scholarly journals A novel Iowa–Mayo validated composite risk assessment tool for allogeneic stem cell transplantation survival outcome prediction

2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Kalyan Nadiminti ◽  
Kimberly Langer ◽  
Ehsan Shabbir ◽  
Mehrdad Hefazi ◽  
Lindsay Dozeman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cox Regression ◽  
Disease Risk ◽  
Risk Index ◽  
Disease Free Survival ◽  
Donor Age ◽  
Hematopoietic Stem ◽  
Cmv Status

AbstractAllogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for many hematologic conditions and is associated with considerable morbidity and mortality. Therefore, prognostic tools are essential to navigate the complex patient, disease, donor, and transplant characteristics that differentially influence outcomes. We developed a novel, comprehensive composite prognostic tool. Using a lasso-penalized Cox regression model (n = 273), performance status, HCT-CI, refined disease-risk index (rDRI), donor and recipient CMV status, and donor age were identified as predictors of disease-free survival (DFS). The results for overall survival (OS) were similar except for recipient CMV status not being included in the model. Models were validated in an external dataset (n = 378) and resulted in a c-statistic of 0.61 and 0.62 for DFS and OS, respectively. Importantly, this tool incorporates donor age as a variable, which has an important role in HSCT outcomes. This needs to be further studied in prospective models. An easy-to-use and a web-based nomogram can be accessed here: https://allohsctsurvivalcalc.iowa.uiowa.edu/.

Disease Risk Index Is the Major Predictor of Outcome Following Myeloablative Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HSCT) and Post-Transplant Cyclophosphamide (PT/Cy)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2010-2010 ◽  
Author(s):  
Scott R. Solomon ◽  
Connie Sizemore ◽  
Xu Zhang ◽  
Melhem Solh ◽  
Lawrence E. Morris ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Hematopoietic Stem ◽  
Major Predictor ◽  
One Year ◽  
Very High

Abstract Disease Risk Index is the Major Predictor of Outcome Following Myeloablative Haploidentical Hematopoietic Stem Cell Transplantation (haplo-HSCT) and Post-Transplant Cyclophosphamide (PT/Cy) Although non-myeloablative (NMA) haplo-HSCT utilizing PT/Cy results in low rates of GVHD, infection, and non-relapse mortality (NRM), relapse remains the predominant cause of treatment failure, occurring in up to 50% of patients. To reduce the risk of relapse often associated with the use of NMA preparative regimens, we have developed a myeloablative haplo-HSCT utilizing PT/Cy. Sixty-four patients have been transplanted following either Busulfan-based (n=20) or TBI-based (n=44) myeloablative conditioning, T-cell replete PBSC infusion, PT/Cy, and tacrolimus/mycophenolate mofetil. Median age was 43 (range 21-60). Patient characteristics included a high/very high disease risk by the Dana-Farber/CIBMTR disease risk index (DRI) in 32 patients (50%), KPS<90 in 69%, and comorbidity index (CMI) of ≥2 in 58% of patients. The most common indications for transplant were AML, ALL, and advanced-phase CML in 55%, 20% and 12% of patients respectively. Median follow-up for surviving patients was 24 months. All patients have engrafted with no late graft failure. Grade II-IV, III-IV acute GVHD and moderate-severe chronic GVHD occurred in 46%, 23%, and 30% respectively. One-year NRM was 10%. Predicted three-year overall survival (OS), disease-free survival (DFS), and relapse are 53%, 53%, and 26% respectively. In multivariate analysis, high/very high DRI was the most significant negative predictor of OS (HR 13.26, p<0.001), followed by CMI≥2 (HR 3.54, p=0.01) and age (HR 1.26, p=0.038, per each 5 year increase in age). DRI was also significantly associated with DFS (HR 10.84, p<0.001), NRM (HR 15.0, p=0.004), and relapse (HR 8.85, p=0.004). In the 32 patients with standard risk disease (low/intermediate DRI), outcomes were significantly improved with one-year NRM of 0% and predicted 3-year OS, DFS, and relapse of 79%, 74% and 9% respectively. Conditioning regimen (TBI vs. Busulfan) had no significant impact on outcome. This analysis confirms that DRI is a strong predictor of outcome following myeloablative haplo-HSCT and PT/Cy and adds to a growing body of literature suggesting that haplo-HSCT is a safe and effective transplant option for patients lacking a matched sibling donor. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Socioeconomic Status and Outcomes Among Mexican Patients Undergoing Allogeneic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4774-4774
Author(s):  
Eucario Leon Rodriguez ◽  
Monica M Rivera Franco
Keyword(s):  
Socioeconomic Status ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Low Ses ◽  
Hematopoietic Stem ◽  
Specific Patient ◽  
Mexican Patients

Abstract Background: Some specific patient and donor demographic factors have been described and associated with outcomes of hematopoietic stem cell transplantation (HSCT). However, associations with the socioeconomic status (SES) remain controversial as some studies including allogeneic HSCT (allo-HSCT) patients have reported that SES associates with worse long-term outcomes and other studies, including both, allogeneic and autologous HSCT have not found an association between SES and overall survival (OS), non-relapse mortality (NRM) or other outcomes. More importantly, these studies have been performed in developed countries and data from developing regions remains scarce. Objective: To associate the SES with outcomes in Mexican patients undergoing allo-HSCT at a National Institute of Health located in Mexico City. Patients and Methods: A retrospective study was performed including 124 consecutive patients undergoing allo-HSCT at the National Institute of Medical Sciences and Nutrition "Salvador Zubiran", from May 1999 to March 2018. SES was established according to the classification assigned by the Department of Social Work (levels I-VII); the lowest level corresponds to 7% out-of-pocket expense (93% subsidized by the Institution) and the highest to 120% (private health insurances). Patients were dichotomized into low SES (levels I-II) and high SES (levels ≥ III). Disease risk index was classified as low, intermediate or high using standard definitions and the HCT-CI score was assigned to each patient. Graft-versus-host disease (GVHD) was evaluated according to NIH guidelines. Endpoints included OS and NRM. Results: Patient characteristics by SES are shown in Table 1. Age, educational attainment, employment status, and financial support were the sociodemographic characteristics that differed between both groups. There were no differences in GVHD between the two groups. For all the cohort, 30, 100-days, and 1-year NRM was 3.2%, 8.8%, and 14.5%, respectively. Figure 1 shows NRM and OS by SES group. Conclusion: Although there were differences regarding diagnosis between the two groups (low and high SES), the DRI was the same between them, as well as the HCT-CI. Further, there were no differences between low and high SES in NRM or OS, demonstrating that our HSCT approaches are standardized and all patients can benefit from them despite their financial status, also highlighting that patients with low SES probably had good outcomes as a result of substantial governmental, NGO, and/or institutional subsidy. Disclosures No relevant conflicts of interest to declare.

scholarly journals External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation

2019 ◽  
Vol 3 (12) ◽  
pp. 1881-1890 ◽  
Author(s):  
Roni Shouval ◽  
Joshua A. Fein ◽  
Aniela Shouval ◽  
Ivetta Danylesko ◽  
Noga Shem-Tov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Risk ◽  
Risk Index ◽  
External Validation ◽  
Prognostic Scores ◽  
Hematopoietic Stem

Abstract Clinical decisions in allogeneic hematopoietic stem cell transplantation (allo-HSCT) are supported by the use of prognostic scores for outcome prediction. Scores vary in their features and in the composition of development cohorts. We sought to externally validate and compare the performance of 8 commonly applied scoring systems on a cohort of allo-HSCT recipients. Among 528 patients studied, acute myeloid leukemia was the leading transplant indication (44%) and 46% of patients had a matched sibling donor. Most models successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. However, discrimination varied (2-year overall survival area under the receiver operating characteristic curve [AUC]: revised Pretransplantation Assessment of Mortality [rPAM], 0.64; PAM, 0.63; revised Disease Risk Index [rDRI], 0.62; Endothelial Activation and Stress Index [EASIx], 0.60; combined European Society for Blood and Marrow Transplantation [EBMT]/Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI], 0.58; EBMT, 0.58; Comorbidity-Age, 0.58; HCT-CI, 0.55); AUC ranges from 0.5 (random) to 1.0 (perfect prediction). rPAM and PAM, which had the greatest predictive capacity across all outcomes, are comprehensive models including patient, disease, and transplantation information. Interestingly, EASIx, a biomarker-driven model, had comparable performance for nonrelapse mortality (NRM; 2-year AUC, 0.65) but no predictive value for relapse (2-year AUC, 0.53). Overall, allo-HSCT prognostic systems may be useful for risk stratification, but individual prediction remains a challenge, as reflected by the scores’ limited discriminative capacity.

scholarly journals Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis

2019 ◽  
Vol 14 (5) ◽  
pp. 719-727 ◽  
Author(s):  
Xianghua Huang ◽  
Wencui Chen ◽  
Guisheng Ren ◽  
Liang Zhao ◽  
Jinzhou Guo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Lupus Nephritis ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem

Background and objectivesOur study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis.Design, setting, participants, & measurementsFrom July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment.ResultsTwenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33–71) months. The mean number of CD34+ cells was (7.3±3.8)×106/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7–9) and 9 (6–10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60–80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%.ConclusionsAutologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.

Non-Myeloablative Autologous Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 156-156
Author(s):  
Laisvyde Statkute ◽  
Yu Oyama ◽  
Ann Traynor ◽  
Larissa Verda ◽  
Walter G. Barr ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lupus Erythematosus ◽  
Disease Free Survival ◽  
Systemic Lupus ◽  
Hematopoietic Stem

Abstract Manifestations of systemic lupus erythematosus (SLE) may in most patients be ameliorated with medications that suppress the immune system. Nevertheless, there remains a subset of SLE patients for whom current strategies are insufficient to control disease. Here we report results of autologous non-myeloablative hematopoietic stem cell transplantation single arm trial performed at Northwestern University Feinberg School of Medicine between February 1997 and January 2005 involving 50 patients with SLE refractory to standard immune suppressive therapies and either organ- or life-threatening visceral involvement. Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) and G-CSF (5 ug/kg/day), enriched ex vivo by CD34+ immunoselection, cryopreserved, and reinfused after treatment with cyclophosphamide (200 mg/kg) and equine anti-thymocyte globulin (90 mg/kg). The primary endpoint was survival, both overall survival and disease free survival. Secondary endpoints include systemic lupus erythematosus disease activity index (SLEDAI), serology (ANA and antids DNA), complement (C3 and C4), and changes in renal and pulmonary organ function assessed pre-treatment and 6 months, 12 months and then yearly for 5 years. Fifty patients were enrolled and underwent stem cell mobilization. Two patients died after mobilization, one from disseminated mucormycosis and another from active lupus after postponing the transplant for 4 months. Forty-eight patients underwent lupus non-myeloablative hematopoietic stem cell transplantation with no treatment related mortality. By intention to treat, treatment related mortality was 2% (1/50). With a mean follow-up of 29 months (range 6 month to 7.5 years ), overall survival was 84%, and probability of disease free survival at 5 years post transplant was 50%. Secondary analysis demonstrated stabilization of renal function and statistically significant improvement (p ≤ .05) in SLEDAI, ANA, anti-ds DNA, complement, and DLCO adjusted for hemoglobin (DLCOadj). In treatment refractory SLE, autologous non-myeloablative hematopoietic stem cell transplantation results in marked amelioration of disease activity, long term disease remission, improvement in serologic markers, and either stabilization or reversal of organ dysfunction.

Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5054-5054
Author(s):  
Amir Peyman ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Louis Fernandez ◽  
Donna L. Forrest ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

Single-Centre Validation Of a Disease Risk Index For Estimating Survival and Relapse In Allogeneic Hematopoietic Stem Cell Transplant Recipients: Sample Size, Adequate Follow-Up, and Use Of Local Data Are Vital Considerations

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2143-2143
Author(s):  
Andrew B M Lim ◽  
Andrew W. Roberts ◽  
Kate Mason ◽  
Ashish R. Bajel ◽  
Jeffrey Szer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Local Data ◽  
Hematopoietic Stem ◽  
Training Cohort ◽  
Wide Range ◽  
Very High

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) is applied for a wide range of malignant hematologic diseases at a wide range of stages of activity, from durable complete remission to resistant relapse. Reporting transplant outcome by disease category alone, without considering disease activity, limits statistical analysis and interpretation of outcomes across time or institutions. Recently a tool for clustering different combinations of disease and disease stage – the Disease Risk Index (DRI) – was developed and validated to stratify for overall survival (OS), progression free survival (PFS) and cumulative incidence of relapse (CIR)1. Aims 1. To independently validate the DRI's ability to stratify patients for OS, PFS and CIR using data from our centre. 2. To determine if absolute estimates of OS, PFS and CIR derived from the original training cohort can be used to accurately predict OS, PFS and CIR for an independent, contemporaneous cohort. 3. To determine approximate thresholds of sample size and follow-up duration below which the DRI may fail to successfully stratify patients for OS, PFS and CIR. Methods From our institutional transplant database, we extracted data from 466 patients undergoing alloHSCT for hematologic malignancy at our institution between the years 2001 and 2011, with median survivor follow-up of 55.2 months (range 5.0-139.0) to validate and further explore the utility of the DRI. Data for time-to-event outcomes was locked for analysis on 14 February 2013. Results We identified that similar to the published findings, the DRI was able to significantly stratify for OS (at 4 years, OS for low DRI 81% [95% CI 70-94%]; intermediate DRI 68% [63-74%]; high DRI 41%, [32-51%]; very high DRI 0%; P < .001; see Figure 1), PFS (at 4 years, PFS for low DRI 72% [59-87%]; intermediate DRI 61% [55-67%]; high DRI 32% [24-42%]; very high DRI 0%; P < .001), and CIR (at 4 years, CIR for low DRI 14% [3-25%]; intermediate DRI 27% [21-32%]; high DRI 48% [39-57%]; not calculable for very high DRI; P < .001). The DRI was not predictive of non-relapse mortality (P = .379). The DRI retained its prognostic power when applied to subgroups of patients who received either myeloablative or non-ablative conditioning; non-T cell depleted transplants; and sibling donor transplants only. When compared with the original published training cohort, survival and relapse outcomes from a contemporaneous cohort (n = 324, alloHSCT between the years 2001 and 2008) from our institution were superior to those of the Boston cohort for low, intermediate and high DRI groups (4 year OS: low DRI 88% [95% CI 77-100%] vs 64% [56-70%]; intermediate DRI 68% [62-75%] vs 46% [42-50%]; high DRI 42% [33-53%] vs 26% [21-31%]; 4 year CIR: low DRI 12% [6-24%] vs 19% [13-24%]; intermediate DRI 26% [20-32%] vs 36% [33-40%]; high DRI 47% [37-57%] vs 55% [50-60%]). These findings underscore the importance of calibration with local data before using the DRI for predicting absolute rates of survival and relapse in individual institutions. To further explore if the DRI retained its power in smaller cohorts, we tested the DRI in smaller subsets of patients selected randomly from our data. We found the DRI successfully stratified a cohort of 100 patients (median survivor follow-up 51.1 months, range 8.5-139.0) for OS (P = .010), PFS (P = .016) and CIR (P = .027), but failed to stratify a cohort of 50 patients (median survivor follow-up 46.2 months, range 10.3-135.5) for survival (P = .385 for OS, P = .167 for PFS, P = .026 for CIR). Likewise, under simulated conditions of shorter follow-up, the DRI successfully stratified a cohort (n = 322) with median surviving follow-up of 40.6 months for OS and PFS, but failed to stratify a cohort (n = 242) with median surviving follow-up of 33.1 months. Conclusion We find the DRI to be a simple, practical and robust tool for pre-transplant risk stratification, and estimation of survival and relapse in alloHSCT recipients, when calibrated with local alloHSCT outcome data. However, users should be familiar with its limitations when applied to smaller cohorts or cohorts with shorter follow-up. References 1. Armand P, Gibson CJ, Cutler C et al. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 2012;120:905-913. Disclosures: No relevant conflicts of interest to declare.

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