Summary
The immunogenicity and safety of Pfizer‐BioNTech BNT162b2 mRNA vaccine in allogeneic haematopoietic stem cell transplantation (HSCT) recipients are unknown. We prospectively followed 152 HSCT ...recipients who were at least six months following transplantation and with no active acute graft‐versus‐host disease (GVHD). Blood samples were taken 2–4 weeks after the second vaccination and analyzed for receptor‐binding domain (RBD) antibodies and neutralizing antibodies (NA). 272 immunocompetent healthcare workers served as controls. At a median of 28 days after the second vaccination, 118 patients (77·6%) developed RBD immunoglobulin G (IgG) with a geometric mean titre (GMT) of 2·61 95% CI (confidence interval), 2·16–3·16. In the control group 269/272 (98·9%) developed RBD IgG, with a GMT of 5·98 (95% CI 5·70–6·28), P < 0·0001. The GMT of NA in HSCT recipients and controls was 116·0 (95% CI 76·5–175·9), and 427·9 (95% CI 354·3–516·7) respectively (P < 0001). Multivariate logistic regression analysis revealed that HSCT recipients with no chronic GVHD and no immunosuppressive therapy at the time of vaccination had significantly higher levels of NA following the second vaccination. Adverse events were minimal and were less common than in healthy controls. In conclusion; the BNT162b2 mRNA vaccination is safe and effective in HSCT recipients, especially those who are immunosuppression‐free. A significant fraction developed protecting NA.
Background
Oral mucositis (OM) is a common toxicity of stem cell transplantation (SCT). We sought to evaluate OM burden, risk factors, and implications in a cohort of allogeneic‐SCT recipients.
...Methods
This was a single‐center study including 115 adult allogeneic‐SCT transplanted between 2016 and 2018 for various hematological conditions. Conditioning intensity was categorized as myeloablative (MAC, 39%), reduced intensity (34%), or reduced toxicity (RTC, 27%) in patients conditioned with fludarabine‐treosulfan. OM was prospectively graded using the Common Terminology Criteria for Adverse Events (v.4.0) system.
Results
Moderate‐to‐severe OM (grade 2‐4) was experienced by 60% of patients. In a univariate analysis, younger age (P = .023), lower body mass index (P = .01), recent smoking (P = .08), recent antibiotics exposure (P = .018), MAC (P < .001), and methotrexate (P = .009) were associated with moderate‐to‐severe OM. In a multivariable logistic regression model, conditioning and graft‐versus‐host disease prophylaxis remained significant. OM risk was lowest with RTC (RTC vs MAC: odd ratio OR 0.05, P < .001), and recent antibiotic exposure trended toward increased risk (OR 1.88, P = .168). OM was associated with longer hospitalization, delayed neutrophil engraftment, and gastrointestinal‐related infections.
Conclusion
Oral mucositis remains a leading SCT complication. Treosulfan‐based conditioning has low mucosal toxicity and is appealing given previous reports on its high efficacy.
Autologous stem cell transplantation (ASCT) is a standard of care in newly-diagnosed multiple myeloma (MM) patients. Several studies before the introduction of novel therapies in MM, demonstrated a ...pegylated G-CSF to be successful in mobilizing peripheral blood stem cells (PBSCs). Lipegfilgrastim is a novel long-acting G-CSF that is produced by the conjugation of a single 20-kDa polyethelene glycol to the natural O-glycosylation site of G-CSF. Twenty-four MM patients were included for PBSCs mobilization with a single SC injection of 6 mg lipegfilgrastim. PBSC collection was started when the CD34
+
count was > 10 × 10
6
cells/L. The target progenitor cells were 6 × 10
6
cells/kg. The median day of apheresis was + 3 (range 2–5) following lipegfilgrastim. Median peripheral blood CD34
+
count pre-mobilization was of 22.65 (range 3.36–105) × 10
6
cells/L. The median number of leukaphaeresis procedures was 2 (range 1–4). The median mobilized CD34
+
cells/kg were 8.26 (range 0.77–12.42). One patient failed to mobilize and two patients mobilized < 6 × 10
6
cells/kg. Toxicity was mild and transient. Twenty-three patients underwent ASCT following high dose melphalan. All patients engrafted. As lipegfilgrastim is administered only once, it is conceivable that it improves both compliance and quality-of-life (NCT02488382).
We present three patients with aggressive non-Hodgkin's B-cell lymphoma (NHL) who received anti-CD19 chimeric antigen receptor T (CAR T) cells therapy after failure of several lines of chemotherapy ...that developed pseudo-progression. One-week clinical and radiological findings were consistent with tumor progression. Positron emission tomography-computed tomography (PET-CT) at 1 month post CAR T cells administration was consistent with treatment response. The rapid tumor growth and subsequent resolution are suggestive of tumor pseudo-progression mediated secondary to infiltration and immune activation of CAR T cells. Overall, 56 adult patients with NHL were enrolled in a phase 1b/2 in house clinical study with CD19 CAR T cells. Out of them 22/56 patients progressed as per PET-CT the 1 month post CAR T cells. In 14 patients, signs of progression started 7-10 days after CAR T cells infusion. In 11/14 patients, it was true progression, while in 3 it was pseudo-progression. Additional studies are warranted to describe the extent of this phenomenon and evaluate correlation with the CAR T activity and long-term disease control.
Risk stratification is important for balancing potential risks and benefits of allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. We retrospectively studied ...1119 patients undergoing allogenic-HSCT in a single center for five hematological indications assessing the prognostic role of LDH at admission for survival (OS), progression-free survival (PFS), relapse incidence (RI), and nonrelapse mortality (NRM). In non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML), higher than median LDH had an adverse effect on survival. The prognostic significance was strongest in AML, with higher LDH levels having lower 1-and 3-year survival 69.2% vs. 50.8%, P < 0.001 and 51.9% vs. 39.2%, P < 0.001, respectively, reduced 1-and 3-year PFS 62.4% vs. 42.1%, P < 0.001 48% vs. 35.2%, P < 0.001, respectively, higher cumulative incidence of 1-and 3-year NRM 11% vs. 17.3%, p = 0.01 and 15.7% vs. 19.6%, P = 0.04, and higher 1-and 3-year relapse incidence (RI) 26.7% vs. 40.7%, p < .0001 36.2% vs. 40.7%, respectively, P < 0.0001). In multivariate analysis LDH maintained significant prognostic capacity in OS, PFS and RI. These findings in AML, validated in an independent cohort, suggest that LDH is a readily available tool that could be integrated into transplant risk assessments to aid decision-making and identify high-risk patients who may benefit from post-transplant pharmacological or cellular strategies.
Second allogeneic hematopoietic stem-cell transplantation (HSCT2) is a therapeutic option for patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) relapsing after a first ...transplant (HSCT1). However, patients allocated to HSCT2 may be a selected group with better prognosis and the added efficacy of HSCT2 is not well established. We retrospectively analyzed 407 consecutive patients with relapsed AML/MDS after HSCT1. Sixty-two patients had HSCT2 (15%) and 345 did not. The 2-year cumulative incidence rates of non-relapse mortality and relapse after HSCT2 were 26% (95% confidence interval 95% CI: 17-39%) and 50% (95% CI: 39-65%), respectively. The 5-year overall survival rates were 25% (95% CI: 14-36%) and 7% (95% CI: 4-10%) in the HSCT2 and no-HSCT2 groups, respectively. Multivariate analysis identified female gender (hazard ratio HR=0.31, P=0.001), short remission duration after HSCT1 (HR=2.31, P=0.05), acute graft-versus-host disease after HSCT1 (HR=2.27, P=0.035), HSCT2 from a haplo-identical donor (HR=13.4, P=0.001) or matched unrelated donor (HR=4.53, P=0.007) and relapse after HSCT1 in earlier years (HR=2.46, P=0.02) as factors predicting overall survival after HSCT2. Multivariate analysis of all patients including HSCT2 as a timedependent variable identified relapse within 6 months after HSCT1 (HR=2.32, P<0.001), acute graft-versus-host disease before relapse (HR=1.47, P=0.005), myeloablative conditioning in HSCT1 (HR=0.67, P=0.011), female gender (HR=0.71, P=0.007), relapse in earlier years (HR=1.33, P=0.031) and not having HSCT2 (HR=1.66, P=0.010) as predictive of overall survival after relapse. In conclusion, HSCT2 is associated with longer survival compared to non-transplant treatments and may be the preferred approach in a subset of patients with relapsed AML/MDS after HSCT1.
Acute graft‐versus‐host disease (GVHD) is the major treatment‐related complication after stem‐cell transplantation (SCT) from unrelated‐donors. Several GVHD prophylaxis regimens have been explored, ...but no regimen has shown superiority. We analyzed transplantation outcomes in 472 consecutive unrelated‐donor SCT recipients, using cyclosporine/methotrexate (MTX, n = 314) or cyclosporine/mycophenolate‐mofetil (MMF, n = 158) for GVHD prophylaxis. Neutrophil engraftment was faster after MMF, days 11 and 14, respectively (P = .001). Acute GVHD grade II‐IV and III‐IV occurred in 47% and 28% after MMF compared to 27% and 12% after MTX, respectively (P < .001). Nonrelapse mortality (NRM) was 44% and 24%, respectively (P < .001). Death associated with GVHD occurred in 25% and 8% (P < .0001), while other NRM causes occurred in 19% and 16%, respectively (P = .39). Relapse mortality was similar. Overall survival was better after MTX, 40% and 29%, respectively (P = .006). However, this difference had only borderline significance when adjusting for differences in patient characteristics (HR, 1.3, P = .08). To minimize potential selection bias we analyzed outcomes on the basis of an intention‐to‐treat like analysis. During the years 2008‐2009, the leading GVHD prophylaxis regimen for unrelated‐donor SCT included MMF (89% of transplants). During the other periods, MTX was used predominantly (82% of transplants). The two periods were otherwise well‐matched. Acute GVHD occurred more often in 2008‐2009. Death associated with GVHD occurred more often, while other NRM causes occurred less often resulting in similar NRM and overall survival. In conclusion, cyclosporine/MMF is associated with faster engraftment and possibly with less organ toxicity than cyclosporine/MTX. However, it is associated with increased rates of acute GVHD and GVHD‐associated deaths.
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