Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma - a case report.

Introduction: An abscopal effect is a clinical observation whereby a local treatment is associated with regression of metastatic cancer at a site distant from the primary location of treatment. Here, we describe the clinical systemic effect induced by regional hyperthermia combined with low-dose chemotherapy and provide immunologic correlates.Case presentation: A 15-year-old patient had been diagnosed with alveolar rhabdomyosarcoma (ARMS). All previous treatment options failed in the patient including haploidentical stem cell transplantation and donor lymphocyte infusion. The patient presented with local and metastatic disease, and upon admission, underwent regional hyperthermia combined with low-dose chemotherapy. Immediately following therapy severe skin reactions were observed. Skin biopsies revealed an intraepithelial lymphocytic infiltration dominated by CD3+/CD8+ T cells with a regular network of dendritic cells. Clinical images compared before and during sequential treatment cycles showed complete metabolic response of the local tumor for more than 10 months of therapy. In addition, metastases completely regressed although they were not direct targets of regional hyperthermia. The systemic effect was associated with enhanced frequency of NK cells and T cells expressing the lectin-like natural-killer group 2 D activating receptor (NKG2D), an increase of the CD56bright subset of NK cells, as well as an increase of effector/memory and effector CD8+ and CD4+ T cells in the blood while the percentage of CD25+FOXP3+ regulatory T cells declined.Conclusions: Regional hyperthermia combined with low-dose chemotherapy had the potential to create a systemic effect which was associated with activation of NK cells and T cells.

Peripheral dendritic cell chimerism in allogeneic hematopoietic stem cell recipients.

BACKGROUND: Relapse and graft-versus-host disease (GVHD) represent major causes of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Although leukocyte and T-cell chimerism analyses are performed routinely suggesting a predictive value on the patients outcome, little is known about chimerism of dendritic cells (DC) representing strong initiators of immune responses. METHODS: In this prospective study, peripheral DC1 (CD11c+) and DC2 (CD123+) chimerism was determined in hematopoetic stem cell recipients. DCs were isolated from peripheral blood by fluorescence activated cell sorting. Chimerism analyses were performed by fluorescent in situ hybridization or by polymerase chain reaction-based typing of short tandem repeats. RESULTS: At time of engraftment, DC chimerism analyses showed complete chimerism in 76.3% (DC1)/79.5% (DC2), mixed chimerism (MC) in 21.0% (DC1)/17.9% (DC2) and no chimerism in 2.7% (DC1)/2.6% (DC2) of the patients. Peripheral DC chimerism had no significant effect on relapse-free or overall survival. Although acute GVHD was observed more often in patients with MC for DC1/DC2 and chronic GVHD occurred more often in patients with MC for DC2, there was no statistically significant correlation. CONCLUSIONS: Although DCs as antigen presenting cells are supposed to have an impact on the induction of GVHD, there was no significant correlation between incidence of GVHD and DC chimerism after HSCT.

[Counting reticulocytes: new importance of an old method]. / Die Bestimmung der Retikulozytenzahl: Eine alte Methode gewinnt neue Bedeutung.

In clinical practice, the reticulocyte count is the most useful method to estimate red cell life span and red cell production. However, experience of hematologists as well as surveys have shown that counting of reticulocytes is often neglected in the diagnostic work-up of unclassified anemias, and many physicians have difficulties in interpreting the results. Formerly, this was partly due to the low precision of manual counts. Today, this method is largely replaced by flow cytometry, available in almost all larger systems for automated blood count analysis, at low costs and sufficient analytic precision. Interpretation is supported by calculated parameters such as the Reticulocyte Production Index. Here, the authors discuss the limits of the analytic methods and the problems of interpretation in the context of the laboratory profile and the clinical setting.

Platelet activation markers in patients with heart assist device.

Clinical use of heart assist devices is often associated with thromboembolic complications. We hypothesized that platelets may be activated in patients receiving assist devices and examined expression of the platelet activation markers CD62, CD63, and thrombospondin using flow cytometry in eight patients with Novacor left ventricular assist system (LVAS) or Berlin Heart. Patients with end-stage heart failure had elevated expression of platelet activation markers before insertion of the assist device. While CD62 (P < 0.05) and thrombospondin expression (n.s.) decreased by the 14th postoperative day, the CD63 expression remained elevated (n.s.). A good correlation was found between CD62 and thrombospondin expression (r = 0.72). Bleeding time ex vivo indicated platelet dysfunction during the first 4 weeks after implantation. No relation between expression of platelet activation markers and bleeding time ex vivo were found. In conclusion, expression of the platelet activation markers CD62, CD63, and thrombospondin is increased in patients with end-stage heart failure before device placement and shows prolonged elevation during the assist period. Future studies in larger patient populations are necessary to identify new and specific markers of platelet activation in this clinical setting.