scholarly journals Comparison of Outcomes between the Cellex and Uvar-Xts Closed-System Extracorporeal Photopheresis (ECP) Devices When Used for Graft-Versus-Host Disease; A Single Center Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4686-4686
Author(s):  
Amber Afzal ◽  
Maryna Tarbunova ◽  
George Despotis ◽  
Brenda J. Grossman
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Dose Reduction ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Buffy Coat ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Steroid Dose

Abstract BACKGROUND: Graft versus host disease (GVHD) is a significant contributor to non-relapse mortality after allogeneic stem cell transplant (SCT). Steroids are first line therapy and extracorporeal photopheresis (ECP) is used as second line therapy for steroid refractory or intolerant patients. ECP has immunomodulatory effects rather than immunosuppressive effect which decreases the risk of infection, and may decreases the risk of disease relapse. There are two ECP instruments approved in the US for the treatment of Cutaneous T Cell Lymphoma (CTLC), however both have been used "off-label" to prevent or treat solid organ transplant rejection, acute and chronic GVHD, and other autoimmune diseases. Until recently the UVAR-XTS instrument has been the most commonly used closed system in the US until the CELLEX was approved in 2009. The CELLEX and the UVAR-XTS procedures are similar in that buffy coat is collected, exposed to methoxsalen (UVADEX®) ex vivo and then UVA light before returning the treated cells back to the patient in a closed looped system. The instruments differ in the collection of the buffy coat; collection is continuous by the CELLEX, and it is intermittent by UVAR-XTS. In addition CELLEX has been shown to be more efficient in collecting mononuclear cells when compared to the UVAR -XTS. Little clinical data is available comparing the clinical efficacy of the two instruments in the setting of GVHD. We designed a single institution retrospective study to compare the efficacy and safety of the two instruments. The primary outcomes analyzed were >/=50% reduction of steroid dose between the initial and final dose during the study period, and the number and type of adverse events that occurred during the ECP procedures. METHODS: Study Population: We reviewed charts of allogeneic stem cell transplant patients who received ECP for the treatment of acute or chronic GVHD between 1/2009 and 12/2015. The patients were divided into two groups based on the type of ECP instrument that was used. One group was exclusively treated with UVAR-XTS while the second group with CELLEX. Patients who received treatments with both instruments were excluded. The frequency of steroid dose reduction by >/=50%, and toxicity was compared between the two instruments while adjusting for age, gender, GVHD severity, number of organs involved by GVHD, type of allogeneic stem cell transplant, conditioning regimen, number of other immunosuppressants, type of anticoagulants (ACDA vs heparin), type of access line, and baseline blood counts. Statistical Analysis: The baseline characteristics of the patients in the two groups were compared using Chi square, Fischer's exact test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. Chi square analysis was used to determine the difference in frequency of >/=50% steroid dose reduction and adverse events between the two groups. Logistic multivariate regression was used to evaluate the potential interactions of all significant covariates. A p value of less than 0.05 was considered to be statistically significant. Statistical analyses were performed using STATA14 software (StataCorp, College Station, TX). RESULTS: We identified 242 allogeneic SCT recipients who received ECP for acute or chronic GVHD in the study period, 146 of whom met the selection criteria. 69 patients had all procedure performed with UVAR-XTS and 77 patients had all procedures performed with CELLEX. There was no significant difference in age, gender, percent of acute GVHD, anticoagulant used, type of transplant, number of organs involved, number of immunosuppressants, vascular access and baseline blood counts between the two treatment cohorts as shown in table 1. Although year of transplant and conditioning regimen were different between the two cohorts, neither of these covariates influenced the impact of instrument on the primary outcome. In multivariate analysis, the patients who underwent ECP with CELLEX were 3 times more likely to have >/=50% steroid dose reduction (p =0.01). The total number of adverse events was similar between the instruments (p = 0.73). (Table 2) CONCLUSION: More than twice as many patients with GVHD treated with the CELLEX had a steroid dose reduction by >/=50% reflecting clinical improvement when compared to the patients treated with the UVAR-XTS. Similar safety profile was observed between the two instruments based on a similar number of adverse events. Disclosures No relevant conflicts of interest to declare.

scholarly journals Busulfan and Fludarabine As Conditioning Regimen for Unrelated Allogeneic Stem Cell Transplant: A Single-Center Experience

2016 ◽  
Vol 22 (3) ◽  
pp. S358
Author(s):  
Grerk Sutamtewagul ◽  
Kamal Kant Singh Abbi ◽  
Umar Farooq ◽  
Sarah L. Mott ◽  
Lindsay Dozeman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Single Center ◽  
Single Center Experience

Conditioning with Fludarabine, Busulfan, and ATG Prior to Reduced-Intensity Allogeneic Stem Cell Transplant for CLL Is Associated with a Low Incidence of Acute Graft-Versus-Host Disease.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4568-4568
Author(s):  
Samantha M. Jaglowski ◽  
Diane Scholl ◽  
Patrick Elder ◽  
Thomas S. Lin ◽  
John C. Byrd ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Graft Versus Host ◽  
Significant Difference ◽  
Reduced Intensity ◽  
Count Recovery

Abstract Abstract 4568 Introduction: Allogeneic stem cell transplant (SCT) is the only potentially curative treatment available for CLL. While transplant-related mortality has decreased with use of reduced-intensity conditioning (RIC) regimens, acute and chronic graft-versus-host-disease (GVHD) remain important causes of morbidity and mortality, with up to 50% of patients developing chronic GVHD (cGVHD). While the optimal way to combat this has not been established, in vitro T cell depletion with ATG or alemtuzumab has been employed to attempt to lessen its incidence. Herein, we report our institutional experience with each of these agents. Patients and methods: Information on all patients who underwent RIC allogeneic SCT at Ohio State from January 1, 2002 to June 29, 2010 was obtained following approval from the ORRP. Data collected by the transplant coordinators was correlated with data in our electronic databases. Comparative statistics were performed using the Fisher exact test and all p-values are two-sided. Results: Between January 1, 2002 and June 29, 2010, 50 patients with CLL/SLL underwent RIC allogeneic SCT at Ohio State. Pretransplant characteristics are listed in Table 1. Thirty patients received fludarabine, busulfan, and ATG (FBA) as a preparative regimen, and 8 patients received alemtuzumab, fludarabine, and TBI (Cam/Flu/TBI). Another 6 patients received fludarabine and busulfan, 4 received fludarabine and cyclophosphamide, one received pentostatin, fludarabine, and ATG, and the patient who had a cord blood transplant received fludarabine, cyclophosphamide, TBI, and ATG. The breakdown of characteristics between patients who received FBA and Cam/Flu/TBI is also provided in Table 1. None of the characteristics were statistically different. Time to count recovery is provided in Table 2. There was not a statistically significant difference in the time to count recovery between FBA and Cam/Flu/TBI. Patients who received Cam/Flu/TBI received significantly more DLIs; patients who received FBA have not required any DLIs. Incidence of acute and chronic GVHD is provided in Table 3. There was not a statistically significant difference in rates or grades of aGVHD, but patients who received Cam/Flu/TBI were more likely to develop extensive cGVHD. Conclusions: While patients who received Cam/Flu/TBI were more likely to receive DLI, these were all done to treat disease recurrence, reflecting changes in group practice over time. There were no failures to engraft with FBA, and while not statistically significant in comparison to Cam/Flu/TBI, only 10% of patients developed grade 3 or 4 aGVHD. All of the patients who received Cam/Flu/TBI and developed cGVHD developed extensive disease. While the Cam/Flu/TBI sample is small, the FBA patients appear to fare no worse in terms of count recovery and development of GVHD without exposure to TBI, and this has become our institutional practice for patients with CLL. Disclosures: Lin: GlaxoSmithKline: Consultancy, Employment.

Chronic Graft-Versus-Host Disease after Allogeneic Stem Cell Transplant with in Vivo T-Cell Depletion By Alemtuzumab: Incidence, Outcome and Pattern of Organ Involvement

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3912-3912 ◽  
Author(s):  
Maria Chiara Finazzi ◽  
Cristina Boschini ◽  
Janice Ward ◽  
Charles Craddock ◽  
Alessandro Rambaldi ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Cell Depletion ◽  
Organ Involvement ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
T Cell Depletion

Abstract Introduction Graft-versus-Host Disease (GvHD) is one of the leading causes of mortality and morbidity following allogeneic stem cell transplant. In vivo T cell depletion by alemtuzumab as part of the transplant conditioning is an effective strategy to reduce the risk of GvHD. While it is recognised that the overall incidence of GvHD is reduced by alemtuzumab, the incidence of chronic GvHD as defined by the National Institute of Health (NIH) consensus criteria, the impact on outcome, and the pattern of organ involvement have not been defined yet in this transplant setting. Methods Consecutive patients (n = 323) undergoing allogeneic stem cell transplantation at the Queen Elizabeth Hospital, Birmingham, between January 1 2008 and June 30 2012 were reviewed in this retrospective, single centre study. Medical records were examined and data regarding the development of GvHD were collected; NIH consensus criteria for diagnosis and staging of chronic GvHD were stringently applied. Clinical characteristics of GvHD occurring in patients transplanted following T cell depletion by alemtuzumab administration (n=248) were compared with those of patients transplanted with a T cell replete graft (n=75). Patients receiving alemtuzumab were mainly treated with reduced-intensity conditioning protocols, while patients in the no-T-cell depletion group were mainly treated with a myeloablative, sibling transplant. Results After a median follow up of 38.4 months, the cumulative incidence (CI) of grade II-IV classic acute GvHD was 35% and 48% for patients transplanted respectively with or without T cell depletion by alemtuzumab (p= 0.041, Figure 1); with a CI of grade III-IV classic acute GvHD of 13% and 27% (p=0.007). The 2-years CI of grade II-IV late acute GvHD was not significantly different in the two groups (20% and 23% for patients respectively treated with or without alemtuzumab, p=0.589, Figure 2). T cell depletion by alemtuzumab significantly reduces the 3 years cumulative incidence of classic chronic GvHD (5% versus 31%, p<0.0001, Figure 3.A), but without a significant difference in the incidence of overlap syndrome between patients with and without T cell depletion (3 years CI respectively 6% and 7%, p=0.839, Figure 3.B). The pattern of organ involvement by classic acute GvHD was similar in patients with and without T cell depletion. The pattern of organ involvement by late acute GvHD in the alemtuzumab group was, however, significantly different compared to the T cell replete group (skin-gut-liver involvement reported respectively in 83%-28%-4% of patients and 56%-48%-20% of patients, p=0.003). Distribution of organ involvement by classic chronic and overlap syndrome was similar in the two groups; however, it seems that alemtuzumab prevents the development of lung GvHD (lung GvHD developed in 4 patients over the 75 patients of the no-T-cell depletion group, while none of the 248 patients transplanted with alemtuzumab experienced lung GvHD). In a multivariate analysis, the development of chronic GvHD was an independent predictor of higher mortality risk (HR 1.66, p = 0.04) and severe NIH global score at peak was confirmed as a poor prognostic factor for survival (HR 2.27, p=0.02). The negative impact of chronic GvHD and of the severe forms of chronic GvHD was independent of age and alemtuzumab administration. Conclusion This retrospective analysis provides for the first time data on the incidence rates of NIH-defined GvHD categories in patients transplanted after T cell depletion by alemtuzumab. Patients transplanted with alemtuzumab experienced a lower incidence of classic acute and classic chronic GvHD compared to patients not receiving T cell depletion. In contrast, alemtuzumab conditioning appeared to have no effect on the incidence of late acute GvHD or overlap syndrome, suggesting that these two entities of GvHD are driven by different immunological mechanisms as compared to classic acute and classic chronic GvHD. We also confirmed the utility of the NIH classification of GvHD and of the NIH global severity score to predict survival in alemtuzumab-conditioned allogeneic stem cell transplant. Disclosures No relevant conflicts of interest to declare.

A validated symptomatic BKV risk assessment score in patient post allogeneic stem cell transplant.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18536-e18536
Author(s):  
Ala Abudayyeh ◽  
Heather Y. Lin ◽  
Maen Abdelrahim ◽  
Gabriela Rondon ◽  
Borje Andersson ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cumulative Incidence ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Large Cohort ◽  
Grading System ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Cell Immunity

e18536 Background: BKV, Polyomavirus hominis 1, is a member of the family Polyomaviridae, is a non-enveloped virion; in the 1980s, it emerged as an important pathogen in SCT recipients. In the absence of sufficient T-cell immunity, BKV reactivation can progress, leading to prolonged hospital stays and increased mortality secondary to late hemorrhagic cystitis, ureteral stenosis, and nephropathy. In our recently completed retrospective study of 2477 SCT patients, 38.1% had developed renal impairment, and BKV viruria was present in 25%. In addition, BKV was found to be an independent predictor of chronic kidney disease and shorter survival. Using the large cohort (2477) patients studied earlier (2004-2012) we have derived a grading system to identify patients with risk of symptomatic BKV. We hypothesize that the current grading system will identify the patients at risk of symptomatic BKV at day 30 post allogeneic stem cell transplant. Methods: We performed a retrospective chart review of all patients who underwent allogeneic SCT from 2012-2016. The data was extracted from the secured database at MD Anderson cancer Center. Using the three variables that were significant predictor for symptomatic BKV derived from our initial study (conditioning regimen, HLA donor status, & underlying cancer diagnosis) we performed the analysis. Predicted cumulative incidence rate of BK infection at 30 days after transplant in 1308 patients were calculated in the presence of death as a competing risk using the “BASELINE” statement in PHREG procedure in SAS. Patients were classified into low, moderate and high risk according to the distribution of the predicted cumulative incidence of BK infection 30 days after transplant. Results: We have shown that the grading system derived from allogeneic SCT population predicted accurately the high, moderate & low risk population for developing symptomatic BKV. Conclusions: We have created and validated a grading system for symptomatic BKV in a large cohort of (1308 patients) to predict risk at day 30 post allogeneic SCT. Using this grading system we would hope to identify high risk patients for BKV and intervene early with novel therapies prior to complications associated.

scholarly journals Risk Factors for Relapse Following Allogeneic Transplant for Acute Myeloid Leukemia in the UCLA Patient Population

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5855-5855
Author(s):  
Harsh Patel ◽  
Alfonso Molina ◽  
Mina Nikanjam ◽  
Gary J. Schiller
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Stem Cell Source ◽  
Donor Type ◽  
Time To Relapse ◽  
Risk Categorization

Abstract Introduction: Allogeneic stem cell transplant for acute myeloid leukemia (AML) is curative for a subset of patients, however carries a substantial risk of adverse outcomes. Additional information identifying factors relating to relapse, in particular early relapse within one year, can be useful in counseling patients on the risks and benefits of this procedure. The current study represents a retrospective analysis on the UCLA patient population with the goal of identifying the subset of patients at higher risk for relapse. Methods: Data were obtained from the UCLA allogeneic stem cell transplant registry and electronic medical record on patients receiving allogeneic stem cell transplants for acute myeloid leukemia between January 2008 and September 2015. Fischer's exact (categorical variables) or t-tests (continuous variables) were used to determine differences between relapsed and non-relapsed patients, while Cox proportional-hazards regression was used to determine how time-to-relapse varied with age, gender, American Society for Blood and Marrow Transplant (ASBMT), risk categorization (low vs. intermediate or high), donor type (matched related vs. matched unrelated or cord blood), stem cell source (peripheral blood vs. bone marrow or cord blood), conditioning regimen (myeloablative vs. reduced intensity), disease status at transplant (first complete remission vs. later remission), and the presence of chronic graft vs. host disease (GVHD) with statistical software (SAS v. 9.4). For the time-to-relapse analyses, patients not relapsing by the last UCLA clinic visit were included as censored patients, while patients who died prior to relapse were treated as a competing risk. Patients who relapsed or died within 100 days of transplant were not included in the chronic GVHD analyses. Results: 164 patients receiving allogeneic stem cell transplant for AML were included in the analysis of which 49 patients had relapsed by June 2016. Median time to relapse was 158 days (range: 41-2449) and for non-relapsed patients median follow-up was 547 days (range: 31 - 2893). Median age for relapsed patients was 54 years (range: 21-71) and for non-relapsed patients was 55 years (range: 18- 75). Chronic GVHD occurred more often in non-relapsed patients (p=0.008), however no significant differences were found between relapsed and non-relapsed patients for age (p=0.99), gender (p=0.24), conditioning regimen (p=0.29), stem cell source (p=0.82), donor type (p=0.86), ASBMT risk categorization (p=0.31), and disease status at transplant (p=0.59). For patients who relapsed within 1 year compared to those who remained in remission at 1 year, chronic GHVD occurred more frequently in patients who remained in remission (p=0.0004), but no significant differences were found for age (p=0.32), gender (p=0.36), conditioning regimen (p=0.34), stem cell source (p=1.00), donor type (p=1.00), ASBMT risk categorization (p=0.27), and disease status at transplant (p=0.70). Time-to-relapse [hazard ratio (95% confidence interval); p-value] was significantly increased by the presence of chronic GVHD [2.88 (1.45-5.70); p=0.0024], while no significant differences were seen with age (1.00 (0.98-1.02); p=0.82), gender [0.75 (0.43-1.31); p=0.31], ASBMT risk categorization [1.49 (0.85-2.58); p=0.16], conditioning regimen [0.70 (0.40-1.24); p=0.22], stem cell source: peripheral blood stem cell vs. bone marrow [1.21 (0.58-2.54);p=0.61] or cord blood [0.91 (0.46-1.82);p=0.80], donor type [1.16 (0.67-2.03); p=0.59], and disease status at transplant [1.28 (0.72-2.27); p=0.41]. Conclusions: The presence of chronic GHVD was found to significantly decrease the risk of relapse after allogeneic stem cell transplant, however no significant differences in factors that can be assessed prior to transplant were found between the relapsed and non-relapsed patient population. It is important to note that the ASBMT criteria may insufficiently assess the risk of relapse since molecular analysis is not routinely captured. Further studies will be needed to determine predictive factors leading to a higher risk of relapse and the patient population that may benefit from clinical trials rather than allogeneic stem cell transplant. Disclosures Schiller: Incyte Corporation: Research Funding.

The impact of initiating posaconazole on tacrolimus pharmacokinetics in allogeneic stem cell transplantation

2019 ◽  
Vol 26 (1) ◽  
pp. 5-12
Author(s):  
Jennifer Collins ◽  
Katherine Shea ◽  
Sandeep Parsad ◽  
Kelly Plach ◽  
Pauline Lee
Keyword(s):  
Stem Cell ◽  
Dose Reduction ◽  
Stem Cell Transplant ◽  
Academic Medical Center ◽  
Tacrolimus Concentration ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Transplant Patients ◽  
The Impact ◽  
Tacrolimus Pharmacokinetics

Background Posaconazole reduces the risk of invasive Aspergillus in transplant patients, but significantly inhibits tacrolimus metabolism. One study demonstrated that a three-fold dose reduction of tacrolimus was required to obtain therapeutic concentrations when used with posaconazole. However, with empiric dose reduction, there is a risk of subtherapeutic tacrolimus levels and subsequent graft failure or graft-versus-host disease. Overall, the existing data on the impact of posaconazole on tacrolimus pharmacokinetics is limited. Objective The purpose of this study is to determine whether tacrolimus doses should be decreased upon initiation of posaconazole in patients receiving an allogeneic stem cell transplant. Methods This is a retrospective chart review at an academic medical center. All allogeneic stem cell transplant adults who received concomitant posaconazole and tacrolimus from February 2016 through December 2017 were included. Results Seventy-nine patients identified using an internal electronic database were analyzed. The median time to therapeutic tacrolimus concentration was significantly longer in patients who did not receive an empiric dose reduction (0% DR, 10d; 1–30% DR, 4d; 31–65% DR, 5d; >65% DR, 4d; p = 0.0395). The rate of supratherapeutic levels was highest amongst patients who did not receive an empiric DR, and was noted to be significant compared to the group that had 31–65% DR ( p < 0.001). Conclusion This study validates our current practice of instituting an empiric 50% dose reduction of oral tacrolimus to 0.03 mg/kg/day when used concomitantly with posaconazole to achieve therapeutic levels in allogeneic stem cell transplant patients.

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