Search

Simple Summary: Patients who recently received a stem cell transplantation are at greater risk for infection due to impairment of their immune system. In order to prevent severe infection, these patients are vaccinated after their stem cell transplantation with childhood immunization vaccines. Timing of this vaccination is important in order to be effective and obtain proper immune response. Postponement of vaccination would lead to better immune response but would also cause longer-lasting risk of infection. This review describes available data on the timing of vaccination and its vaccine responses. Optimal timing of vaccination might require an individualized approach per patient. Consensus on timing of post-hematopoietic stem cell transplantation (HSCT) vaccination is currently lacking and is therefore assessed in this review. PubMed was searched systematically for articles concerning vaccination post-HSCT and included a basis in predefined criteria. To enable comparison, data were extracted and tables were constructed per vaccine, displaying vaccine response as either seroprotection or seroconversion for allogeneic HSCT (alloHSCT) and autologous HSCT (autoHSCT) separately. A total of 33 studies were included with 1914 patients in total: 1654 alloHSCT recipients and 260 autoHSCT recipients. In alloHSCT recipients, influenza vaccine at 7–48 months post-transplant resulted in responses of 10–97%. After 12 months post-transplant, responses were >45%. Pneumococcal vaccination 3–25 months post-transplant resulted in responses of 43–99%, with the response increasing with time. Diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b at 6–17 months post-transplant: 26–100%. Meningococcal vaccination at 12 months post-transplant: 65%. Hepatitis B vaccine at 6–23 months post-transplant: 40–94%. Measles, mumps and rubella at 41–69 months post-transplant: 19–72%. In general, autoHSCT recipients obtained slightly higher responses compared with alloHSCT recipients. Conclusively, responses to childhood immunization vaccines post-HSCT are poor in comparison with healthy individuals. Therefore, evaluation of response might be indicated. Timing of revaccination is essential for optimal response. An individualized approach might be necessary for optimizing vaccine responses. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia. Methods: Patients who underwent a first CBT without PTCy (N = 902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N = 280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk. Results: The incidence of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p = 0.07) and 15% versus 11% (p = 0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p < 0.01) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%, p < 0.01) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR = 2.09, 95% CI 1.46–2.99, p < 0.0001), and relapse (HR = 1.35, 95% CI 1–1.83, p = 0.05), which resulted in worse leukemia-free survival (LFS) (HR = 1.68, 95% CI 1.34–2.12, p < 0.0001), overall survival (OS) (HR = 1.7, 95% CI 1.33–2.17, p < 0.0001), and GVHD-free, relapse-free survival (GRFS) (HR = 1.49, 95% CI 1.21–1.83, p < 0.0001) compared to MMUD. The risk of grade II–IV acute GVHD (p = 0.052) and chronic GVHD (p = 0.69) did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis. Conclusions: CBT was associated with lower LFS, OS, and GRFS due to higher NRM, compared to MMUD allo-HCT with PTCy. In the absence of a fully matched donor, 9/10 MMUD with PTCy may be preferred over CBT. [ABSTRACT FROM AUTHOR]

Lymphocyte numbers need to be quite tightly regulated. It is generally assumed that lymphocyte production and lifespan increase homeostatically when lymphocyte numbers are low and, vice versa, return to normal once cell numbers have normalized. This widely accepted concept is largely based on experiments in mice, but is hardly investigated in vivo in humans. Here we quantified lymphocyte production and loss rates in vivo in patients 0.5-1 year after their autologous hematopoietic stem cell transplantation (autoHSCT). We indeed found that the production rates of most T- and B-cell subsets in autoHSCT-patients were two to eight times higher than in healthy controls, but went hand in hand with a threefold to ninefold increase in cell loss rates. Both rates also did not normalize when cell numbers did. This shows that increased lymphocyte production and loss rates occur even long after autoHSCT and can persist in the face of apparently normal cell numbers. [ABSTRACT FROM AUTHOR]

Autologous haematopoietic stem cell transplantation (HSCT) is the only treatment that is able to induce long-term, drug-free and symptom-free remission in several refractory autoimmune rheumatic diseases. Over 3,000 HSCT procedures for rheumatic and nonrheumatic severe autoimmune diseases have been performed worldwide. Specific conditioning regimens are currently used to eradicate the autoreactive immunological memory of patients. Although in vivo immune cell depletion with antithymocyte globulin or anti-CD52 is the norm for many regimens, ex vivo selection of CD34+ stem cells from the graft is controversial. Following the extensive immune depletion associated with serotherapy and chemotherapy, HSCT effectively resets the immune system by renewing the CD4+ T cell compartment, especially the regulatory T cell population. The risk of transplant-related mortality (TRM) within the first 100 days should be weighed against the risk of disease-related mortality, and the careful selection and screening of patients before transplantation is essential. Systemic sclerosis is the first autoimmune disease for which HSCT has been shown, in a randomized, controlled trial, to be associated with increased TRM in the first year but a significant long-term, event-free survival benefit afterwards. In this Review, we discuss the immunological mechanisms of HSCT in various autoimmune diseases and current HSCT regimens. After carefully taking into consideration the risks and benefits of HSCT and alternative therapies, we also discuss the efficacy, complications and proposed indications of this procedure. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 35-year-old female patient with diffuse cutaneous systemic sclerosis (dcSSc) that underwent a second haematopoietic stem cell transplantation (HSCT). Topics explored include the clinical and physical examination of the patient, reduction in the skin thickening initially presented by the patient following HSCT, and the favourable outcome reported after the second HSCT.

Hematopoietic stem cell transplantation with HLA-DPB1–mismatched donors leads to an increased risk of acute graft-versus-host disease (GVHD). Studies have indicated a prognostic value for classifying HLA-DPB1 mismatches based on T cell–epitope (TCE) groups. The aim of this study was to determine the contribution of indirect recognition of HLA-DP–derived epitopes, as determined with the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) method. We therefore conducted a retrospective single-center analysis on 80 patients transplanted with a 10/10 matched unrelated donor that was HLA-DPB1 mismatched. HLA-DPB1 mismatches that were classified as GVH nonpermissive by the TCE algorithm correlated to higher numbers of HLA class I as well as HLA class II presented PIRCHE (PIRCHE-I and -II) compared with permissive or host-versus-graft nonpermissive mismatches. Patients with acute GVHD grades II to IV presented significantly higher numbers of PIRCHE-I compared with patients without acute GVHD ( P < .05). Patients were divided into 2 groups based on the presence or absence of PIRCHE. Patients with PIRCHE-I or -II have an increased hazard of acute GVHD when compared with patients without PIRCHE-I or -II (hazard ratio [HR], 3.19; 95% confidence interval [CI], 1.10 to 9.19; P < .05; and HR, 4.07; 95% CI, .97 to 17.19; P = .06, respectively). Patients classified as having an HLA-DPB1 permissive mismatch by the TCE model had an increased risk of acute GVHD when comparing presence of PIRCHE-I with absence of PIRCHE-I (HR, 2.96; 95% CI, .84 to 10.39; P = .09). We therefore conclude that the data presented in this study describe an attractive and feasible possibility to better select permissible HLA-DPB1 mismatches by including both a direct and an indirect recognition model. [ABSTRACT FROM AUTHOR]