Higher cyclosporine-A concentration increases the risk of relapse in AML following allogeneic stem cell transplantation from unrelated donors using anti-thymocyte globulin.

Cyclosporine-A (CsA) is used to prevent acute graft-versus-host disease (aGvHD). European Society for Blood and Marrow transplantation (EBMT) recommends a CsA target serum concentration of 200-300 µg/L during the first month after allogeneic hematopoietic stem cell transplantation (HSCT). With this study, we investigated whether a median CsA concentration > 200 µg/L (CsAhigh) the first month after HSCT, compared to ≤ 200 µg/L (CsAlow), increased the relapse risk of acute myloid leukemia (AML), using unrelated donors (URD) and antithymocyte globulin (ATG). Data was collected from 157 patients with AML, transplanted 2010-2016. The cumulative incidence of relapse (CIR) at 60 months was 50% in the CsAhigh versus 32% in the CsAlow group (p = 0.016). In univariate analysis, CsAhigh versus CsAlow (p = 0.028), 10-unit increase of CsA as a continuous variable (p = 0.017) and high risk disease (p = 0.003) were associated with higher CIR. The results remained after adjusting for disease risk. Death following relapse occurred more frequently in the CsAhigh group (p = 0.0076). There were no significant differences in rates of aGvHD, chronic GvHD (cGvHD), EBV/CMV-infections or overall survival (OS) between the two groups. In conclusion, we found that a median CsA concentration > 200 µg/L, the first month after HSCT, results in higher CIR of AML when combined with ATG.

[Thrombotic thrombocytopenic purpura - a rare diagnosis]. / En sällsynt diagnos: trombotisk trombocytopen purpura (TTP).

Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening thrombotic microangiopathy (TMA) characterized by a microangiopathic hemolytic anemia and severe thrombocytopenia, due to platelet consumption. Microthrombi form in small vessels, leading to organ ischemia, most commonly in the central nervous system (CNS). The pathophysiology of TTP is related to a deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), an enzyme that cleaves the von Willebrand multimer. In the absence of ADAMTS13, the von Willebrand multimer is unfolded into an elongated active form that causes platelet activation and aggregation in arterioles and capillaries. Acquired TTP is caused by autoantibodies against ADAMTS13.  The hemolytic anemia is typically DAT-negative and caused by shattering of erythrocytes when passing the microthrombi. Rapid recognition is crucial for the outcome and to initiate the appropriate treatment. It may take several days to get the test results for ADAMTS13 and when there is a high clinical probability for TTP, plasmapheresis must be initiated pending test results. PLASMIC score can be used in determining the probability of low ADAMTS13 in a hospitalized patient with thrombocytopenia and hemolysis to identify the patients that could benefit from early TTP-specific treatment.  First line treatment for acute TTP includes daily plasma exchange, steroids and rituximab. Caplacizumab is an anti-von-Willebrand factor-directed antibody fragment that targets the A1 domain of the von Willebrand factor, thereby inhibiting the interaction between von Willebrand factor multimers and platelets. The treatment has been shown to have beneficial effects when added to standard treatment, without having immunosuppressive effects.

Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlap S1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.

Vaccination against tick-borne encephalitis (TBE) after autologous and allogeneic stem cell transplantation.

INTRODUCTION: Our aim was to assess response and side effects of 4 doses of TBE vaccine to patients (pts) after allo- and autologous stem cell transplantation (SCT). PATIENTS: Included were 104 pts with leukaemia, myeloma and lymphoma, median age 61 yrs. METHODS: Vaccine (FSME-Immun®) was given at 9, 10, 12, and 21 months post-transplant. Serum samples were obtained before and after vaccinations. Healthy controls (n = 27) received 3 vaccinations. Assessments of TBE specific IgG antibodies were performed by Enzygnost anti-TBE ELISA test (Siemens, Sweden). RESULTS: Antibody levels (>12 U/mL; "seropositivity") were seen in 77% and 80% of pts after allo- and autoSCT; IgG levels; 89 vs 94 U/mL. Ongoing chronic GvHD and immunosuppression (n = 29) was associated with sero-negativity in the last sample (p = 0.007). All controls (n = 27) developed protective antibody levels. CONCLUSIONS: TBE vaccination was safe, and 4 doses starting 9 months post-SCT, induced seropositivity in a vast majority of pts.