scholarly journals Phase I Clinical Trial of Targeted Marrow Irradiation in Combination with Fludarabine and Busulfan for Conditioning of Hematopoietic Cell Transplant in High Risk Patients

2018 ◽  
Vol 24 (3) ◽  
pp. S321
Author(s):  
Paolo Caimi ◽  
Naveed Ali ◽  
Brenda Cooper ◽  
Richard Creger ◽  
Ehsan Malek ◽  
...  
2019 ◽  
Vol 25 (10) ◽  
pp. 2031-2039 ◽  
Author(s):  
Vanessa P. Tolbert ◽  
Christopher C. Dvorak ◽  
Carla Golden ◽  
Madhav Vissa ◽  
Nura El-Haj ◽  
...  

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2032-2032 ◽  
Author(s):  
Henry J. Conter ◽  
Nhu-Nhu Nguyen ◽  
Gabriela Rondon ◽  
Julianne Chen ◽  
Elizabeth J Shpall ◽  
...  

Abstract Abstract 2032 Background: Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) preferentially afflict patients 65 years of age and older. Patients in this age group are likely to have underlying comorbid conditions. These comorbidities affect treatment planning decisions and clinical outcomes. Here we report comorbidity-stratified outcomes of patients older than 64 treated at MD Anderson Cancer Center from 1996 until 2011, inclusive, treated with allogeneic stem cell transplant (ASCT). Methods: 182 patients older than 64 received an ASCT for AML (n=143) or MDS (n=39). Patient charts were reviewed and comorbidity data abstracted using a standardized form. Burden of comorbidity was assessed using the Hematopoetic Stem Cell Transplant-Specific Comorbidity Index (HSCT-CI). Low-risk, intermediate-risk, and high-risk patients were categorised at 0, 1–2, and >=3 points as per the HSCT-CI. 157 patients were evaluable for pre-transplant comorbidity. Outcomes of interest were cumulative incidence of transplant-related mortality (TRM), cumulative incidence of relapse-related mortality (RRM), incidence of acute and chronic graft-versus-host disease (GVHD), and overall survival (OS). These were estimated from the date of transplantation. Results: The median age of transplanted patients was 67 (range 65–79), and 37 patients age 70 and older were treated. The majority of patients were intermediate-risk and high-risk patients (table), 9 patients had HSCT-CI scores of >=5. Median follow-up for alive patients was 12.6 months (n=63; range 0–118). Cumulative incidence of TRM was 6% at 100 days, 14% at 1 year, 23% at 2 years, and 36% at 5 years (figure). Cumulative incidence of RRM was 36% at 1 year, 42% at 2 years, and 47% at 5 years. HSCT-CI did not independently predict for either TRM or RRM (log-rank test p=0.95). The incidence of grade III and IV acute GVHD was 10% of all patients. The cumulative incidence of chronic GVHD was 25% at 1 year, 27% at 2 years, and 30% at 5 years, with no association between GVHD and HSCT-CI comorbidity. Conclusion: ASCT is a curative option for selected patients over age 64. HSCT-CI did not predict TRM or survival on this cohort of high-risk patients. Disease relapse was of greater concern than TRM, and so novel approaches to relapse prevention are needed. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2285-2285
Author(s):  
Ashanka M Beligaswatte ◽  
Eleni Tsiopelas ◽  
Ian Humphreys ◽  
Greg Bennett ◽  
Kathryn Robinson ◽  
...  

Abstract Abstract 2285 Background: HLA allo-immunized patients often receive matched platelets only after demonstrating platelet transfusion refractoriness (PTR). If further risk stratification was possible, high risk patients could be considered for pre-emptive HLA-matched platelets, cryopreserved autologous platelets, or possibly thrombopoietin analogues. Micro-bead flow cytometry is widely used to detect anti-HLA antibodies, and mean fluorescence intensities (MFI) obtained from these assays correlate with antibody titers. We asked whether MFIs could be used to stratify the risk of PTR among allo-immunized patients. Study design: We retrospectively identified 387 patients who received an autologous stem cell transplant or induction therapy for acute leukemia, between January 2005 and March 2012. All patients had a serum sample taken for HLA antibody assay within 6 weeks of commencing cellular blood product transfusions. No patient was scheduled to receive prophylactic HLA matched platelets. The primary endpoint was the development of PTR. To minimize the influence of sensitization occurring after screening, only outcomes during the first 2 weeks from commencing cellular blood product transfusions were considered. PTR was defined as having received ≥ 2 consecutive RDPLT transfusions associated with an 18–24h corrected count increment of < 2.5 at 18 – 24 hours. Antibody testing was performed using a micro-bead flow cytometry assay (Lifecodes LifeScreen Deluxe, with positive results confirmed by Lifecodes Class I ID assay, Gen-Probe Transplant Diagnostics, Stamford, CT) either during the treatment period, or on serum samples stored at −30°C. Mean fluorescence intensities (MFI) were acquired using a Luminex 100 analyzer (Luminex Corporation, Austin, TX), and analyzed using Lifecodes Quicktype v2.5.5 (Gen-Probe Transplant Diagnostics, Stamford, CT). We defined the predictor variable avgMFI to be the average MFI of the 7 individual beads in the assay, weighted by whether the presence of antibodies was confirmed or not: where w = 1 if the presence of antibodies is confirmed, and 0 otherwise; and subscript i refers to the ith class I bead. Results: Antibodies were detected in 57 (14.7%) patients of whom 45 (78.9%) were female. A total of 1443 random donor platelet (RDPLT) transfusions (mean platelet count 2.4×1011/unit) were studied. Sixty six (17%) patients developed PTR, of whom 28 had detectable antibodies; 29 of 321 patients who did not develop PTR also tested positive. Among antibody positive patients, median avgMFI for refractory patients was 4589 versus 349 for patients who were not, Wilcoxon rank sum test P< 0.0001. (Figure 1). The area under the receiver operating characteristic curve for avgMFI as a predictor of PTR was 0.8633 (95% confidence interval: 0.7664 – 0.9602). Higher avgMFIs also correlated with a broader range of target antigens, likely due to increasingly avid binding to cross-reactive epitopes. (Spearman's r = 0.7736 for correlation between avgMFI and panel reactive antibody percentages (cPRA), calculated in reference to the general American population, and used here as a surrogate for the range of antibody specificities). cPRA was >80% in 25/27 patients with avgMFI>1000, suggesting poor ability to discriminate among patients with moderate to high antibody titers, and was not an independent predictor of PTR. Hence, while the increased probability of encountering a cognate antigen on a RDPLT may partly explain the correlation between avgMFI and PTR, the avidity of binding, represented in vitro by the MFIs, appears to be a more significant determinant of risk. In conclusion, we provide evidence for the concept that PTR risk due to HLA allo-immunization is usefully predicted by the MFIs of antibodies detected using micro-bead flow cytometry. Our model allows cut-offs for identifying high risk patients to be based on the degree of risk acceptable in a given clinical situation. This should enable hematology units to develop risk-adapted strategies for supporting allo-immunized thrombocytopenic patients. Disclosures: No relevant conflicts of interest to declare.


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