1.
Reduced-Intensity/Reduced-Toxicity Conditioning Approaches Are Tolerated in XIAP Deficiency but Patients Fare Poorly with Acute GVHD
Arnold, D. E., Nofal, R., Wakefield, C., Lehmberg, K., Wustrau, K., Albert, M. H., Morris, E. C., Heimall, J. R., Bunin, N. J., Kumar, A., et al
Journal of clinical immunology. 2021;:1-10
Abstract
X-linked inhibitor of apoptosis (XIAP) deficiency is an inherited primary immunodeficiency characterized by chronic inflammasome overactivity and associated with hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD). Allogeneic hematopoietic cell transplantation (HCT) with fully myeloablative conditioning may be curative but has been associated with poor outcomes. Reports of reduced-intensity conditioning (RIC) and reduced-toxicity conditioning (RTC) regimens suggest these approaches are well tolerated, but outcomes are not well established. Retrospective data were collected from an international cohort of 40 patients with XIAP deficiency who underwent HCT with RIC or RTC. Thirty-three (83%) patients had a history of HLH, and thirteen (33%) patients had IBD. Median age at HCT was 6.5 years. Grafts were from HLA-matched (n?=?30, 75%) and HLA-mismatched (n?=?10, 25%) donors. There were no cases of primary graft failure. Two (5%) patients experienced secondary graft failure, and three (8%) patients ultimately received a second HCT. Nine (23%) patients developed grade II-IV acute GVHD, and 3 (8%) developed extensive chronic GVHD. The estimated 2-year overall and event-free survival rates were 74% (CI 55-86%) and 64% (CI 46-77%), respectively. Recipient and donor HLA mismatch and grade II-IV acute GVHD were negatively associated with survival on multivariate analysis with hazard ratios of 5.8 (CI 1.5-23.3, p?=?0.01) and 8.2 (CI 2.1-32.7, p?0.01), respectively. These data suggest that XIAP patients tolerate RIC and RTC with survival rates similar to HCT of other genetic HLH disorders. Every effort should be made to prevent acute GVHD in XIAP-deficient patients who undergo allogeneic HCT.
2.
Predictors of lost to follow-up among pediatric and adult hematopoietic cell transplant survivors: A report from the Center for International Blood and Marrow Transplant Research
Buchbinder, D., Brazauskas, R., Bo-Subait, K., Ballen, K., Parsons, S., John, T., Hahn, T., Sharma, A., Steinberg, A., D'Souza, A., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
BACKGROUND Follow-up is integral for hematopoietic cell transplant (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of, and predictors for, being lost to follow-up. METHODS Two-year survivors of first allogeneic (10,367 adults and 3,865 children) or autologous (7,291 adults and 467 children) HCT for malignant/non-malignant disorders from 2002-2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. RESULTS The 10-year cumulative incidence of being lost to follow-up among adult allogeneic and autologous HCT survivors was 13% (95% CI, 12-14) and 15% (95% CI, 14-16), respectively. Among pediatric HCT survivors, estimates were 25% (95% CI, 24-27) and 24% (95% CI, 20-29), respectively. In adult allogeneic HCT survivors, younger age, non-malignant disease, public/no insurance (reference: private), living farther from the HCT center, and being unmarried were associated with being lost to follow-up. For adult autologous HCT survivors, older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) were associated with greater risk of being lost to follow-up. Among pediatric allogeneic HCT survivors, older age, public/no insurance (reference: private), and non-malignant disease were associated with being lost to follow-up. Among pediatric autologous HCT survivors, older age was associated with greater risk of being lost to follow-up. CONCLUSION Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.
3.
Hematopoietic stem cell transplantation as treatment for patients with DOCK8 deficiency
Aydin, S. E., Freeman, A. F., Al-Herz, W., Al-Mousa, H. A., Arnaout, R. K., Aydin, R. C., Barlogis, V., Belohradsky, B. H., Bonfim, C., Bredius, R. G., et al
The journal of allergy and clinical immunology. In practice. 2018
Abstract
BACKGROUND Biallelic variations in the DOCK8 gene cause a combined immunodeficiency with eczema, recurrent bacterial and viral infections, and malignancy. Natural disease outcome is dismal, but allogeneic hematopoietic stem cell transplantation (HSCT) can cure the disease. OBJECTIVE To determine outcome of HSCT for DOCK8 deficiency and define possible outcome variables. METHODS We performed a retrospective study of the results of HSCT in a large international cohort of DOCK8 deficient patients. RESULTS We identified 81 patients from 22 centers transplanted at a median age of 9.7 years (range: 0.7-27.2) between 1995 and 2015. After median follow-up of 26 months (3-135), 68 of 81 patients are alive (84%). Severe acute (III-IV) or chronic graft versus host disease (GVHD) occurred in 11% and 10% respectively. Causes of death wereinfections (n=5), GVHD (5), multi-organ failure (2) and pre-existent lymphoma (1). Survival after matched related (n=40) or unrelated (35) HSCT was 89% and 81%, respectively. Reduced toxicity conditioning based on either treosulfan or reduced-dose busulfan resulted in superior survival compared to fully myeloablative busulfan-based regimens (97% vs. 78%; p=0.049). 96% of patients aged <8 years at HSCT survived, compared to 78% of those ≥8 years (p=0.06). Of 73 patients with chimerism data available, 65 (89%) had >90% donor T-cell chimerism at last follow-up. Not all disease manifestations responded equally well to HSCT eczema, infections and Mollusca resolved better than food allergies or failure to thrive. CONCLUSION HSCT is curative in most DOCK8 deficient patients, confirming this approach as the treatment of choice. HSCT using a reduced toxicity regimen may offer the best chance for survival.