Feasibility of up-front autologous stem cell transplantation for high risk diffuse large B-cell lymphoma – non-randomized analysis of 58 consecutive patients

IntroductionHigh-dose chemotherapy supported by autologous stem cell transplantation (ASCT) continues to be a standard of care for relapsed diffuse large B-cell lymphoma (DLBCL) and may be considered as a frontline consolidation for a proportion of patients with high-risk features. AimWe evaluated the feasibility and safety of ASCT for high-risk DLBCL who are in first complete remission after standard treatment with chemotherapy ± rituximab. Material and methodsA retrospective analysis of 58 patients (36 males and 22 females) receiving up-front ASCT between 1996 and 2018 for remission consolidation. ResultsOf the diagnosed, fifty patients were in clinical stage ≥ III. Forty-two (72%) of transplanted patients had age-adjusted IPI ≥ 2. The “B” symptoms were present in 34 patients. The conditioning consisted of cyclophosphamide, carmustine, etoposide (CBV) in 32 patients, carmustine, cytarabine, etoposide, melphalan (BEAM) in 18, and 8 patients received bendamustine, cytarabine, etoposide, melphalan (BeEAM). The transplant-related mortality was 0% at day +30 and +100 after ASCT. Median overall survival (OS) was 4.2 years whereas progression-free survival (PFS) reached 3.0 years. The estimated 5-year OS and PFS were found to be 66% and 64%, respectively. The presence of “B” symptoms remained significance in multivariate analysis (HR 4.17 [95% CI: 1.19–14.5]; = 0.02). No grade 3 or 4 non-hematological adverse events were observed. ConclusionsUp-front ASCT was found to be a safe and feasible procedure with long-term remission in approximately 70% of patients

Systemic mastocytosis with chronic myelomonocytic leukemia followed by transformation into acute myeloid leukemia

IntroductionSystemic mastocytosis (SM) with an associated hematological neoplasm (SM-AHN) constitutes about 40% of all patients with SM. AHN commonly includes myeloid neoplasms and chronic myelomonocytic leukemia (CMML) is seen in about 30% of these patients. Case reportA 67-year-old male presented to hematologist with fatigue and significant weight loss. Abdominal ultrasound and computed tomography (CT) detected hepatosplenomegaly, abdominal lymphadenopathy, and ascites. He was anemic with leukocytosis and eosinophilia. Trephine biopsy showed > 30% of spindle-shaped mast cells. The mutation was present. Serum tryptase level was elevated to 62 ng/mL. The patient was diagnosed with aggressive SM and received six cycles of cladribine with partial response. Three years later, he developed severe anemia. Eosinophilia and monocytosis (5.6 × 10/L) were demonstrated in blood film. Hepatosplenomegaly and abdominal lymphadenopathy were also present. Trephine biopsy did not demonstrate the presence of spindle-shaped mast cells, but dysplasia in erythroid and myeloid lineages was evident. The histological result of lymph node biopsy as well as blood and bone marrow findings were in line with CMML. He received hydroxyurea, but he transformed soon into fatal acute monocytic leukemia. ConclusionsThe prognosis of SM-AHN depends on AHN component. Leukemic transformation of AHN component may occur in a proportion of patients

Allogeneic stem cell transplantation remains an effective therapeutic approach for patients with therapy-related acute myeloid leukemia

Introduction: Therapy-related acute myeloid leukemia (t-AML) remains a late consequence of exposure to cytotoxic chemo- and/or radiotherapy for prior malignant or non-malignant disorders. The prognosis of t-AML is extremely poor, and allogeneic stem cell transplantation (allo-SCT) seems to be the most effective therapeutic approach.We evaluated the efficacy and safety of allo-SCT for t-AML preceded by solid tumors and lymphomas. Material and methods: Study patients were retrospectively identified using our institutional database. Nineteen patients (12 female, 7 male), median age 53 years, underwent allo-SCT for t-AML between 2006 and 2018. Results: Prior malignancy was diagnosed at median age of 43.9 years. Among 19 patients included in the study, 6 (32%) had prior breast cancer, 2 (11%) were diagnosed with papillary thyroid cancer, and 2 (11%) were treated for lymphoma. A variety of other cancers were diagnosed in the remaining 9 patients. Median time from previous malignancy to devel­opment of t-AML was 4.9 years. Fourteen patients (74%) were transplanted in first complete remission (CR1), 4 patients (21%) were in CR2, and 1 patient received graft being in active disease. 10 patients (53%) are alive at last contact in CR. Patients died mainly from infectious complications. Median follow-up from prior malignancy and from transplanta­tion was 9.5 years and 1.82 years, respectively. The 2-year overall survival (OS) was 57%. Median OS for survivors is 4.08 years. Grafts from unrelated donors and the presence of acute graft-versus-host disease affected OS. Conclusions: Allo-SCT remains an effective therapy for t-AM

Autologous stem cell transplantation in the treatment of multiple myeloma with 17p deletion

Introduction Deletion of chromosome 17p [del(17p)] in patients with multiple myeloma is associated with a poor prognosis. High‑dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of treatment in this population. Objectives The aim of the study was to compare the treatment outcomes with high‑dose chemotherapy and ASCT with standard treatment in patients with del(17p). Patients and methods We collected data from 12 Polish centers between 2011 and 2017. The records of 97 patients with p53 deletion were assessed, including 29 individuals treated with ACST and 68 receiving standard treatment alone. Results During the follow‑up, 45 patients died and the overall survival (OS) for the whole group was 33 months (range, 1–66 months), with a median progression‑free survival (PFS) of 13 months (range, 1–46 months). The prognostic factors of OS in a multivariable analysis were calcium levels at diagnosis within the reference range (hazard ratio [HR], 0.24; 95% CI, 0.12–0.48) and at least partial remission achieved after the first‑line treatment (HR, 0.25; 95% CI, 0.12–0.51). Treatment with ASCT was an important factor in improving survival (HR, 3.23; 95% CI, 1.52–6.84). Abnormal kidney function at the time of diagnosis reduced the PFS (HR, 0.46; 95% CI, 0.22–0.94). When the analysis was limited only to patients who could be candidates for ASCT, the survival benefit of the procedure was lost (P = 0.21). Conclusions Patients with multiple myeloma with del(17p) do not benefit from high‑dose chemotherapy followed by ACST

Analysis and influence of anti-HLA antibodies after allogeneic hematopoietic stem cell transplantation from HLA-mismatched unrelated donors

Przeciwciała skierowane przeciw głównemu układowi zgodności tkankowej są istotnym czynnikiem odpowiedzialnym za odrzucenie przeszczepu w przypadku transplantacji narządów litych. Ich wpływ na wyniki allogenicznego przeszczepienia komórek krwiotwórczych, szczególnie od dawcy niezgodnego w układzie HLA, nie został dotychczas poznany. Wobec wzrastającej liczby allotransplantacji komórek krwiotwórczych od dawców niespokrewnionych nie w pełni zgodnych w układzie HLA, zaistniała potrzeba zbadania występowania oraz wpływu przeciwciał anty-HLA na wyniki procedury przeszczepowej. Celem naszej pracy było zbadanie występowania, swoistości oraz wpływu przeciwciał anty-HLA na wyniki przeszczepienia macierzystych komórek krwiotwórczych od dawców niespokrewnionych nie w pełni zgodnych w układzie HLA z biorcą przeszczepu. Do badania włączono 30 pacjentów poddanych transplantacji komórek krwiotwórczych w Klinice Hematologii i Transplantacji Szpiku SUM w Katowicach w latach 2001–2007. Przeciwciała anty-HLA były wykrywane przy użyciu techniki DynaChip w surowicach pobranych od chorych w różnym czasie od przeprowadzonej procedury przeszczepowej. Technika DynaChip łączy w sobie zmodyfikowaną metodę ELISA z techniką microchipów wykorzystującą rozpuszczalne, oczyszczone glikoproteiny HLA zarówno klasy I, jak i II, opłaszczone na powierzchni studzienek. Wstępne obserwacje wskazują, że po allotransplantacji są wytwarzane przeciwciała skierowane przeciw głównemu układowi zgodności tkankowej i mogą one mieć potencjalny wpływ na wyniki procedury transplantacyjnej.Antibodies against human leukocyte antigen (anti-HLA Abs) are important factors responsible for graft rejection in solid organ transplantation, but their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unknown. As the number of patients who are treated with HLA-mismatched HSCT (including cord blood, haploidentical and unrelated HSCTs) constantly increases, the presence and influence of anti-HLA antibodies on the HSCT outcome is unknown. Thus we have examined incidence and influence of anti-HLA antibodies on outcomes of allo-HSCT from HLAmismatched unrelated donors. Abs were identified in sera collected from 30 recipients. We have used automated DynaChip assay which uses microchips bearing purified class I and II HLA antigens for detection of anti-HLA Abs. The preliminary results indicate that anti-HLA Abs appear post transplant in mismatched allo-HSCT recipients and may be potentially responsible for the occurrence of post-transplant complications

Badanie chimeryzmu specyficznego liniowo po allogenicznym przeszczepieniu komórek macierzystych

IntroductionDonor lineage-specific chimerism of hematopoietic cells enables very precise monitoring of engraftment in selected cell lines after allogeneic stem cell transplantation (allo-SCT).Materials and methodsThe study group consisted of 12 acute leukemia patients who underwent allo-SCT in the Department of Hematology and Bone Marrow Transplantation in Katowice, Poland. Lineage-specific chimerism was assessed in B cells (CD19+ CD38−/+), plasma cells (CD19+ CD38++), T cells (CD3+ or CD7+ CD56−), monocytes (CD14+), and immature progenitor cells deriving from myeloid line (CD34+CD19). We also assessed erythrocyte chimerism by flow cytometry.ResultsAll patients engrafted. 8 out of 10 patients presented normal donor hematopoiesis. Lineage specific chimerism in these patients corresponded with chimerism analysis in unsorted material and with undetectable minimal residual disease (MRD). Relapse of the underlying disease was diagnosed in 2 patients. In both cases loss of donor chimerism occurred in leukemia specific cell line and corresponded with detectable MRD. One patient with secondary graft failure presented decreasing lineage specific chimerism in all subpopulations, with negative MRD status. In 10 patients normal hematopoiesis of donor-origin was assessed by flow cytometry. In one case no donor-derived erythrocytes were detected and the diagnosis of pure red cell aplasia was set.ConclusionsLineage specific chimerism as a method of high sensitivity and specificity allows for precise assessment of donor chimerism especially in clinically ambiguous situations. Assessment of erythrocyte chimerism by flow cytometry is a reliable method of monitoring erythroblastic line engraftment. Presented results are preliminary and the study is being continued

Multiparameter flow cytometry for assessment of minimal residual disease in patients with myelodysplastic syndromes treated with allogeneic stem cell transplantation

BackgroundMyelodysplastic syndromes (MDSs) are a heterogeneous group of clonal myeloid neoplasms. Allogeneic stem cell transplantation (allo-SCT) remains the curative method for MDS treatment. Little is known about the monitoring of minimal residual disease (MRD) in patients with MDS after allo-SCT. AimWe aimed to evaluate the significance of leukemia-associated immunophenotypes (LAIPs) identified in acute myeloid leukemia (AML) for MRD monitoring in patients with MDS after allo-SCT. Material and methodsSeven males and 4 females with a median age of 55 years were included. The diagnosis of MDS was established according to 2016 World Health Organization (WHO) criteria. The significance of eight LAIPs in bone marrow samples using multiparameter flow cytometry (MFC) was evaluated for MRD. ResultsEight patients were positive for several LAIPs before allo-SCT. The identified LAIPs included the presence of aberrant lymphoid antigens on myeloblasts and lack of CD33 expression on myeloblasts. All studied MDS patients were negative for LAIPs at Day +30 after the procedure. This was followed by full-donor chimerism in all cases. The Ogata score after allo-SCT decreased in all patients in whom it was indicative for MDS before allo-SCT. ConclusionsMFC could be useful in monitoring MRD in MDS patients after allo-SCT. Further studies in this field are needed

The meaning of the activity of senior citizens in the aspect of social exclusion.

Celem niniejszej pracy dyplomowej jest podjęcie rozważań na temat aktywności seniorów w kontekście wykluczenia społecznego. Przedstawione aspekty starości oraz teorie opisujące przystosowanie do niej dadzą możliwość poznania sposobów przechodzenia przez ostatni etap życia. Zwrócenie uwagi na aktywność seniorów pozwoli zrozumieć jej wpływ na funkcjonowanie osób starszych. Przedstawione formy aktywizacji społecznej seniorów oraz dobre praktyki umożliwią poznanie nietypowych sposobów przeciwdziałania wykluczeniu społecznemu seniorów.The aim of the following dissertation is to take into consideration the activity of the senior citizens in regard with social exclusion. The aspects of old age and the theories describing adaptation to it presented here will enable the reader to recognize different ways of living through the last stage of one's life. Drawing attention to the activity of the senior citizens will enable us to understand it's influence on the functioning of the elderly. Different forms of social activation of the senior citizens as well as good practice shown here will enable recognition of the atypical countermeasures to the social exclusion of the elderly

Real-Life Data on the Efficacy and Safety of Letermovir for Primary Prophylaxis of Cytomegalovirus in Allogeneic Hematopoietic Stem Cell Recipients: A Single-Center Analysis

Objective: Cytomegalovirus (CMV) reactivation is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Introduction of letermovir (LMV) seems to improve posttransplant outcomes, but delayed-onset CMV reactivation still remains a challenge. In this study, we report on our first experience with LMV prophylaxis in 93 CMV-seropositive adult patients receiving HSCT in our center. Materials and Methods: We retrospectively analyzed the data of 93 adult CMV-seropositive recipients receiving LMV as CMV prophylaxis after HSCT for hematological malignancies between 2019 and 2023. The starting LMV dose was 480 mg daily, reduced to 240 mg daily for those receiving cyclosporin A co-administration. CMV DNA in the blood was measured by real-time polymerase chain reaction weekly for the first 2 months after transplantation, then every other week until the end of immunosuppressive treatment. LMV was continued to day +100 or to CMV reactivation. Results: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV “blips” while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118- 152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects. Conclusion: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV “blips” while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118- 152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects