[Rare diseases recognizable from blood smears]. / Seltene Erkrankungen am Blutbild erkennen.

The examination of peripheral blood smears is not only essential for the differential diagnostics of hematological diseases but can also provide important indications for general internal diseases, infections, hereditary diseases and poisoning. By the systematic analysis of a blood smear for alterations to thrombocytes, erythrocytes and leukocytes, a blood smear investigation can make a decisive contribution to the formulation of a diagnosis. In this way evidence of rare diseases can also be gained when taking the corresponding clinical findings into consideration.

Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation.

BACKGROUND: Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT) has a dismal prognosis with limited therapeutic options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental treatment alternative in this situation. Information on long-term outcome is not available. METHODS: We performed a long-term follow-up analysis of a previously reported cohort of 29 FLT3-ITD-positive AML patients, which were treated in relapse after allo-SCT with sorafenib monotherapy. FINDINGS: With a median follow-up of 7.5 years, 6 of 29 patients (21%) are still alive. Excluding one patient who received a second allo-SCT, five patients (17%) achieved sustained complete remissions with sorafenib. Four of these patients are in treatment-free remission for a median of 4.4 years. INTERPRETATION: Sorafenib may enable cure of a proportion of very poor risk FLT3-ITD-positive AML relapsing after allo-SCT.

[Complications after allogeneic bone marrow and stem cell transplantation]. / Komplikationen der allogenen Knochenmark- und Stammzelltransplantation.

Since the 1970s there has been an increase in the number of bone marrow and stem cell transplantations as well as a decrease in transplantation-associated fatalities due to improved transplantation techniques and supportive therapy. Annually nearly 50,000 transplantations are conducted worldwide with matched family grafts and matched or sometimes mismatched unrelated donor grafts. The number of long-term survivors is increasing and the late complications of this relatively aggressive therapy are now becoming apparent. This article is essentially concerned with the delayed complications of bone marrow and stem cell transplantations. Despite curing the malignant primary disease the total survival of transplantation patients is reduced. The main reasons are infection, organ dysfunction and therapy-associated secondary neoplasms. Among the high risk factors are total body irradiation, chronic graft versus host disease as well as treatment during childhood. Guidelines for the follow-up care of these long-term survivors were first published in 2006 and then updated in 2011.

[Side effects of tumor pharmacotherapy. What internists should know]. / Nebenwirkungen der medikamentösen Tumortherapie. Was Internisten wissen sollten.

Cytotoxic drugs have been used in the therapy of malignant tumors for the last 70 years. However, side effects of cytotoxic drugs are very common and often dose-limiting. Although many protocols have been optimized, side effects are still frequently life-threatening. Nausea and vomiting are among the most frequently reported side effects, in addition to mucositis and fatigue. Bone marrow toxicity can lead to neutropenic sepsis, thrombocytopenic bleeding, or anemia with the respective sequelae. In addition to these unspecific side effects, organ toxicity is class or drug specific and may involve the kidney, liver, heart, lung, skin, or central nervous system. As most protocols can be administered on an outpatient basis, knowledge of these side effects is important for the general internist.

[Sorafenib in relapsed and refractory FLT3-ITD positive acute myeloid leukemia: a novel treatment option]. / Sorafenib bei rezidivierter und therapierefraktärer FLT3-ITD-positiver akuter myeloischer Leukämie: eine neue Behandlungsoption.

BACKGROUND: The therapeutic options for relapsed or refractory FLT3-ITD positive AML are limited, particularly in case of a prior allogenic stem cell transplantation (SCT) or poor performance status. The clinical value of a targeted intervention using the FLT3-ITD-specific inhibitor sorafenib in this situation is largely unknown. PATIENTS AND METHODS: Between 2007 and 2010 eight patients (4 men, 4 women; age 40-75 years) with relapsed or refractory FLT3-ITD positive acute myeloid leukemia (AML) before (n=4) and after allogenic SCT (n=5) were treated off-label with sorafenib. RESULTS: All patients showed rapid hematological responses. There were three complete molecular remissions when sorafenib was given after allogenic SCT. Two of them are ongoing for 12 and 15 months, respectively. Long-term remissions after prior allogenic SCT were associated with the re-establishment of a chronic graft versus host reaction. Side effects could be controlled by dose reduction. CONCLUSION: Sorafenib is apparently an effective treatment alternative for patients with relapsed or refractory FLT3-ITD positive AML. In the context of a prior allogenic SCT it may have curative potential via inducing a synergism between targeted inhibition of FLT3-ITD and anti-leukemic immunity.

[General and special anaemia diagnostics]. / Allgemeine und spezielle Anämiediagnostik.

Worldwide, anaemia is one of the most frequent diseases. Its cause is obvious in many cases, especially with overt bleeding. Patients are often referred to many invasive but unnecessary diagnostic procedures. A diagnostic work-flow should enable clinicians to diagnose anaemia specifically and start the appropriate therapy, even in the case of rare causes. This article summarizes the necessary diagnostic procedures for anaemia.

Local irradiation prior to stem cell harvest has no influence on CD34+ yield: a quantitative analysis.

In patients with multiple myeloma, irradiation of bone marrow prior to mobilization of autologous peripheral blood progenitor cells (PBPCs) may lead to a reduced yield of CD34+ cells. Quantitative effects have not been sufficiently assessed. We retrospectively performed a multivariate analysis in 114 patients (67 men, 47 women) with multiple myeloma, of whom 53 (47%) patients had been irradiated prior to mobilization chemotherapy. High-dose cyclophosphamide followed by granulocyte colony-stimulating factor was used for mobilization in 84% of patients. In addition to previous chemotherapy, we quantitatively evaluated the dose and fractionation of prior irradiation, the volume of the irradiated bone marrow, and the time interval between radiation therapy and mobilization of PBPCs. The median volume of irradiated bone marrow was 9% (range 1-30%) of the estimated total hematopoietic bone marrow. The irradiated bone marrow volume and the number of CD34+ cells per kilogram of body weight in the first leukapheresis product showed no correlation. However, the time between irradiation and mobilization seemed to influence the yield of CD34+ cells. A comparison of irradiated patients with nonirradiated patients revealed no differences with respect to the CD34+ cell counts. We did not find a significant influence of the extent or the total dose of irradiation on the yield of CD34+ cells in the first leukapheresis product in patients with multiple myeloma. However, there may be an inverse correlation between the time elapsed since the last irradiation and the number of mobilized CD34+ cells.

Steroid-hormone receptors in cell lines and tumor biopsies of human lung cancer.

Female gender is a significant independent favorable prognostic factor in lung cancer. To study the possible role of sex hormones in lung cancer, the expression of sex-steroid receptors and the glucocorticoid receptor was investigated in 29 lung-cancer cell lines stemming from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) by means of immunocytochemistry, ligand-binding assays and RNA expression via polymerase chain reaction. In at least 2 methods of investigation, NSCLC cell lines showed a low expression of estrogen receptor in 6, progesterone receptor in 13 and androgen receptor in 12 out of 17 cases examined; sex-steroid-receptor expression was virtually absent in SCLC cell lines. The glucocorticoid receptor was expressed in all 29 cell lines studied. Additionally, 52 tumor samples from primary lung cancer were investigated for their receptor expression by means of immunohistochemistry. Among patients with primary lung-cancer sex-steroid-receptor expression in tumor biopsies was detected most frequently in female patients (in 69% of 16 cases, vs. 42% of 36 tumors from men) and in patients with adenocarcinoma. Further research will focus on these subgroups. Immunohistology is a feasible method of studying steroid-receptor expression in lung cancer.

Expression of insulin-like growth factor receptors I and II in normal human lung and in lung cancer.

Insulin-like growth factors are potent mitogenic factors in human lung cancer in vitro, acting via specific receptors. Using monoclonal antibodies we demonstrate the expression of insulin-like growth factor receptor I in bronchial epithelial cells of normal lung and in primary lung cancer (22/24 cases), being most prominent in squamous cell carcinoma. Electron microscopy on lung cancer cell lines reveals a distinct reaction pattern on the plasma membrane. Immunoreaction with a specific antibody directed against the insulin-like growth factor receptor II suggests a weak expression in primary lung cancer. Our findings underline the significance of the autocrine pathway of insulin-like growth factors in lung cancer.