Liver Transplantation for Budd-Chiari Syndrome From Myeloproliferative Neoplasms - Management and Long-Term Results.

Myeloproliferative neoplasms can cause primary Budd-Chiari-Syndrome with acute or chronic liver failure necessitating liver transplantation. However, preventing the recurrence remains challenging and the need for post-transplant anticoagulant and cytoreductive treatment is not sufficiently clear. We analyzed the treatment regimens for all patients who presented to our department with PBCS from MPN between 2004 and 2021. Eight patients underwent liver transplantation - 6 of them due to an acute liver failure. Post-transplant, all patients received anticoagulant and 7 patients cytoreductive medication. The mean survival after transplantation was 13.25 years. Liver transplantation shows favorable long-term outcome when combined with post-transplant anticoagulant and cytoreductive treatment.

Venous and Arterial Thromboembolism in Lung Cancer Patients: A Retrospective Analysis.

Background: Patients with lung cancer face an increased incidence of venous (VTE) and arterial (ATE) thromboembolism. Risk factors for thrombosis remain unclear, particularly the impact of the use of immune checkpoint inhibitors (ICIs). We sought to compare the incidence of VTE and ATE in lung cancer patients receiving platinum-based therapy versus those receiving ICIs alone or in combination with chemotherapy and to validate the Khorana risk score for predicting VTE in the era of ICIs. Methods: A retrospective single-institution data analysis of 173 patients diagnosed with locally advanced or metastatic lung cancer at the Jena University hospital between 2015 and 2021. Results: The study revealed a high incidence of VTE (17.9%) and ATE (5.8%). The VTE risk was higher in patients diagnosed with adenocarcinoma (OR 0.29, 95% CI 0.09-0.93) than in patients with other histological types. A prior venous event was associated with an increased risk of recurrent VTE (OR 4.46, 95% CI 1.20-16.63). The incidence of thrombosis under first-line platinum-based chemotherapy did not differ from the incidence under ICIs (p = 0.19). There were no differences in the subgroup of patients who received ICIs alone or combined immunochemotherapy (p = 0.43). The Khorana score failed to predict the risk of VTE correctly. Conclusions: We did not find evidence supporting the theory that ICI therapy (alone or combined) increases the risk of thrombotic events. Adenocarcinoma and a prior history of VTE were strongly associated with an increased risk of VTE. Other scores for thrombotic risk assessment in lung cancer patients should be tested in prospective studies.

The risk of infections in multiple myeloma before and after the advent of novel agents: a 12-year survey.

Infections represent a major cause of morbidity and mortality in multiple myeloma and are linked to both therapy- and disease-related factors. Although it has been suggested that the rate of infections increased since the introduction of novel agents, controversies still exist. To better assess the risk factors associated with infections in the era of novel agents, we conducted a large retrospective analysis of 479 myeloma patients treated at Jena University Hospital over a period of 12 years. During their disease history, 65% of patients developed at least one infection, and 37% of therapies were associated with at least one infectious episode. The rate of infections was constant over the years, with no increase in infectious complications after the routine implementation of novel agents. Infections were mainly bacterial and strongly associated with high disease burden, relapsed disease, and treatment with high-dose chemotherapy. Varicella zoster virus (VZV) reactivations occurred late during treatment (median time between high-dose chemotherapy and VZV reactivation 6 months, range 0-44 months), and fewer patients developed a VZV reactivation after 2009 (p = 0.001). Infections are still one of the major causes of morbidity in myeloma patients, and prophylactic measures are urgently needed to reduce this potentially lethal complication.

Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH).

Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients. This review discusses the causes, differential diagnoses, prevention, and management of bleeding episodes in patients with MPN, aiming at defining updated standards of care in these often challenging situations.

Lack of association of platelet-derived growth factor (PDGF) receptor autoantibodies and severity of chronic graft-versus-host disease (GvHD).

PURPOSE: The existence of platelet-derived growth factor (PDGF) receptor autoantibodies in systemic sclerosis is conflicting, and such antibodies were also detected in patients with chronic graft-versus-host disease (GvHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). We therefore aimed to screen for PDGF receptor autoantibodies in patients with chronic GvHD. PATIENTS AND METHODS: We evaluated the existence of PDGF receptor autoantibodies in 39 patients, while 17 patients presented with a limited and 8 patients with an extensive chronic GvHD, respectively. Furthermore, 14 out of 39 patients had no chronic GvHD. RESULTS: We detected at least low levels of PDGF receptor autoantibodies in nearly all (35 of 39) patients after allogeneic PBSCT. Interestingly, only one of six patients with high levels of PDGF receptor autoantibodies presented with an extensive chronic GvHD, while the remaining six patients had no clinical signs of chronic GvHD. Thus, there was no correlation between the quantitative detection of antibodies directed against the PDGF receptor and the presence or severity of chronic GvHD. CONCLUSION: Platelet-derived growth factor receptor autoantibodies could easily be detected in patient sera. Nevertheless, we did not observe any correlation between the presence of PDGF receptor autoantibodies and the severity of chronic GvHD in patients who underwent allogeneic PBSCT.

Reconstitution and functional analyses of neutrophils and distinct subsets of monocytes after allogeneic stem cell transplantation.

PURPOSE: The aim of the study was to investigate the recovery of the innate immune system within the first 100 days after allogeneic peripheral blood stem cell transplantation (PBSCT) and to elucidate a potential correlation with such important events as severe infectious complications or graft-versus-host disease (GvHD). METHODS: In 30 consecutive patients who underwent allogeneic PBSCT, absolute numbers of neutrophils and monocytes were determined and different functional analyses performed at different time points (day +30, +60 and +90, respectively). The capacity to phagocyte Escherichia coli (E. coli) as well as the induction of oxidative burst after incubation with different stimuli (Phorbol-12-myristate-13-acetate; PMA, the chemotactic peptide N-formyl-Met-Leu-Phe; f-MLP or opsonized E. coli) were analysed after engraftment. RESULTS: There was a rapid reconstitution concerning the capability of both neutrophils and monocytes to phagocyte E. coli without a significant increase between day +30 and +90. In contrast, a twofold increase of monocyte oxidative burst after incubation with PMA at day +90 was observed (P = 0.017). Furthermore, the ability of neutrophils to induce oxidative burst after ingestion with E. coli was impaired on day +30 with a significant functional reconstitution on day +60 (P = 0.01). The oxidative burst activity following incubation with f-MLP did not show significant changes after stem cell engraftment. Analysis of numeric reconstitution of CD14+CD16+ monocytes demonstrated a potential correlation with a decreased incidence of chronic GvHD. CONCLUSION: The functional recovery of neutrophils and monocytes in the early period after allogeneic PBSCT differs not only concerning phagocytosis and oxidative burst but also with respect to the stimulus and the cell population that was analysed for oxidative burst activity. The subset of CD16+CD14+ monocytes might be a predictor for a reduced risk of chronic GvHD.

Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care--SAKK 33/99.

PURPOSE: Immunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective in patients with immune-mediated marrow failure. PATIENTS AND METHODS: This trial was designed to assess the impact of immunosuppression on hematopoiesis, transfusion requirements, transformation, and survival in patients with MDS randomly assigned to 15 mg/kg of horse ATG for 5 days and oral CSA for 180 days (ATG+CSA) or best supportive care (BSC), stratified by treatment center and International Prognostic Scoring System (IPSS) risk score. Primary end point was best hematologic response at 6 months. Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤ 2 and transfusion dependency of less than 2 years in duration. RESULTS: Between 2000 and 2006, 45 patients received ATG+CSA (median age, 62 years; range, 23 to 75 years; 56% men) and 43 patients received BSC (median age, 65 years; range, 24 to 76 years; 81% men). IPSS score was low, intermediate-1, intermediate-2, high, and not evaluable in eight, 24, seven, one, and five patients on ATG+CSA, respectively, and eight, 25, five, zero, and five patients on BSC, respectively. Refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess of blasts (RAEB) -I, RAEB-II, and hypoplastic disease were present in 21, six, nine, zero, and nine patients on ATG+CSA, respectively, and 18, eight, 11, two, and four patients on BSC, respectively. By month 6, 13 of 45 patients on ATG+CSA had a hematologic response compared with four of 43 patients on BSC (P = .0156). Two-year transformation-free survival (TFS) rates were 46% (95% CI, 28% to 62%) and 55% (95% CI, 34% to 70%) for ATG+CSA and BSC patients, respectively (P = .730), whereas overall survival (OS) estimates were 49% (95% CI, 31% to 66%) and 63% (95% CI, 42% to 78%), respectively (P = .828). CONCLUSION: This open-label randomized phase III trial demonstrates that ATG+CSA treatment seems to be associated with hematologic response in a subset of patients without apparent impact on TFS and OS.

Safety and impact of donor-type red blood cell transfusion before allogeneic peripheral blood progenitor cell transplantation with major ABO mismatch.

BACKGROUND: Changes within the ABO system are regularly observed phenomena in allogeneic bone marrow transplantation (BMT) and peripheral blood progenitor cell transplantation (PBPCT). Major ABO mismatch can lead to different clinical problems including acute hemolysis after infusion of the allograft, delay of red blood cell (RBC) engraftment, or even manifestation of pure red cell aplasia (PRCA). STUDY DESIGN AND METHODS: This retrospective study demonstrates the safety and the impact of donor-type RBC transfusion before allogeneic PBPCT in major ABO settings as routinely performed at our transplantation unit. This study reports on transfusion of mismatched RBCs at the end of the conditioning period in 35 patients who underwent allogeneic PBPCT, which led to a decrease in isoagglutinin titers in most cases. RESULTS: A decrease of isoagglutinin titer after donor-type RBC transfusion can significantly reduce the demand of RBC transfusion between transplantation and Day +30 (p = 0.003). Interestingly, patients who developed PRCA were not observed, a complication being regularly documented by other groups. CONCLUSION: A decrease of isoagglutinin titers by in vivo immunoadsorption before allogeneic PBPCT does not only lack severe complication but also leads to a reduction in demand of RBC transfusion after engraftment and may reduce the incidence of PRCA in these patients.

Double high-dose chemotherapy with adriamycin, paclitaxel, cyclophosphamide, and thiotepa followed by autologous peripheral blood stem cell transplantation in women with metastatic breast cancer.

To determine the feasibility, time to progression, and event-free survival, twenty-two women with metastatic breast cancer received two cycles of high-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) early after first-line induction chemotherapy. The median age of the ten (45.5%) pre- and 12 (54.5%) postmenopausal women was 48 (range: 33-60) years. Sixteen patients (72.7%) had at least two or more metastatic sites involved. Protocol induction and mobilization chemotherapy including granulocyte-colony stimulating-factor (G-CSF) consisted of two cycles with adriamycin (60 mg/m(2)) i.v. and paclitaxel (200 mg/m(2)) i.v. After collection of at least 4 x 10(6)/kg bodyweight peripheral blood stem cells, the first HDCT-course of adriamycin (60 mg/m(2)), paclitaxel (200 mg/m(2)) cyclophosphamide (4 g/m(2)), and thiotepa (800 mg/m(2)) (ATCT) was given to at least stable disease (SD) patients. Six to eight weeks later, the second HDCT-ATCT was administered. Each HDCT-cycle was followed by PBSCT with a median of 3.81 x 10(6)/kg bodyweight CD-34 positive cells (range: 1.85-10.38). All women showed median leukocyte engraftment (>1,000 x 10(9)/l) on day +9.4 (range: 7-13) and median platelet engraftment (>20,000 x 10(9)/l) on day +12.3 (range: 8-15). There were no apparent differences in the clinical course and non-hematologic toxicity between the two HDCT-cycles. Of the 21 patients evaluable for response, eight (38.1%) patients achieved complete remission (CR), ten (47.6%) patients showed a partial remission (PR), two patients (9.5%) no change, and one patient (4.8%) progressive disease. After a median observation time of 36 (range 28-55) months, six (28.6%) women are alive, four (19.0%) of them in continuous CR, including two women with stable bone lesions, respectively, and 15 (71.4%) died due to progressive disease. Median time to progression (TTP) was 8 (range 4-19) months. A high initial response rate of early HDCT, including the most active drugs adriamycin and paclitaxel, can be achieved with tolerable toxicity in metastatic breast cancer. New approaches for maintaining primary tumor response achieved with efficacious high-dose chemotherapy are warranted.