Multidrug Resistance-1 Gene Polymorphism Associated with the Outcomes after Allogeneic HLA-Identical Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1757-1757
Author(s):  
Dong Hwan Kim ◽  
Seok Bong Jeon ◽  
Jin Ho Baek ◽  
Nan Young Lee ◽  
Jong Gwang Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Multidrug Resistance ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Mdr1 Gene ◽  
Solid Organ ◽  
Blood Concentrations

Abstract Background: The pharmacokinetic impact of multidrug resistance-1 (MDR1) gene single nucleotide polymorphisms (SNPs) has been already investigated in solid organ transplantation field, however, data is still lacking in an allogeneic stem cell transplantation (SCT) setting. Methods: A total of 82 patients receiving an allogeneic HLA-identical sibling (n=70) or unrelated SCT (n=12) with graft-versus-host disease (GVHD) prophylaxis of cyclosporine-A (CSA) plus methotrexate (MTX) were included in the current study. Two SNPs of MDR1 gene (C3435T and G2677T/A) were analyzed using PCR/RFLP assay. Results: As regards G2677T/A SNP, GG genotype showed a higher incidence of NRM compared to non-GG genotype (67% vs. 32%, p=0.0073), yet not C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival (OS) was significantly correlated with G2677T/A genotype (p=0.0048), yet not with C3435T (p=0.5041) or MDR1 haplotype (p=0.4086). However, no difference in the relapse incidence was noted according to G2677T/A, C3435T genotype or MDR1 haplotype. In a multivariate analysis, those patients without GG genotype at G2677T/A were found to have favorable prognosis in terms of OS (p=0.003) or NRM (p=0.031) along with occurrence of chronic GVHD (p<0.001 for OS, p=0.001 for NRM), standard disease risk (p=0.045 for OS) or acute grade 0,1 GVHD (p=0.019 for NRM). However, no correlation was found between the blood concentrations of CSA and MDR1 genotype and CSA neurotoxicity and MDR1 genotype. Conclusion: The G2677T/A genotype seemed to be associated with the transplantation outcomes, especially NRM. Further study is warranted to clarify its mechanism of MDR1 SNPs other than pharmacokinetic aspects. Figure. Overall survival (A) and cumulative incidence of non-relapse mortality (B) according to G2677T/A MDR1 genotype Figure. Overall survival (A) and cumulative incidence of non-relapse mortality (B) according to G2677T/A MDR1 genotype

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

Psychosocial Factors as Measured by the Transplant Evaluation Rating Scale (TERS) Predict Length of Hospitalization and Transplant Outcomes Following Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 75-75 ◽  
Author(s):  
Dawn S. Speckhart ◽  
Scott R. Solomon
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Rating Scale ◽  
Solid Organ ◽  
Hematopoietic Stem ◽  
Transplant Patients ◽  
Transplant Evaluation ◽  
Length Of Hospitalization

Abstract Although psychological and social factors are recognized as being important in the evaluation of patients for hematopoietic stem cell transplantation (HSCT), no standard approach to psychosocial assessment currently exists. In solid organ transplantation, psychosocial assessments have been integrated into the selection of appropriate candidates, and certain psychosocial variables, such as active substance abuse, have been shown to negatively impact outcomes in solid organ transplant patients. To determine whether similar factors impact outcomes in patients undergoing HSCT, we prospectively conducted psychosocial assessments on 221 consecutive patients (155 autologous, 66 allogeneic) undergoing HSCT. The relationship between psychosocial variables, such as those assessed on the Transplant Evaluation Rating Scale (TERS), and objective outcomes, such as length of hospitalization and survival was evaluated. Based on the patient’s TERS score, each patient was stratified into one of two groups (low/moderate risk (n=187) vs. high risk (n=34)) based on their predicted psychosocial risk for problems during transplant. Although the two groups were similar in regards to known pre-transplant prognostic factors such as age, performance status, disease risk, and transplant type, there was a significant difference in the median length of hospitalization between patients who score low/moderate (10 days) and those who scored high (21.5 days) on the TERS. This difference was significant both for patients receiving autologous (9 vs. 15 days, p<.02) and allogeneic transplants (16 vs. 45 days, p<.001). Furthermore, 2-year overall survival was significantly improved in allogeneic transplant patients who score low/moderate vs. those that scored high on the TERS (72% vs. 46%; p<=.02). These findings suggest a strong correlation between pre-transplant psychosocial risk factors, resource utilization and patient outcome in HSCT. Figure 1. Overall survival following allogeneic stem cell transplantation according to TERS score Figure 1. Overall survival following allogeneic stem cell transplantation according to TERS score

Evaluation of NIH Consensus Criteria for Classification of Late Acute and Chronic Gvhd in Reduce Intensity Conditioning (RIC) Stem Cell Transplantation (SCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1139-1139 ◽  
Author(s):  
Jifang Zhou ◽  
Sylvain Thepot ◽  
Aurrore Perrot ◽  
Marie Robin ◽  
Regis Peffault de Latour ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Time Dependent ◽  
Increased Risk ◽  
Nih Consensus Criteria

Abstract Abstract 1139 Poster Board I-161 Background Chronic graft-versus-host disease (GVHD) occurs frequently after allogeneic stem cell transplantation (SCT) and has an impact on morbidity and survival. The National Institutes of Heath (NIH) consensus criteria for the diagnosis of GVHD, emphasized clinical manifestations of GVHD rather than the classical time of onset (day 100). Incidence and impact in term of relapse and no-relapse mortality (NRM) of this new classification is not well known after RIC. Methods We retrospectively reviewed 116 consecutive patients (pts) in Saint Louis' Hospital undergoing an SCT for hematologic malignancy and surviving at least day + 100 after RIC between August 2005 and December 2008. We evaluated non-relapse mortality (NRM) and recurrent malignancy. Cumulative incidence was computed using death as a competing event. Incidence of relapse and NRM was counted from 100 days post-transplant for patients without chronic GVHD or from chronic GVHD onset. Patients with relapse/progression before chronic GVHD onset were considered as not having chronic GVHD in these analyses. The association of occurrence of chronic GVHD with the risk of relapse and non-relapse death was analyzed using time-dependent covariates in cause-specific proportional hazards models. Results Among 116 pts ( M/F: 71/45), with a median age of 53 years old (19-68 years) 28 pts (24%) were transplanted for acute leukemia in, 11 pts (9%) for chronic leukemia, 27 pts (23%) for lymphoma, 30 pts (26%) for MPD/MDS and 20 pts (17%) for plasma cell disorder. Sixty-three pts (54%) received HLA-identical sibling transplantation, 53 pts (46%) received transplantation from unrelated donors. Source of stem cells was mobilized peripheral blood stem cell for 108 pts (93%), bone marrow for 4 pts (3%) and 4 cord blood (3%). After a median follow-up of 18 months (range 5-45 months), a total of 67 pts (58%) developed chronic GVHD according to the Seattle day 100 landmark criteria and when using NIH consensus criteria, 55 pts (47%) developed chronic GVHD, including 43 pts (53%) with classic chronic GVHD and 8 pts (10%) overlap syndrome. Patients reclassified included; 3 pts with late onset acute GvHD, 19 pts had recurrent and 8 had persistent acute GVHD (numbers do not to previous sentence because some of these patients latter developed chronic GvHD). The cumulative incidence of chronic GVHD at 36 months was 64% (95%CI; 53%-73%) when using Seattle criteria compared to 56% (95%CI; 45%-67%) with NIH chronic GVHD criteria. Two-year Cumulative incidences of relapse and NRM using both classifications are summarized in Table. In Cox model with GvHD as a time dependent covariate, the NRM was significantly higher in patients with late onset, persistent and recurrent acute GVHD compared to no GVHD (hazard ratio (HR) 31, 47 and 30; p = 0.005, p <0.0001, p <0.0001, respectively), whereas the NRM was statistically increased in case of chronic GVHD using Seattle day 100 criteria (HR: 2.8; P=0.034). Conclusion The cumulative incidence of chronic GVHD “decrease” about 10% when using NIH consensus criteria compared to Seattle criteria in our cohort of RIC. Most of the NRM occurred beyond 100 days after SCT was due to the increased risk of NRM in patients with late onset, recurrent or persistent acute GVHD. Disclosures No relevant conflicts of interest to declare.

Comparative Analysis of Outcomes of Allogeneic Peripheral Blood Stem Cell Transplantation From Related and Unrelated Donors.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3381-3381
Author(s):  
Byung Woog Kang ◽  
Shi Nae Kim ◽  
Joon Ho Moon ◽  
Joo-Seop Jung ◽  
Goon-Jae Cho ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Peripheral Blood Stem Cell ◽  
Chronic Gvhd ◽  
P Value ◽  
Cmv Infection ◽  
Blood Stem Cell Transplantation

Abstract Abstract 3381 Poster Board III-269 This study compared the results of allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated and related donors, and involved 235 consecutive patients from 10 centers who received an allogeneic PBSCT for hematological malignancies between Jan 2004 and Dec 2008. Among these patients, 160 (68.1%) received an HLA-matched related PBSCT and 75 (31.9%) a matched unrelated PBSCT. Sixty-five patients (27.7%) had a high-risk disease status at transplantation. The cumulative incidence of acute graft-versus-host disease (GVHD) was 43.9% for the related PBSCT group and 59.3% for the unrelated PBSCT group (P-value:0.011). Although the cumulative incidence of chronic GVHD was no different between the related (54.2%) and unrelated (64.9%; P-value:0.199) PBSCT groups, the cumulative incidence of extensive chronic GVHD was higher among the unrelated PBSCT group (34.9%) than among the related PBSCT group (17.0%; P-value:0.015). Plus, the unrelated PBSCT group showed a higher cumulative incidence of CMV infection (44.6%) than the related PBSCT group (26.8%; P-value:0.002). The overall survival rate at four-year was 58.2% versus 49.1% (p=0.698) and the cumulative incidence of relapse 28.4% versus 25.0% (P-value:0.289) for the related and unrelated PBSCT groups, respectively. Among the factors examined, unrelated PBSCT (P-value:0.024), the CD34-positive cell count (>6 × 106/kg; P-value:0.041), and CMV infection (P-value:0.066) were all related with a higher incidence of extensive chronic GVHD. However, in a multivariate analysis, only unrelated PBSCT was identified as a risk factor for the development of extensive chronic GVHD (hazard ratio=2.012, 95% confidence interval=1.006-4.023; P-value:0.048). In conclusion, the overall survival and relapse incidence were not significantly different between the related and unrelated PBSCT groups. However, a higher incidence of CMV infection and extensive chronic GVHD was observed in the unrelated PBSCT group. Disclosures: No relevant conflicts of interest to declare.

Impact of antithymocyte globulin (ATG)-containing conditioning regimens on patients undergoing allogeneic stem cell transplantation (allo-CST) for poor risk cytogenetic IPSS myelodysplastic syndrome (PRC-MDS): A report from the French Society of Stem Cell Transplantation and Cell  Therapy (SFGM-TC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6542-6542
Author(s):  
Ibrahim Yakoub-Agha ◽  
Gandhi Laurent Damaj ◽  
Marie Robin ◽  
Stephane Vigouroux ◽  
Alice Garnier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
French Society ◽  
Poor Risk ◽  
Increased Risk

6542 Background: Due to a risk of relapse of underlying disease in patients with PRC-MDS, the use of ATG, incorporated within the conditioning regimen prior to allo-SCT, is still controversial. Methods: Inclusion criteria included patients aged over 18 (n=101) who received allo-SCT transplanted between 1999 and 2009 from either a sibling (n=68) or HLA-allele-MUD (10/10) (n=33) for PRC-MDS. HLA matching was double-checked by the national Bone Marrow Donor Registry. Results: According to the FAB/WHO classification at diagnosis, 22 pts had RA/RARS/RCMD, 40 RAEB1, 30 REAB2 and 9 RAEB-t/AML. 34 pts had progressed to a more advanced disease before allo-SCT. At diagnosis, 89 patients had an IPSS int-2 or higher. At transplant, 36 pts were responders (CR, PR, CRm) and 62 with progressive disease (relapsed/refractory, untreated or stable disease without hematological improvement). Median age at transplantation was 54 years (range, 22-69). Pts received myeloablative conditioning (n=46) and nonmyeloablative (n=55). In this series, 48 patients received ATG as part of conditioning ('ATG' group), whereas 53 did not ('no-ATG’ group). As of April 1st 2011, 44 patients died of relapse and 22 of TRM. 3-year relapse, overall and event-free survival rates were not significantly different between the two groups. In contrast, the cumulative incidence of grade 2-4 acute GVHD was 48% in the no-ATG group and 30% ATG group (P <.005). Although the cumulative incidence of chronic GVHD was similar in the no-ATG and ATG groups, a trend for a lower TRM was observed in the ATG group (p=.06). In multivariate analysis, the absence of use of ATG was associated with an increased risk of acute grade 2-4 [HR = 1.92, p=.044]. Conclusions: The addition of ATG to the conditioning regimen resulted in a decreased incidence of acute GVHD without increasing relapse rates and compromising survival of patients undergoing allo-SCT for poor risk cytogenetic MDS.

Donor C3435T Polymorphism in the Multidrug Resistance 1 (MDR1) Gene Is Associated with the Incidence of Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2868-2868
Author(s):  
Avichai Shimoni ◽  
Olga Ostrovsky ◽  
Hanan Galski ◽  
Izhar Hardan ◽  
Noga Shem-Tov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Mdr1 Gene ◽  
C3435t Polymorphism ◽  
Graft Versus Host ◽  
Significant Factors

Abstract Graft-versus-Host disease (GVHD) is the most significant treatment-related complication after allogeneic stem cell transplantation (alloSCT). HLA, KIR and cytokine gene polymorphisms were previously reported to be involved in determining the risk of GVHD after alloSCT. The current study was designed to explore the role of polymorphism in the multi-drug resistance 1 (MDR1) gene in predicting GVHD. Single nucleotide polymorphisms at C3435T and G2677T were determined in patients (pts) and donors using RFLP- based assay and correlated with the occurrence of acute and chronic GVHD after alloSCT. The study included 115 pts with various hematological malignancies after alloSCT from related (n=73) or unrelated (n=42) donors. Fifty pts had myeloablative and 65 had reduced-intensity conditioning. C3435T polymorphism included CC, CT and TT genotypes. CC genotype was detected in 36% and 34% of pts and donors, respectively. CT and TT genotypes were detected in 47%/47%, and 17%/19% respectively. G2677T polymorphism included GG, GT and TT genotypes that were detected in 29%/34%, 55%/49%, and 16%/17% of pts and donor pairs, respectively. The incidence of acute and chronic GVHD were found to be increased after alloSCT in pt-donor pairs when the donor had CC in the C3435T site. The cumulative incidence of acute GVHD grade II–IV after alloSCT was 53% (95%CI, 37–74), 40% (28–57) and 42% (25–71) when the donors had CC, CT and TT in the C3435T site, respectively (p=NS), while the cumulative incidence of acute GVHD grade III–IV was 38% (24–62), 18% (9–35) and 18% (6–50), respectively (p=0.02). Multivariable analysis determined donor CC (HR 2.4, p=0.05) and alloSCT from female to male (HR 5.1, p=0.03) as the most significant factors predicting for severe acute GVHD while donor, disease and conditioning types were not significant. Pt C3435T polymorphism and pt or donor G2677T polymorphisms had no correlation with GVHD. Similarly the cumulative incidence of chronic GVHD was 84% (95%CI, 68–100), 53% (38–75) and 38% (39–63) when the donors had CC, CT and TT in the C3435T site, respectively (p=0.02). Multivariable analysis determined donor CC (HR 2.2, p=0.01), alloSCT from female to male (HR 2.5, p=0.03) and alloSCT from unrelated donor (HR 1.8, p=0.05) as the most significant factors predicting for chronic GVHD. The same three factors predicted for extensive chronic GVHD. The CC genotype in C3435T is known to be associated with higher expression level of P-glycoprotein (Pgp). We speculate that increased Pgp may result in lower intracellular levels of cyclosporine in donor T-cells leading to higher incidence of GVHD. Furthermore, Pgp may be involved in transporting Th1 and Th2 cytokines that are critical to the pathogenesis of acute and chronic GVHD, respectively. Further studies will be required to determine the mechanism of the association of C3435T polymorphism, Pgp expression and GVHD. In conclusion, C3435T polymorphism in the MDR1 gene may be an important factor in predicting GVHD and may be considered when selecting the most suitable donor.

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.

Prediction of Allogeneic Stem Cell Transplantation Mortality in Patients with Acute Leukemia (AL) Using the AL- European Society for Blood and Marrow Transplantation (EBMT) Risk Score in the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO) Data Set: A Study on Behalf of the AL Working Party (ALWP) of the EBMT and GITMO

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 989-989
Author(s):  
Roni Shouval ◽  
Francesca Bonifazi ◽  
Joshua Fein ◽  
Cristina Boschini ◽  
Elena Oldani ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Cumulative Probability ◽  
Allogeneic Hsct ◽  
Hazard Ratios ◽  
Independent Cohort

Abstract * AR and AN contributed equally to the abstract Background: When considering a high risk, but potentially curative procedure, such as an allogeneic hematopoietic stem cell transplantation (HSCT), prognostic models may help decision making. We have previously developed the Acute Leukemia (AL)-EBMT score for prediction of mortality following allogeneic HSCT in AL patients (Shouval et al., JCO, 2015). The score is based on 10 variables including: disease status,Karnofsky performance status, recipient age, diagnosis, interval between diagnosis to HSCT, conditioning regimen, donor type, donor and recipient CMVserostatus combination, HSCT year, and center experience (HSCT/year). External validation of the score on an independent cohort of AL patients is of importance. Methods: This was a retrospective validation study on an independent cohort of AL patients from the Italian national transplantation network (GITMO). Inclusion criteria included adult AL patients, receiving an allogeneic HSCTbetween 2000-2014. Competing risks analysis was used to calculate the 2 years non-relapse related mortality (NRM) cumulative incidence, using the Gray test to test differences between ADT score groups. Overall survival (OS), and leukemia free survival (LFS) at 2 years were estimated using the Kaplan-Meier method; hazard ratios were computed between subgroups using Cox regression for OS and LFS and competing risk regression for NRM. Competing risk regression was used to compute NRM cumulative incidence rates, considering non-transplant mortality as the competing event. The predictive ability of the AL-EBMT score was assessed using time-dependent receiver-operator curves (AUC) analysis. Results: A total of 1,848 patients from 61 Italian transplant centers were analyzed. The median age was 45.9 (IQR 35.2-55). Indications for HSCT were Acute Myeloid Leukemia (67.8%) and Acute Lymphoblastic Leukemia (32.2%). The majority of patients were in first complete remission (60.6%), and received myeloablative conditioning (81.3%). Median follow-up was 2 years (1.9-2.1, 95% CI). The AL-EBMT score was categorized according totertiles (low, intermediate, high) on the original ALWP-EBMT cohort. Increasing score intervals corresponded with decreasing probability for 2 year OS (95% CI), ranging from 75.52% (70.69-80.68) to 36.93% (32.81-41.56), and increasing probability of 2 years NRM ranging from 10.9% (7.97-14.93) to 27.39% (23.84-31.48) (Table 1, Figure 1). The highest scoring group was associated with a hazard ratio (95% CI) of 2.89 (2.01-4.16) for 2 year NRM and 3.66 (2,85-4.72) for death at 2 years (Table 2). The categorized score discrimination (AUC) for 2 year OS, LFS, and NRM was 66.42, 66.15, and 67, respectively. Conclusion: This is the first study externally validating the AL-EBMT score. The score identified 3 distinctive risk groups and was predictive of survival related outcome. It can be used as a decision support tool when considering an allogeneic HSCT in acute leukemia patients. Table 1 Cumulative Probability of NRM and OS (95% CI) at 2 Years Table 1. Cumulative Probability of NRM and OS (95% CI) at 2 Years Table 2 Hazard Ratios for Outcomes at 2 years Table 2. Hazard Ratios for Outcomes at 2 years Figure 1. Overall Survival Stratified by the AL-EBMT Score Figure 1. Overall Survival Stratified by the AL-EBMT Score Disclosures No relevant conflicts of interest to declare.

Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation

2019 ◽  
Vol 37 (5) ◽  
pp. 375-385 ◽  
Author(s):  
Mareike Frick ◽  
Willy Chan ◽  
Christopher Maximilian Arends ◽  
Raphael Hablesreiter ◽  
Adriane Halik ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Increased Risk

Purpose Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). Methods We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incidence of relapse/progression (CIR/P), and overall survival (OS). Results A total of 92 clonal mutations with a median variant allele frequency of 5.9% were identified in 80 (16.0%) of 500 donors. CHIP prevalence was higher in donors related to patients with myeloid compared with lymphoid malignancies (19.2% v 6.3%; P ≤ .001). In recipients allografted with donor CHIP, we found a high cumulative incidence of chronic GVHD (cGVHD; hazard ratio [HR], 1.73; 95% CI, 1.21 to 2.49; P = .003) and lower CIR/P (univariate: HR, 0.62; 95% CI, 0.40 to 0.97; P = .027; multivariate: HR, 0.63; 95% CI, 0.41 to 0.98; P = .042) but no effect on nonrelapse mortality. Serial quantification of 25 mutations showed engraftment of 24 of 25 clones and disproportionate expansion in half of them. Donor-cell leukemia was observed in two recipients. OS was not affected by donor CHIP status (HR, 0.88; 95% CI, 0.65 to 1.321; P = .434). Conclusion Allogeneic HSCT from donors with CHIP seems safe and results in similar survival in the setting of older, related donors. Future studies in younger and unrelated donors are warranted to extend these results. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that donor CHIP might foster cGVHD development and reduce relapse/progression risk.

scholarly journals Invasive Fungal Infection in the Setting of Peripheral Blood Non-Manipulated Haploidentical Stem Cell Transplantation with Postransplant Cyclophosphamide

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5710-5710
Author(s):  
Nieves Dorado ◽  
Gillen Oarbeascoa ◽  
Miguel Argüello ◽  
Pascual Balsalobre ◽  
David Serrano ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Fungal Infection ◽  
Amphotericin B ◽  
Cell Transplantation ◽  
Invasive Fungal Infection ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Pulmonary Involvement

Abstract Introduction: Invasive Fungal Infection (IFI) is a serious complication after allogeneic stem cell transplantation (alloSCT). Its incidence and outcome are not well characterized in the setting of peripheral blood, non-manipulated haploidentical stem cell transplantation with postransplant cyclophosphamide (HaploSCT). The aim of the study is to analyze our experience among patients who underwent HaploSCT at our institution and developed an IFI, in order to identify the incidence, risk factors and its impact in survival. Materials and methods: One hundred and thirty-three patients underwent peripheral blood HaploSCT with postransplant cyclophosphamide at our institution between 2011 and 2017. IFI was classified according to the EORTC definitions. Proven and probable IFI were included. Results: Patients´ characteristics are shown in Table 1. Patients received primary antifungal prophylaxis with micafungin from the day before stem cell infusion, during admission and until neutrophil engraftment was stablished. Patients on steroid treatment due to GVHD received prophylaxis with micafungin or posaconazole. Twenty-three episodes of IFI were observed in 20 patients, 10 proven and 13 probable, with a cumulative incidence of IFI of 15% at 500 days. Most commonly isolated organism was Aspergillus spp (5 cases), followed by Candida spp (4 cases: 1 C. kruseii and 3 C. parapsilosis) and Fusarium spp (2 cases). Additionally we observed some isolated cases of Inonotus spp,Mucor spp and Trichosporon Ashii. Pulmonary involvement was the most frequent presentation (11 cases), followed by fungemia (5 cases, 4 Candida and 1 Trichosporon Ashii) and skin-pulmonary involvement (2 cases). Thirteen cases were diagnosed early, in the pre-engraftment period, 5 just after the engraftment and 5 cases developed later. Among patients with late occurrence of IFI, median time of IFI was 220 days, and all of them were associated with GVHD (3 grade III-IV acute GVHD and 2 moderate/severe chronic GVHD). IFI outcome was favorable in 14 out of the 23 documented IFI, with antifungal therapy. Treatment chosen was liposomal amphotericin B in 7 cases, voriconazole in 5 and combined treatment (with amphotericin B and azole) in 6. Death related to IFI was documented in 7 out of the 20 patients, with an IFI mortality cumulative incidence of 6.4%. Prior transplant (OR 4.5, p <0.01) and especially alloHSCT were associated to IFI development (OR 8.2, p <0.01). We did not find any other risk factor associated to IFI, like time of engraftment, disease, conditioning regimen, sequential regimen, grades II-IV GVHD or severe/moderate chronic GVHD. Conclusions: In our experience, cumulative incidence of IFI in the setting of HaploSCT was similar than the one observed in other studies with alloSCT. Mortality associated to IFI in the whole cohort was low (6.4 %). The most significant factor related to IFI development was having received a previous transplant, especially alloSCT. Therefore, this high risk population should be closely monitored and could benefit from prophylaxis with azoles. Disclosures No relevant conflicts of interest to declare.

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