at second donation, so did the CD34+cells/L blood processed (0.74, p <0.0001). An average G-CSF dose above 960mcg was also associated with an increase in CD34+cells/L blood processed compared to donors who received less than 960mcg (1.04, p=0.005). (Table 2A). Pre-apheresis peripheral blood CD34+ cells on Day 5 of second donation were also affected by the inter-donation interval, with higher cell counts associated with a longer time interval (>12 months) between donations (1.23, p<0.0001). Further, independent of the inter-donation interval, GCSF doses greater than 960mcg per day associated with higher pre-apheresis CD34+ cells at second donation (1.26, p<0.0001); as was a higher baseline WBC count (>6.9) (1.3, p<0.0001) (Table 2B). Conclusions: In this large retrospective study of second time unrelated PBSC donors, a longer inter-donation interval was confirmed to be associated with better PBSC mobilization and collection. Given hematopoietic stem cell cycling times of 9-12 months in humans, where possible, repeat donors may be chosen based on these intervals to optimize PBSC yields. Changes in BMI are also to be considered while recruiting repeat donors. Some of these parameters may be improved marginally by increasing G-CSF dose within permissible limits. In most instances, however, sub-optimal mobilizers at first donation appear to donate suboptimal numbers of HSC at their subsequent donation. Disclosures Pulsipher: CSL Behring: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding; Bellicum: Consultancy; Amgen: Other: Lecture; Jazz: Other: Education for employees; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Medac: Honoraria. Shaw:Therakos: Other: Speaker Engagement.

Plerixafor (Mozobil ®)Plus G-CSF Is Effective in Mobilizing Hematopoietic Stem Cells in Patients with Concurrent Thrombocytopenia Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3229-3229 ◽  
Author(s):  
Ivana N Micallef ◽  
Eric Jacobsen ◽  
Paul Shaughnessy ◽  
Sachin Marulkar ◽  
Purvi Mody ◽  
...  
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Platelet Counts ◽  
Cd34 Cells ◽  
Low Platelet Count ◽  
Equity Ownership

Abstract Abstract 3229 Poster Board III-166 Introduction Low platelet count prior to mobilization is a significant predictive factor for mobilization failure in patients with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) undergoing autologous hematopoietic stem cell (HSC) transplantation (auto-HSCT; Hosing C, et al, Am J Hematol. 2009). The purpose of this study is to assess the efficacy of HSC mobilization with plerixafor plus G-CSF in patients with concomitant thrombocytopenia undergoing auto-HSCT. Methods Patients who had failed successful HSC collection with any mobilization regimen were remobilized with plerixafor plus G-CSF as part of a compassionate use program (CUP). Mobilization failure was defined as the inability to collect 2 ×106 CD34+ cells/kg or inability to achieve a peripheral blood count of ≥10 CD34+ cells/μl without having undergone apheresis. As part of the CUP, G-CSF (10μg/kg) was administered subcutaneously (SC) every morning for 4 days. Plerixafor (0.24 mg/kg SC) was administered in the evening on Day 4, approximately 11 hours prior to the initiation of apheresis the following day. On Day 5, G-CSF was administered and apheresis was initiated. Plerixafor, G-CSF and apheresis were repeated daily until patients collected the minimum of 2 × 106 CD34+ cells/kg for auto-HSCT. Patients in the CUP with available data on pre-mobilization platelet counts were included in this analysis. While patients with a platelet count <85 × 109/L were excluded from the CUP, some patients received waivers and were included in this analysis. Efficacy of remobilization with plerixafor + G-CSF was evaluated in patients with platelet counts ≤ 100 × 109/L or ≤ 150 × 109/L. Results Of the 833 patients in the plerixafor CUP database, pre-mobilization platelet counts were available for 219 patients (NHL=115, MM=66, HD=20 and other=18.). Of these, 92 patients (NHL=49, MM=25, HD=8 and other=10) had pre-mobilization platelet counts ≤ 150 × 109/L; the median platelet count was 115 × 109/L (range, 50-150). The median age was 60 years (range 20-76) and 60.4% of the patients were male. Fifty-nine patients (64.1%) collected ≥2 × 109 CD34+ cells/kg and 13 patients (14.1%) achieved ≥5 × 106 CD34+ cells/kg. The median CD34+ cell yield was 2.56 × 106 CD34+ cells/kg. The proportion of patients proceeding to transplant was 68.5%. The median time to neutrophil and platelet engraftment was 12 days and 22 days, respectively. Similar results were obtained when efficacy of plerixafor + G-CSF was evaluated in 29 patients with platelet counts ≤ 100 × 109/L (NHL=12, MM=10, HD=3 and other=4). The median platelet count in these patients was 83 × 109/L (range, 50-100). The median age was 59 years (range 23-73) and 60.4% of the patients were male. The minimal and optimal cell dose was achieved in 19(65.5%) and 3(10.3%) patients, respectively. The median CD34+ cell yield was 2.92 × 106 CD34+ cells/kg. The proportion of patients proceeding to transplant was 62.1%. The median time to neutrophil and platelet engraftment was 12 days and 23 days, respectively. Conclusions For patients mobilized with G-CSF alone or chemotherapy ±G-CSF, a low platelet count prior to mobilization is a significant predictor of mobilization failure. These data demonstrate that in patients with thrombocytopenia who have failed prior mobilization attempts, remobilization with plerixafor plus G-CSF allows ∼65% of the patients to collect the minimal cell dose to proceed to transplantation. Thus, in patients predicted or proven to be poor mobilizers, addition of plerixafor may increase stem cell yields. Future studies should investigate the efficacy of plerixafor + G-CSF in front line mobilization in patients with low platelet counts prior to mobilization. Disclosures Micallef: Genzyme Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jacobsen:Genzyme Corporation: Research Funding. Shaughnessy:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Marulkar:Genzyme Corporation: Employment, Equity Ownership. Mody:Genzyme Corporation: Employment, Equity Ownership. van Rhee:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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