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Following chemotherapy and/or the administration of growth factors, such as granulocyte-colony stimulated factor (G-CSF), hematopoietic stem cells (HSC) mobilize from bone marrow to peripheral blood. This review aims to systematically present the structure of the HSC “niche” and elucidate the mechanisms of their mobilization. However, this field is constantly evolving and new pathways and molecules have been shown to contribute to the mobilization process. Understanding the importance and the possible primary pathophysiologic role of each pathway is rather difficult, since they share various overlapping components. The primary initiating event for the mobilization of HSC is chemotherapy-induced endogenous G-CSF production or exogenous G-CSF administration. G-CSF induces proliferation and expansion of the myelomonocytic series, which leads to proteolytic enzyme activation. These enzymes result in disruption of various receptor-ligand bonds, which leads to the disanchorage of HSC from the bone marrow stroma. In everyday clinical practice, CXC chemokine receptor-4 (CXCR4) antagonists are now being used as mobilization agents in order to improve HSC collection. Furthermore, based on the proposed mechanisms of HSC mobilization, novel mobilizing agents have been developed and are currently evaluated in preclinical and clinical studies.

Despite high cure rates, treatment of childhood Hodgkin Lymphoma (HL) is associated with late effects caused mainly by radiotherapy (RT). In the GPOH-HD95 trial of the German Society of Pediatric Oncology and Hematology that was recently published in the Journal of Clinical Oncology, RT was spared in patients achieving a stringently defined complete remission (CR) with chemotherapy and reduced in patients with a good partial remission (PR). Overall, RT-treated patients had superior PFS, but overall survival (OS) was almost identical within each risk-stratified treatment group irrespectively of the use of RT. In the low-risk group, RT could be safely omitted in 20% of patients. In contrast, failure rates were considered unacceptable, when RT was omitted in intermediate or high risk patients achieving a CR. However, salvage therapy was successful, equalizing overall survival between irradiated and non-irradiated patients. Although GPOH-HD95 points out to the omission of RT in selected patients achieving a CR after chemotherapy, especially those in the low-risk group, more than 80% of the patients are still irradiated. Notably, the GPOH-HD95 was not a randomized trial. In conclusion, according to the GPOH-HD95 trial, RT can be safely omitted in pediatric and adolescent patients with low-risk, early stage HL achieving a stringently defined CR after 2 cycles of OPPA or OEPA chemotherapy. RT dose could also be reduced in case of good PR by conventional imaging. However, conventional response assessment is not the optimal means to decide whether RT is needed or not. It is now increasingly recognized that RT can be omitted in many patients with HL without compromising the final outcome and it appears wise to try to stringently limit RT in those patients who really need it. This might be achieved through the use of modern functional imaging (PET/CT). Such efforts are already in progress and results regarding efficacy are awaited relatively soon.

Despite high cure rates, treatment of childhood Hodgkin Lymphoma (HL) is associated with late effects caused mainly by radiotherapy (RT). In the GPOH-HD95 trial of the German Society of Pediatric Oncology and Hematology that was recently published in the Journal of Clinical Oncology, RT was spared in patients achieving a stringently defined complete remission (CR) with chemotherapy and reduced in patients with a good partial remission (PR). Overall, RT-treated patients had superior PFS, but overall survival (OS) was almost identical within each risk-stratified treatment group irrespectively of the use of RT. In the low-risk group, RT could be safely omitted in 20% of patients. In contrast, failure rates were considered unacceptable, when RT was omitted in intermediate or high risk patients achieving a CR. However, salvage therapy was successful, equalizing overall survival between irradiated and non-irradiated patients. Although GPOH-HD95 points out to the omission of RT in selected patients achieving a CR after chemotherapy, especially those in the low-risk group, more than 80% of the patients are still irradiated. Notably, the GPOH-HD95 was not a randomized trial. In conclusion, according to the GPOH-HD95 trial, RT can be safely omitted in pediatric and adolescent patients with low-risk, early stage HL achieving a stringently defined CR after 2 cycles of OPPA or OEPA chemotherapy. RT dose could also be reduced in case of good PR by conventional imaging. However, conventional response assessment is not the optimal means to decide whether RT is needed or not. It is now increasingly recognized that RT can be omitted in many patients with HL without compromising the final outcome and it appears wise to try to stringently limit RT in those patients who really need it. This might be achieved through the use of modern functional imaging (PET/CT). Such efforts are already in progress and results regarding efficacy are awaited relatively soon.

Dickkopf-1 is an inhibitor of Wnt signaling, which is crucial for osteoblast differentiation. We evaluated serum levels of Dickkopf-1 in 66 patients with thalassemia-induced osteoporosis who received therapy with zoledronic acid in a placebo-controlled, randomized trial. At baseline, thalassemia patients had increased serum levels of Dickkopf-1 that correlated with reduced bone mineral density of the lumbar spine and the distal radius. High Dickkopf-1 also correlated with increased bone resorption and reduced bone formation markets. Zoledronic acid produced a reduction in serum Dickkopf-1, which was associated with bone mineral density increase after 12 months of therapy. On the contrary, placebo group showed a borderline increase of Dickkopf-1, which was higher in patients who showed deterioration in pain scores. These results suggest that Dickkopf-1 is implicated in the pathogenesis of osteoporosis in thalassemia and reveal Dickkopf-1 as a possible target for the development of novel agents for the management of thalassemia-induced osteoporosis (ClinicalTrials. got., Identifier: NCT00346242).