scholarly journals Pre-HCT Telomere Abnormalities and Mortality after Unrelated Donor Hematopoietic Cell Transplant for Severe Aplastic Anemia

2019 ◽  
Vol 25 (3) ◽  
pp. S417
Author(s):  
Youjin Wang ◽  
Lisa J. McReynolds ◽  
Bari J. Ballew ◽  
Hormuzd A. Katki ◽  
Casey L. Dagnall ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Hematopoietic Cell ◽  
Severe Aplastic Anemia ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

Germline Mutations in Patients Receiving Unrelated Donor Hematopoietic Cell Transplant for Severe Aplastic Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 68-68
Author(s):  
Shahinaz M. Gadalla ◽  
Bari J Ballew ◽  
Michael D Haagenson ◽  
Stephen R. Spellman ◽  
Belynda Hicks ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Genetic Variants ◽  
Snp Array ◽  
Hematopoietic Cell ◽  
Genetic Evidence ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Pathogenic Variants ◽  
High Incidence

Abstract Background. The correct classification of patients presenting with aplastic anemia is essential for proper clinical management. This study aimed to identify patients with unrecognized pathogenic variants associated with inherited bone marrow failure syndromes (IBMFS) in patients receiving hematopoietic cell transplant (HCT) for acquired aplastic anemia (AAA), and to evaluate their impact on patient survival. Methods. We performed whole exome sequencing (WES) and genome-wide SNP array genotyping on pre-HCT blood samples from 608 patients who received unrelated donor HCT for severe aplastic anemia in 175 centers reporting to the Center for International Blood and Marrow Transplant Research (CIBMTR) and research samples available in the CIBMTR Repository. An IBMFS was the reported diagnosis in 92/608 patients. From generated genomic data and mode of IBMFS inheritance, we developed a bioinformatic algorithm to identify deleterious mutations in 52 known IBMFS genes. Cox proportional hazard models were used for survival analyses. Variables included in the model were selected by a stepwise backward procedure with a p-threshold of 0.05 for entry and 0.1 for retention. Results. We validated our algorithm in 16 patients with genetically confirmed dyskeratosis congenita (DC, n=12) and Fanconi anemia (FA, n=4) from the NCI IBMFS cohort. Our algorithm was 88% sensitive and 100% specific in identifying the exact mutation in those patients. In HCT recipients, analysis of 52 IBMFS genes identified 130 pathogenic variants in the 92 patients with reported IBMFS and 277 in the 516 patients with reported AAA. Our algorithm combining WES and SNP array data identified genetic evidence of an IBMFS in 59.8% (55/92) of patients reported to have an IBMFS. In patients originally classified as AAA, 10.5% (54/516) had genetic evidence of an IBMFS; 88.7% of them received HCT at ≤ 40 years old, and DC was the most commonly unrecognized disorder (n=26, 5%). Other identified IBMFS by our algorithm included: Diamond-Blackfan anemia (n=8, 1.5%), and FA, myelodysplastic syndrome, or severe congenital neutropenia with 6 patients each (1.2% each), and 1 patient with amegakaryocytic thrombocytopenia (0.2%). Among patients with reported AAA who were ≤ 40 years old, the 3 years survival probability for patients with DC-associated genetic variants (n=26) was 53% (95% CI=35-73%), for patients with genetic variants in other IBMFS (n=20, 4 had FA) was 75% (95% CI=56-94%), and for those with no genetic evidence of IBMFS was 69% (95% CI=64-74%), p log-rank= 0.02. Compared to patients with no genetic evidence of IBMFS, worse post-HCT survival was noted with DC-associated genetic variants (HR=1.75, 95% CI=1.03-2.97, p=0.04), but no survival difference was noted with other IBMFS variants (HR=0.42, 95% CI=0.16-1.15, p=0.09) Conclusions. We identified a high incidence of unidentified IBMFS in patients undergoing HCT for AAA, which was associated with worse post-HCT survival in those with unrecognized DC. Our study supports the importance of comprehensive genetic testing for patients presenting with AA, given the high incidence of underlying genetic abnormalities that have implications for donor selection, family counseling and selection of the preparative regimen Disclosures No relevant conflicts of interest to declare.

scholarly journals Steroid-dependent acute GVHD after allogeneic hematopoietic cell transplantation: risk factors and clinical outcomes

2021 ◽  
Vol 5 (5) ◽  
pp. 1352-1359
Author(s):  
Najla El Jurdi ◽  
Ahmad Rayes ◽  
Margaret L. MacMillan ◽  
Shernan G. Holtan ◽  
Todd E. DeFor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Steroid Dependent ◽  
Steroid Sensitive

Abstract Acute graft-versus-host disease (aGVHD) has various risk factors and outcomes. We defined distinct aGVHD treatment response groups based on response to first-line corticosteroids: steroid sensitive (SS), steroid resistant (SR), and the rarely studied steroid dependent (SD) aGVHD. In 1143 consecutive adult and pediatric allogeneic hematopoietic cell transplant recipients, 385 (34%) developed aGVHD, with 10% having SS aGVHD, 9% SD aGVHD, and 14% SR aGVHD. The only factor significantly associated with SD in comparison with SS was older age (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4-11.3, when comparing 18- to 60-year-olds with <18-year-olds). Factors significantly associated with SR in comparison with SS were unrelated donor (OR, 3.0; 95% CI, 1.2-7.4) and Minnesota high-risk aGVHD (OR, 2.4; 95% CI, 1.3-4.6). SR aGVHD was independently associated with higher risk for 2-year overall mortality (hazards ratio [HR], 1.8; 95% CI, 1.2-2.8) and nonrelapse mortality (NRM; HR, 2.1; 95% CI, 1.2-3.9). SS and SD GVHD groups had similar overall survival and NRM. The cumulative incidence of chronic GVHD was highest in the SD group, followed by the SR and SS groups (46%, 41%, and 29%, respectively). SD and SS GVHD had similar prognoses, both markedly better than those of the SR groups.

scholarly journals Impact of Obesity on Outcomes of Elderly Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Myeloid Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4667-4667
Author(s):  
Ensi Voshtina ◽  
Aniko Szabo ◽  
Mehdi Hamadani ◽  
Tim S. Fenske ◽  
Anita D'Souza ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Cumulative Incidence ◽  
Hematopoietic Cell ◽  
Morbidly Obese ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Myeloid Malignancies ◽  
Co Morbidity ◽  
Equity Ownership

Abstract Background Allogeneic hematopoietic cell transplantation (AHCT) is a high risk treatment option for patients (pts) with myeloid malignancies. Advanced age and obesity can impact outcomes after AHCT. Previous registry studies of all age groups found that obesity does not affect AHCT outcomes. However, obesity can hasten age-related decline in physical function and exacerbate comorbid conditions in older pts. In this study we evaluated outcomes of both non-obese and obese elderly pts undergoing AHCT for myeloid malignancies. Methods We performed a retrospective, single-center analysis of all pts age≥60 who underwent unrelated or related AHCT for myeloid malignancies (acute myeloid leukemia [AML], myelodysplastic syndrome [MDS], or myeloproliferative neoplasms [MPN]) between 2010 and 2015. Descriptive statistics were used to measure baseline characteristics. A hematopoietic cell transplant co-morbidity index (HCT-CI) score was calculated for all pts. Acute graft-versus-host disease (aGVHD) was defined as occurring in <100 days after transplant (Tx) and chronic GVHD (cGVHD) as occurring ≥100 days. Pts were stratified by body mass index (BMI) ≥30 or <30. Comparative analysis was done using chi-squared and Fischer's exact tests. The Kaplan-Meier method was used to calculate overall survival (OS) and progression free survival (PFS), which were estimated from date of AHCT to death, progression, or last follow-up. A log-rank test was used to compare OS and PFS of pts with BMI≥30 to those with BMI<30. Results Of 86 pts that met inclusion criteria, 41 pts (48%) had a BMI≥30 and 45 pts (52%) had BMI<30 (Table 1). Among the BMI≥30, 15 pts had BMI≥35 (range 30-49). Median age at Tx was 66 years in both groups. There was no difference in mean age, sex, cytogenetic risk (good, intermediate, poor), disease indication (AML, MDS, MPN), donor (related vs unrelated), and KPS≥90 in the two groups. In pts with BMI≥30, 46% (N=19) underwent myeloablative conditioning compared to 29% (N=13) in the BMI<30 (p=0.09). GVHD prophylaxis included tacrolimus (tac) in all pts except one who received post-transplant Cytoxan. There were 3 pts with BMI≥30 with <8/8 unrelated donor who received ATG in addition to tac. Pre-Tx bone marrow biopsy revealed that 3 pts (7%) in the BMI≥30 group had >5% blasts and 9 pts (20%) had >5% blasts in the BMI<30 group (p=0.12). There were significantly more pts in the BMI≥30 group with a HCT-CI score≥3 (30 pts vs 13 pts, p<0.01). When excluding points for obesity, there were still more pts with a BMI≥30 with a HCT-CI≥3 (25 pts vs 13 pts, p<0.01). The median OS was 36 months (m) for BMI<30 pts and 24 m for BMI≥30 (Figure 1), but this was not statistically significant (p=0.55). Median PFS was 10.1 m in the BMI<30 group and 13.6 m in the ≥30 group (p=0.93) (Figure 2). Sixteen pts (36%) with BMI<30 had aGVHD while only 8 pts (20%) with BMI>30 (p=0.10). One-year cumulative incidence of cGVHD was 56% (BMI≥30) vs 38% (BMI<30), p=0.09. Among pts admitted for Tx (N=76) mean length of stay (LOS) was 25 days in BMI<30 and 26 days in BMI≥30 (p=0.64). There were more pts (34% vs 16%) with BMI≥30 who were re-admitted within 30 days of discharge (p=0.045). We performed an exploratory analysis of pts with BMI≥35 (N=15) compared to all other pts with BMI<35 to see if outcomes were worse only in those with morbid obesity. Again, we found no difference in age, sex, intensity of conditioning, indication for Tx, or disease status prior to Tx between the two groups. There were more pts with HCT-CI≥3 in the BMI≥35 group (p=0.047). The median OS was not reached (NR) in the ≥35 group while it was 23.7 m in the <35 group (p=0.08). Median PFS was also NR in the ≥35 group but was 10.8 m in the <35 group (p=0.19). There was no difference in aGVHD or cumulative incidence of cGVHD at 1 year. Interestingly the LOS among hospitalized pts was longer in the ≥35 group at 28.5 days vs 25.2 days (p=0.09) and there were more pts readmitted within 30 days of completing their Tx in the BMI≥35 group (47% vs 20%, p=0.03). Conclusions In elderly pts (age>60) with myeloid malignancies undergoing AHCT, outcomes were not affected by either obesity or morbid obesity. Obesity was associated with increased re-hospitalization within 30 days of discharge after Tx. Morbidly obese pts had a trend towards a longer hospitalization stay and an increased rate of readmissions within 30 days of discharge from their Tx. In elderly pts, BMI should not preclude consideration of a curative AHCT. Figure 1 Figure 1. Figure 2 Figure 2. Table 1 Table 1. Disclosures Hamadani: Takeda: Research Funding. Shah:Oncosec: Equity Ownership; Exelixis: Equity Ownership; Geron: Equity Ownership.

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