Risk Factors for Major Transplant Related Outcomes In Pediatric Patients with Chronic Graft-Versus-Host Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 211-211
Author(s):  
David A. Jacobsohn ◽  
Mukta Arora ◽  
John P. Klein ◽  
Joseph H. Antin ◽  
Brian J. Bolwell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Blood Cell ◽  
Immune Suppression ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Peripheral Blood Cell ◽  
Myelogenous Leukemia

Abstract Abstract 211 The adverse impact of chronic GVHD (cGvHD) on health and quality of life is especially critical in children because of their longer life expectancy and problems impacting growth and development. Although risk-factors for developing cGvHD in children are reported, little is known about risk factors for non-relapse mortality (NRM) in children with cGvHD. Identification of predictors for mortality in children with cGvHD could permit risk-adapted therapy, help plan for clinical trials and assist in counseling. We performed a multivariate analysis using data from CIBMTR to identify transplant- and cGvHD-related risk factors for NRM and survival in a cohort of 1117 subjects aged 0–20 years, transplanted from related donors, unrelated donors (URD), or unrelated cord blood (UCB) in 1995–2004 for acute myelogenous leukemia (AML), acute lymphoid leukemia (ALL), chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS). Median age was 12 years. Characteristics of cGvHD at diagnosis were: progressive onset (49%), total bilirubin >2 mg/dL (16%), thrombocytopenia (platelets <100 × 109/L, 32%) and Karnofsky/Lansky (KPS/L) score <80 (24%). Probabilities of NRM at 1, 3, and 5 years after diagnosis of cGvHD were 17% (95% CI: 14–19%), 22% (20-25%) and 24% (21-27%), respectively. Multivariate analysis indentified four factors significantly associated (p<0.01) with higher NRM: (1) HLA-partially-matched or -mismatched URD; (2) peripheral blood cell graft; (3) KPS/L <80 at cGVHD diagnosis; and (4) platelets <100 × 109/L at cGVHD diagnosis. Survival after diagnosis of cGVHD at 1-, 3- and 5-years was 75% (72-77%), 63% (60-66%), and 59% (56-62%). Factors significantly associated with worse survival were: (1) age >10 years; (2) transplant from an HLA-partially-matched or -mismatched URD; (3) advanced disease at transplant; (4) KPS/L <80; and (5) platelets <100 × 109/L. The cumulative incidence of NRM at 5 years was higher for children with KPS/L <80 (46%; CI: 40–52%) than for those with a higher KPS/L score (15%; CI: 12–18%; p<0.001). This translated to poorer survival of 42% (36-48%) vs. 66% (CI: 63–70%; p<0.001), respectively. 5 year cumulative incidence of NRM was also higher in children with platelets <100 × 109/L: 37% (32-43%) vs. 15% (CI: 12–18%; p<0.001). This also resulted in poorer survival (47%, CI: 42–52%; vs. 67%, CI: 63–71%; p<0.001). Cumulative incidence of discontinuation of systemic immune suppression (death and relapse treated as competing risks) at 1, 3 and 5 years after diagnosis of cGvHD were 22% (20-25%), 34% (31-37%), and 37% (34-40%). In conclusion, we identified several factors adversely correlated with NRM and survival children with cGvHD. The correlation between peripheral blood cell grafts and increased NRM without poorer survival may be explained by fewer relapses. This is the first large study elucidating factors affecting outcome after diagnosis of cGvHD in children. Our results may be useful for risk stratification.SurvivalNRMRelative Risk95% CIPRelative Risk95% CIPAge (baseline: 0–9 years)    10-191.321.091.600.005NSKPS/L (baseline: 80–100)<.001<.001    <801.891.522.34<.0013.012.293.96<.001    unknown1.341.001.780.051.641.122.430.015Platelets (x10e9/L) (baseline: ≥ 100)<.001<.001    <1001.631.322.01<0.0012.321.763.07<.001    Unknown1.330.991.780.061.731.182.520.005Donor (baseline: HLA-identical siblings)0.003<0.001    Other related1.681.132.520.0111.670.962.960.07    HLA-well-matchedunrelated1.401.021.940.041.250.801.960.33    Partially matched unrelated1.691.232.310.0011.941.282.940.002    Mismatched unrelated1.751.272.42<0.0012.311.493.59<0.001No data1.020.641.620.941.220.602.130.71Disease State (baseline: Early)<0.0010.005    Intermediate0.960.781.180.700.650.500.850.07    Advanced1.561.192.040.0010.920.631.350.68Graft (baseline: BM)0.002    BloodNS1.761.282.41<0.001    Cord BloodNS1.070.671.700.78NS=Not SignificantCumulative Incidence of NRM by Platelets and KPS/L at Diagnosis of cGvHDCumulative Incidence of NRM by Platelets and KPS/L at Diagnosis of cGvHDSurvival and Cumulative Incidence of Discontinuation of Immune SuppressionSurvival and Cumulative Incidence of Discontinuation of Immune Suppression Disclosures: No relevant conflicts of interest to declare.

scholarly journals Chromosome Studies in Normal and Leukemic Rats

Blood ◽  
1964 ◽  
Vol 23 (5) ◽  
pp. 564-571 ◽  
Author(s):  
G. DOWD ◽  
K. DUNN ◽  
WILLIAM C. MOLONEY
Keyword(s):  
Bone Marrow ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Species Differences ◽  
Peripheral Blood Cell ◽  
Myelogenous Leukemia ◽  
Peripheral Blood Cells ◽  
X Ray ◽  
Normal Rat

Abstract 1. Adequate chromosome preparations were obtained in 70 per cent of normal rat peripheral blood cell cultures. However, cultures of peripheral blood cells from leukemic rats were almost universally unsuccessful. 2. In x-ray- and 3MCA-induced leukemias direct bone marrow preparations provided adequate metaphases in eight of 12 cases. Failures were attributed in four cases to scanty material obtained from fibrotic marrows. 3. No consistent chromosome abnormalities, such as those reported in human myelogenous leukemia, were found in these leukemic rats. However, the series of cases is small, and species differences and other factors may have influenced the results of these studies.

Encoraging Results after Alternative Donor Transplantation for Myelodysplastic Syndrome.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1964-1964
Author(s):  
Franco Locatelli ◽  
Adrienne Moreno-Madureira ◽  
Pierre Teira ◽  
Mary Eapen ◽  
Mei-Jie Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Marrow Transplant ◽  
Hematopoietic Stem ◽  
Monosomy 7 ◽  
Neutrophil Recovery ◽  
Blood And Marrow Transplant

Abstract Hematopoietic stem cell transplantation (HSCT) remains the treatment of choice for children with myelodysplastic syndromes (MDS). Umbilical cord blood (UCB) represents an alternative source of hematopoietic stem cells for transplantation in children without a HLA-matched sibling. We examined risk factors influencing outcomes after UCB transplantation (UCBT) in 70 children (40 males and 30 females; median age 7 years, range 0.8–18) with MDS reported to the European Working Group of MDS in Childhood, the Center for International Blood and Marrow Transplant Research or the Eurocord-European Blood and Marrow Transplant Group. Excluded were patients who had received prior autologous/allogeneic HSCT and those with Down syndrome, Fanconi anemia, or MDS that evolved to AML prior to HSCT. Patients had refractory cytopenia (RC, n=31), refractory anemia with excess blasts (RAEB, n=30), and RAEB in transformation (RAEB-t, n=9). All patients received a single UCB unit and myeloablative preparatory regimen. Karyotype analysis (available for 68 of 70 patients) was normal in 22 patients, while the remaining 46 had cytogenetic abnormalities, the most frequent being monosomy 7 (n= 23). In all pairs but one, donor-recipient histocompatibility was determined by serology (low-resolution typing) for HLA-A and -B and allele-level typing for DRB1. UCB units were HLA matched (A, B, DRB1) in 4 cases, 1-locus, 2-loci and 3-loci mismatched in 34, 26 and 5 cases, respectively. The day-60 probability of neutrophil recovery was 76%; in multivariate analysis, transplantation of HLA matched or 1-locus mismatched UCB, irradiation-containing preparatory regimen, cell dose ≥ 6x107/kg (pre-cryopreservation) and monosomy 7 were associated with faster neutrophil recovery. The 100-day probability of grade II-IV acute graft-versus-host disease (GVHD) was 30% (95% CI, 20–41). The 3-year cumulative incidence of chronic GVHD was 23% (95%CI 14–33). Five of 16 patients with chronic GVHD had limited and 11 extensive chronic GVHD. Twenty-nine patients died from transplantation-related complications, the 3-year cumulative incidence of transplantation-related mortality (TRM) was 41% (95% CI 29–52). Three deaths were related to GVHD. In multivariate analysis, TRM was lower when transplants were performed after 2001 (HR 0.41, 95%CI 0.20–0.84, p=0.015). Thirteen patients had recurrent disease and 11 were dead at last follow up. No variable predicted disease recurrence. With a medium follow-up of 39 months (range 10 – 105), the 3-year probability of disease-free survival (DFS) for the entire cohort was 39%; it was 50% when transplantation was performed after 2001 compared to 27% in the earlier period (p=0.02). After 2001, patients received UCB containing higher cell doses and the interval from diagnosis to transplantation was shorter. The 3-year DFS was 61% for the 23 patients with monosomy 7 compared to 30% for patients with other karyotypes (p=0.042). In multivariate analysis, year of transplantation (prior to 2001) and cytogenetic abnormalities other than monosomy 7 were independent risk factors predicting treatment failure, HR 2.38, (95% CI: 1.14–5.0, p=0.02) and HR 2.04,(95% CI: 1.11–3.70, p=0.02), respectively. The 3-year DFS was not influenced by MDS variant. Given the relatively small sample size the influence of MDS variant on transplant-outcome requires validation in a larger series. These data indicate that UCBT is an acceptable alternative in children with MDS without a HLA-matched related or unrelated adult bone marrow donor. The results of UCBT have improved in recent years and monosomy 7 does not confer an unfavourable outcome.

Hyperlipidemia After Allogeneic Stem Cell Transplantation: Prevalence, Risk Factors and Impact on Prognosis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3458-3458
Author(s):  
Yuki Kagoya ◽  
Sachiko Seo ◽  
Yasuhito Nannya ◽  
Mineo Kurokawa
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Calcineurin Inhibitors

Abstract Abstract 3458 Introduction: Hyperlipidemia is one of the late complications after allogeneic stem cell transplantation (SCT). Although intrahepatic cholestasis caused by chronic graft-versus host disease (GVHD) or calcineurin inhibitors has been considered to be one of the etiologies, its prevalence, risk factors, and the impact on prognosis have not been investigated well. Methods: We performed a retrospective analysis of 194 adult patients who underwent allogeneic SCT between 1995 and 2008 in our institute, and survived more than 100 days after SCT. Hypercholesterolemia or hypertriglyceridemia was defined as more than 240 mg/dl or 200 mg/dl, respectively, at two successive tests at least one week apart after the first 100 days after SCT. Cumulative incidence of hypercholesterolemia or hypertriglyceridemia was analyzed. The time to the development of hypercholesterolemia or hypertriglyceridemia was calculated and the multivariate analysis of pre- and posttransplant variables was performed by a Cox proportional hazards model. Chonic GVHD, chronic liver dysfunction (CLD; defined as more than twice the upper limit of normal for aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase, or total bilirubin >3 mg/dl over 3 months) and administration of calcineurin inhibitors were studied as posttransplant factors, which were assessed as time-dependent variables. To analyze the prognosis of patients who developed persistent hyperlipidemia, the multivariate analysis of overall survival (OS), relapse rate, and non-relapse mortality (NRM) was carried out by a landmark approach. Persistent hyperlipidemia was defined as hypercholesterolemia or hypertriglyceridemia continuing more than 3 months. Results: Overall, 83 (42.8%) and 98 (50.5%) patients developed hypercholesterolemia and hypertriglyceridemia, respectively. The median follow-up period of serum cholesterol and triglyceride values in surviving patients was 44 months. The cumulative incidence of each abnormality at 3 years after SCT was 38.1% (95% confidence interval [CI]: 31.0–45.1%), and 46.0% (95% CI: 38.8–52.9%), respectively. In a multivariate analysis, the development of chronic GVHD was independently associated with both hypercholesterolemia (hazard ratio [HR] 2.05, 95% CI: 1.23–3.43, P<0.01) and hypertriglyceridemia (HR 2.04, 95% CI: 1.30–3.18, P<0.01). Besides, CLD was significantly associated with hypercholesterolemia (HR 2.20, 95% CI: 1.39–2.50, P<0.01). Administration of calcineurin inhibitors was not an independent risk factor for the development of hypercholesterolemia (HR 1.23, 95% CI: 0.73–2.08, P=0.43) or hypertriglyceridemia (HR 1.03, 95% CI: 0.61–1.54, P=0.89). Among pretransplant factors, prior hypercholesterolemia and hypertriglyceridemia were associated with posttransplant hypercholesterolemia (HR 2.76, 95% CI: 1.07–7.17, P=0.04) and hypertriglyceridemia (HR 2.04, 95% CI: 1.27–3.27, P<0.01), respectively. Persistent hyperlipidemia was found in 49 patients (25.3%), of which 35 patients (71.4%) developed hyperlipidemia within one year. The median interval to the occurrence of hyperlipidemia of the patients was 180 days after SCT. In univariate analysis, patients with persistent hyperlipidemia had a tendency of better 3-year OS (77.3% vs 64.7%, P=0.23). Multivariate analysis showed that the development of persistent hyperlipidemia was independently associated with better OS (HR: 0.49, P=0.049). Further, although not statistically significant, patients with persistent hyperlipidemia had a tendency of lower 3-year cumulative relapse rate (15.7% vs 20.3%). There were no significant differences in 3-year NRM between patients with or without hyperlipidemia (12.3% vs 13.9%). Conclusions: Both hypercholesterolemia and hypertriglyceridemia are very common complications after SCT. Patients with persistent hyperlipidemia, however, have significantly better OS. Considering a strong association between the development of hyperlipidemia and chronic GVHD, and a tendency of lower relapse rate in patients with persistent hyperlipidemia, hyperlipidemia is regarded as one of the symptoms accompanied with chronic GVHD. Unless severe, its incidence indicates a better control of the primary disease and an improved prognosis. Disclosures: No relevant conflicts of interest to declare.

Risk Factors and Outcome of Chronic GVHD: Analysis of 5,660 Patients Undergoing Unrelated Bone Marrow Transplantation through the Japan Marrow Donor Program.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 139-139
Author(s):  
Chiaki Nakaseko ◽  
Miki Nishimura ◽  
Shinnichi Ozawa ◽  
Ryuko Cho ◽  
Chikako Ohwada ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Post Transplant ◽  
Risk Of Death ◽  
Significant Difference ◽  
Late Morbidity

Abstract Background: Chronic GVHD (cGVHD) remains the major cause of late morbidity and mortality after allogeneic stem cell transplantation. However, there are limited data available on cGVHD after unrelated BMT (UR-BMT). We retrospectively analyzed the data of 5,660 patients who underwent UR-BMT through the Japan Marrow Donor Program (JMDP) between January 1993 and June 2004. Methods: Data were collected by the JMDP using a standard report form. Follow-up reports were submitted at 100 days, 1 year, and then annually after transplantation. Overall survival (OS) was estimated by the Kaplan-Meier method and patients surviving beyond day 100 after transplant were analyzed for the development of cGVHD. The log-rank test was used for univariate analysis and time-dependent Cox proportional hazards modeling was used for multivariate analysis. The cumulative incidence of cGVHD and of relapse was calculated using the Gray method considering death without cGVHD and death without relapse as respective competing risks. Results: The median age of all patients was 28 years and the median follow-up was 433.5 days after transplant. Estimated 5-year OS of all patients and those with hematological malignancies was 47.4% and 45.5%, respectively. A total of 3,974 patients survived beyond day 100 after transplant and their cumulative incidence of cGVHD was 43.2% at day 500 and 44.9% at day 2,000 post-transplant. The cumulative incidence of extensive cGVHD was 28.8% at day 2,000 post-transplant. In multivariate analysis, variables predicting cGVHD were recipient age (p=0.000), donor age (p=0.002), diagnosis of hematological malignancy (HR=1.99, p=0.000), HLA class I mismatch by either serology or DNA typing (HR=1.24, p=0.020), acute GVHD (I: HR=1.50, p=0.000; II: HR=2.07, p=0.000; III and IV: HR=2.25, p=0.000) and no platelet recovery over 50,000/mm3 before day 100 (HR=1.36, P=0.002). There was a significant difference between patients &lt;20 and ≥20 years old (HR=1.27, p=0.000). However, there were no significant differences between any adults grouped by age decade (p=0.894). OS at 5 years in patients surviving &gt;100 days post-transplant was 62.4% without cGVHD, 68.0% with limited cGVHD, and 55.4% with extensive cGVHD (p=0.000). In the patients with hematological malignancies, OS at 5 years was 58.8%, 67.3% and 55.8%, respectively (p=0.000). Cumulative incidence of relapse of hematological malignancies at day 2,000 in patients surviving &gt;100 days post-transplant was 17.6% with limited cGVHD, 18.4% with extensive cGVHD and 27.1% without cGVHD (P=0.000). Conclusions: This study provides strong evidence of risk factors for developing cGVHD after UR-BMT and suggests that limited cGVHD provides a survival benefit to patients with hematological malignancies by reducing the risk of relapse without increasing the risk of death from cGVHD. There was a significant difference in occurrence of cGVHD between patients &lt;20 and ≥20 years old but no differences comparing any age ≥20 years.

A Relapse Risk Score to Predict Acute Myeloid Leukemia Relapse After Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation Based on Pre-Transplant Variables.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3450-3450 ◽  
Author(s):  
Boglarka Gyurkocza ◽  
Rainer Storb ◽  
Barry E. Storer ◽  
Thomas Chauncey ◽  
Thoralf Lange ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Blood Cell ◽  
Risk Score ◽  
Peripheral Blood ◽  
Risk Groups ◽  
Peripheral Blood Cell ◽  
Blood Cell Count ◽  
Relapse Risk ◽  
Count Recovery

Abstract Abstract 3450 Objective: Allogeneic hematopoietic cell transplantation (HCT) following a variety of reduced-intensity conditioning regimens has been reported to produce encouraging results in patients with AML. In these studies disease relapse was the main cause of treatment failure, with 2–4 year relapse rates ranging between 32–61% resulting in overall survivals of 28–45% at 2–4 years. Our goal here was to examine whether pre-HCT variables could identify patients at high risk for relapse following nonmyeloablative allogeneic HCT, who thus would become candidates for additional interventions to reduce the risk of AML relapse. Methods: The data were derived from 274 consecutive Seattle Consortium patients (median age: 60 years) with de novo or secondary AML who underwent allogeneic HCT from related or unrelated donors after conditioning with 2 Gy total body irradiation (TBI) with or without fludarabine (90 mg/m2) as recently reported (Gyurkocza et al., JCO 2010 Jun 10;28(17):2859–2867). Cox regression was used to perform multivariate analysis of risk factors for relapse in a subset of 231 patients in morphologic leukemia-free state (defined as less than 5% marrow blasts) with (n=134) or without (n=97) peripheral blood cell count recovery (defined as platelets > 100,000/ml and neutrophils > 1,000/ml) at the time of HCT. In this multivariate model, AML beyond 1st complete remission (CR1), unfavorable cytogenetics (according to SWOG criteria), incomplete peripheral blood cell count recovery before HCT, and shorter time between diagnosis and HCT were associated with statistically significantly higher risk of relapse (Table 1). From this multivariate model we developed a relapse risk score that summarizes the contribution of multiple risk factors by assigning weights based on the relative magnitude of the log hazard ratios associated with the principal risk factors. From a starting score of 0, points were added or subtracted based on the following factors: 2nd CR: +1 point; 3rd or later CR: +2 points; unfavorable cytogenetics: +1 point; absence of pre-HCT peripheral blood cell count recovery: +0.5 points; time from diagnosis to HCT > 18 months, -2 points (Table 2). Patients were then stratified into 2 relapse risk groups according to whether the total risk score was ≤0 (low-risk) or >0 (high-risk). Results: Stratification of patients according to the proposed Relapse Risk Score resulted in a clear separation of the two risk groups, with 5-year relapse rates of 50% and 17% in the high- and low-risk groups, respectively (Figure 1A). Five-year overall survival rates were 26% and 50% in the high- and low-risk groups, respectively (Figure 1B). Conclusion: Our Relapse Risk Score may be a useful tool to identify patients with AML at high risk for relapse, who could potentially benefit from additional interventions to reduce the risk of relapse following allogeneic HCT. We are currently attempting validation in an independent cohort of patients with AML to make this Risk Score more generalizable. Relapse/Progression (A) and Overall Survival (B) rates stratified by Relapse Risk Score. Disclosures: Off Label Use: Off label usage of fludarabine, cyclosporine, tacrolimus and mycophenolate mofetil is discussed.

A Retrospective Analysis of 344 Fludarabine Melphalan RIC Allogeneic Stem Cell Transplants for Myeloid and Lymphoid Malignancies In Australia and New Zealand 1998–2008,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4143-4143
Author(s):  
Adam J Bryant ◽  
Elango Pillai ◽  
Glen Kennedy ◽  
Anna Kalff ◽  
David Ritchie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
New Zealand ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
P Value ◽  
Myeloid Malignancies ◽  
Lymphoid Malignancies ◽  
Significant Difference ◽  
Cell Transplants

Abstract Abstract 4143 AIM: Fludarabine Melphalan (FluMel) is the commonest Reduced Intensity Conditioning (RIC) regimen used in Australia and New Zealand. This study aims to assess the relative benefit of this regimen in both lymphoid and myeloid malignancies and to further delineate risk factors associated with an improved survival using RIC conditioning. METHOD: This was an ABMTRR based retrospective study assessing the outcome of FluMel RIC allografting in 9 Australian and New Zealand Centres between 1998 and 2008. Data was collected from centres using an excel based eCRF emailed to centres. Analysis was performed using Stata software and a p value less than 0.05 was considered significant. RESULTS: Median follow up was 3.4 years. There were 342 patients with a median age of 54 years (18–68) and 61% were male. 234 patients had myeloid malignancies with AML (n=166) being the commonest indication whereas there were 110 lymphoid patients with NHL (n=64) the main indication. TRM at D100 was 14% with no significant difference between the groups. OS and DFS were similar between myeloid and lymphoid patients (50% and 43% at 5 years respectively). There was no difference in the cumulative incidence of relapse and GVHD between the groups. Multivariate analysis revealed 4 adverse risk factors for DFS: non-HLA identical sibling donor, not in remission at transplant, previous autologous transplant, and recipient CMV +ve. The presence of Chronic GVHD was associated with a better DFS predominantly due to a marked reduction in relapse (HR 0.44, p=0.003). CONCLUSION: This is one of the largest analyses of Fludarabine Melphalan RIC transpants performed. This dataset confirms that FluMel provides durable remissions in both myeloid and lymphoid malignancies with 50% overall survival at 5 years. The multivariate analysis provides important clues for improving outcomes when planning FluMel conditioning in patients with haematological malignancies. Disclosures: No relevant conflicts of interest to declare.

The NIH Chronic Gvhd Global Score and the CIBMTR Risk Score Correlate Well with Failure Free Survival Following Frontline Systemic Corticosteroid Therapy for Chronic Gvhd

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3925-3925
Author(s):  
Jieun Uhm ◽  
Nada Hamad ◽  
Elizabeth M Shin ◽  
Vikas Gupta ◽  
John Kuruvilla ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Treatment Outcomes ◽  
Risk Score ◽  
Cumulative Incidence ◽  
Systemic Treatment ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Overlap Syndrome ◽  
Global Score ◽  
Free Survival

Abstract Introduction: While the National Institutes of Health (NIH) consensus criteria (NCC) on diagnosis and staging of cGVHD are now widely used, minimal attempts have been made to validate its ability to predict the outcomes of cGVHD treatment. Arora et al. analyzed data from the Center for International Blood and Marrow Transplant Registry (CIBMTR) and suggested that the CIBMTR risk score is a predictive factor for overall survival (OS) and non-relapse mortality (NRM). The failure free survival (FFS) has been recently proposed as an endpoint for clinical trials on treatment of cGVHD. With this study we aimed to evaluate if the cGVHD global score by the NCC and the CIBMTR risk groups (RG) could predict the treatment outcomes of frontline systemic steroid therapy for cGVHD. Method: We retrospectively reviewed 668 consecutive patients who underwent allo-HCT between 2004 and 2012 at the Princess Margaret Cancer Centre, Toronto, Canada. We then identified 312 patients who had a diagnosis of cGVHD and received at least one systemic treatment for this. Thirty-five patients were excluded from the analysis as they were not treated with systemic corticosteroids and the remaining 277 patients were included in the final analysis. Chronic GVHD was reclassified and graded using the NCC. The CIBMTR risk score was also calculated and patients were stratified into 3 RGs accordingly. We evaluated the treatment outcomes including OS, NRM, relapse and FFS. FFS was defined as time to a switch in systemic therapy (i.e. failure of the treatment), NRM or relapse. The Kaplan-Meier method was used for OS and FFS. The cumulative incidences of NRM and relapse were calculated considering competing risks. Multivariate analysis was performed using the Cox proportional hazard regression model for OS and FFS. The Fine-Gray method was used for the incidences of NRM and relapse in multivariate analysis. Results: With a median follow-up duration of 26 months among survivors, the median to onset of cGVHD was 140 days (range, 45-381). One hundred and two patients (36.9%) were classified as classical cGVHD and 175 patients (63.1%) as overlap syndrome. At the onset of cGVHD 90 patients (32.5%) had mild cGVHD by the NIH global score (NIH GS), moderate in 143 patients (51.6%) and severe in 44 patients (15.9%). Thirty-three patients (11.9%) presented with progressive type onset (PTO). The CIBMTR risk score was available in 227 patients and we were able to stratify them into those with RG1 (score 0-2; n=32, 14.1%), RG2 (score 3-6; n=162; 71.4%) and RG3-6 (score ≥7; n=33, 14.5%). The median FFS of the 277 patients was 255 days. A severe GS correlated with the worst FFS: median FFS duration was 164 days in severe vs 238 days in moderate vs 304 days in mild (p=0.001). The CIBMTR RG also reflected the prognosis of patients after cGVHD treatment: the higher the RG the shorter the median duration of FFS: 166 days in RG3-6 vs 291 days in RG2 vs 501 days in RG1 (p=0.003). The OS at 2 years from the onset of cGVHD was 74.3%. A severe GS was associated with a worse OS: 55.1% in severe vs 79.9% in moderate vs 76% in mild grade (p<0.001). The CIBMTR RG was predictive of OS: 92% in RG1 vs 81.5% in RG2 vs 38.9% in RG3-6 (p<0.001). The cumulative incidence of NRM was 7.6% at 2 years. The NIH GS was predictive of NRM. The 2-year NRM rate was lowest with a mild GS at 2.4%, intermediate with a score of moderate at 4.8%, but significantly higher with a severe score at 27.5% (p<0.001). The CIBMTR RGs were also predictive of NRM: 0% for RG1, 6.1% for RG2 and 21.9% for RG3-6 (p=0.001). The cumulative incidence of relapse at 2 years was 9.2% and it was not associated with either the NIH GS or CIBMTR RGs.. Multivariate analysis confirmed that an NIH GS of severe and the CIBMTR RG3-6 and the overlap syndrome were associated with worse FFS: A severe NIH GS hazard ratio (HR) 1.65, p=0.011; CIBMTR RG3-6, HR 2.39, p=0.006; overlap syndrome, HR 1.38, p=0.058. A NIH GS of severe and CIBMTR RG3-6 were verified as adverse risk factors for NRM: A severe NIH GS, HR 6.31, p=0.001; CIBMTR RG3-6, HR 3.44, p=0.0081. CIBMTR RG3-6 and PTO were identified as unfavorable factors for OS: CIBMTR RG3-6, HR 5.14, p=0.002; PTO, HR 3.20, p<0.001. Conclusion: The NIH GS and CIBMTR RG for cGVHD correlated well with FFS and NRM following first line systemic treatment for cGVHD with corticosteroid-based regimens. Disclosures No relevant conflicts of interest to declare.

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