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1.
Eur J Haematol ; 98(2): 160-168, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27706846

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate the predictive capacity of the European LeukemiaNet (ELN) classification of genetic risk in patients with acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation (alloSCT). METHODS: We retrospectively analysed 274 patients transplanted at our centre between 2004 and 2014. RESULTS: The ELN grouping is comparable to the Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) stratification in predicting the outcome after alloSCT [overall P = 0.0064 for disease-free survival (DFS), overall P = 0.003 for relapse]. Patients with an intermediate-1 profile have a significantly elevated 5-yr relapse incidence as compared to favourable risk patients, that is 40% vs. 15%, [hazard ratio (HR) 2.58, P = 0.048]. An intermediate-1 risk profile is an independent predictor for relapse as determined by multivariate Cox regression analysis (HR 3.05, P = 0.023). In intermediate-1 patients, the presence of an FLT3 internal tandem duplication (FLT3-ITD) is associated with a significantly increased relapse incidence (P = 0.0323), and a lower DFS (P = 0.0465). FLT3-ITD is an independent predictor for overall survival, DFS and relapse incidence in the intermediate-1 subgroup. CONCLUSIONS: The ELN stratification of genetic risk predicts the outcome of patients with AML undergoing alloSCT. Patients with an intermediate-1 profile have a high risk for treatment failure due to relapse, which prompts the development of alternative treatment strategies.


Subject(s)
Genetic Variation , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Adolescent , Adult , Combined Modality Therapy , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Prognosis , Proportional Hazards Models , Recurrence , Retrospective Studies , Transplantation Conditioning , Transplantation, Homologous , Treatment Failure , Treatment Outcome , Young Adult
2.
Clin Breast Cancer ; 16(6): 514-519, 2016 12.
Article in English | MEDLINE | ID: mdl-27395417

ABSTRACT

BACKGROUND: Pegylated liposomal doxorubicin (PLD) has shown to be as effective as conventional doxorubicin in the treatment of metastatic breast cancer but provides a lower risk of cardiotoxicity. This phase 2 study in heavily pretreated patients with metastatic breast cancer was initiated to evaluate a biweekly instead of a 4-week schedule of PLD in order to obtain a more flexible and tolerable regimen. PATIENTS AND METHODS: A total of 25 patients with 2 or more prior lines of chemotherapy for metastatic disease were treated with PLD (25 mg/m2) at 2-week intervals for a maximum of 12 courses. Pretreatment with anthracyclines was allowed as long as the cumulative doxorubicin dose at study entry was below 400 mg/m2. Most patients were pretreated with anthracyclines, taxanes, vinorelbine, alkylating agents, and capecitabine. RESULTS: The clinical benefit rate, ie, objective response or stable disease, for at least 6 months was 22.7% for all patients and 22.2% in anthracycline- and taxane-pretreated patients, respectively. Median duration of clinical benefit and median time to progression were 12.5 months (95% confidence interval [CI], 10.1-32.3) and 7 weeks (95% CI, 5.4-8.6), respectively. Median overall survival was 9.6 months (95% CI, 5.4-13.9). One- and 2-year survival rates were 38% and 4%, respectively. Myelosuppression was low, with no grade 3 or 4 neutropenia or thrombocytopenia. Most common nonhematologic toxicities were nausea, alopecia, asthenia, and hand-foot syndrome. The low rate of hematologic toxicity and hand-foot syndrome is clinically noteworthy. CONCLUSION: Biweekly PLD is an easily manageable schedule with a favorable toxicity profile. Efficacy was moderate in heavily pretreated patients.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Doxorubicin/analogs & derivatives , Adult , Aged , Anthracyclines/therapeutic use , Antibiotics, Antineoplastic/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Capecitabine/therapeutic use , Cardiotoxicity/epidemiology , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Doxorubicin/therapeutic use , Drug Administration Schedule , Female , Hand-Foot Syndrome/epidemiology , Hand-Foot Syndrome/etiology , Humans , Middle Aged , Neutropenia/chemically induced , Neutropenia/epidemiology , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Polyethylene Glycols/therapeutic use , Taxoids/therapeutic use , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Treatment Outcome , Vinblastine/analogs & derivatives , Vinblastine/therapeutic use , Vinorelbine
3.
Anticancer Res ; 36(6): 2631-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27272771

ABSTRACT

BACKGROUND: Bone is a frequent site of metastases in advanced cancer and is associated with significant skeletal morbidity. Current treatment options are aimed at preserving and improving functional independence and quality of life. MATERIALS AND METHODS: A review of current literature focusing on diagnostic tools and treatment approaches of bone metastasis in advanced cancer was performed and conclusions were incorporated into diagnostic and treatment algorithms. RESULTS: Radiologic imaging has added valuable tools for screening and diagnostics of bone metastasis. Clinical management of skeletal metastasis includes improved pain management, introduction of bone modifying agents and advancements in surgical and radiation therapy. We propose three algorithms enhancing the sensitivity of diagnostics and improving multidisciplinary management of vertebral and non-vertebral bone metastasis. CONCLUSION: Bone metastases are an expression of a systemic disease. Treatment options include highly specialized modalities yet need to be tailored to individual needs. Algorithms help standardize treatment procedures and can improve treatment outcome in a multidisciplinary setting.


Subject(s)
Bone Neoplasms/therapy , Algorithms , Bone Neoplasms/diagnosis , Bone Neoplasms/pathology , Humans , Neoplasm Metastasis
4.
Eur J Haematol ; 95(6): 498-506, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25598394

ABSTRACT

For patients with refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (alloSCT) represents the only curative approach. We here analyzed the long-term outcome of 131 consecutive patients with active AML, which was either primary refractory or unresponsive to salvage chemotherapy, transplanted at our center between 1997 and 2013. After a median follow-up of 48 months for the surviving patients, disease-free survival (DFS) at 5 yr post alloSCT was 26% (94% CI: 17-35). Relapses, most of which occurred within the first 2 yr from transplant, were the predominant cause of treatment failure affecting 48% (95%CI: 40-58) of patients, whereas non-relapse mortality was 26% (95%CI: 20-36) at 5 yr and thereafter. A marrow blast count ≥20% before alloSCT was an independent prognosticator associated with an inferior DFS (HR: 1.58, P = 0.027), whereas the development of chronic graft-versus-host disease (cGvHD) predicted an improved DFS (HR 0.21, P < 0.001) and a decreased relapse incidence (HR: 0.18, P = 0.026), respectively. These results indicate that alloSCT represents a curative treatment option in a substantial proportion of patients with refractory AML. A pretransplant blast count <20% before alloSCT and the development of cGvHD are the most important predictors of long-term disease control.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Retrospective Studies , Salvage Therapy , Tissue Donors , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome , Young Adult
5.
Eur J Haematol ; 94(5): 431-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25220715

ABSTRACT

For patients with acute myeloid leukemia (AML) early achievement of remission during induction treatment is an important predictor for long-term outcome irrespective of the type of consolidation therapy employed. Here, we retrospectively examined the prognostic impact of early remission (ER) vs. delayed remission (DR) in a cohort of 132 AML patients with an intermediate-risk karyotype undergoing allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1). In contrast to patients showing DR, patients achieving ER had a significantly higher 3-yr overall survival (OS) and disease-free survival (DFS) of 76% vs. 54% (P = 0.03) and 76% vs. 53% (P = 0.03). Likewise, 3 yr after alloSCT the cumulative incidence of relapse (CI-R) was significantly lower in the ER subgroup as compared to patients achieving DR, that is, 10% vs. 35% (P = 0.004), whereas non-relapse mortality (NRM) did not differ significantly. Multivariate analysis identified DR as an independent prognosticator for an inferior DFS (HR 3.37, P = 0.002) and a higher CI-R (HR 3.55, P = 0.002). Taken together, these data may indicate that the rapid achievement of remission predicts a favorable outcome in patients with intermediate-risk AML undergoing alloSCT in CR1. In turn, the adverse effect of DR may not be fully overcome by alloSCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Induction Chemotherapy , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Adult , Aged , Antineoplastic Agents/therapeutic use , Female , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Multivariate Analysis , Recurrence , Remission Induction , Retrospective Studies , Survival Analysis , Time Factors , Transplantation, Homologous , Treatment Outcome
6.
Breast Care (Basel) ; 6(6): 441-445, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22419897

ABSTRACT

BACKGROUND: Thrombotic microangiopathy (TMA) is defined as thrombocytopenia and microangiopathic hemolytic anemia. Cancer-associated TMA, a rare but fatal condition, seems an entity distinct from classical thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS). PATIENTS AND METHODS: All patients with breast cancer-associated TMA treated at our institution between 2003 and 2008 were analyzed retrospectively. To elucidate pathophysiological mechanisms, we measured the serum activity of the metalloprotease ADAMTS13. RESULTS: 8 patients were identified. All showed bone marrow infiltration of breast cancer as well as thrombocytopenia, schistocytes, and hemolytic anemia. ADAMTS13 activity was mildly decreased in 4/6 patients (20-108%, normal range 30-120%), but none showed severely low levels as is characteristic of classical TTP. 6 patients were treated with anthracycline-containing fractionated chemotherapy, 5/6 patients experienced partial response. Overall survival was 13 months. Fractionated chemotherapy was well tolerated. CONCLUSIONS: Cancer-associated TMA has an underlying mechanism different from classical TTP. While bone marrow infiltration might be of major relevance, ADAMTS13 deficiency seems to be an epiphenomenon. Fractionated chemotherapy resulted in higher remission rates and comparatively long survival.

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