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Abstract: Background: Dermatofibrosarcoma protuberans (DFSP) is a rare, malignant dermal mesenchymal neoplasm characterized by a slow, infiltrative growth. These neoplasms have a high tendency to recur locally after surgical excision. However, metastasizing cases are exceedingly rare. Cytogenetically, DFSP is characterized by a t(17;22)(22;q13) aberration with fusion of the COL1A1 gene on chromosome 17 with the PDGFB gene on chromosome 22. Here, we report on a successful treatment of a patient with a targeted therapy using the tyrosine kinase inhibitor Imatinib mesylate in neoadjuvant intention. Patients and methods: A patient with recurrent and initially unresectable but non-metastatic DFSP of the scalp received Imatinib over 3 months with increasing dosage from 400 mg/day to 800 mg/day orally. Due to the location of the DFSP in our patient, we intended to decrease tumor size preoperatively to allow complete surgical resection. Response to therapy was assessed by computed tomography. Results: Preoperative treatment with Imatinib resulted in decrease of tumor size by over 60% in the greatest dimension during 3 months of therapy, enabling the complete resection of the DFSP by radical surgery with achieving an acceptable cosmetic result. Surgery was followed by adjuvant Imatinib therapy over 6 months. Conclusions: Imatinib mesylate is effective in neoadjuvant treatment of primary unresectable dermatofibrosarcoma protuberans and can be considered as a useful option in the therapy regimen.

Zober: Deutsche Krebshilfe: Other: grant. Knop:Celgene Corporation: Consultancy. Einsele:Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Engelhardt:Deutsch Krebshilfe: Other: grant.

Introduction:Cancer pts present with a highly heterogeneous health status and treatment choices are often numerous. Therefore, careful assessment of individuals' condition is highly relevant. In order to define best possible and tolerable treatment options, novel parameters and metrics for non-disease variables are needed. Albeit impairment in the Karnofsky Performance Status (KPS), Activities of Daily Living (IADL or ADL) and quality of life (QoL) are predictive for outcome in cancer and MM pts, the prognostic variables within a defined and prospectively assessed battery of established functional tests have rarely been delineated nor have their combination with disease-related risk factors or molecular markers been meticulously assessed. Their prognostic value for functional decline and overall survival (OS) has also not been tested and validated prospectively.

A total of 46 patients (24 female, 22 male) with acute myeloid leukemia (AML) received RIC allogeneic blood stem cell transplants from either fully HLA-compatible family donors (n=14) or unrelated HLA-compatible donors (n=32) between 3/1999 and 3/2007. The unselected consecutive single centre study patients (median age: 52 years, range: 22–64) were at high risk for treatment-related complications (older age, previous infectious complications, impaired organ function). 67% (n=31) of the cohort were not in first remisson but in an advanced status of AML. All patients received 30 mg·m−2 Fludarabine i.v. day −10 to −5, Busulfan 4mg·kg−1 orally day −5 to −4, and 10 mg·kg−1 i.v. Antithymocyteglobulin (ATG-Fresenius®) day −4 to −1 as RIC prior to allogeneic stem cell transplantation. A median of unselected 6.8 x 106 CD-34 positive stem cells (range: 1.9–14.3) were given. GvHD-prophylaxis consisted of Cyclosporin 3mg·kg−1 continuous infusion in case of 10/10 HLA compatibility donor situation (n=34), with the addition of mycophenolate mofetil 2gr. i.v. primarily starting from day +10 in one antigen mismatched HLA-unrelated donor situation (n=12). Nine patients (19.6%) died of therapy related mortality, due to GvHD (n=3), infections (n=4), or both (n=2). Relapses occurred in 18 patients (39%), in five patients even more than one year after transplantation. The median observation time of the study group was 19 months (range: 3–101), the product-limit estimates (Kaplan-Meier) of overall survival (OS) at 36 months were 0.48 (±0.08), of event-free survival (EFS) 0.44 (±0.08), respectively. Figure Figure Disease-status (remisson vs. advanced) failed to have a significant impact in OS or EFS, whereas donor status (related vs. unrelated) resulted in OS at 24 months 0.76 (±0.12) for related donors and 0.4 (±0.09) for unrelated donors (p=0.017, log-rank test). RIC with Fludarabine/Busulfan/ATG prior to allogeneic stem cell transplantation results in a consistently sustained long-term outcome for this otherwise adverse patient subgroup, favouring family-matched donor selection.

Recombinant human erythropoietin (rHuEPO) stimulates progenitor cells of erythropoiesis and increases erythrocyte production. This prospective, placebo-controlled, double-blind trial was designed to evaluate the use of erythropoietin versus red blood cell transfusions (RBC) to evade detrimental effects of anaemia during the first weeks after allogeneic peripheral blood stem cell transplantation (alloPBSCT). Between 4/2002 and 4/2004, 52 patients recieved either 10.000 units rHuEPO [Erypho(R)] 3 times a week subcutaneously or placebo, stratified according to AB0-incompatibility. Applications were started after stem cell transfusion (day +1) and lasted up until in mean day +39.5 [range: 29–50] or until haematocrit (HC) levels reached 0.38. Both groups underwent identical supportive care and RBC transfusion policy. Need for transfusion was defined by HC< 0.27. At time of transplantation, 18 (35%) patients were in remission, and 34 (65%) in advanced stage of their disease. Within the 22 female and 30 male patients (median age: 44.5 years [range:17–64]) 52 % (n=27) received for conditioning treatment a total body irradiation-based regimen, 4% (n=2) high dose treosulfan and cyclophosphamid, and 48 % (n=25) a dose reduced conditioning including fludarabine, busulfan/melphalan and anti-thymocyte globuline, respectively. Thirteen (25 %) patients received transplant from HLA-identical family donors, 26 (50%) from HLA-matched unrelated and 13 (25 %) from mis-matched alternative donors. The two study groups were well balanced regarding age, gender, disease status, graft characteristics, and conditioning regimens. Two patients were excluded from the study due to graft failure on day 21 and one patient refused further treatment on day 37. Eight side effects were observed in the rHuEPO group (3 x local haematoma, 3 x bone/muscle pain, 1 x dizziness, 1 x headache), whereas one was reported in the placebo group (1x headache). No serious adverse event related to study drug was noted. The mean numbers of RBC transfusions were 10.8 ± 5.5 [range: 4–18] with placebo and 9.9 ± 4.2 [range: 6–19] with rHuEPO up to day +50. These effects were identical in the unrelated donor group (n=24) with 11.4 ± 5.7 versus 10.4 ± 4.1, and in the HLA-identical family donor group (n=28) 10.8 ± 5.5 versus 9.4 ± 2.4. Interestingly, in the minor AB0-group (n=15) the rHuEPO arm needed 8.1 ± 3.4 as compared to 12.4 ± 4.2 RBC transfusion in the placebo arm. No differences were observed in the major AB0 group (n=12). Reticulocytes, by similar lab counts on day 0 in both groups, were significantly enhanced on day +30 in the rHuEPO arm. (62.6 ± 18.9 versus 29.3 ± 14.3; p < 0.001). Mean HC on day + 30 was 0.28 ± 0.03, on day + 50 0.33 ± 0.05 in the placebo arm, 0.31 ± 0.03 and 0.36 ± 0.04 in the rHuEPO arm, respectively. Overall survival of the total group after the first 100 days was 49/52 (94,2%).One (3.8%) patient died in placebo-group, and 2 (7.7%) patients in the rHuEPO-group. Further clinical parameters like engraftment, acute graft-versus-host disease (GvHD) and relapse rate were not different between the two treatment groups so far. After alloPBSCT rHuEPO can be given without initial clinical relevant side effects. We conclude that the reconstitution of erythropoiesis seems to be accelerated by early treatment with rHuEPO and reduces number of RBC-transfusions in AB0 minor incompatibility situation after alloPBSCT.

Recombinant human erythropoietin (rHuEPO) stimulates progenitor cells of erythropoiesis and increases erythrocyte production. This prospective, placebo-controlled, double-blind trial was designed to evaluate the use of erythropoietin versus red blood cell transfusions (RBC) to evade detrimental effects of anaemia during the first weeks after allogeneic peripheral blood stem cell transplantation (alloPBSCT). Between 4/2002 and 4/2004, 52 patients recieved either 10.000 units rHuEPO [Erypho(R)] 3 times a week subcutaneously or placebo, stratified according to AB0-incompatibility. Applications were started after stem cell transfusion (day +1) and lasted up until in mean day +39.5 [range: 29–50] or until haematocrit (HC) levels reached 0.38. Both groups underwent identical supportive care and RBC transfusion policy. Need for transfusion was defined by HC< 0.27. At time of transplantation, 18 (35%) patients were in remission, and 34 (65%) in advanced stage of their disease. Within the 22 female and 30 male patients (median age: 44.5 years [range:17–64]) 52 % (n=27) received for conditioning treatment a total body irradiation-based regimen, 4% (n=2) high dose treosulfan and cyclophosphamid, and 48 % (n=25) a dose reduced conditioning including fludarabine, busulfan/melphalan and anti-thymocyte globuline, respectively. Thirteen (25 %) patients received transplant from HLA-identical family donors, 26 (50%) from HLA-matched unrelated and 13 (25 %) from mis-matched alternative donors. The two study groups were well balanced regarding age, gender, disease status, graft characteristics, and conditioning regimens. Two patients were excluded from the study due to graft failure on day 21 and one patient refused further treatment on day 37. Eight side effects were observed in the rHuEPO group (3 x local haematoma, 3 x bone/muscle pain, 1 x dizziness, 1 x headache), whereas one was reported in the placebo group (1x headache). No serious adverse event related to study drug was noted. The mean numbers of RBC transfusions were 10.8 ± 5.5 [range: 4–18] with placebo and 9.9 ± 4.2 [range: 6–19] with rHuEPO up to day +50. These effects were identical in the unrelated donor group (n=24) with 11.4 ± 5.7 versus 10.4 ± 4.1, and in the HLA-identical family donor group (n=28) 10.8 ± 5.5 versus 9.4 ± 2.4. Interestingly, in the minor AB0-group (n=15) the rHuEPO arm needed 8.1 ± 3.4 as compared to 12.4 ± 4.2 RBC transfusion in the placebo arm. No differences were observed in the major AB0 group (n=12). Reticulocytes, by similar lab counts on day 0 in both groups, were significantly enhanced on day +30 in the rHuEPO arm. (62.6 ± 18.9 versus 29.3 ± 14.3; p < 0.001). Mean HC on day + 30 was 0.28 ± 0.03, on day + 50 0.33 ± 0.05 in the placebo arm, 0.31 ± 0.03 and 0.36 ± 0.04 in the rHuEPO arm, respectively. Overall survival of the total group after the first 100 days was 49/52 (94,2%).One (3.8%) patient died in placebo-group, and 2 (7.7%) patients in the rHuEPO-group. Further clinical parameters like engraftment, acute graft-versus-host disease (GvHD) and relapse rate were not different between the two treatment groups so far. After alloPBSCT rHuEPO can be given without initial clinical relevant side effects. We conclude that the reconstitution of erythropoiesis seems to be accelerated by early treatment with rHuEPO and reduces number of RBC-transfusions in AB0 minor incompatibility situation after alloPBSCT.