scholarly journals Community Health Status and Long-Term Outcomes in 1-Year Survivors of Autologous and Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 422-422
Author(s):  
Julia H. Joo ◽  
Sanghee Hong ◽  
Lisa A. Rybicki ◽  
Betty K. Hamilton ◽  
Navneet S. Majhail

Abstract Background: Race/ethnicity and socioeconomic status (SES) have been associated with access to and outcomes after hematopoietic cell transplantation (HCT). The role of health disparity factors beyond race/SES in HCT outcomes, however, has not been well described. This is especially true for long-term HCT survivors, for whom local socio-demographic factors may have a greater impact on outcomes because patients may no longer be under close monitoring of their transplant center. The County Health Rankings and Roadmaps (CHRR) provides updated aggregated information from several publicly available datasets to comprehensively describe the health status of US counties. A recent report demonstrated an association between community health status and 1-year non-relapse mortality in a CIBMTR cohort of allogeneic HCT recipients (Hong et al., Cancer 2021). We conducted a single-center retrospective cohort study to investigate the association between community health and long-term outcomes in 1-year autologous and allogeneic HCT survivors. Methods: Our study included 1,812 consecutive adult patients from Cleveland Clinic's BMT Program database who received their first allogeneic or autologous HCT between 2003 and 2017 and survived at least 1 year after their transplant. We used patient community risk score (PCS) as the surrogate for community health. PCS was nationally standardized and calculated as the sum of weighted Z-scores of the 23 county-level community health factors considered in CHRR. The 23 factors fell under 4 categories of health factors: health behavior (tobacco and alcohol use, etc.), clinical care (access and quality of care), social and economic factors (education, community safety, etc.), and physical environment (environmental quality and built environment). Higher PCS indicate worse community health. We evaluated the association of PCS with overall survival (OS), relapse, and non-relapse mortality (NRM) with Cox or Fine and Gray regression separately for autologous and allogeneic HCTs. Considered co-variables included pre-transplant sociodemographic data, disease diagnosis, and transplant factors. Results: Autologous HCT recipients (n=1,313) lived in 133 of 3,141 CHRR counties, 90% in Ohio. Similarly, allogeneic recipients (n=499) were from 88 counties, 88% in Ohio. Patient characteristics are shown in Table 1. The median (range) PCS scores for autologous and allogeneic HCT recipients were 0.03 (-0.85, 0.97) and 0.03 (-0.85, 0.58), respectively. For comparison, the PCS for the complete US CHRR dataset ranged from -1.43 to 2.54 and ranged from -1.6 to 2.0 in the prior CIBMTR study that included allogeneic HCT recipients (Hong et al., Cancer 2021). PCS was not associated with OS, relapse, or NRM for autologous or allogeneic HCT recipients in univariable analysis, nor were the four categories of health factors that contribute to the total PCS (Table 2). In addition, race and estimated median household income were not associated with mortality. Similar findings were noted in multivariable analysis. Conclusion: In our single center study, PCS was not associated with OS, relapse, or NRM in allogeneic or autologous HCT recipients who survived at least 1 year after HCT. A limitation of our analysis is that our cohort represented a single center with regional representation, where long-term follow up care is provided through a dedicated survivorship clinic and there is a strong emphasis on psychosocial support. A national cohort with greater geographical diversity is needed to better define the association of community factors and outcomes in long-term HCT survivors. Figure 1 Figure 1. Disclosures Hamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2782-2782 ◽  
Author(s):  
Matthew J. Wieduwilt ◽  
Jun Yin ◽  
Meir Wetzler ◽  
Geoffrey L. Uy ◽  
Bayard L Powell ◽  
...  

Abstract Background: Potent inhibitors of BCR-ABL1have improved remission results and altered post-remission therapy for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Dasatinib plus dexamethasone followed by hematopoietic cell transplantation (HCT) promises high response rates, reduced toxicity, and durable remissions. Methods: We conducted a Phase II trial at 17 U.S. centers with the primary objective being to estimate the 3-year overall survival and disease-free survival of patients with Ph+ ALL treated with dasatinib and dexamethasone for remission induction and intensification, central nervous system (CNS) prophylaxis, consolidation with reduced-intensity conditioning (RIC) allogeneic HCT, autologous HCT, or etoposide and cytarabine, and dasatinib-based maintenance. Eligible patients had untreated Ph+ ALL, were ≥18 years old, and had normal cardiac function. Induction (Course I) used dasatinib 140 mg oral daily and dexamethasone 10 mg/m2/day oral or intravenous (IV) days 1-7. For patients with ≤20% blasts in the Course I, Day 15 bone marrow biopsy, intensification (course II) continued daily dasatinib with another 7 days of dexamethasone. Those with >20% lymphoblasts also received vincristine (VCR) and daunorubicin (DNR). Patients (n=3) not in CR/CRi after Course II received a second induction (Course III) with dasatinib, cyclophosphamide, VCR, DNR, and dexamethasone. After Course II or III, CNS prophylaxis (Course IV) consisted of IV VCR and IV, oral, and intrathecal methotrexate (MTX). Dasatinib was restarted at serum [MTX] <0.05 microM. Course V consisted of HCT or chemotherapy. Patients aged 18-70 years with an HLA-matched donor underwent RIC allogeneic HCT; otherwise they underwent autologous HCT. Allogeneic HCT conditioning used fludarabine 30 mg/m2/day IV day -7 through -3, alemtuzumab 20 mg/day IV day -7 through -3, and melphalan 140 mg/m2 once on day -2. GVHD prophylaxis with tacrolimus began day -2. Patients undergoing autologous HCT received etoposide 10 mg/kg/day (age >65 years, 5 mg/kg/day) continuous IV for 4 days and cytarabine 2 g/m2 (age >65 years, 1 g/m2) IV every 12 hours for 8 doses (EA) then G-CSF for mobilization. Autologous HCT conditioning used melphalan 100 mg/m2/day on days -2 and -1. Patients >70 years or unable to undergo HCT received EA alone. Dasatinib maintenance (Course VI) began on day 30 of Course V and continued for 12 months and until 2 consecutively negative bone marrow BCR-ABL1RT-PCR assays 3 months apart or until relapse. Dasatinib levels were measured on day 15 of induction. Results: Sixty-six patients enrolled from 12/15/2010 to 11/14/2014; 65 received dasatinib and are evaluable. Median age was 60 years (22-87); 49% were male. Median presenting WBC count was 23.1 x 103/ul (0.3-453.6). No deaths occurred during induction or intensification. CR or CRi occurred 31 patients (48%) by Day 15 of induction and in 62 patients overall (95%; CR 86%). Median dasatinib levels in serum and CSF on Day 15 of induction were 30.3 ng/mL (<3-308) and 0.29 ng/mL (<0.2-1.37), respectively suggesting approximately 1% of plasma dasatinib penetrates into the CSF, less than the unbound fraction (6%). Fifty-four patients started Course IV, 38 Course V, and 37 Course VI. Fourteen patients continue on protocol therapy. Of 38 patients receiving Course V, 22 had allogeneic HCT, 6 had autologous HCT, and 10 had EA chemotherapy. Median age of allogeneic HCT recipients was 61 years (31-69). Robust autologous stem cell mobilization was observed [median CD34+ cell count, 90 x 106/kg (31-166, n=6)]. Dasatinib maintenance was feasible after allogeneic HCT, autologous HCT, and chemotherapy alone with no missed doses in 59%, 83%, and 63% of cycles, respectively. Ten patients have relapsed with one isolated CNS relapse. No relapses have occurred after allogeneic HCT with 3 relapses after autologous HCT and one after Course V EA alone. Median follow up for survivors is 22.8 months (longest, 51 months). There have been 23 deaths: 5 treatment-related (4 after allogeneic HCT, 1 after course V EA), 16 disease-related and 2 unrelated. Conclusions: Dasatinib with dexamethasone yields CR rates comparable to those reported with tyrosine kinase inhibitors combined with conventional chemotherapy. Post-remission therapy with reduced-intensity allogeneic HCT, autologous HCT, or chemotherapy followed by dasatinib maintenance is feasible. Survival follow up is maturing. Disclosures Stock: Sigma-Tau: Honoraria, Research Funding; Royalties for a chapter in Up to Date: Patents & Royalties; ADC Therapeutics: Honoraria; Amgen: Honoraria; Gilead Sciences: Honoraria. Beumer:Bristol-Myers Squibb: Research Funding. Stone:Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Juno Therapeutics: Consultancy; Karyopharm: Consultancy; Sunesis Pharmaceuticals: Consultancy; Agios: Consultancy; Amgen: Consultancy; Celator: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Jansen: Consultancy; Merck: Consultancy; ONO: Consultancy; Roche: Consultancy; Seattle Genetics: Consultancy; Xenetic Biosciences: Consultancy. Larson:Bristol-Myers Squibb: Consultancy; Astellas: Consultancy, Research Funding.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 634-634
Author(s):  
F. Lennie Wong ◽  
Liton Francisco ◽  
Stephen J. Forman ◽  
Mitzi Gonzales ◽  
Melanie Sabado ◽  
...  

Abstract The growing number of long-term HCT survivors has created the need to identify factors that could play a critical role in the survivors’ reintegration into daily life, which in turn would inform the quality of life (QOL) of the survivors. Using a longitudinal study design, we administered the City of Hope-QOL instrument to evaluate the four domains of QOL (physical, psychological, social, and spiritual well-being), as well as fatigue, anxiety, distress, and return to full-time work in a large cohort of patients undergoing HCT at City of Hope. The outcomes were evaluated before transplantation, at 6m, 1y, 2y, and 3y. Longitudinal trends for these outcomes were evaluated using the Generalized Estimating Equation method, adjusting for potential confounders such as age, race, BMI, disease. Our cohort included 313 adults (median age at HCT 48y; 56% males) undergoing autologous (n=181) or allogeneic (n=132) HCT for hematologic malignancies or severe aplastic anemia; 111 patients (65.3% of eligible) completed 3y follow-up so far. Overall, the mean scores for psychological, social, and spiritual well-being improved significantly over time compared to pre-HCT levels (p<.05); that for physical well-being did not demonstrate a significant change from the pre-HCT levels. Although HCT survivors in general appeared to recover well, we identified subgroups that faced long-term limitations. Notably, longitudinal trends of mean scores for all four QOL domains were significantly worse (p<.05) for allogeneic HCT recipients with cGVHD compared to allogeneic HCT recipients without cGVHD or autologous HCT recipients (Figure); the latter two groups were statistically indistinguishable for all domains of QOL. Moreover, physical and spiritual well-being of patients with cGVHD continued to decline with time, while that of allogeneic recipients without cGVHD or autologous HCT recipients improved or remained unchanged with time after HCT. All patients combined, anxiety, fatigue, distress improved significantly after 6m to 1y after HCT compared to the pre-HCT time-point. However, patients with cGVHD reported higher levels of anxiety, fatigue (Figure), and distress when compared to those without cGVHD. The prevalence of the most fatigued patients (worst 20th percentile of fatigue score) decreased from 39% before transplant to 26% at 3y (p=.02). However, during the post-HCT time points, the prevalence was two-fold higher for allogeneic recipients with cGVHD compared to allogeneic recipients without cGVHD or autologous HCT recipients (p<.005). About 25% of patients reported returning to full-time work at 6m, which increased to 58% at 3y (p<.0001). Multivariate analysis showed that females, those older than 50 years, and those with higher levels of fatigue were less likely to return to full-time work. This study demonstrates that at 3y after HCT 25% of patients are significantly fatigued and over 40% do not return to full-time work, and that patients with cGVHD represent a vulnerable subgroup, requiring effective, multidisciplinary interventions. Figure Figure


Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 372-397 ◽  
Author(s):  
Rainer F. Storb ◽  
Guido Lucarelli ◽  
Peter A. McSweeney ◽  
Richard W. Childs

Abstract Allogeneic hematopoietic cell transplantation (HCT) has been successfully used as replacement therapy for patients with aplastic anemia and hemoglobinopathies. Both autologous and allogeneic HCT following high-dose chemotherapy can correct manifestations of autoimmune diseases. The impressive allogeneic graft-versus-tumor effects seen in patients given HCT for hematological malignancies have stimulated trials of allogeneic immunotherapy in patients with otherwise refractory metastatic solid tumors. This session will update the status of HCT in the treatment of benign hematological diseases and solid tumors. In Section I, Dr. Rainer Storb reviews the development of nonmyeloablative conditioning for patients with severe aplastic anemia who have HLA-matched family members. He also describes the results in patients with aplastic anemia given HCT from unrelated donors after failure of responding to immunosuppressive therapy. The importance of leuko-poor and in vitro irradiated blood product transfusions for avoiding graft rejection will be discussed. In Section II, Dr. Guido Lucarelli reviews the status of marrow transplantation for thalassemia major and updates results obtained in children with class I and class II severity of thalassemia. He also describes results of new protocols for class III patients and efforts to extend HCT to thalassemic patients without HLA-matched family members. In Section III, Dr. Peter McSweeney reviews the current status of HCT for severe autoimmune diseases. He summarizes the results of autologous HCT for systemic sclerosis, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus, and reviews the status of planned Phase III studies for autologous HCT for these diseases in North America and Europe. He also discusses a possible role of allogeneic HCT in the treatment of these diseases. In Section IV, Dr. Richard Childs discusses the development and application of nonmyeloablative HCT as allogeneic immunotherapy for treatment-refractory solid tumors. He reviews the results of pilot clinical trials demonstrating graft-versus-solid tumor effects in a variety of metastatic cancers and describes efforts to characterize the immune cell populations mediating these effects, as well as newer methods to target the donor immune system to the tumor.


2006 ◽  
Vol 163 (suppl_11) ◽  
pp. S142-S142
Author(s):  
C.J Benally ◽  
M Everett ◽  
J Moses ◽  
E Yazzie

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 26-27
Author(s):  
Tamar Berger ◽  
Odil Giladi ◽  
Dafna Yahav ◽  
Haim Ben-Zvi ◽  
Oren Pasvolsky ◽  
...  

Diarrhea affects a significant proportion of patients undergoing hematopoietic cell transplantation (HCT). In this single center retrospective study, we explored the diagnostic yield of stool cultures for enteric pathogens among patients undergoing HCT. Between May 2007 and April 2020, a total of 1072 individuals underwent autologous (n=603) and allogeneic (n=469) HCT. Overall, 947 stool culture samples were obtained from 561 (52%) patients with diarrheal illness during hospitalization for HCT. Most (99%) samples were obtained beyond 3 days of admission and mainly (77%) during neutropenia. Overall, only four (autologous HCT, n=3; allogeneic HCT, n=1) patients were diagnosed with positive stool culture (0.42%) and in all cases, Campylobacter spp. was the pathogen identified. All isolates grew from the first stool culture obtained. The number of stool cultures needed-to-test to diagnose one case of bacterial infection was 237. The cost of diagnosing one case of bacterial infectious diarrhea was 8,770 US dollars. The median time from admission to positive stool culture sample was 12 (range, 7 to 13) days. Patients with a positive stool culture did not have discerning clinical or laboratory characteristics. In conclusion, according to our experience, the yield of stool cultures for enteropathogens in patients undergoing HCT is extremely low and thus should be avoided in most cases. Disclosures Wolach: Amgen: Other: Fees for lectures and Consultancy; Janssen: Other: Fees for lectures and Consultancy; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures and Consultancy, Research Funding; Astellas: Consultancy, Honoraria, Other: Fees for lectures and Consultancy.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1030-1030
Author(s):  
Lucy A Godley ◽  
Uchenna O. Njiaju ◽  
Margaret Green ◽  
Howard Weiner ◽  
Shang Lin ◽  
...  

Abstract Abstract 1030 Poster Board I-52 Few clinical protocols have focused exclusively on the care of patients with therapy-related myeloid neoplasms (t-MN), and typically the disease confers a poor prognosis. We conducted a clinical trial exclusively for these patients. Between February 2003 and February 2009, we enrolled 32 adult patients with untreated t-MN. The median age was 56 years old (range, 23-83), and 38% were >60 years old. Eight patients (25%) had a total combined Charlson comorbidity index of >4, indicating that they were at high-risk for toxicity from the treatment, either due to older age or medical co-morbidities. T-MN developed following cytotoxic therapy for a malignant disease in 28 patients (88%), following cytotoxic therapy for rheumatologic disease in 2 patients (6%), and with immunosuppressive therapy after solid organ transplants in 2 patients (6%). The latency interval was highly variable, but the greatest fraction of patients (28%) experienced a latency of 4 - 9 years between their primary cytotoxic treatment and development of t-MN (median latency, 3.6 years; range 0.9-23 years). In 8 patients (25%), the latency was 2 years or less. 84% of patients had clonal cytogenetic abnormalities; 35% had a complex karyotype; 45% had abnormalities of chromosomes 5 or 7 or both.; 5 patients had t(9;11). All patients received induction chemotherapy with high-dose cytarabine (3,000mg/m2 over 4 hours) followed immediately by mitoxantrone (30mg/m2 over 1 hour), both given once on days 1 and 5 in a timed-sequential schedule. The complete remission (CR) rate after a single course was 66% and the partial remission (PR) rate was 16%, for an overall response rate of 82%. Grade 4 cardiac dysfunction occurred in 4 patients, resulting in the early death of one. Three of these patients had normal ejection fractions prior to beginning induction chemotherapy (including the patient who died), and one began therapy with an ejection fraction of 43%. Among the 21 patients who achieved a CR, 13 (62%) received consolidation therapy with allogeneic HCT, 4 (19%) received an autologous HCT, and 3 (14%) received only further chemotherapy. Three of the 5 patients who achieved a PR received an allogeneic HCT. Long-term disease-free survival (DFS) was observed in patients with each of the 3 modalities of consolidation therapy. The median overall survival (OS) was 399 days (range, 15-1972+), and OS at 1 year was 51%. Survival was significantly better among those patients who achieved a CR (median, 673 days) compared to those who had a PR (median, 126 days) to induction chemotherapy (P=0.003). OS at 1 year was 74% for patients who had achieved a CR compared with 20% for patients who had achieved a PR to induction. Median DFS was 415 days, with 59% of patients remaining disease-free at 1 year. OS was significantly longer in patients who underwent HCT compared to those who did not. The median survival for patients who received an allogeneic HCT was 673 days (range, 74-1798+) compared to 399 days for patients who received an autologous HCT (range, 353-917+), and 93 days for patients who received no transplant (range, 15-1972+) (P=0.002). OS at 1 year was 72% for patients who had undergone an allogeneic HCT, 75% for patients who had an autologous HCT, and 17% for patients who had not received a transplant. The DFS at 1 year was 67% for patients who underwent either an allogeneic or autologous stem cell transplant compared to 25% for those who did not have a transplant. To date, 9 patients (28%) remain alive and disease-free: 7 (22%) after allogeneic HCT; 1 after autologous HCT; and 1 after consolidation with only chemotherapy. Overall, remission induction therapy with high-dose cytarabine and mitoxantrone is an effective and tolerable regimen for patients with t-MN, allowing aggressive consolidation regimens, HCT, and long-term disease-free survival. Disclosures: Stock: Genzyme: Research Funding.


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