scholarly journals Pre-Transplant Ferritin, Albumin and Platelet Count Add Prognostic Information to Comorbidities for Allogeneic Hematopoietic Cell Transplantation (HCT) Outcomes: A Multi-Center Discovery-Validation Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 421-421
Author(s):  
Jennifer E. Vaughn ◽  
Barry E. Storer ◽  
Philippe Armand ◽  
Roberto Raimondi ◽  
Christopher J Gibson ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Validation Study ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Karnofsky Performance Status ◽  
Statistical Significance ◽  
Prognostic Information ◽  
Allogeneic Hct ◽  
C Statistic

Abstract Albumin, ferritin, and peripheral blood counts broadly capture health status in patients undergoing allogeneic stem cell transplantation (HCT). Whether they add any prognostic information to the HCT-Comorbidity Index (HCT-CI) is unknown. We analyzed the independent prognostic role of a group of 5 biomarkers (ferritin, albumin, absolute neutrophil count (ANC), hemoglobin (Hgb), and platelet (Plt) count) in pts given allogeneic HCT for hematologic malignancies. This was a multi-center, retrospective discovery-validation study comprising data from 3917 recipients of allogeneic HCT at the Fred Hutchinson Cancer Research Institute (FHCRC) (n=1789) and Dana Farber Cancer Institute (DF) (n=716) in the US and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) (n=1412) in Italy (Table 1). Proportional hazard models were used to estimate the hazards of non-relapse mortality (NRM) and survival after adjustment for the HCT-CI, donor type, CMV serostatus, regimen intensity, age, disease risk and Karnofsky Performance Status (KPS). These were stratified by institution. Model performances were tested by c-statistic estimates. In an initial analysis within the FHCRC population, ANC of <500 and Hgb of < 9 were not associated with outcomes in the models. Alternatively, ferritin >1000 (HR 1.98; p=0.0003) and >2500 (HR 1.97; p=0.0005); albumin <3.5 (HR 1.63; p<0.00001) and <3.0 (HR 1.73 p<0.0001); and Plt <100k (HR 1.65; p<0.0001), <50k (HR 1.52; p<0.0001) , and <20K (HR 1.54; p<0.008) were all statistically significantly associated with NRM. Results were validated in a larger population from DF and GITMO. In multivariate models, adjusted for previously mentioned variables, ferritin >2500 and incremental decreases in albumin and Plt counts had statistically significant associations with both NRM and survival (Table 2). Of note, HCT-CI scores (2, 3 and >4) also retained significant associations with NRM and survival in the presence of the three biomarker values and in both cohorts. Subsequent multivariate analyses stratified the whole cohort (n=3917) into a training (n=2352) and a validation (n=1407) set. In both sets, albumin <3.5, plts <100K, and ferritin >2500 had statistical significance associations with NRM and survival. Each of the three biomarker values were subsequently assigned a weight of 1 following the same equation used to develop the HCT-CI. The augmented HCT-CI/biomarker index had higher c-statistic estimate (0.61) for prediction of NRM compared to the HCT-CI alone (0.58) in the validation set. Ferritin, albumin, and Plt counts are simple and valid prognostic biomarkers for transplant outcomes and should be considered in combination with the HCT-CI in risk assessment prior to allogeneic HCT. The physiology behind these associations warrants further investigation to identify areas of intervention that may improve outcomes. Table 1: Pt characteristics FHCRC(N=1789) DF/GITMO(N=2128) N (%) N (%) Donor Related 900 (50) 1062 (50) Unrelated 889 (50) 1053 (50) Disease risk Low 740 (41) 866 (43) High 1049 (59) 1157 (57) Age < 50 1025 (57) 1120 (53) ≥ 50 764 (43) 1008 (47) Conditioning MA 983 (55) 1100 (52) RIC/NMA 806 (45) 1004 (48) Pt CMV - 773 (43) 505 (24) + 1016 (57) 1581 (76) KPS ≤ 90 691 (39) 644 (33) 90-100 1098 (61) 1304 (67) Table 2: Multivariate analysis showing the associations between biomarkers and NRM and survival. NRM Survival Marker HR1 P1 HR1 P1 FHCRC Albumin ≥3.5 1.0 1.0 <3.5 - 3.0 1.44 0.002 1.45 <0.0001 <3.0 1.77 <0.0001 1.77 <0.0001 Unk 1.15 0.38 1.19 0.11 Plts ≥100K 1.0 1.0 <100K – 50K 1.48 0.0007 1.28 0.003 <50K – 20K 1.49 0.003 1.37 0.001 <20K 1.64 0.005 1.58 0.0004 Unk 0.66 0.47 0.48 0.14 Ferritin ≤1000 1.0 1.0 >1000 - 2500 1.60 0.03 1.70 0.0006 >2500 2.08 0.001 1.63 0.007 Unk 1.42 0.03 1.44 0.002 HCT-CI 0 1.0 1.0 1 1.29 0.12 1.31 0.02 2 1.50 0.01 1.42 0.001 3 2.29 <0.0001 2.04 <0.0001 ≥ 4 2.94 <0.0001 2.42 <0.0001 DF/GITMO Albumin ≥3.5 1.0 1.0 <3.5 - 3.0 1.60 0.0001 1.36 0.0005 <3.0 2.77 <0.0001 2.18 <0.0001 Unk 1.61 0.01 1.11 0.49 Plts ≥100K 1.0 1.0 <100K – 50K 1.08 0.56 1.02 0.85 <50K – 20K 1.17 0.28 1.21 0.06 <20K 1.38 0.04 1.35 0.009 Unk 0.64 0.10 0.82 0.28 Ferritin ≤1000 1.0 1.0 >1000 - 2500 1.11 0.43 1.23 0.02 >2500 1.60 0.002 1.69 <0.0001 Unk 1.13 0.33 1.12 0.19 HCT-CI 0 1.0 1.0 1 1.31 0.05 1.14 0.19 2 1.29 0.10 1.25 0.04 3 1.48 0.006 1.46 0.0001 ≥ 4 1.74 <0.0001 1.66 <0.0001 1 Adjusted for donor , CMV serostatus , regimen intensity , age , disease risk , KPS ; stratified on institution. Unk=Unknown Disclosures No relevant conflicts of interest to declare.

Interaction of Age and Comorbidities and Their Impacts on Hematopoietic Cell Transplantation (HCT) Outcomes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 665-665 ◽  
Author(s):  
Fabiana Ostronoff ◽  
Barry Storer ◽  
Rainer Storb ◽  
Smita Bhatia ◽  
Richard T. Maziarz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Outcome Prediction ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Pulmonary Function Tests ◽  
Age Groups ◽  
Outcome Analysis ◽  
Training Set ◽  
Allogeneic Hct

Abstract Abstract 665 Historically, age has been the main patient (pt)-specific decision-making factor for allogeneic HCT. The HCT comorbidity index (CI) was developed to capture pretransplant comorbidities. The index predicts non-relapse mortality (NRM) and has revolutionized outcome analysis for allogeneic HCT. Whether calendar age adds additional level of information to the HCT-CI in outcome prediction is unknown. Here, we investigated 1) how well the HCT-CI predicts outcomes across different age groups and 2) whether age could be incorporated into the HCT-CI. Data from 3033 consecutive pts treated with allogeneic HCT between January 2000 and December 2006 from HLA-matched related or unrelated donors at five collaborating institutions were used for this study. All data were collected by a single investigator, who was blinded from the final outcomes of pts, to ensure consistent comorbidity coding. Median age was 45 (range 0.1–74.5) years. Overall, there was a weak correlation between increasing age and increasing HCT-CI scores (r=0.26). Pts were randomly divided into training (n=1853) and validation (n=1180) sets. In the training set, the HCT-CI predicted increased cumulative incidence rates of NRM and worsening of overall survival (OS) rates consistently in the 5 separate age groups (Table 1). Pulmonary function tests were not performed in 51% of pts <20 years of age, which might have affected the assignment of HCT-CI scores. Scores of 0, 1–2, and ≥3 were assigned to 28%, 32%, and 40%, respectively, of pts ≥20 years of age compared to 55%, 27%, and 18% of pts <20 years of age. Nevertheless, HCT-CI scores predicted OS of 73%, 61%, and 41% (p<0.0001), respectively, among pts <20 years of age. Table 1: NRM and OS by HCT-CI scores across different age groups in the training set Age groups, years Cumulative incidences of NRM p Rates of overall survival p HCT-CI scores HCT-CI scores 0 1–2 ≥3 0 1–2 ≥3 0–19 (n=245) 8 26 28 <0.001 73 61 41 <0.001 20–39 (n=475) 11 20 39 <0.001 80 62 33 <0.001 40–49 (n=429) 12 26 43 <0.001 75 56 39 <0.001 50–59 (n=457) 21 31 39 <0.001 60 48 33 <0.001 ≥60 (n=247) 7 27 38 <0.001 63 47 27 <0.001 A proportional hazards model was used to estimate the hazard ratios (HRs) for NRM and OS associated with different age intervals and other covariates, including the HCT-CI scores (Table 2). In this model, tests of homogeneity of HRs associated with HCT-CI scores of 1–2 and ≥3 across age groups were not rejected for either NRM (p=0.66 and p=0.86, respectively) or OS (p=0.76 and p=0.24, respectively). Increasing HCT-CI scores were associated with the highest HRs for NRM compared to other covariates. Pts in age groups 40–50, 50–60, and >60 years had HRs for NRM ranging between 1.48–1.84 compared to pts <20 years of age. Accordingly, age >40 years was assigned a score of 1 to be added to the HCT-CI scores. In the validation set, although we continued to observe increases in HRs for NRM with increasing age, only minor improvement in c-statistics for NRM (0.66 versus 0.68) was detected when age was added to the HCT-CI. Table 2: Multivariate risk factors in the training set (n=1853) Non-relapse mortality HR* P Age     0–19 (13%) 1.0     20–39 (26%) 1.21 0.29     40–49 (23%) 1.48 0.04     50–59 (25%) 1.75 0.004     60+ (13%) 1.84 0.005 HCT-CI     0 (31%) 1.0     1–2 (33%) 2.13 <0.0001     3+ (37%) 3.63 <0.0001 Donor     Related (55%) 1.0     Unrelated (45%) 1.42 0.0001 Regimen intensity     Myeloablative (62%) 1.0     Reduced-intensity (15%) 0.71 0.01     Nonmyeloablative (23%) 0.61 0.0001 Use of ATG     No (92%) 1.0     Yes (18%) 0.90 0.61 Diagnoses     Myeloid (59%) 1.0     Lymphoid (35%) 1.25 0.03     Other cancers (2%) 0.73 0.44     Aplastic Anemia (2%) 1.40 0.49     Non-malignant diseases (2%) 4.69 <0.0001 Disease Risk     Low (38%) 1.0     High (62%) 1.65 <0.0001 Stem cell source     BM (20%) 1.0     PBSC (80%) 1.38 0.02 Pt CMV sero-status     Negative (36%) 1.0     Positive (64%) 1.52 <0.0001 Prior regimens     0–3 (76%) 1.0     4+ (34%) 1.13 0.25 Karnofsky performance status percentages     >80 (75%) 1.0     ≤80 (25%) 1.41 0.0004 * also adjusted for institution type These results indicate that the HCT-CI is valid for outcome prediction across all age groups and that age per se has a relatively minor impact on HCT outcome prediction in models that account for comorbidities. Age >40 years had an impact equivalent to a single comorbidity with a weight of 1, and therefore should be assigned a score of 1 when using the HCT-CI/Age composite index. Disclosures: No relevant conflicts of interest to declare.

Bone Marrow Wilms Tumor Gene 1 Expression before Allogeneic Hematopoietic Cell Transplantation Correlates with Relapse in Acute Myeloid Leukemia Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2376-2376
Author(s):  
Semra Aydin ◽  
Chiara Frairia ◽  
Ernesta Audisio ◽  
Ludovica Riera ◽  
Sabrina Aliberti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Hematopoietic Cell ◽  
Additional Tool ◽  
Allogeneic Hct ◽  
The Impact ◽  
Risk Of Relapse ◽  
Acute Myeloid

Abstract Introduction Evaluation of WT1 expression is becoming an attractive marker in acute myeloid leukaemia (AML) for minimal residual disease (MRD) detection. Recent studies correlate therapy response with WT1 copy levels in the bone marrow (BM) offering an additional tool beside multiparameter flow-cytometry (MFC). No well-known data are available regarding its impact on the outcome after hematopoietic cell transplantation (HCT). Patients/Methods One hundred and two consecutive clinically and molecularly well characterized AML patients (pts) were transplanted in a single hematology center from 2004 to 2013. Indication for allogeneic HCT included high cytogenetic and molecular risk according to WHO criteria, high leukocytosis, extramedullary manifestations or secondary AML at diagnosis. Further, primary induction failure was considered as an indication for allogeneic HCT. WT1 expression was analyzed by real time polymerase chain reaction (RT-PCR), using the standardized European LeukemiaNet method on BM samples before HCT and during each follow up control. Only pts in first CR before HCT were included in the analysis. Cumulative incidence of relapse (CIR) was estimated considering death for other causes than relapse as a competing event. Univariate and multivariate Fine & Gray Regression models were used to test the association between CIR and pre-HCT BM WT1 levels. Linearity of the relationship between CIR and the WT1 level was investigated using a mathematical transformation (restricted cubic spline). Aim of this retrospective analysis was to investigate the impact of pre-HCT BM WT1 expression in first CR pts on predicting relapse after HCT. Results A BM WT1 evaluation pre-HCT was available in 89 out of 102 pts. Among them, 62 achieved a CR after induction treatment. Relapsed pts in CR after reinduction chemotherapy (n=16) or with disease persistence pre-HCT (n=2) and pts refractory to treatment (n=9) were excluded from analysis. The patient subgroup displaying a first CR before HCT had a median age at diagnosis of 49 years (range: 20-65). Patient/donor relationship involved 26 (42%) sibling, 32 (52%) matched unrelated and 4 (6%) haplo-identical donors. On the basis of standard cytogenetics, molecular biology and clinical criteria (global disease risk) pts were classified according to the following risk groups: 54 (87%) high, 5 (8%) intermediate and 3 (5%) low risk. Acute GVHD occurred in 24 (39%) whereas chronic GVHD was documented in 18 (28%) pts. Twenty-six (42%) deaths were documented after HCT, 21 (34%) due to relapse and 5 (8%) because of treatment related mortality (TRM). Pre-HCT BM WT1 expression was correlated with CIR. A cut point of 150 WT1 copies was applied according to the slope change of relapse hazard, and subsequently used for CIR analysis. Pts displaying a pre-HCT BM WT1 level > 150 copies (n=18) had a higher CIR (2-year CIR 52.5%, 95% CI: 27.1-77.8) compared to pts with a BM WT1 level ≤ 150 copies (n=44, 2-year CIR 27.7% (95% CI: 13.4-42.1). WT1 copy level > 150 showed a significantly higher risk of relapse in univariate analysis (HR 2.9, 95% CI 1.2-6.7, p=0.014). In multivariate analysis pre-HCT BM WT1 expression was confirmed as a significant independent risk factor for CIR when adjusted for patient/donor relationship, presence of GVHD, global disease risk and competitive risk of mortality due to TRM (HR 3.4, 95% CI 1.3-8.5, p=0,010), Figure. Conclusions In the present study, pre-HCT BM WT1 levels discriminated significantly for CIR in a cohort of AML in first CR. A cut off level of 150 BM WT1 copies pre-HCT had a powerful statistically significant discriminating value to predict the risk of relapse, independently from already established risk factors. The prognostic value of WT1 was confirmed also when TRM as competitive risk for mortality was added in the multivariable model. Based on these results, WT1 is a promising candidate as MRD tool. Further prospective studies are required to confirm these results. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cation Leak in Red Blood Cells of Patients with Wiskott-Aldrich Syndrome Leads to Non-Immunologic Hemolysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1338-1338
Author(s):  
Robert A. Sokolic ◽  
Satheesh Chonat ◽  
Mary Risinger ◽  
Michael Eckhaus ◽  
Elizabeth Garabedian ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Actin Polymerization ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Hematopoietic Cell ◽  
Target Cells ◽  
Screening Assay ◽  
Wiskott Aldrich Syndrome ◽  
Immune Hemolysis

Abstract Wiskott-Aldrich Syndrome (WAS) is a primary immunodeficiency that is associated with microthrombocytopenia. Autoimmunity is one of the defining characteristics of severe WAS, and can contribute to the decision to proceed to hematopoietic cell transplantation. Autoimmune Hemolytic Anemia (AIHA) is one of the most common autoimmune syndromes found in WAS. Even in the absence of AIHA, some patients with WAS have anemia, and this is often of unclear etiology. We studied 29 patients with WAS, 6 of whom had had splenectomy, on 46 occasions. All patients were found to have anisopoikilocytosis. Common red blood cell (RBC) variants included stomatocytes, xerocytes, eccentrocytes, dacryocytes, spherocytes and target cells. Two WAS knockout mice whose blood smears were studied also had poikilocytosis, with dacryocytes predominating. The average hemoglobin in humans with WAS was 13.3 g/dL. In 19/46 measurements, hemoglobin was below the lower limit of normal for age. LDH was elevated in 1/43 measurements, and bilirubin was elevated in 7 of 46 measurements, 4 measurements being from a patient with molecularly diagnosed Gilbert’s syndrome. Average MCHC was 34.7 g/dL, with MCHC being elevated in 3/43 measurements. Despite these unremarkable screening assays, haptoglobin was decreased in 10/45 measurements and undetectable in 6 of these 10. The average plasma free hemoglobin and plasma free oxyhemoglobin were elevated to 21.4 and 14.7 mg/dL respectively. Analysis of osmotic fragility revealed average numbers near the lower end of the normal range, with fragility in 0.6 g/dL NaCl being abnormally low in 29/35 specimens and fragility in 0.65 g/dL NaCl being abnormally low in 9/35 specimens. A standard Coomb’s test was positive in 6/39 specimens. 4 such assays were positive for IgG, 1 for C3 and 1 for neither molecule despite a positive screening assay. Using enhanced methodology, 1/5 specimens was positive only with polyspecific serum. Overall, immune mediated hemolysis was detected by either method in 6/39 specimens. These data were interpreted to be consistent with a subclinical non-immune hemolysis in 33/41 specimens from 28/29 patients. In order to evaluate these findings further, ektacytometry was performed in 5 specimens from 5 patients and intracellular cations were measured in 4 of these specimens. Ektacytometry revealed Omin of 135.8±5.1 mOsm/kg in patients with WAS and 156.4±5.3 mOsm/kg in control specimens (P=0.0002). Sodium and potassium concentrations in patients were 53.3±12.7 mmol/kg hemoglobin and 282.3±13.1 mmol/kg hemoglobin respectively. In control specimens, the concentrations were 4.4±10.5 mmol/kg hemoglobin and 297.5±14.4 mmol/kg hemoglobin (P=0.3196 and 0.1684). These data are consistent with non-immune hemolysis in most patients with Wiskott-Aldrich syndrome. This hemolysis is associated with a xerocytic ekatacytometry curve, although cation concentrations in the small number of specimens tested only trended to statistical significance. This is the first intrinsic red cell defect described in patients with WAS, emphasizing that this disease truly affects all hematopoietic lineages and not only cells of the immune system. Whether the roles of the WAS protein in actin polymerization or signal transduction are involved in these abnormal functions remains unclear and requires additional research. These findings also have implications for clinical management of WAS as they indicate that hemolysis is commonly present without necessarily defining the autoimmune, severe clinical phenotype in these patients. As autoimmunity is often an important consideration in the decision to proceed to hematopoietic cell transplantation, these data should inform the decision-making process toward this and other therapeutic modalities for WAS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of Comorbidities in Prognostic Evaluation of Outcomes Following Allogeneic Hematopoietic Cell Transplantation (HCT) from HLA-Mismatched (MM) and Umbilical Cord Blood (UCB) Donor Grafts

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2583-2583
Author(s):  
Mahmoud Elsawy ◽  
Barry E. Storer ◽  
Brenda M. Sandmaier ◽  
Colleen Delaney ◽  
Frederick R. Appelbaum ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Statistical Significance ◽  
Kappa Statistic ◽  
Weighted Kappa ◽  
Hematopoietic Cell ◽  
Primary Disease ◽  
C Statistic ◽  
Comorbidity Scores

Abstract Comorbidities could provide important prognostic information about the treatment of a primary disease. The hematopoietic cell transplantation comorbidity index (HCT-CI) has been extensively evaluated and validated in the settings of allogeneic HCT from HLA-matched donors. Transplants from HLA-MM grafts have more risks for graft-rejection and graft-versus-host disease (GVHD), hence more non-relapse mortality (NRM) compared to HLA-matched grafts. Likewise, cord blood HCT carry relatively higher risks for delayed engraftment and infection. Whether comorbidities convey the same prognostic influence on outcomes after HLA-MM and UCB compared to HLA-matched HCT is unknown. To this end, we evaluated the prognostic capacity of HCT-CI among a retrospective cohort of 325 patients (pts), who were consecutively treated between 2000 and 2010 with allo-HCT using HLA-MM (n=184) or UCB (n=141) grafts. Pts receiving HLA-haploidentical grafts were not included in this analysis. Comorbidities were graded per the newly established guidelines for scoring the HCT-CI (Sorror ML, Blood. 2013). A sample of 30 patients was coded by two evaluators to assess the level of inter-rater reliability for scoring comorbidities. Cumulative incidences and Kaplan Meier estimates were used to evaluate NRM and survival, respectively. Relapse or progression of the primary disease was treated as a competing risk for NRM. Proportional hazards models were used to estimate the hazard ratio (HR) for NRM and survival associated with HCT-CI scores in each of the two groups. Performance of the model in predicting outcomes after each graft source was validated using c-statistic estimates for continuous prediction. IRR was evaluated using weighted kappa statistic estimates. Results showed an excellent level of agreement on comorbidity coding between two evaluators with kappa statistic estimate of 0.89 (SE 0.06) and weighted kappa estimate of 0.95 (SE 0.03). Overall, pts received high-dose (n=192), reduced–intensity (n=81), or nonmyeloablative (n=52) conditioning regimens. Diagnoses were acute (n=192) or chronic (n=34) leukemia, myelodysplastic syndromes (n=40), lymphoma (n=32), and others (n=27). HCT-CI scores of 0-2 and ≥3 were found in 148 and 177 pts, respectively. Pts characteristics among each group of donor source are described (Table). Recipients of HLA-MM grafts, who had HCT-CI scores of 0-2 experienced NRM incidences of 20% at 2-year compared to 40% among those with scores of ≥3. The figures for 2-year overall survival (OS) rates were 62% vs. 38%, respectively. Higher HCT-CI scores (≥3 vs. 0-2) were associated with increased HR [95% confidence interval (CI)] for NRM [2.96 (1.71-5.26), p< 0.0001] and OS [2.35 (1.54-3.59), p< 0.0001]. Additionally, the prognostic significance of the model was validated by calculating c-statistics estimates of 0.64 and 0.61 for NRM and OS, respectively. Likewise, recipients of UCD grafts, who had scores of ≥3 experienced higher incidences of NRM at 2-year (42%) compared to those with scores of 0-2 (30%) and lower rates of OS (45% vs. 60%), respectively. Pts with higher comorbidity scores had higher HRs for NRM [1.62 (0.93-2.81)] and OS [1.57 (0.97-2.54)] but with borderline statistical significance (p=0.09 and p=0.07, respectively). C-statistic estimates were 0.59 for NRM and 0.59 for survival. The HCT-CI can clearly risk-stratify the outcomes after HLA-MM grafts. While a trend for discriminating outcomes after UCB HCT by comorbidity scores was noted, the magnitude of statistical significance might has been affected by the relatively smaller number of those patients. Future studies are warranted to explore the use of the HCT-CI in optimizing the decision-making process about the most appropriate graft source for pts who lack a suitably HLA-matched graft. It could also be a key factor in stratifying randomized studies designed to compare outcomes after alternative graft sources. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Prospective Validation of the Predictive Power of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) for HCT Outcomes At US Transplant Centers: A Center for International Blood and Marrow Transplant Research (CIBMTR) Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 733-733 ◽  
Author(s):  
Mohamed L. Sorror ◽  
Brent R. Logan ◽  
Xiaochun Zhu ◽  
J. Douglas Rizzo ◽  
Kenneth R. Cooke ◽  
...  
Keyword(s):  
Predictive Power ◽  
Hematopoietic Cell Transplantation ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Karnofsky Performance Status ◽  
P Value ◽  
High Dose ◽  
Kappa Statistics ◽  
Allogeneic Hct ◽  
Significant Difference

Abstract Abstract 733 In 2005, the HCT-CI was introduced by a single institution as a weighted scoring system to predict mortality risk following allogeneic HCT. Since then, not all investigators were able to validate the HCT-CI after testing in their respective institutions. In 2007, a new prospective multi-institutional observational study was initiated at the CIBMTR to collect comorbidities from all transplant centers by their respective evaluators and to validate the predictive power of the HCT-CI in a large sample of patients (pts). The HCT-CI was adapted into the Pre-Transplant Essential Data (pre-TED) collection form #2400. Data managers from all institutions attended an education session on comorbidity coding per the HCT-CI at the 2007 Tandem BMT Meeting in Keystone, Colarodo. This session was then made public to all data managers at the CIBMTR website. <>The study accrued 8115 consecutive pts treated with allogeneic HCT from 12/2007 to 12/2009 from related (47%) or unrelated (53%) donors. Median age was 52 [range 1–78) years. Conditioning regimens were high-dose (67%) or either reduced-intensity (RIC) or nonmyeloablative (NST) regimens (34%). Diagnoses were acute (54%) or chronic (12%) leukemia, myelodysplastic syndromes (16%), lymphomas (16%), and others (2%). GVHD prophylaxis regimens were cyclosporine-based (22%), tacrolimus-based (68%), or others (10%). Stem cell source was marrow (17%) or peripheral blood mononuclear cells (83%). Karnofsky performance status scores were <90% (33%), ≥ 90% (62%), or missing (5%). HCT-CI scores were 0 (47%), 1 (15%), 2 (11%), 3 (12%), 4 (7%), 5 (3%), ≥6 (4%), or missing (1%). About 11% of pts with score 0 had other comorbidities listed. Overall, pts experienced cumulative incidence of transplant-related mortality (TRM) of 28% and a survival rate of 48% at 3-years. Pts with HCT-CI scores of 0 vs. 1–2 vs. ≥3 had 3-year TRM incidences of 24%, 28%, and 35% (p <0.001) and 3-year overall survival (OS) rates of 54%, 47%, and 38%, respectively (p <0.001, Figure). Proportional hazards models were used to estimate the hazard ratio (HR) for TRM and OS associated with HCT-CI scores. The models were adjusted for all previously mentioned covariates in addition to disease status, CMV serology status, gender, and race. Increasing HCT-CI scores (1–2 and ≥3 vs. 0) were associated with increases in the HR [95% confidence interval (CI)] for TRM [1.12 (1.00–1.26) and 1.47 (1.31–1.65), respectively, p<0.0001] and OS [1.12 (1.03–1.22) and 1.36 (1.25–1.48), respectively, p<0.0001] in the overall pt population. No statistically significant difference could be detected between pts with score 0 + other comorbidities vs. score 0 for TRM (HR 0.93, p= 0.385) or OS (HR 0.96, p= 0.474). When the HCT-CI was modeled as scores of 0, 1, 2, 3, 4, and ≥5 the HR for TRM were 1.00 vs. 1.12 vs. 1.13 vs. 1.31 vs. 1.52 vs. 1.77, respectively (, p<0.0001) and for OS were 1.00 vs. 1.13 vs. 1.12 vs. 1.22 vs. 1.39 vs. 1.62 (p<0.0001). Likewise, the HCT-CI could discriminate outcomes well among pts given high-dose or RIC/NST regimens and those diagnosed with lymphoid or myeloid diseases (Table 1). The inter-rater reliability (IRR) rate among data managers versus their respective investigators was assessed in 3 institutions. Weighted kappa statistics were 0.54, 0.81, and 0.47 respectively, indicating fair-moderate agreement rate among evaluators. The HCT-CI is a valid tool to discriminate relative risks for TRM and OS after HCT across different institutions, different conditioning intensities, and different diagnoses. The HCT-CI should be used as a standard-of-care health measure in counseling pts for HCT, in clinical trial design, and in adjusting statistical analyses for HCT outcomes. Future efforts will focus on improving the IRR of the HCT-CI. Table 1: Multivariate analyses TRM OS HCT-CI scores HR p-value HR p-value High-dose regimens 0 1.00 <0.0001 1.00 <0.0001 1 1.19 1.14 2 1.12 1.10 3 1.34 1.19 4 1.53 1.41 5+ 1.88 1.64 RIC/NST regimens 0 1.00 0.001 1.00 <0.0001 1 0.95 1.12 2 1.10 1.12 3 1.27 1.27 4 1.46 1.39 5+ 1.66 1.65 Lymphoid diseases 0 1.00 <0.0001 1.00 <0.0001 1 1.16 1.15 2 1.24 1.12 3 1.37 1.32 4 2.13 1.67 5+ 2.15 1.88 Myeloid diseases 0 1.00 <0.0001 1.00 <0.0001 1 1.12 1.13 2 1.00 1.06 3 1.25 1.14 4 1.29 1.27 5+ 1.63 1.52 Figure: 3-year OS as stratified by HCT-CI scores of 0 vs. 1–2 vs. ≥3 Figure:. 3-year OS as stratified by HCT-CI scores of 0 vs. 1–2 vs. ≥3 Disclosures: No relevant conflicts of interest to declare.

Haploidentical Transplantation As Salvage Therapy For Disease Relapse After Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2084-2084
Author(s):  
Christiane Dorn ◽  
Sebastian P. Haen ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Median Time ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
The Other ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct

Abstract Introduction Therapeutic options and outcome for patients with relapse after allogeneic hematopoietic cell transplantation (HCT) are poor. For individual patients, a second or even third allogeneic HCT can be considered with curative intention. However, treatment-related mortality (TRM) and the risk of relapse after secondary allogeneic HCT are high. Therefore, the use of a haploidentical graft allowing for profound NK- and T-cell-alloreactivity after a reduced-intensity conditioning regimen (RIC) may optimize disease control by enabling potent graft versus leukemia effects and reduction of TRM. Methods We here retrospectively evaluated 26 consecutive patients undergoing haploidentical HCT as second (n=24) or third (n=2) allogeneic HCT at our center between 2003-2012. Diagnoses comprised relapse of AML (n=17) or ALL (n=7), blast crisis of CML (n=1) and transplant failure (n=1). There were 16 male and 9 female patients with a median age of 36 years (range 18-59). Results For RIC, fludarabin, thiotepa and melphalan were used in 16 patients, clofarabin, thiotepa and melphalan in 6 patients and other regimens containing variable combinations of cyclophosphamide, busulfan, TBI and treosulfan in 4 patients. Grafts were manipulated by CD3/CD19 depletion (n=19), TCRαβ depletion (n=1) or CD34 selection (n=6) and consisted of a median of 7.71 x 106 CD34+cells/kg bodyweight. The median interval from first HCT to second HCT was 18 months (range 5-145), and 10 and 16 months from second HCT to third HCT in the two patients undergoing a third HCT. Only 35% (n=9) of the patients receiving a second HCT were in complete remission (CR), while 65% (n=16) were in partial remission (PR). Among the patients receiving a third HCT, one had active disease, while the other was in CR. All patients achieved engraftment of the neutrophils at a median time of 11 days (range 8-26) and platelet engraftment was reached at a median time of 15 days (range 9-35, except one patient at day 375). At present, 5 patients (19%) are alive and in CR with a median follow-up of 1870 days (range 281-3941), while 35% (n=9) died from relapse; non-relapse-mortality was 46% (n=12). Kaplan-Meier estimated overall survival for all patients at 1 year was 33% (52% for patients in CR versus 18% in PR) and at 3 years 17% (26% for patients in CR versus 12% in PR). Causes of death in patients with second HCT included severe infections (n=8), organ failure (n=1), haemorrhage (n=1) and progressive multifocal leukoencephalopathy (n=2). Of the patients with third HCT, one died from respiratory insufficiency due to pulmonary haemorrhage, the other is still alive and in CR. Acute graft versus host disease (GVHD) occurred in 11 patients with predominantly mild presentation (grade 1: n=9, grade 2: n=2), limited chronic GVHD was apparent in 5 patients with no case of extensive GVHD. Conclusion Haploidentical HCT is a feasible salvage concept for patients with relapse after HCT with promising results even in patients not in CR. Disclosures: No relevant conflicts of interest to declare.

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

2021 ◽  
pp. 107815522110604
Author(s):  
Kelly G Hawks ◽  
Amanda Fegley ◽  
Roy T Sabo ◽  
Catherine H Roberts ◽  
Amir A Toor
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
Clinically Significant ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Introduction Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. Methods In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. Results Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. Conclusion Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

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