Key Points• Residual ATG exposure delays CD4 1 T-cell reconstitution more severely after CBT than after BMT.• Filgrastim (G-CSF), given early after CBT, enhances ATGmediated T-cell clearance in patients with residual ATG exposure.Residual antithymocyte globulin (ATG; Thymoglobulin) exposure after allogeneic hemato-subsequently increasing morbidity and mortality. This effect seems particularly present after cord blood transplantation (CBT) compared to bone marrow transplantation (BMT).The reason for this is currently unknown. We investigated the effect of active-ATG exposure on CD4 1 IR after BMT and CBT in 275 patients (CBT n 5 155, BMT n 5 120; median age, 7.8 years; range, 0.16-19.2 years) receiving their first allogeneic HCT between January 2008 and September 2016. Multivariate log-rank tests (with correction for covariates) revealed that CD4 1 IR was faster after CBT than after BMT with ,10 active-ATG 3 day/mL (P 5 .018) residual exposure. In contrast, .10 active-ATG 3 day/mL exposure severely impaired CD4 1 IR after CBT (P , .001), but not after BMT (P 5 .74). To decipher these differences, we performed ATG-binding and ATG-cytotoxicity experiments using cord blood-and bone marrow graft-derived T-cell subsets, B cells, natural killer cells, and monocytes. No differences were observed. Nevertheless, a major covariate in our cohort was Filgrastim treatment (only given after CBT). We found that Filgrastim (granulocyte colony-stimulating factor [G-CSF]) exposure highly increased neutrophil-mediated ATG cytotoxicity (by 40-fold [0.5 vs 20%; P 5 .002]), which explained the enhanced T-cell clearance after CBT. These findings imply revision of the use (and/or timing) of G-CSF in patients with residual ATG exposure.
190 patients (response rate = 66%, 10 centers) enrolled on a multi-center observational study to develop and validate endpoint measures for cGVHD treatment. Employment status classified as work/ school, unemployed/ disabled and homemaker/ retired was assessed at enrollment and at survey completion. Financial burden was defined as reporting ≥1 of the following: difficulty paying medical bills, not having enough money at the end of the month, reducing spending on home, using retirement savings, borrowing money/ selling assets, or bankruptcy. Multivariable logistic regression models examined the factors (socio-demographic, cGVHD severity, physical and mental functioning (SF-36) and activity level (modified adjusted activity score) closest to survey completion) associated with being able to work/ go to school and financial burden. Results: Median age was 57 years (range 12-79) and 87% were White. Median time from HCT to cGVHD onset was 7.5 months and from enrollment to financial survey was 12.9 months. Median physical and mental component scores closest to survey completion (median time 21 days) were 40 (range 9-58) and 50 (range 9-70) respectively. Patients reporting annual income <$25, 000 increased from 10% at enrollment to 20% at the time of survey. There was no significant change in proportion of patients at work/ school from enrollment to the survey (33 vs. 38%; P = .36). All except one patient had insurance at the time of the survey (49% private; 43% Medicaid/Medicare). 34% had faced delayed/denied insurance coverage for cGVHD treatments. 66% reported financial burden. 45% reported their financial burden was due to their or their caregiver's inability to go back to work or a lower salary. Income ≥ $75, 000 (OR 12.2; P = .01), younger age (OR = .94, P = .001), higher PCS-36 (OR = 1.1, P = .003) and MCS-36(OR = 1.1, P = .01) were associated with being able to work/ go to school. Income ≥ $75, 000 was associated with lower financial burden (OR .12; P = .025) when adjusted for all other factors. Conclusions: Significant negative effects on finances and employment were observed in this large multi-center cohort of cGVHD patients. Future research should investigate use of tailored resources such as structured rehabilitation programs, vocational assistance, interventions to increase employment rights awareness, financial planning and assistance programs to ameliorate adverse financial and work-related implications in these patients.
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