In the present review, the authors report the published evidence on the use of functional imaging with FDG-PET/CT in assessing the final response to treatment in Hodgkin lymphoma. Despite a very high ...overall Negative Predictive Value of post-chemotherapy PET on treatment outcome ranging from 94% to 86%, according to different treatment intensity, the Positive Predicting Value proved much lower (40–25%). In the present review the Authors discuss the role of PET to guide consolidation RT over a RM after different chemotherapy regimens, both in early and in advanced-stage disease. A particular emphasis is dedicated to the peculiar issue of the qualitative versus semi-quantitative methods for End-of Therapy PET scan interpretation. A short hint will be given on the role of FDG-PET to assess the treatment outcome after immune checkpoint inhibitors.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In this study, we performed an analysis of the impact of performance enhancing polymorphisms (PEPs) on gymnastic aptitude while considering epistatic effects. Seven PEPs (rs1815739, rs8192678, ...rs4253778, rs6265, rs5443, rs1076560, rs362584) were considered in a case (gymnasts)-control (sedentary individuals) setting. The study sample comprised of two athletes' sets: 27 elite (aged 24.8 ± 2.1 years) and 46 sub-elite (aged 19.7 ± 2.4 years) sportsmen as well as a control group of 245 sedentary individuals (aged 22.5 ± 2.1 years). The DNA was derived from saliva and PEP alleles were determined by PCR, RT-PCR. Following Multifactor Dimensionality Reduction, logistic regression models were built. The synergistic effect for rs1815739 x rs362584 reached 5.43%. The rs1815739 x rs362584 epistatic regression model exhibited a good fit to the data (Chi-squared = 33.758, p ≈ 0) achieving a significant improvement in sportsmen identification over naïve guessing. The area under the receiver operating characteristic curve was 0.715 (Z-score = 38.917, p ≈ 0). In contrast, the additive ACTN3 -SNAP-25 logistic regression model has been verified as non-significant. We demonstrate that a gene involved in the differentiation of muscle architecture-ACTN3 and a gene, which plays an important role in the nervous system-SNAP-25 interact. From the perspective originally established by the Berlin Academy of Science in 1751, the matter of communication between the brain and muscles via nerves adopts molecular manifestations. Further in-vitro investigations are required to explain the molecular details of the rs1815739 -rs362584 interaction.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic ...marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B‐cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard‐risk patients with minimal residual disease negativity after six cycles de‐escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, p < 0.001) and in those who de‐escalated from KRd to R (27/38, p < 0.001) compared to the KRd arm (9/36). In patients who switched from KRd to R, the concentrations of uninvolved immunoglobulin and the number of B‐cell unique sequences increased over time, approaching values observed in the R arm. There were no differences in progression‐free survival between the patients with at least partial immunoglobulin recovery and the remaining population. Our analysis indicates that patients receiving continuous therapy after ASCT experience prolonged immunoparesis, limiting prognostic significance of polyclonal immunoglobulin recovery in this setting.
In multiple myeloma, recovery from immunoparesis after autologous haematopoietic stem cell transplantation has historically been associated with improved outcomes. However, these findings have not been validated among patients uniformly treated with modern maintenance. This subanalysis of the ATLAS trial, which randomized patients to receive maintenance with carfilzomib, lenalidomide and dexamethasone, or lenalidomide alone, does not confirm the prognostic significance of polyclonal immunoglobulin recovery. The design of the ATLAS trial, including the de‐escalation of therapy in a subset of patients initially treated with carfilzomib, lenalidomide and dexamethasone, allowed for the analysis of the effects of different treatment regimens on humoral immunity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We report a lymphoma patient with profound B-cell deficiency after chemotherapy combined with anti-CD20 antibody successfully treated with remdesivir and convalescent plasma for prolonged SARS-CoV-2 ...infection. Viral clearance was likely attributed to the robust expansion and activation of TCR Vβ2 CD8+ cytotoxic T cells and CD16 + CD56- NK cells. This is the first presentation of TCR-specific T cell oligoclonal response in COVID-19. Our study suggests that B-cell depleted patients may effectively respond to anti-SARS-CoV-2 treatment when NK and antigen-specific Tc cell response is induced.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In everyday gynecological practice, there is an unmet need to manage survivors after allogeneic hematopoietic cell transplantation (allo-HCT). The major gynecological complications include premature ...ovarian insufficiency (POI), chronic graft-versus-host disease (cGVHD) of the anogenital zone (cGVHDgyn), and secondary neoplasms. Aiming to assess a real-life scale of problems associated with HCT, we performed a detailed analysis of a consecutive series of females after allo-HCT who were referred for a routine gynecological evaluation. The study includes 38 females after allo-HCT in whom gynecological examination with cervical smear and USG were performed, followed by colposcopy according to NCCN guidelines. NIH scoring system was used to classify a grade of cGVHDgyn. The incidence of cGVHD was 71% whereas GVHDgyn was 29%, including 5 patients with score 3 at the time of diagnosis. The other manifestations (frequently noted) included the skin, mucosa, eyes, and liver. Menopause was diagnosed in 93% females, and in 81% of them, POI criteria were fulfilled. Ovarian function resumed in 2 cases. The rate of abnormal cytology was 26%: 4 ASCUS, 1 AGUS, 1 LSIL, 3 HSIL/ASC-H, and one cytological suspicion of cervical cancer. GVHDgyn was documented in 10 patients, and 6 of them had abnormal cervical cytology. Early topical estrogen therapy led to a significant reduction in vaginal dryness (
p
< 0.05), dyspareunia (
p
< 0.05), and less frequent cGVHDgyn (
p
< 0.05). GVHDgyn develops in about 30% of long-term allo-HCT survivors. Topical estrogens and hormonal replacement therapy alleviate symptoms and prevent the occurrence of severe consequences of menopause.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Primary refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) and mixed phenotype myeloid/T-cell acute leukemia have dismal prognoses. New treatment approaches, preferably targeting ...specific leukemic aberrations to overcome resistance, are urgently needed. The bright expression of the CD38 antigen found in several cases of T-ALL led to an investigation into the role of anti-CD38 antibodies in the treatment of T-ALL. Here, we present three cases of resistant and relapsed T-ALL and myeloid/T-cell treated with daratumumab-based therapy, including venetoclax and bortezomib (Dara-Ven-Bor). All patients achieved complete remission, with minimal residual disease negativity within four weeks of treatment, allowing them to proceed to allogeneic hematopoietic cell transplantation. The toxicity of the triple schema was acceptable. Our patients and other cases reviewed here suggest that daratumumab combined with venetoclax and bortezomib may be a very effective and relatively safe salvage treatment, even in primary resistant T-ALL.
Development of secondary CML has only been casually described, with few reports attempting to analyze and explain the mechanisms behind this phenomenon. Reported cases vary with regard to presumed ...pathogenesis and clinical characteristics, but similarities can be observed. This report presents the case of a patient diagnosed with CALR and ASXL1-mutated primary myelofibrosis who developed CML 13 years after the initial diagnosis. In contrast with previously reported cases, this patient did not have JAK2 or ABL1 gene mutations, and also exhibited primary resistance to tyrosine kinase inhibitor (TKI) treatment. Here, we analyze the molecular evolution of CML and describe successful treatment with concomitant therapy including a TKI and JAK inhibitor. This report aims to deepen clinical experience and further broaden knowledge about chronic myeloproliferative neoplasms.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Comorbidities impair the prognosis of diffuse large B-cell lymphoma (DLBCL). Type 2 diabetes mellitus (DMT2) increases the risk of other comorbidities, e.g., heart failure (HF). Thus, we hypothesized ...that pre-existing DMT2 may negatively affect the outcome of DLBCL. To verify this, DLBCL patients treated with (R)-CHOP were enrolled. 469 patients were eligible, with a median age of 57 years; 356 patients had advanced-stage DLBCL. 126 patients had high-intermediate and 83 high-risk international prognostic index (IPI). Seventy-six patients had DMT2, 46 HF; 26 patients suffered from both DMT2 and HF. In the analyzed group DMT2 or HF significantly shortened overall survival (OS) and progression free survival (PFS): the 5-year OS for patients with DMT2 was 64% vs 79% and for those with HF: 49% vs 79%. The 5-year PFS for DMT2 was 50.6% vs 62.5% and for HF 39.4% vs 63.2%. The relapse/progression incidence was comparable between groups; the non-relapse/progression mortality (NRPM) was significantly higher solely in DMT2 patients (5-year NRPM 22.5% vs 8.4%). The risk of death was higher in patients with higher IPI (HR = 1.85) and with DMT2 (HR = 1.87). To conclude, pre-existing DMT2, in addition to a higher IPI and HF, was a negative predictor for OS and PFS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The immunization of allogeneic hematopoietic cell transplantation (HCT) recipients against vaccine-preventable diseases is a part of posttransplantation guidelines. We conducted a prospective study ...to assess clinical and immunological parameters that would determine the response and long-term maintenance of protective antibody titers upon the hepatitis B virus (HBV) vaccination after HCT. The investigated variables included: vaccination of the HCT recipients and their donors prior to HCT, chronic graft versus host disease (cGVHD) and the timing of post-HCT vaccination, and B- and T-cell subtype status. Forty-two patients were immunized with three or more doses of recombinant hepatitis B surface antigen (rHBsAg) administered according to the individualized schedule of 0-1-2-6-(12) months. After vaccination, seroconversion was achieved in the whole group. The vaccines were categorized according to the antibody (Ab) titers as weak (WRs; 28.7%), good (GRs; 38%) or very good responders (VGRs; 3.3%). In multivariate logistic regression, severe cGVHD (OR= 15.5), and preceding donor immunization (OR= 0.13) were independent predictors of a weak response to vaccination. A prior belonging to the WR group impaired the durability of protection (OR= 0.17) at a median follow-up of 11.5 years. Patients with severe cGVHD showed a trend toward lower median Ab titers, although they required a higher rate of booster vaccine doses. All VGRs had CD4+ cells > 0.2 x 10
/L. There was a lower mean rate of CD4+IL2+ lymphocytes in WRs. Vaccination demonstrated the immunomodulatory effect on B-cell and T-cell subsets and a Th1/Th2 cytokine profile, while shifts depended on a history of severe cGVHD and the type of vaccine responder. To conclude, vaccination of HCT donors against HBV allows a better response to vaccination in the respective HCT recipients. Double doses of rHBsAg should be considered in patients with cGVHD and in those not immunized before HCT. A dedicated intensified vaccination schedule should be administered to WRs.
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