This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.
This single-center retrospective study analyzed 85 consecutive patients who underwent allogeneic stem cell transplantation (allo-SCT) with the aim to assess whether there is a correlation between exposure to cyclosporine-A (CsA; as measured by CsA concentrations during the first month after allo-SCT) and the risk for developing severe grade III-IV acute graft-versus-host disease (aGVHD). The median concentrations of CsA in the blood at 1, 2, 3, and 4 weeks after allo-SCT were 348 (range: 172-733), 284 (range: 137-535), 274 (range: 107-649), and 247 (range: 37-695) ng/mL, respectively. Overall, grade II-IV aGVHD occurred in 36 patients (42%) at a median of 29 (range: 6-100) days after allo-SCT. The incidence of grade III-IV aGVHD (n = 20) was 23% (95% confidence interval [CI], 14%-32%). In univariate analysis, patients receiving allo-SCT from an HLA-matched unrelated donor had a higher risk of grade III-IV aGVHD, and patients having the lowest CsA concentration in the first and second weeks after allo-SCT had a significantly higher risk of grade III-IV aGVHD. In a multivariate logistic regression analysis, a higher CsA concentration measured during the first week following graft infusion was the strongest parameter significantly associated with a reduced risk of severe grade II-IV aGVHD (P = .012; relative risk [RR] = 0.24; 95% CI, 0.08-0.73). Of note, when adjusted by donor type, CsA concentration in week 1 remained significantly associated with risk of severe grade II-IV aGVHD (P = .014). We conclude that precise monitoring of CsA concentrations and adjustment of CsA dose early after allo-SCT may be effective to prevent onset of severe aGVHD.
T he FMS-like tyrosine kinase 3 (FLT3) gene is mutated in 25-30% of patients with acute myeloid leukemia (AML). Because of the poor prognosis associated with FLT3-internal tandem duplication mutated AML, allogeneic hematopoietic stem-cell transplantation (SCT) was commonly performed in first complete remission. Remarkable progress
ABSTRACTconventional chemotherapy, we conducted a retrospective comparative study assessing the outcome of 473 adult patients with Ph + ALL who, between 2000 and 2010, underwent allo-SCT in CR1 with HLA-identical siblings or matched unrelated donors, with a special emphasis on the impact of TKIs.
Methods
Study design, data collection and selection criteriaPatients with Ph + ALL reported to the registry of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) were included in this study. For the purpose of this specific analysis, participating centers were requested to enroll consecutive Ph+ALL cases diagnosed between January 2000 and December 2010. The study aimed to include cases of Ph+ B-ALL receiving first allo-SCT from an HLA-identical sibling donor (MSD) or HLA-matched unrelated donor (at least 6/6 HLA matching) (MUD) who: i) were aged 18 years or over at time of transplant; ii) were in CR1; iii) were transplanted between 2000 and 2010; iv) received allogeneic unmanipulated bone marrow (BM) or peripheral blood stem cells (PBSC) as stem cell source; v) received a standard myeloablative conditioning (MAC) regimen or a reduced-intensity conditioning (RIC) regimen according to Bacigalupo's criteria; 28 and vi) whose complete clinical data and outcomes were available. A total of 473 allo-SCT recipients from 77 participating centers met these eligibility criteria. Institutional review board approval was obtained from all participating institutions.
Minimal residual disease assessmentInvestigators were asked to provide minimal residual disease (MRD) data at time of transplant. As the most commonly accepted level of sensitivity for a given sample to be considered PCR negative is 10 -4 BCR/ABL copies, we distinguished two groups for the purpose of this analysis: a "low-risk" group with MRD ≤10 -4, and a "high-risk" group with a ratio >10 -4 .
29,30
Statistical analyses and definitionsThe primary end points were leukemia-free survival (LFS), relapse incidence (RI), and non-relapse mortality (NRM). Secondary end points were overall survival (OS), acute graft-versus-host disease (aGvHD) and chronic graft-versus-host-disease (cGvHD).Patient-related, disease-related, and transplant-related variables were compared between the 2 groups receiving or not TKI before transplantation using the χ 2 statistics for categorical variables and the Mann-Whitney test for continuous variables. Factors that differed significantly between the two groups with P values less than 0.05, and all factors associated with a P value less than 0.10 by univariate analysis were included in the final models. Cumulative incidence functions (CIF) were used to estimate RI and NRM in a competing risk setting, because death and relapse compete with each other. To study cGvHD, we considered relapse and death to be competing events. Probabilities of LFS and OS were calculated using Kaplan-Meier estimates. Univariate analyses were performed using Gray's test for CIF and the log rank test for LFS and OS. Association...
Fecal microbiota transplantation is an effective treatment in recurrent
Clostridium difficile
infection. Promising results to eradicate multidrug-resistant bacteria have also been reported with this procedure, but there are safety concerns in immunocompromised patients. We report results in ten adult patients colonized with multidrug-resistant bacteria, undergoing fecal microbiota transplantation before (n=4) or after (n=6) allogeneic hematopoietic stem cell transplantation for hematologic malignancies. were obtained from healthy related or unrelated donors. Fecal material was delivered either by enema or
via
nasogastric tube. Patients were colonized or had infections from either carbapenemase-producing bacteria (n=8) or vancomycin-resistant enterococci (n=2). Median age at fecal microbiota transplantation was 48 (range, 16-64) years. Three patients needed a second transplant from the same donor due to initial failure of the procedure. With a median follow up of 13 (range, 4-40) months, decolonization was achieved in seven of ten patients. In all patients, fecal micro-biota transplantation was safe: one patient presented with constipation during the first five days after FMT and two patients had grade I diarrhea. One case of gut grade III acute graft-
versus
-host disease occurred after fecal microbiota transplantation. In patients carrying or infected by multidrug-resistant bacteria, fecal microbiota transplantation is an effective and safe decolonization strategy, even in those with hematologic malignancies undergoing hematopoietic stem cell transplantation.
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