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The Benefits of the Post-Transplant Cyclophosphamide in Both Haploidentical and Mismatched Unrelated Donor Setting in Allogeneic Stem Cells Transplantation
Dybko, J., Sobczyk-Kruszelnicka, M., Makuch, S., Agrawal, S., Dudek, K., Giebel, S., Gil, L.
International journal of molecular sciences. 2023;24(6)
Abstract
Allogeneic hematopoietic cell transplantation (alloHSCT) is a standard therapeutic approach for acute leukemias and many other hematologic malignancies. The proper choice of immunosuppressants applicable to different types of transplantations still requires strict and careful consideration, and data in this regard are divergent. For this reason, in this single-centered, retrospective study, we aimed to compare the outcome of 145 patients who received post-transplant cyclophosphamide (PTCy) for MMUD and haplo-HSCT or GvHD prophylaxis for MMUD-HSCT alone. We attempted to verify if PTCy is an optimal strategy in MMUD setting. Ninety-three recipients (93/145; 64.1%) underwent haplo-HSCT while 52 (52/145; 35.9%) underwent MMUD-HSCT. There were 110 patients who received PTCy (93 in haplo and 17 in MMUD group) and 35 patients received conventional GvHD prophylaxis based on antithymocyte globulin (ATG), cyclosporine (CsA), and methotrexate (Mtx) in the MMUD group only. Our study revealed that patients receiving post-transplant cyclophosphamide (PTCy) show decreased acute GvHD rates and CMV reactivation as well as a statistically lower number of CMV copies before and after antiviral treatment compared to the CsA + Mtx + ATG group. Taking into account chronic GvHD, the main predictors are donor age, ≥40 years, and haplo-HSCT administration. Furthermore, the survival rate of patients following MMUD-HSCT and receiving PTCy with tacrolimus and mycophenolate mofetil was more than eight times greater in comparison to patients receiving CsA + Mtx + ATG (OR = 8.31, p = 0.003). These data taken together suggest that the use of PTCy displays more benefits in terms of survival rate compared to ATG regardless of the type of transplantation performed. Nevertheless, more studies with a larger sample size are required to confirm the conflicting results in the literature studies.
2.
Impact of decontamination therapy on gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic cell transplantation in children: Decontamination therapy in allo-HCT
Gałązka, P., Styczyński, J., Czyżewski, K., Salamonowicz-Bodzioch, M., Frączkiewicz, J., Zając-Spychała, O., Zaucha-Prażmo, A., Goździk, J., Biliński, J., Basak, G. W.
Current research in translational medicine. 2021;69(3):103298
Abstract
INTRODUCTION Gut colonization with antibiotic-resistant bacteria (ARB) is associated with a significantly decreased overall survival in adult patients undergoing allo-HCT because of an increased treatment-related mortality. OBJECTIVE The objective of this multicenter study was the analysis of impact of gut colonization status and the use of antibiotics on development of gastro-intestinal (GI) graft-versus-host disease (GVHD) of allo-HCT in children. METHODS All consecutive patients who underwent allo-HCT over a period of three years in all pediatric HCT centers in Poland were analyzed for the impact of gut colonization on GI GVHD, with respect to standard of care including prophylaxis of infections and supportive therapy. RESULTS At the time of allo-HCT, 44.2% of pediatric patients were colonized by ARB. Decontamination therapy with antibiotics was applied in 78% of children. Gut decontamination prophylactic therapy with antibiotics decreased the risk of acute GI GVHD. The use of gentamicin contributed to decreased rate of GVHD, while the use of ciprofloxacin and colistin contributed to increased incidence of GVHD after allo-HCT in children. Sepsis with ARB and non-MFD transplant contributed significantly to worse survival, while neither colonization nor gut decontamination had an impact on overall survival. CONCLUSIONS Gut decontamination therapy contributed to lower incidence of acute GI GVHD in children undergoing allo-HCT, and the use of specific antibiotics might be responsible for this effect.
3.
Factors Associated With Successful Discontinuation of Immune Suppression After Allogeneic Hematopoietic Cell Transplantation
Pidala, J., Martens, M., Anasetti, C., Carreras, J., Horowitz, M., Lee, S. J., Antin, J., Cutler, C., Logan, B.
JAMA oncology. 2019
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Abstract
Importance: Immune suppression discontinuation is routinely attempted after allogeneic hematopoietic cell transplantation (HCT) and under current practices may lead to graft-vs-host disease (GVHD)-associated morbidity and death. However, the likelihood and predictive factors associated with successful immune suppression discontinuation after HCT are poorly understood. Objectives: To examine factors associated with successful immune suppression discontinuation and risk for immune suppression discontinuation failure under conventional HCT approaches and develop a practical tool to estimate successful immune suppression discontinuation likelihood at the clinical point of care. Design, Setting, and Participants: Using long-term follow-up data from 2 national Blood and Marrow Transplant Clinical Trial Network studies (N = 827), a multistate model was developed to investigate the probability and variables associated with immune suppression discontinuation success. The study began in July 2015, and analyses were completed in August 2019. Main Outcomes and Measures: Immune suppression discontinuation and immune suppression discontinuation failure. Results: Of the 827 patients included in the analysis, 456 were men (55.1%). Median age at transplant was 44 (range, <1-67) years. With median follow-up of 72 (range, 11-124) months, 20.0% of the patients were alive and not receiving immune suppression at 5 years. Older recipient age (adjusted odds ratio [aOR] of >50 vs <30 years, 0.27, 99% CI, 0.14-0.50; P < .001), mismatched unrelated donor (aOR, mismatched unrelated vs matched related, 0.37; 99% CI, 0.14-0.97; P = .008), peripheral blood graft (aOR of peripheral blood graft vs bone marrow, 0.46; 99% CI, 0.26-0.82; P < .001), and advanced stage disease (aOR of advanced vs early disease, 0.45; 99% CI, 0.23-0.86, P = 0.002), were significantly associated with decreased odds of immune suppression discontinuation. Failed attempts at immune suppression discontinuation (127 patients [37.1% of total immune suppression discontinuation events]) resulting in GVHD were significantly associated with use of peripheral blood stem cells (HR, 2.62; 99% CI, 1.30-5.29; P < .001), prior GVHD, and earlier immune suppression discontinuation attempts. Earlier immune suppression discontinuation was not associated with protection from cancer relapse after HCT (adjusted hazard ratio for discontinuation vs not, 1.95; 99% CI, 0.88-4.31; P = .03).Dynamic prediction models were developed to provide future immune suppression discontinuation probability according to individual patient characteristics. Conclusions and Relevance: Successful immune suppression discontinuation is uncommon in the setting of peripheral blood stem cell grafts. The data suggest earlier attempts at ISD conferred no long-term benefit, given frequent ISD failure, limited subsequent success after initial failed ISD attempt, and no evidence of relapse reduction. Using a risk model-based clinical application, physicians may be able to identify individual patients' probability of successful immune suppression discontinuation.
PICO Summary
Population
Patients enrolled in two national Blood and Marrow Transplant Clinical Network studies (n=827)
Intervention
Successful immune suppression discontinuation
Comparison
Continued immune suppression or failure to discontinue immune suppression.
Outcome
With median follow-up of 72 months, 20.0% of the patients were alive and not receiving immune suppression at 5 years. Older recipient age, mismatched unrelated donor, peripheral blood graft, and advanced stage disease, were significantly associated with decreased odds of immune suppression discontinuation. Failed attempts at immune suppression discontinuation (127 patients) resulting in GVHD were significantly associated with use of peripheral blood stem cells, prior GVHD, and earlier immune suppression discontinuation attempts. Earlier immune suppression discontinuation was not associated with protection from cancer relapse after HCT.