Torquetenovirus (TTV) has been proposed as a marker of immune function in patients receiving immunosuppression after solid organ transplantation. This study aimed to define TTV plasma dynamics and investigate clinical associations in patients following allogeneic hematopoietic stem cell transplantation (HSCT). This was a single-center prospective longitudinal study involving 50 consecutive patients treated with HSCT between March 2015 and April 2016. TTV plasma DNA levels were measured with quantitative PCR at 12 consecutive time points during the first year after HSCT. Forty of the 50 patients (80%) had detectable TTV viremia before HSCT (median level, 5.37 log10 copies/mL; interquartile range [IQR], 3.51-6.44 log10 copies/mL). All patients subsequently developed TTV viremia during the follow-up period. Plasma viral loads evolved dynamically over time, with a peak of 8.32 log10 copies/mL (IQR, 7.33-9.35 log10 copies/mL) occurring at 79 days (IQR, 50-117 days) following HSCT and a stable plateau toward the end of the follow-up period. The type of malignancy, the use of antithymocyte globulin during conditioning, and the occurrence of acute graft-versus-host disease requiring systemic therapy had temporary effects on TTV dynamics. TTV levels showed a significant correlation with absolute lymphocyte counts following engraftment (r = -.27; P < .01) and with cytomegalovirus (CMV; r=.39; P < .01) and Epstein-Barr virus (EBV; r=.45; P = .02) viral loads during phases of viremia. Immune-related clinical events were not predicted by TTV levels. TTV viremia occurred universally and was sustained throughout the first year after HSCT. Several variables and events before and after HSCT were correlated with TTV levels and hint toward immune marker properties of TTV, but their complex interactions might perturb the capability of TTV to predict immune-related complications in this population.
Objective: Limited data exist on gender-specific aspects in hematologic malignancies and have been obtained mostly in non-Hodgkin lymphomas. The objective of this study was to investigate gender-specific aspects in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). Methods: A retrospective data analysis of 191 patients with MM who underwent ASCT was performed. Data collected from clinical records included age, sex, stage, induction therapy, outcome of induction, kind of stem cell mobilization, response to induction therapy and ASCT, cytogenetic aberrations, progression-free survival, and overall survival. Results: Eighty-one patients (42%) were female, whereas 110 patients were male (58%). No differences between female and male patients could be observed according to the international staging system (ISS) (e.g., ISS III: 14.8 vs. 17.3%), type of paraprotein, and cytogenetic aberrations (e.g., Del(13q): 32.7 vs. 28.9%). Five-year overall survival rates, when calculated from time to ASCT until death, were 27.2 and 36.4% and, when calculated from time to diagnosis until death, were 34.6 and 44.5%, respectively, and did not differ between groups according to ISS subgroups. Conclusion: Prognosis and baseline characteristics were identical and no differences could be observed between female and male patients with MM undergoing ASCT.
Purpose Treatment of refractory Hodgkin disease deserves specific considerations. Recently, alemtuzumab-BEAM has been introduced in allogeneic hematopoietic stem cell transplantation (HSCT) in these patients.MethodsWe retrospectively analyzed the outcome of 20 patients with relapsed/refractory Hodgkin’s lymphoma (HL) who received allogeneic HSCT following conditioning therapy with alemtuzumab-BEAM.ResultsTreatment-related toxicity was tolerable. Half of the patients (50 %) had infections. Of these, 50 % were found to have pneumonia or catheter-related infections. In 20 %, an oral mucositis was observed. Acute graft-versus-host disease (GvHD) (≥grade 2) was seen in three patients. Complete remission (CR) could be achieved in 17 patients (85 %), 2 patients had persistent Hodgkin disease, and 1 patient died from infection prior to CR evaluation. Median progression-free survival and overall survival were 17.9 and 67.5 months, respectively. From the 17 CR patients, 8 had a relapse after a median of 10 months. Notably, of the eight patients relapsing after HSCT, all patients received another salvage treatment and four patients are still alive, whereas the other four patients died due to further progress. Six out of the remaining nine patients are still in CR, whereas the other three died from chronic GvHD and multi-organ failure. Overall, seven patients experienced chronic GvHD.ConclusionIn summary, alemtuzumab-BEAM is a well-tolerated conditioning therapy for allogeneic HSCT with high response rates in refractory HL.
Objective: Umbilical cord blood (UCB) is an important graft source for hematopoietic stem cell transplantation (SCT). Due to less stringent human leukocyte antigen (HLA) matching criteria compared to bone marrow or peripheral blood stem cells, UCB enables patients lacking an HLA-matched donor to receive potentially curative SCT. Methods: We retrospectively analyzed the efficacy and safety of UCB transplantation (UCBT) at our center. Results: Between June 2009 and June 2015, 27 UCBT were performed in 25 patients. Reasons for the use of UCB were lack of adequate related or unrelated stem cell donor (n = 20) and graft failure after previous SCT (n = 7). Median time to neutrophil engraftment was 22 days. Four patients experienced primary graft failure. Thirteen patients developed acute graft-versus-host disease (GVHD), whereupon 6 subsequently also developed chronic GVHD. After a median follow-up time of 19 months, 9 patients relapsed and 12 patients died. Cause of death was relapse in 8 and transplant-related events in 4 patients. Median overall survival and progression-free survival have not been reached yet. Conclusion: In our experience, UCBT is an alternative graft source for patients lacking a suitable related or unrelated donor and a feasible treatment option for patients experiencing graft failure after previous SCT.
Background: Patients suffering from chronic lymphocytic leukemia (CLL) are observed and treated intra- as well as extramural during the course of their disease. Generally, hematological centers only see patients who are eligible for active treatment and/or candidates for clinical trials. Thus, a bias between published and real-life patients' data is likely. In our "Hämatologieverbund der WGKK" we take care of CLL patients who are under observation as well as of patients who are in need of treatment. This allows representative analyses of comorbidities and treatment periods during the course of the disease in an in- and outpatient setting. Therefore, a bias in the analyzed population can be excluded. Although new potent oral drugs are now available for the treatment of CLL, still some toxicities are of concern. Disease-related factors as IGHV-mutation and/or TP53-mutation/17p deletion guide specific treatment decisions, but patient-related factors such as age and comorbidities become more and more important. Especially the comorbidities in the usually elderly CLL-population might influence the choice of treatment. Depending on the side effects, caution has to be taken to decide the appropriate individual drug for the patients. Real world data concerning functional status and comorbidities of CLL patients may help to improve treatment results. In a retrospective study 888 patients diagnosed with CLL, having been observed and cared for within the "Hämatologieverbund der WGKK" between 2012 and 2018, were identified and analyzed according to their whole history of disease. Comorbidities were assessed in detail during the whole course of the disease. Results: At time of diagnosis, the median age was 67.5 years. 96.6% of patients presented with an ECOG-status of 0-1. 89.1% of patients had Binet-stadium A, 8.6% had Binet-stadium B and 2.3% had Binet-stadium C. In 43.2% of patients pathological lymph nodes had been observed and 7.7% of patients reported suffering from constitutional symptoms. 7.5% of patients presented with a del(17p)/TP53 mutation status of ≥10%, while 57.0% of patients were IGHV-mutated. 258 of 888 (29.1%) patients received at least one line of treatment (median 1.7, range 1-6), whereas 71% of patients did not require therapy in the observation period. The most common treatment regimens were: rituximab-bendamustine (BR) (N=135), ibrutinib (N=48), FCR (N=58), chlorambucil combinations (N=39) and venetoclax (N=10). Patients treated with ibrutinib had a comorbidity rate of 41.7% and patients who received BR had a comorbidity rate of 31.9% at time of diagnosis. The mean time from diagnosis to first treatment was 4.0 years (range: 0.0-31.8 years). The median observation time was 6.4 years in both treated and untreated patients (SD 5.6 years, max. 37.0 years). Between the observation period from 2012 to 2018, 17.3% of patients died. Comorbidities were assessed using the Charlson Comorbidity Index (CCI). 40.0% of patients had at least one comorbidity according to the CCI. Interestingly, patients who received treatment showed the higher percentage of comorbidities (50%) documented during the whole observation period, than patients who never received any treatment (36%). Treated patients showed a rate of comorbidities at time of diagnosis of 30.6%, which increased to 50% during the observation period. Besides the established CCI, we investigated details of cardiovascular comorbidities, including arterial hypertension, in patients who received treatment at time of diagnosis and during the whole observation period (details are shown in Fig. 1). Patients who received ibrutinib in general had more comorbidities compared to all treated patients. Conclusion: We think that our patient population is representative and the number of patients with p53- and/or IGHV-mutation is similar to previously reported data. It is interesting that the rate of comorbidities in our population group was higher than expected. Especially the rate of cardiovascular comorbidities including arterial hypertension was impressive. Also, patients requiring treatment had more comorbidities than those under surveillance during the observation period. We conclude, that in the era of new drugs with specific toxicities (cardiovascular, renal, pulmonary), awareness, diagnosis and consequent treatment of possibly co-existing comorbidities should be in the central focus in patients suffering from CLL. Disclosures Keil: Pfizer: Honoraria; Roche: Honoraria; Takeda: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; AbbVie: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Novartis: Honoraria; Bionorica: Honoraria, Research Funding; Celgene: Honoraria; Janssen: Honoraria, Research Funding. Noesslinger:Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria.
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