Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center.

Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach. Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting. Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18-44) underwent allo-SCT between 2002 and 2020. Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%. Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.

The efficacy and safety of autologous stem cell transplantation in relapsed chemosensitive and chemoresistant patients with diffuse large B-cell lymphoma.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains a valuable therapeutic approach for relapsed and refractory (R/R) patients with diffuse large B-cell lymphoma (DLBCL). The aim of the study was to evaluate the safety and clinical outcome of ASCT for R/R DLBCL. We present a retrospective series of ASCT for 53 DLBCL patients (30 males and 23 females) at the median age of 51 years. Patients were eligible for transplantation if they achieved partial, second, or subsequent response or remained stable to at least 2 prior treatments. Median overall (OS) and progression-free (PFS) survivals were 9 and 6.3 years, respectively. The estimated 4-year OS and PFS were found to be 75% and 69%, respectively. In univariate analysis liver involvement, clinical stage at diagnosis, lymphocyte/monocyte count, and status of clinical response at ASCT were found to influence OS, however, only absolute lymphocyte count remained significant in multivariate analysis (HR 1.42 [95% CI: 1.08-1.87]; p=0.01). Median follow-up from ASCT to the last contact was 4.4 years (range 0.03-18.7). In total, 26 patients died from disease progression and subsequent resistance to chemotherapy. At the last contact, 27 patients were alive in remission. Only a single patient died shortly after ASCT due to infectious complications. Grade 3 or 4 non-hematological side effects were not observed in the remaining patients. ASCT for RR DLBCL is a safe procedure with a high probability of overall and progression-free survival.

Safety profile of a single pegylated asparaginase (PEG-ASP) dose in remission induction for acute lymphoblastic leukemia (ALL).

The incorporation of pegylated asparaginase (PEG-ASP) in pediatric and adult acute lymphoblastic leukemia (ALL) protocols remains a worldwide therapeutic approach. However the safety profile remains a challenge, and herein we report the toxicity of an intravenous single dose of 1000 IU/m2 PEG-ASP administered in remission induction for adult ALL patients. Thirty-two patients at median diagnostic age of 32 years (median of 19-65) were included in this analysis. Most patients had B-cell lymphoblastic leukemia (n=26; 78%) and 81% of cases were <55 years at study entry. 75% of patients had <30x109/l leukocyte count at diagnosis and median follow-up was 14 months (range 0.8-69). All grade 3/4 adverse events (AEs) after PEG-ASP administration were observed in 24 patients (75%). The most common grade 3/4 AEs were: decreased fibrinogen (58%), increased bilirubin (31%) and increased GGTP (27%). Clinical manifestations related to PEG-ASP were seen in 9 patients and included: abdominal pain (n=6), thrombosis (n=2), diarrhea (n=1) and pancreatitis (n=1). The median time from PEG-ASP administration to first toxic symptoms was 7 days (range 1-19), and there were also 4 (13%) early induction deaths. All deaths were observed in ≥50-year-old patients after a median of 5 days following PEG-ASP (range 1-9). Three of these four patients had massive obesity. While all expired patients had grade 4 neutropenia and thrombocytopenia at the time of death, sepsis was not present. Administration of PEG-ASP in induction remission for ALL patients resulted in a significant, but mostly reversible hepatotoxicity. This PEG-ASP treatment should be administered with caution for older, obese patients.

Immunogenic disparities of 11 minor histocompatibility antigens (mHAs) in HLA-matched unrelated allogeneic hematopoietic SCT.

We determined the alleles of 11 mHAs and investigated the association of immunogenic mHA mismatches between a donor and a recipient with a course of allogeneic hematopoietic SCT (allo-HSCT) from 10/10 alleles HLA-matched unrelated donors in 92 recipients after myeloablative conditioning between 2004 and 2006. The frequency analysis of mHA alleles, genotypes and phenotypes accompanied by appropriate restriction HLA Ags allowed for an estimation of the probability of immunogenic mismatches, which was the highest for HA-1, HA-8 and HY. GVH-directed disparity of mHAs with broad tissue distribution, especially of the sex-related HY Ag, influenced the results of allo-HSCT from HLA-matched unrelated donors by not only increasing the probability of chronic GVHD (cGVHD) but also by decreasing the relapse rate.

Interferon alpha induces a good molecular response in a patient with chronic eosinophilic leukemia (CEL) carrying the JAK2V617F point mutation.

The JAK2 V617F point mutation is very rare in hypereosinophilic syndrome and/or chronic eosinophilic leukemia. Here we report on a patient with chronic eosinophilic leukemia and detectable JAK2 mutant clone, who achieved a good molecular response to interferon alpha-2a after 4 months of treatment. The molecular response correlated with only moderate haematological improvement.

A laboratory comparison of the efficacy of battery-operated, non-rechargeable power toothbrushes.

PURPOSE: To evaluate the cleaning efficacy of three battery-operated, non-rechargeable, oscillating/rotating power toothbrushes, using a robot system to simulate normal clinical toothbrush use. MATERIALS AND METHODS: The study compared the cleaning efficacy of the new Braun Oral-B D4/EB4 with the Actibrush and the Dr. Best Powerclean in two independent experiments. Plaque substitute was applied to the artificial teeth of typodonts, which were cleaned by the robot system for a total of 2 minutes at a brushing force of 1.95 N. The remaining plaque substitute on buccal + lingual/palatal and occlusal surfaces, as well as gingival margin and interproximal sites, was measured using a computerized vision system. RESULTS: The new D4/EB4 was found to remove more plaque substitute than the Actibrush at all sites, and for all surfaces, lingual surfaces and occlusal surfaces the difference in favor of the D4/EB4 was statistically significant (P < 0.05). In comparison with the Powerclean toothbrush, the D4/EB4 was significantly more effective at all sites (P < 0.001). These results indicate that not all battery-operated oscillating/rotating power toothbrushes have equal efficacy with respect to plaque removal and that, in this series of laboratory experiments, the Braun Oral-B D4/EB4 was more effective than the Actibrush and the Dr. Best Powerclean.

Doppler sonographic examination of reactive hyperemia in the diagnosis of peripheral vascular disease.

Fifty-four patients with angiographically confirmed peripheral vascular disease (PVD) were examined in order to find out whether the occlusive form of this disease can be better diagnosed by measuring the reappearance time and mean velocity of the blood flow during reactive hyperemia than by determining the peripheral systolic blood pressure, using Doppler ultrasound for both measurements. It was shown that the Doppler pressure was only reliable for a screening diagnosis of PVD. However, using the reappearance time of reactive hyperemia, it was possible to distinguish specific localization types of sclerosis; while reactive hyperemia already reached its half maximum in controls in 4.6 s this occurred in the stenosis type of PVD after 6.9 s, in the upper leg occlusion type after 21.6 s, in the lower leg occlusion type after 46.6 s, and in the multilevel disease after 70.1 s. The delay in the half-maximum reappearance time was significantly different, not only in comparison with controls (P less than 0.001) but also in the specific types of occlusive PVD as compared with one another (P less than 0.01). Regarding the intensity of velocity it could also be shown that the mean velocity of blood flow during reactive hyperemia was lower in all patients with PVD than in controls. Again this alteration during reactive hyperemia was significant, not only in comparison with controls (P less than 0.001), but also when the specific stages of severity according to Fontaine were compared with one another (P less than 0.05).2+n the basis of these findings it can be stated that in

Sonographic examination of gastric motility in diabetics with autonomic neuropathy.

The frequency, intensity and velocity of antral contractions were measured by ultrasonography in 32 patients with insulin-dependent diabetes mellitus and in 12 controls before and up to 60 min after a test breakfast. The examination showed that motility was lower in the diabetics with autonomic neuropathy than in those without and in the non-diabetic controls. The frequency of contractions was determined in the 3 groups as follows: 3.6 +/- 2.0 vs. 4.8 +/- 1.7 vs. 4.8 +/- 1.6 contractions per 2 min (p less than 0.0025); the intensity of contractions was 30.9 +/- 8.2 vs. 41.4 +/- 5.2 vs. 57.5 +/- 8.8 delta % of antral area (p less than 0.025, resp. p less than 0.0005); the velocity of contractions was 4.8 +/- 1.5 vs. 8.2 +/- 1.2 vs. 9.95 + 2.8 delta % of antral area/sec (p less than 0.0125 resp. p less than 0.005). There was a significant difference in the intensity and velocity of contractions between the patients without autonomic neuropathy and the non-diabetic controls (p less than 0.0025 resp. p less than 0.025). 10 min after the test breakfast the motility indices reached a maximum and then decreased continuously towards the end of the test period (p less than 0.01). 20 min after the test meal this decrease was significantly faster in the patients with autonomic neuropathy than in those without and in controls. In all the diabetics the velocity was positively correlated to the coefficient of the variation from beat to beat of the heart, and also positively correlated to the increase of blood glucose concentrations (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Experience with the use of communicative movement therapy in children and adolescents]. / Erfahrungen über die Anwendung der kommunikativen Bewegungstherapie bei Kindern und Jugendlichen.

Our experience shows that the use of communicative motion therapy for children and youths demands greater flexibility in the handling of the task and exercise conception and of the verbalization phases than when this form of treatment is used for adults. The behaviour of the therepeutist is particularly important. In contrast to his role when treating adults, he must be integrated more completely into the group and must act as an indirect leader. Although this makes the group more or less leader-centred, it loses none of its inherent dynamics if the therapeutist uses appropriate forms of communication.