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Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant.

ABSTRACT: Infection, relapse, and GVHD can complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the effect of poor immune recovery on infection risk is well-established, there are limited data on the effect of immune reconstitution on relapse and survival, especially following T-cell depletion (TCD). To characterize the pattern of immune reconstitution in the first year after transplant and its effects on survival and relapse, we performed a retrospective study in 375 recipients of a myeloablative TCD allo-HSCT for hematologic malignancies. We noted that different subsets recover sequentially, CD8?+?T cells first, followed by total CD4?+?and naïve CD4?+?T cells, indicating thymic recovery during the first year after HSCT. In the multivariate model, a fully HLA-matched donor and recovery of T-cell function, assessed by PHA response at 6 months, were the only factors independently associated with OS and EFS. In conclusion, T-cell recovery is an important predictor of outcome after TCD allo-HSCT.

SUBMITTER: Goldberg JD

PROVIDER: S-EPMC5454777 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant.

Goldberg Jenna D JD Zheng Junting J Ratan Ravin R Small Trudy N TN Lai Kuan-Chi KC Boulad Farid F Castro-Malaspina Hugo H Giralt Sergio A SA Jakubowski Ann A AA Kernan Nancy A NA O'Reilly Richard J RJ Papadopoulos Esperanza B EB Young James W JW van den Brink Marcel R M MR Heller Glenn G Perales Miguel-Angel MA

Leukemia & lymphoma 20170110 8

Infection, relapse, and GVHD can complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the effect of poor immune recovery on infection risk is well-established, there are limited data on the effect of immune reconstitution on relapse and survival, especially following T-cell depletion (TCD). To characterize the pattern of immune reconstitution in the first year after transplant and its effects on survival and relapse, we performed a retrospective study in 375 recipi ...[more]

PMID: 28073320

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Project description:Abnormal pulmonary function is prevalent in survivors of allogeneic hematopoietic cell transplantation (HCT). Post-transplantation recovery of pulmonary function, and its effect on survival, in children are not known. This retrospective cohort study of 308 children followed for 10 years after HCT at a single institution included 2 groups of patients. Group 1 comprised 188 patients with 3 or more pulmonary function test (PFT) results, of which at least 1 was abnormal, and group 2 comprised 120 patients with 3 or more PFTs, all of which were normal. Pulmonary function normalized post-transplantation in 51 patients (27%) in group 1. Obstructive lung disease, restrictive lung disease, mixed lung disease, and normal pattern were seen in 43%, 25%, 5%, and 27% of patients, respectively, at a median of 5 years (range, 0.5 to 11.9 years) post-transplantation. Lung volumes recovered better than spirometric indices. Pulmonary complications were seen in 80 patients (43%) in group 1. Patients who recovered pulmonary function had better overall survival (P = .006), which did not differ significantly from that in patients in group 2 with normal lung function post-transplantation (P = .80). After adjusting for duration of follow-up, pulmonary complications (P = .01), and lower pretransplantation forced vital capacity z-scores (P = .01) were associated with poor recovery. T cell depletion (P < .001), lower pretransplantation forced expired volume in 1 second z-scores (P = .006), and chronic graft-versus-host disease (P < .001) increased the risk for pulmonary complications. Nonrecovery of lung function with pulmonary complications (P = .03), acute graft-versus-host disease (P = .004), and mechanical ventilation (P < .001) were risk factors for nonrelapse mortality. Normalization of pulmonary function is possible in long-term survivors of allogeneic HCT. Strategies to decrease the risk of pulmonary complications may improve outcomes.

Project description:Importance:Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective:To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants:In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures:Allogeneic hematopoietic cell transplant. Main Outcomes and Measures:Survival trends, disease relapse, and toxicity. Results:A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P = .007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P = .01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance:Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.

Project description:BackgroundSecond allogeneic hematopoietic stem cell transplant (HCT) remains as an option for disease relapse after initial HCT.MethodsWe analyzed retrospectively the outcomes of 65 consecutive patients who underwent a second HCT for disease relapse at the University of Chicago. Univariate and multivariate analysis were conducted, and a scoring system was generated to select the patients who would benefit second HCT.ResultsAll except four patients received T cell depleted (TCD) first HCT. The majority of patients had AML (n = 47) and high risk MDS (n = 5). The median age at second HCT was 45 years (11-73). 13 patients (20%) achieved CR before second HCT. 98% (n = 64) and 72% (n = 47) patients achieved neutrophil and platelet engraftment at a median interval of 10 and 18 days, respectively, following the second HCT. With a median follow up of 23 (5.5-140) months for survivors after second HCT, the estimated 2 years PFS was 17.5% and the 2 years OS was 22.6%. The day 100 cumulative incidence of non-relapse mortality rate was 23.6%, and the cumulative incidence of aGVHD and cGVHD were 16.9% and 7.7% respectively at 1 year after second HCT. In univariate analysis, patients with remission duration after first HCT of > 12 months and those in CR before second HCT had significantly better PFS and OS. A scoring system using disease status before second HCT (CR = 0 vs. non-CR = 1), and remission duration after first HCT (< 6 = 2, 6-12 = 1 and > 12 months = 0) was generated as an approach to classify patients into different risk categories in the purpose to provide guidance to the transplant physician to inform the outcomes to potential patients undergoing 2nd HCT. A score of < 2 (n = 26) identified a group with PFS and OS of 31.6% and 36.2% at 2 years after second HCT.ConclusionIn conclusion, second HCT is a viable option for disease relapse after TCD HCT for patients entering second HCT in remission and/or remission duration > 12 months after first HCT with acceptable rates of GVHD and donor engraftment.

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Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant.

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Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant.

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