A Prospective Cost Analysis of Non-Myeloablative Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2239-2239
Author(s):  
Chris Skedgel ◽  
Jo-Ann Edwards ◽  
Jean Roy ◽  
Andrea McNeil ◽  
Yvonne Gulliver ◽  
...  

Abstract Hematopoietic stem cell transplantation (HSCT) is an intensive medical therapy used to treat both malignant and non-malignant conditions. Non-myeloablative transplantation (NMT) is an emerging transplant modality often performed on an outpatient basis. While NMT is associated with fewer acute complications compared to myeloablative HSCT, long-term complications, particularly chronic graft vs host disease (GvHD), are of concern. To our knowledge, there have been few economic evaluations of NMT and none in a Canadian healthcare environment. We prospectively developed and validated a process for capturing the costs and outcomes of NMT in order to estimate the cost per patient of NMT at a Canadian transplant centre. Ten consecutive patients undergoing NMT were followed from the first day of conditioning (Day −11) until either 1 year post-transplant or death. Donor costs were also recorded. All patient encounters, procedures and interventions during the study period were prospectively recorded. Nursing and other non-physician human resource costs were calculated based on recorded contact times and salaries. Physician costs were derived from Nova Scotia fee codes. Costs of hospital admissions were derived from Ontario Case Costing Initiative (OCCI) data and were specific to the primary diagnosis. Drug costs were based on acquisition costs at hospital and community pharmacies. Materials and equipment costs were based on costs at the QEII Health Sciences Centre, Halifax NS. The proportion of administrative costs to direct costs was derived from OCCI data and applied to local direct costs. All costs are in 2005 Canadian dollars ($CAN). Ten patients were followed for a median of 12 months (range 3.6–12) from September 2003 to April 2005. Eight patients were male and the median age of the cohort was 60 years (19–73). Five patients had AML; 3 had lymphoma and 2 had multiple myeloma.Cyclophosphamide and fludarabine were used as conditioning and tacrolimus and mycophenolate mofetil were used as GvHD prophylaxis. There were 7 hospital admissions among the 10 patients: 3 before day 100 and 4 after day 100. Eight patients survived at least one year post-transplant. No patients developed acute GvHD, while all 8 patients surviving to 1 year post-transplant developed chronic GvHD. Three patients relapsed within 1 year. The average cost per NMT was $CAN 43,377 of which $CAN 31,761 were recipient costs, $CAN 2,562 were donor costs and $CAN 8,675 were equipment and overhead costs. The key cost driver was hospital admissions for complications and/or palliative care at $CAN 9,793 per recipient. Physician fees ($CAN 6,958) and chemotherapy ($CAN 6,485) were also significant. Compared to published estimates of the cost of myeloablative HSCT, NMT appears considerably less costly in the first year post-transplant. Our analysis suggests that the lower cost of NMT was largely attributable to the limited amount of inpatient care these patients received. Further follow-up will be informative since the major complications of NMT including chronic GvHD and relapse may impact per transplant cost after the first year post-transplant. Direct comparison with myeloablative HSCT using our prospective costing method is also planned.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2107-2107
Author(s):  
Christopher R. D'Angelo ◽  
Aric C. Hall ◽  
Kyungmann Kim ◽  
Ryan J. Mattison ◽  
Walter L. Longo ◽  
...  

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for myelodysplastic syndrome (MDS) and high-risk acute myeloid leukemia (AML). Patients with high-risk disease have a markedly increased risk of relapse and death following transplant (Armand et al, Blood, 2014). Those who remain disease-free are at risk of severe morbidity from graft-versus- host-disease (GvHD). These issues highlight the importance of improved allo-HSCT platforms designed to reduce relapse rate without increasing risk of GvHD. Decitabine has minimal non-hematologic toxicity and proven efficacy in myeloid diseases (Blum et al, PNAS, 2010). Use of post-transplant cyclophosphamide has demonstrated improved rates of GvHD following allo-HSCT using haplo-identical donors (Bashey et al, JCO, 2013). No studies have reported on outcomes in patients undergoing decitabine immediately prior to transplantation followed by post-transplant cyclophosphamide (PTCy). We hypothesized that the combination of decitabine induction prior to transplant and PTCy would be safe and result in improved disease control with low rates of GVHD, translating into improved survival in a high-risk transplant cohort. Methods In this single-arm, single institution trial, eligible patients received 10 days of IV decitabine at 20mg/m2 no sooner than 24 days and no later than 17 days prior to conditioning. Myeloablative conditioning included fludarabine (50mg/m2 day-5-2), busulfan (IV 3.2mg/kg/day -5-2), and 4 Gy total body irradiation on day -1. Patients above age 65 received a 25% busulfan dose reduction. Patients received a fully or partially matched related bone marrow graft on day 0. GvHD prophylaxis included 50mg/kg of IV cyclophosphamide on day +3-4. Patients with fully matched donors received only PTCy while those with partially matched donors also received mycophenolate mofetil through day +35 and tacrolimus through day +180. Results We enrolled 20 patients, fifteen patients with AML and 5 with MDS. The cohort had a median age of 64 (29-73) and was predominantly male (14/20, 70%). Eight (40%) patients scored as high risk by the HSCT comorbidity index. Eighteen patients (90%) had a high or very high-risk score by the refined disease risk index. All patients received decitabine and 18/20 (90%) underwent transplantation; 2 patients did not receive a transplant due to infectious complications. The majority of patients received a haplo-identical graft (13/18, 72%), and the remaining 5 received a matched related graft. Outcomes are reported in table 2 and figure 1. There were no engraftment failures. Five patients, 3 MDS and 2 AML, are long-term survivors with median follow-up over 3 years. One patient developed donor derived MDS and required a second transplant. Most transplanted patients (13/18, 72%) survived to day 100 with a median post-transplant survival of 138 days. There were 15 deaths on study with the majority due to underlying disease. Six patients (6/20, 30%) died of infectious complications or did not receive a transplant due to infection. Incidence of grade 3-4 acute GvHD was low among those surviving at least 40 days from transplant (3/17, 17%). There were also low rates of chronic GvHD among the 12 patients alive without ongoing GvHD at day 100 (2/12, 17%). Conclusions Decitabine induction followed by myeloablative conditioning in this high-risk population resulted in a high treatment related mortality of 40%. Still, outcomes fell into an expected range for high-risk myeloid disease in an elderly and comorbid population. Based on expected outcomes for high-risk patients from the literature (Armand et al, Blood, 2014), decitabine did not markedly improve overall survival outcomes, recognizing that no direct comparisons are available in our limited study population. Decitabine may increase the risk of peri-transplant infections by contributing to a cumulative immunologic insult combined with disease-related immunosuppression and transplant-related toxicity, highlighting the importance of strict vigilance for infections within this setting. Diligent monitoring may improve infectious outcomes as shown in the second half of the cohort; only two out of the latter 10 patients on protocol died of treatment related complications. There were no cases of engraftment failure. Rates of acute and chronic GvHD using a PTCy platform were low and support other studies reporting this benefit. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2848-2848
Author(s):  
Marie Robin ◽  
Raphaël Porcher ◽  
Renato De Castro Araujo ◽  
Régis Peffault de Latour ◽  
Agnès Devergie ◽  
...  

Abstract After allogeneic hematopoietic stem cell transplantation (HSCT), late infections represent a major cause of morbidity and mortality but little has been previously reported. In a retrospective cohort study, late infections incidence was determined in 196 long-term survivors after matched related HSCT. Only patients transplanted for aplastic anemia, chronic myeloid leukemia (CML) and acute myeloblastic leukemia (AML) were included in this study. Median follow-up was 8 years. Among 30 patients who died beyond the first year, 9 patients died from graft-versus-host disease (GVHD) and 10 from infections. Bacterial late severe infections occurred in 30 patients, yielding an 8-year cumulative incidence of 15%. Late invasive fungal infection occurred in 8 patients corresponding to a cumulative incidence of 3.6%. Most viral infections were hepatitis C and VZV and overall late viral infection incidence was 35%. We identified 3 risk factors for bacterial infections in multiple analysis: CMV status (positive recipient and negative donor), irradiation based conditioning regimen and extensive chronic GVHD within the first year. Extensive chronic GVHD was the only risk factor of non-HCV viral infection in patients transplanted for AML or CML. Thus, late life threatening infections may occur in nearly a fourth of late survivors even after matched related transplantation and are associated not only with chronic GVHD but also with irradiation and to CMV status prior to transplantation.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1-1 ◽  
Author(s):  
Cornelis N. De Jong ◽  
Ellen Meijer ◽  
Katerina Bakunina ◽  
Erfan Nur ◽  
Marinus van Marwijk Kooij ◽  
...  

Background Allogeneic hematopoietic stem cell transplantation (alloHSCT) has been established as a powerful treatment modality for patients with hematological malignancies. The graft-versus-leukemia effect, however, is strongly associated with the occurrence of graft-versus-host disease (GVHD) and subsequent transplant-related mortality (TRM). Several strategies are applied in order to prevent GVHD following T-cell replete alloHSCT including conventional immunosuppression (CIS) with post-transplant administration of cyclosporine A (CyA) and mycophenolic acid (MA), or post-transplant cyclophosphamide (PT-Cy) either or not combined with CIS. Studies in haplo- and HLA matched donor transplantation have shown that PT-Cy is well tolerated and associated with low rates of severe GVHD and TRM. However, evidence from randomized clinical trials on the efficacy of PT-Cy as compared to CIS in the setting of HLA matched alloHSCT is scarce. Aims In the present prospective randomized, multicenter, phase III trial we set out to compare a PT-Cy based immunosuppressive regimen with CIS and address the question whether PT-Cy would be associated with improved GVHD-free/relapse-free survival (GRFS). Endpoints included time to acute and chronic GVHD, progression free survival (PFS), GRFS, overall survival (OS), and adverse events. Methods Hematological patients (pts) with a matched related donor or at least an 8 out of 8 matched unrelated donor were included. Pts randomized for the CIS regimen received CyA twice daily until day +120 followed by tapering until day +180 and MA 16 mg/kg twice daily with a maximum dose of 2160 mg a day until day 84 post-transplant. Pts randomized for PT-Cy received 50 mg/kg of cyclophosphamide on day +3 and +4 combined with CyA from day +5 until day +70. Results A total of 160 pts was randomized 1:2 between CIS and PT-Cy, of whom 94% proceeded to transplant (52 versus 99 pts). Median age was 58 years (range: 20-70), 66% were male. Two pts received myeloablative conditioning. The donor type was matched related in 31% and matched unrelated in 69% of pts. Transplants were derived from peripheral blood in 97% of pts and consisted of median 6.14x106/kg CD34+ cells/kg (range: 1.36-19.4) and median 230x106/kg CD3+ T cells (range: 0-519). Baseline patient and transplantation characteristics were equally distributed between the two treatment arms. The cumulative incidence (CI) at six months of grade II-IV acute GVHD was 48% in recipients of CIS versus 32% following PT-Cy (SHR 0.52, 95%CI 0.31-0.87, p=0.014), and grade III-IV 12% versus 6%. In recipients of PT-Cy, acute GVHD was generally limited to stage 1 skin involvement, whereas more severe skin involvement and bowel involvement were observed following CIS. The two-year CI of chronic extensive GVHD was 50% in recipients of CIS versus 19% following PT-Cy (SHR 0.38, 95%CI 0.21-0.67, p=0.001). The three-year estimate of PFS was 60% (44%-73%) and 58% (46%-67%). The three-year CI of progression/relapse was 26% in the CIS arm versus 32% in the PT-Cy arm. The three-year estimate of OS was 69% (53%-80%) and 63% (52%-73%). The one-year estimate (95% confidence interval) of GRFS was 22% (12%-34%) and 45% (35%-55%), respectively. Conclusion Use of high-dose PT-Cy results in a significant reduction in severe acute and chronic GVHD without affecting relapse, thereby resulting in improved GRFS. Hence, a more intensified immunosuppression regimen with PT-Cy might be preferred as GVHD prophylaxis in the setting of RIC alloHSCT. Figure Disclosures Nur: Novartis Pharmaceuticals: Consultancy. Maertens:Cidara: Other: Personal fees and non-financial support; Gilead Sciences: Other: Grants, personal fees and non-financial support; Amplyx: Other: Personal fees and non-financial support; Merck: Other: Personal fees and non-financial support; Pfizer: Other: Grant and personal fees; Astellas Pharma: Other: Personal fees and non-financial support; F2G: Other: Personal fees and non-financial support. Deeren:Alexion, Amgen, Janssen, Roche, Sunesis, Takeda, Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.


2010 ◽  
Vol 28 (14) ◽  
pp. 2365-2372 ◽  
Author(s):  
Madeleine Duvic ◽  
Michele Donato ◽  
Bouthaina Dabaja ◽  
Heather Richmond ◽  
Lotika Singh ◽  
...  

Purpose Transformed mycosis fungoides (MF) and Sézary syndrome (SS) are currently incurable. We studied the safety and efficacy of total skin electron beam with allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with cutaneous T-cell lymphoma (CTCL). Patients and Methods Nineteen patients with advanced CTCL (median age, 50 years; four prior therapies) underwent total skin electron beam radiation followed by allogeneic HSCT between July 2001 and July 2008. Sixteen patients were conditioned with fludarabine (125 mg/m2) and melphalan (140 mg/m2) plus thymoglobulin (for mismatched donors). Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus/mini methotrexate. Results Eighteen patients experienced engraftment, and one died as a result of sepsis on day 16. Median time to recovery of absolute neutrophil count (ANC) was 12 days. Fifteen achieved full donor chimerism, 12 had acute GVHD, and 12 were treated for chronic GVHD. The overall intent-to-treat response was 68%, and the complete response rate was 58%. Four of six patients died in complete remission as a result of bacterial sepsis (n = 2), chronic GVHD and fungal infection (n = 1), or lung cancer (n = 1); only two died as a result of progressive disease. Eight experienced relapse in skin; five regained complete response with reduced immunosuppression or donor lymphocyte infusions. Eleven of 13 are currently in complete remissions, with median follow-up of 19 months (range, 1.3 to 8.3 years). Median overall survival has not been reached. Conclusion Total skin electron beam followed by allogeneic stem-cell transplantation merits additional evaluation for a selected group of patients with refractory, advanced, cutaneous T-cell lymphoma with evidence for graft-versus-tumor effect.


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