scholarly journals Donor Telomere Length and Outcomes after Allogeneic Unrelated Hematopoietic Cell Transplant in Patients with Acute Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 520-520 ◽  
Author(s):  
Shahinaz M. Gadalla ◽  
Tao Wang ◽  
David Loftus ◽  
Lyssa Friedman ◽  
Casey Dagnall ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Telomere Length ◽  
Cancer Genomics ◽  
Disease Free Survival ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Specific Distribution ◽  
Neutrophil Engraftment

Abstract Introduction. A recent study showed that receiving a hematopoietic cell transplant (HCT) from donors with long leukocyte relative telomere length (RTL) was associated with improved survival in patients with severe aplastic anemia who primarily received bone marrow grafts at age <40 years. Here, we tested the effect of donor RTL on post-HCT outcomes in a large cohort of patients with acute leukemia. Methods. From the Center for International Blood and Marrow Transplant Research (CIBMTR®) database, we identified 1,097 patients who received unrelated HCT for acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) and fulfilled the following criteria: 1) HCT between 2004 and 2012, 2) available pre-HCT blood sample for the donor, 3) 8/8 HLA matching, and 3) myeloablative conditioning. We used qPCR to measure RTL; 1084 samples completed testing (597 measured at Telomere Diagnostics, Inc. and 487 at the Cancer Genomics Research Laboratory, NCI). Telomere Diagnostics samples were randomly divided into discovery (n=300) and validation (n=297) cohorts; the NCI samples served as a 2nd validation cohort (N=500). Cox proportional hazard models were used for statistical analyses. All analyses were adjusted for donor age together with clinical factors that met statistical inclusion criteria in a multivariate model. Donor RTL was categorized into short (≤25th percentile based on cohort-specific distribution), or long otherwise. Follow-up ended in November 2014. Results. All patient demographics, disease- and HCT-related characteristics were similar in the discovery, 1st, and 2nd validation cohorts with the exception of graft source (peripheral blood stem cells in 67%, 60%, and 70%, respectively, p=0.008), and year of HCT (0%, 0%, and 37% between 2008-2012, respectively, p<0.001). Results from the discovery cohort suggested that long donor RTL may be associated with: 1) improved overall survival (HR=0.73, 95% CI=0.52-1.03, p=0.08), and disease-free survival (HR=0.73, 95% CI=0.52-1.03, p=0.07); 2) higher probability of neutrophil engraftment (HR=1.3, 95% CI=0.99-1.71, p=0.06), and 3) decreased risk of relapse (HR=0.61, 95% CI=0.38-1.00, p=0.05) and acute graft-versus-host disease II-IV (HR=0.68, 95% CI=0.46-1.0, p=0.05). However, none of these results were replicated in the two validation cohorts with the exception of a higher probability of neutrophil engraftment observed in the 2nd (HR=1.24, 95% CI=1.0-1.54, p=0.05), but not the 1st validation (HR=0.84, 95% CI=0.63-1.11, p=0.21). All three cohorts were combined for a final exploratory analysis and no associations (all p>0.3) were found between donor telomere length and any outcomes. Conclusions. Donor telomere length is not associated with outcomes in unrelated donor HCT for patients with acute leukemia. Table. Impact of donor RTL comparing the three longest quartiles to the shortest quartile. Table. Impact of donor RTL comparing the three longest quartiles to the shortest quartile. Disclosures Loftus: Telomere Diagnostics, Inc.: Consultancy. Friedman:Telomere Diagnostics, Inc.: Consultancy. Buturovic:Clinical Persona: Consultancy. Blauwkamp:Telomere Diagnostics, Inc.: Employment. Shelton:Telomere Diagnostics, Inc.: Employment.

scholarly journals No association between donor telomere length and outcomes after allogeneic unrelated hematopoietic cell transplant in patients with acute leukemia

2017 ◽  
Vol 53 (4) ◽  
pp. 383-391 ◽  
Author(s):  
Shahinaz M. Gadalla ◽  
Tao Wang ◽  
David Loftus ◽  
Lyssa Friedman ◽  
Casey Dagnall ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Telomere Length ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

scholarly journals Telomere length in hematopoietic cell transplant

Blood ◽  
2020 ◽  
Vol 136 (26) ◽  
pp. 2972-2973
Author(s):  
Shahinaz M. Gadalla
Keyword(s):  
Telomere Length ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

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 &lt;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.

Allogeneic hematopoietic cell transplant for multiple myeloma: Comparative results of planned therapy versus salvage therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7035-7035
Author(s):  
L. Shune ◽  
D. J. Weisdorf ◽  
B. McClune ◽  
L. Ma ◽  
L. J. Burns ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Therapy Group ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hct ◽  
Autologous Hct ◽  
Related Mortality

7035 Background: Despite advances in therapy for multiple myeloma, the disease remains incurable using chemotherapy or immune-modulating agents alone. Several newer hematopoietic cell transplant (HCT) strategies including tandem HCT, and non- myeloablative (NMA) regimens have reported encouraging results. However, the appropriate timing for utilizing these strategies is not clear. Methods: We report outcomes in 51 patients with multiple myeloma who received an allogeneic HCT; either as salvage therapy (after failing a prior autologous HCT), n= 15 or as planned therapy, n= 36, between the years 1996 and 2008 at University of Minnesota. Results: Patients in salvage therapy group were significantly older than in planned therapy group (median age 58 versus 49 years) and had a longer interval from diagnosis to transplant (median 47 versus 10 months). Forty four patients received a HCT from a HLA-identical sibling. Five received umbilical cord blood (four in salvage therapy, one in planned therapy group) and two received unrelated donor HCT (one in each group). Thirteen patients in planned therapy group underwent a tandem transplant (planned autologous followed by NMA sibling HCT). All patients in salvage therapy group, and 50% in planned therapy group received NMA HCT. Patients in salvage therapy group were more heavily pre-treated, all having failed a prior autologous HCT. Complete response was seen in 34% versus 47% of recipients in the two groups, respectively. After a median follow-up of 24 and 41 months, similar relapse was seen, but transplant related mortality (TRM) was significantly higher in salvage therapy group, leading to significantly lower two year survival and disease free survival (DFS) in salvage group. Conclusions: Good overall survival and low transplant related mortality was seen in patients undergoing a planned allogeneic transplant. In heavily pre-treated patients, receiving allogeneic HCT as salvage therapy, despite lower relapse, the high TRM led to lower survival. [Table: see text] No significant financial relationships to disclose.

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