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Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy. Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing any second cancer 25-30 years after the diagnosis, resulting in a cumulative incidence of 16-23% at that time. The risk for secondary solid tumors can be mainly attributed to radiotherapy. There is strong evidence of an increasing risk for secondary solid tumors with time since treatment. Tumor-specific analysis of the risk for second cancers revealed statistically significant excesses for stomach, pancreas, bladder, rectum, prostate, and kidney cancer, as well as for cancer of the thyroid, melanoma, sarcomas, and non-Hodgkin's lymphoma. No significantly elevated risk for secondary solid tumors was observed after treatment with chemotherapy alone. The risk of secondary leukemia was associated with both radiotherapy and in particular with chemotherapy. In recent clinical surveys of patients with testicular cancer, estimates of the risk of leukemia after chemotherapy have ranged from 10- to 300-fold. An elevated risk was observed within the first two decades after diagnosis, later the risk was as expected in the normal population. Etoposide seems to be leukemogenic, especially at cumulative doses higher than 2 g/m2, although the effects of dose and schedule as well as the effects of other cytotoxic agents and radiotherapy remain to be finally clarified. Based on currently available data in patients with testicular cancer, it can be concluded that a significant elevated risk for the development of secondary leukemia exits after chemotherapy. However this risk does by far not outweigh the therapeutic benefit of etoposid-based therapy in patients with germ cell tumors. Secondary Raynaud's phenomenon is the main late vascular toxicity affecting about one third of patients after curative chemotherapy for testicular cancer. Hypertension will occur in one fifths of the patients. The incidence of vascular toxicity appears to be lower following PEB-therapy compared to PVB-therapy and major vascular events seem to be rare. Other frequent symptomatic toxicities are ototoxicity and peripheral neuropathy. A major risk factor for the development of toxicity is the cumulative dose of cisplatin given. Alterations of gonadotropin levels and Leydig cell insufficiency persist in more than half of young patients cured from testicular cancer by cisplatin-based combination chemotherapy. Approximately one fourth of patients have low serum magnesium or phosphat levels, or elevated creatinine levels. These toxicities seldomly result in clinical symptoms. We conclude that 3-4 courses with bleomycin, cisplatin and etoposide in testicular cancer patients will only rarely lead to symptomatic impairment of organ functions and a decrease of quality of life. Germ cell cancers have served as a valuable model for the development of new treatment strategies contributing largely to defining the role of cisplatinum, etoposide and recently ifosfamide in medical oncology. However, germ cell cancer may also be a useful model for investigating the long term side effects of the oncological therapies. Thus, germ cell cancer is not only a "model for a curable neoplasm" (L.H. Einhorn) but can also be seen as a "model for the study of late sequelae of modern oncological therapies". [ABSTRACT FROM AUTHOR]

More and more follow-up care gets important in the treatment of oncological patients. In addition to detection of recurrent and secondary diseases, the focus should be put particularly on identifying and medicating sequelae associated with therapy. Anamnesis and clinical examination remain at the centre of follow-up treatment. Further contents of follow-up care are based on the disease situation, previous therapies and individual risk factors. For most entities there is no recommendation for routine radiological diagnosis in asymptomatic patients. However, imaging measures are indicated especially when symptoms require clarification. The increasing rate of oral long-term and permanent therapies implies new tasks in after-care. Here, potential side effects have to be registered specifically. Furthermore, treatment success should be monitored regularly., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

History and Admission Findings: We report the case of a 59-year-old male who was admitted to hospital with acute chest pain. Coronary heart disease was known from the medical history. The patient reported recurrent ostealgia and susceptibility for infection during the last months before admission., Investigations: A 75% stenosis of the circumflex branch was treated with a drug eluting stent. Platelet aggregation was inhibited with acetylsalicylic acid and clopidogrel. Due to persisting ostealgia and inflammatory state, spondylodiscitis was excluded in MRI. However, platelets remained low after successful treatment of the infection., Diagnosis, Treatment and Course: Bone marrow biopsy revealed an acute lymphoblastic leukemia with positive detection of the Philadelphia chromosome. After chemotherapy and allogenic hematopoietic cell transplantation the patient remains in remission of his acute lymphoblastic leukemia., Conclusions: Especially in patients with documented history of coronary heart disease, the differential diagnosis of chest pain can be challenging. In this case, the chest pain was based on a subacute coronary ischemia as well as on proliferation of the acute lymphoblastic leukemia. The management of dual oral anticoagulation was performed with higher transfusion limits for thrombocytes and continuous application of thrombocyte aggregation inhibitors., (© Georg Thieme Verlag KG Stuttgart · New York.)

Unlabelled: MEDICAL HISTORY AND CLINICAL COURSE: A 42-year-old patient with hairy cell leukemia had been treated for 3 years by a hematologist in private practice. Initially the patient received 1 course of cladribine upon which the disease went into complete remission. 6 weeks ago a relapse was diagnosed and combination therapy with cladibrin and rituximab was initiated. Now the patient presented to the emergency room with shortness of breath and pain when breathing., Investigations, Treatment and Course: In the chest x-ray, patchy infiltrates and pleural effusions were found on both sides. The subsequently performed computed tomography showed bilateral compactions with an Halo suspicious for fungal infiltrates. Upon admission to the hospital, an empirical antibiotic therapy with clarithromycin and piperacillin/tazobactam was initiated, which was later escalated to meropenem and linezolid. Additionally, an antifungal therapy with voriconazole was started and later switched to liposomal amphotericin B. At his admission, a positive aspergillus antigen could be detected in the microbiological laboratory. Under antimycotic treatment the aspergillus antigen was repeatedly negative. The patient presented with pronounced cytopenias and after a switch of therapy to vemurafenib and filgrastim, the hematopoiesis could only be stimulated insufficiently. The patient was transferred to the intensive care unit three days after admission with severe respiratory failure. He died on day 8 after admission. AUTOPSY AND DIAGNOSIS: Diagnosis was consistent with relapse of hairy cell leukemia with positive BRAF mutation and a bone marrow infiltration > 80 %. Autopsy revealed a significant hepato-splenomegaly, a lack of erythro-, granulo- and thrombopoiesis. Clots interspersed with fungal hyphae were found in both lungs and an infarction of the spleen with evidence of fungal hyphae was detected. The cultural findings post mortem on yeast or mold were negative., Conclusion: Patients with refractory hairy cell leukemia and prolonged neutropenia are at increased risk for systemic fungal infections. Therefore, prohylactic antimycotic therapy should be considered early in this group of patients. The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. In the present case, the patient could unfortunately not be stabilized due to the septic complications., (© Georg Thieme Verlag KG Stuttgart · New York.)

History and Admission Findings: We report on the case of a young women presenting with macrohaematuria, petechiae and strong headaches., Investigations: Laboratory showed a thrombotic microangiopathy with helmet cells, increased LDH levels (>600 U/l), and thrombocytopenia (<40,000/μl)., Diagnosis, Treatment and Course: Due to strong haemolytic activity and headache with blurred vision, immediate plasma separation with fresh frozen plasma was commenced. Markedly decreased ADAMTS13 activity and detection of anti-ADAMTS13 antibodies were consistent with the diagnosis of idiopathic thrombotic thrombocytopenic purpura. In total, 11 plasma separations were required to stop disease activity. In parallel, immunosuppressive therapy using glucocorticoids was initiated. The patient was discharged from the hospital in a good general condition and with normalized laboratory findings 26 days after hospitalization., Conclusions: All patients with anemia and thrombocytopenia should be tested for haemolysis and helmet cells. An early diagnosis and initiation of necessary therapy are determining for the clinical outcome., (© Georg Thieme Verlag KG Stuttgart · New York.)

History and Admission Findings: We report on a 24-year-old male patient who presented with worsening of the general condition and abdominal pain., Investigations: On physical examination, gynecomastia was noted. Laboratory tests showed manifest hyperthyroidism. The beta-hCG levels were markedly increased. By ultrasound, the thyroid gland was hyperperfused without thyroid nodules. Several large echo mixed lesions were found in the liver. The testes appeared normal., Diagnosis: In light of the typical laboratory findings, a non-seminomatous extragonadal germ cell tumor was diagnosed. Hyperthyroidism was most probably HCG induced., Treatment and Course: Initially the patient was treated with thyreostatic drugs. After initiation of chemotherapy and a marked decrease in beta-hCG, thyreostatic therapy could be terminated., Conclusions: Germ cell tumors may cause an increase in beta-hCG concentration. By cross-reacting with the TSH-receptor this could induce hyperthyroidism. Germ cell tumors are therefore a rare differential diagnosis of hyperthyreoidism., (© Georg Thieme Verlag KG Stuttgart · New York.)

History and Admission Findings: We report on a 65-year-old female patient with a recent diagnosis of adenocarcinoma of the sigmoid colon and massive hematochezia in the context of a general bleeding disorder., Investigations: Disseminated malignant disease with hepatic metastases as well as bone marrow involvement was demonstrated. Moreover, circulating tumor cells were demonstrated by flow cytometry. The patient had right lower quadrant abdominal pain due to a spontaneous psoas intramuscular hematoma., Diagnosis, Treatment and Course: At the time of admission to our hospital, the patient displayed microangiopathic hemolytic anemia and secondary hyperfibrinolysis with a pronounced bleeding tendency. Moreover, there was an acute renal failure which improved with fluid resuscitation. With immediate chemotherapy consisting of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX regimen) and cetuximab initiated with the second course, plasmatic coagulation could be stabilized. Consequently, treatment with tranexamic acid, fibrinogen, fresh frozen plasma as well as red blood cell and platelet infusions could be stopped. Continuation of chemotherapy was possible on an outpatient basis and the further course was associated with a good quality of life until her near end. The patient died at home 7 months after initial diagnosis of her colon cancer due to progressive disease with CNS metastases., Conclusions: Disseminated intravascular coagulation with microangiopathic hemolysis and secondary hyperfibrinolysis is a rare albeit possible event in disseminated colorectal cancer, especially when the bone marrow is involved. Treatment of the underlying cause is the most important therapeutic measure., (© Georg Thieme Verlag KG Stuttgart · New York.)

History and Admission Findings: A 27-year-old male patient with a past medical history of HIV presented with acute myeloid leukemia for allogeneic hematopoietic stem cell transplantation (HSCT). Highly active anti-retroviral therapy suppressed the viral load below detection threshold., Investigations: There were no contraindications for allogeneic HSCT., Treatment and Course: Myeloablative conditioning consisted of total body irradiation and cyclophosphamide. Anti-thymocyte globulin, tacrolimus and mycophenolate mofetil were used for immunosuppression. Combined anti-retroviral therapy (nucleoside and nucleotide analog reverse-transcriptase inhibitor, boostered protease inhibitor, maraviroc and raltegravir) was maintained for allogeneic HSCT and viral load remained below detection threshold. No graft-versus-host disease or serious infectious complications occurred. The patient showed good graft function with stable hematopoiesis. Localized Kaposi's sarcoma was diagnosed six months after allogeneic HSCT and treated successfully with surgical excision and reduction of immunosuppression. Almost one year after allogeneic HSCT, the CD4+ cell count is rising and viral load remains below detection threshold with combined anti-retroviral therapy., Conclusion: Allogeneic HSCT can be safely performed in HIV positive patients. Kaposi's sarcoma is a rare event after allogeneic HSCT and linked to strong immunosuppression.

Numerous epidemiological studies have demonstrated an association between increased risk of cancer development and progression and type 2 diabetes mellitus as well as obesity. The underlying mechanisms remain elusive, but hyperinsulinaemia in the presence of insulin resistance appears to be an important factor. Hyperinsulinaemia may favour tumorigenesis, as insulin has not only metabolic actions, but is also mitogenic at high concentrations. Besides, susceptibility of tumour cells against insulin may be increased due to changes in the insulin receptor profile. A diabetes therapy with insulin or sulfonylureas, which leads to elevated exogenous or endogenous insulin levels, appears to be related with an increased cancer risk, whereas administration of metformin or thiazolidinediones, which is associated with a decrease of insulin concentrations, results in risk reduction. However, in light of the numerous epidemiological studies showing an association between increased cancer risk and reduced physical activity one cannot exclude that hyperinsulinaemia in the presence of insulin resistance is only a surrogate parameter of reduced physical activity. In the past years, several insulin analogues have been developed which may have altered mitogenic actions compared to human insulin due to their structural changes. For the long-acting analogue insulin glargine, in vitro data, though controversial, pointed to an increased mitogenicity that was, however, not confirmed by in vivo studies. Recently, six clinical studies have been published that analysed the association between the application of insulin glargine (Lantus) and cancer development. The current clinical data do not allow the conclusion that treatment with insulin glargine is associated with increased cancer risk. On the other hand, prospective studies that exclude an impact on cancer risk in risk populations are currently not available. Future studies are required to investigate whether a subpopulation characterised by a less rapid metabolization of insulin glargine in vivo may be at increased cancer risk. In the present article, we give an overview on the association between diabetes mellitus, its treatment with insulin analogues, and cancer.

History and Admission Findings: We report on a 47-year-old male patient who was admitted for exercise-induced dyspnea and easy fatigability. Physical examination revealed reduced breath and percussion sounds of the left basal lung., Investigations: Laboratory investigations revealed leucocytosis and elevated C-reactive protein levels. Chest X-ray showed an area of increased opacity of the left lower hemithorax. Computed tomography (CT) confirmed an encapsulated, septated pleural effusion. The aspirate was purulent with abundant neutrophil granulocytes and a pH value of 7.1., Diagnosis, Treatment and Course: A diagnosis of left-sided pleural empyema was made, most probably following pneumonia. Antibiotic treatment with amoxicillin and clavulan acid was initiated and after insertion of a chest drain pleural irrigation with daily 200,000 I.U. streptokinase was performed for five days. The drainage was removed after ten days and after four months CT showed a complete remission of the lef-sided pleural empyema., Conclusions: Parapneumonic effusions are frequent with broad clinical range from trivial to life-threatening. Therapy decision is based on the characteristics of the effusion and the patient's clinical status and should be made within an interdisciplinary cooperation between internists and (thoracic) surgeons.

History and Admission Findings: A 56-year-old woman presented with progressive dyspnea and polyneuropathia. Medical history revealed a bronchial asthma and hypertension. She was in a reduced general condition and had to be admitted to the intensive care unit for mechanical ventilation the same day., Investigations: The computed tomography of the chest revealed distinct pulmonary infiltrates. Laboratory findings showed significantly elevated inflammatory markers as well as an eosinophilia in the differential blood count and the bronchial lavage. Diagnostics for infections were all negative as were antinuclear and anti-neutrophil cytoplasmatic antibodies (ANCAs)., Diagnosis, Treatment and Course: An ANCA negative Churg Strauss Syndrome (CSS) was diagnosed in accordance with extravascular and blood eosinophilia, pulmonary infiltrates and the neurological symptoms. Aggressive therapy with high dose glucocorticosteroids and cyclophosphamide (CYC) pulses was initiated. The patient improved rapidly and was extubated 6 days after the initiation of treatment. After 6 cycles of CYC with 750 mg/m2 and a maintenance treatment with azathioprine and 5mg prednisolone the patient is still in complete remission 2,5 years after the diagnosis., Conclusion: The CSS belongs to the ANCA-associated vasculitides. The patient described here presented with all the characteristic organ involvements of CSS and a fulminate worsening. The fast diagnosis and aggressive therapy which was started only hours after admission to the intensive care unit induced a long lasting remission., (Copyright (c) Georg Thieme Verlag KG Stuttgart--New York.)

Transplantations of autologous or allogeneic stem cells from bone marrow or peripheral blood are preformed for the treatment of resistant autoimmune diseases. Data have been systematically collected since 1996. We describe the historical development of this procedure for autoimmune diseases, the possible mechanisms of action, the options for stem cell collection, purging and conditioning (high-dose chemotherapy, combination with monoclonal anti-T- or B-cell antibodies, total body irradiation), as well as the reported outcomes in the literature.

Colorectal carcinoma is the second common cause of death from cancer. For a long period patients with metastatic disease were considered incurable except for a small subgroup with isolated surgically complete removable lesions in the lungs and the liver. Chemotherapy was a treatment of unproven value, beneficial in very few patients. However, in the last two decades it has become a well-documented survival prolonging treatment, postponing tumor symptoms in the majority of patients, and potentially curing some patients if combined with aggressive surgery.

More than 50% of patients with pancreatic or biliary tract cancer are diagnosed in advanced and curatively unresectable tumor stages. To date, chemotherapeutic treatment yielded disappointing results in these patients with 5-year survival rates of 0-15%, leading to therapeutic nihilism in many patients. However, with the availability of new cytostatic agents as well as the introduction of the novel clinical endpoint "clinical benefit response" at least some improvements may be possible in patients with pancreatic cancer. Several randomized studies have shown a clinical and survival benefit for patients treated with chemotherapy as compared to patients treated with best supportive care alone. Gemcitabine was the first agent, which was investigated for its potential to improve symptoms as well as overall well being. A significant clinical benefit response can be achieved in up to 40% of patients with advanced pancreatic cancer. Gemcitabine is currently also investigated in combination chemotherapy regimens. First results with combination chemotherapy regimens such as cisplatin/gemcitabine have shown promising results. In addition, taxanes such as docetaxel also appear to have a certain activity in patients with pancreatic cancer. In contrast, topoisomerase I-inhibiting drugs seems to have no efficacy in the treatment of this disease. New and experimental therapeutic options such as angiogenesis-inhibition, matrixmetalloproteinase-inhibition or the use of monoclonal antibodies are currently evaluated within clinical studies. Only a few small studies reporting about chemotherapy in patients with biliary tract cancer have been published. This is mainly due to the rarity of this tumor entity, but also due to the rapid onset of symptoms such as hyperbilirubinemia, which will limit the number of potentially available drugs. 5-FU is the most widely investigated drug inducing remissions in 10-15% of patients. It is unclear whether new agents such as gemcitabine or the taxanes will led to an improvement of the prognosis of these patients. Although the recent advances in the treatment with these new therapeutic options are far from being satisfactory, it appears that a first small step ahead has been made the treatment of these diseases.

Purpose: Methodological work was performed in the field of magnetic resonance imaging (MRI) and spectroscopy (MRS) in order to develop suitable tools for non-invasive characterization of hematopoietic bone marrow. The methods were applied for the assessment of normal values in healthy persons and to examine patients with generalized hematological diseases or to monitor effects of therapies influencing the composition of bone marrow., Methods: Besides standard techniques of MRI as T1- or T2-weighted methods, chemical shift techniques for selective visualization of water or lipid components were applied. The method of magnetization transfer (MT) contrast was used with the intention to differentiate between multiple water containing tissue compartments (intra- vs. extracellular space). A further approach was the determination of the magnetic field distribution within spongy bone marrow. Besides investigations in healthy volunteers, prospective clinical studies were carried out in patients suffering from acute leukemia during their initial treatment and in patients who underwent high-dose therapy with following peripheral blood stem cell transplantation (PBSCT)., Results: Especially MR techniques for selective imaging of water of fat signals and proton spectroscopy yielded a high sensitivity to primarily pathological or therapeutically induced changes of hematopoietic bone marrow. Application of MT allowed an improved differentiation of the tissue compartments under PBSCT, which might result in temporary edema. Storage of hemosiderin in bone marrow after blood transfusions and simultaneous hematopoietic insufficiency could be revealed by methods sensitive to magnetic field inhomogeneities., Conclusions: Methods of MRI and MRS allow to non-invasively characterize hematopoietic bone marrow in the course of hematological diseases and during therapy. Marked changes in the composition of hematological bone marrow are detectable for extensive marrow areas. The prognostic relevance of the findings has to be evaluated in future follow-up studies.

Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy. Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing any second cancer 25-30 years after the diagnosis, resulting in a cumulative incidence of 16-23% at that time. The risk for secondary solid tumors can be mainly attributed to radiotherapy. There is strong evidence of an increasing risk for secondary solid tumors with time since treatment. Tumor-specific analysis of the risk for second cancers revealed statistically significant excesses for stomach, pancreas, bladder, rectum, prostate, and kidney cancer, as well as for cancer of the thyroid, melanoma, sarcomas, and non-Hodgkin's lymphoma. No significantly elevated risk for secondary solid tumors was observed after treatment with chemotherapy alone. The risk of secondary leukemia was associated with both radiotherapy and in particular with chemotherapy. In recent clinical surveys of patients with testicular cancer, estimates of the risk of leukemia after chemotherapy have ranged from 10- to 300-fold. An elevated risk was observed within the first two decades after diagnosis, later the risk was as expected in the normal population. Etoposide seems to be leukemogenic, especially at cumulative doses higher than 2 g/m2, although the effects of dose and schedule as well as the effects of other cytotoxic agents and radiotherapy remain to be finally clarified. Based on currently available data in patients with testicular cancer, it can be concluded that a significant elevated risk for the development of secondary leukemia exits after chemotherapy. However this risk does by far not outweigh the therapeutic benefit of etoposid-based therapy in patients with germ cell tumors. Secondary Raynaud's phenomenon is the main late vascular toxicity affecting about one third of patients after curative chemotherapy for testicular cancer. Hypertension will occur in one fifths of the patients. The incidence of vascular toxicity appears to be lower following PEB-therapy compared to PVB-therapy and major vascular events seem to be rare. Other frequent symptomatic toxicities are ototoxicity and peripheral neuropathy. A major risk factor for the development of toxicity is the cumulative dose of cisplatin given. Alterations of gonadotropin levels and Leydig cell insufficiency persist in more than half of young patients cured from testicular cancer by cisplatin-based combination chemotherapy. Approximately one fourth of patients have low serum magnesium or phosphat levels, or elevated creatinine levels. These toxicities seldomly result in clinical symptoms. We conclude that 3-4 courses with bleomycin, cisplatin and etoposide in testicular cancer patients will only rarely lead to symptomatic impairment of organ functions and a decrease of quality of life. Germ cell cancers have served as a valuable model for the development of new treatment strategies contributing largely to defining the role of cisplatinum, etoposide and recently ifosfamide in medical oncology. However, germ cell cancer may also be a useful model for investigating the long term side effects of the oncological therapies. Thus, germ cell cancer is not only a "model for a curable neoplasm" (L.H. Einhorn) but can also be seen as a "model for the study of late sequelae of modern oncological therapies".

With an annual incidence rate of 30 to 40 per 100,000 colorectal carcinoma is the second most frequent malignancy in Germany. Despite the poor outcome of patients suffering from this disease important advances have been made in the standardisation and improvement of palliative and adjuvant treatment in patients with colorectal cancer. For the systemic chemotherapy 5-fluorouracil (5-FU) remains the most important cytotoxic agent and biomodulation of the therapeutic activity of 5-FU with methotrexate or particularly folinic acid has been clinically established, yielding response rates in 20 to 35% of patients. Current investigations of systemic treatment are aiming into three directions: 1. investigation of high-dose continuous (24-hours) 5-FU application (with or without modulation by folinic acid); 2. evaluation of new, effective cytotoxic agents, among which the camphotecin derivative CPT-11 (irenotecan) and the specific thymidilate synthase inhibitor Tomudex appear to be the most promising drugs as single agents and/or in combination with 5-FU; 3. use of orally available fluoropyrimidine derivatives with high bioavailability which may substantially improve the quality of life in palliative therapy. The postoperative adjuvant treatment of patients with Dukes C colorectal cancer is established clinical practice and the combination of 5-FU and levamisol given for one year will result in an improved overall survival of about 15% at five years compared to surgery alone. Although this regimen remains the current standard treatment, alternatives for the adjuvant treatment may be the use of 5-FU and folinic acid given for only half a year post surgery, locoregional perfusion of the liver with 5-FU alone via the portal vene by 7-day continuous application or the use of 17-1A monoclonal antibody immunotherapy after curative resection. Further improvement may be achieved by the combination of immunotherapy and chemotherapy which is currently tested in clinical studies. Future recommendations for the adjuvant treatment of colorectal cancer will not only be based on therapeutic efficacy but will also have to take costs of treatment into account. Better definition of high-risk patient groups for adjuvant treatment is needed.

Megakaryocytic progenitor cells only complete a limited number of mitotic events; early in megakaryopoiesis, these cells loose their capacity for cell division and acquire the ability for endoreduplication--a phenomenon that is unique to the megakaryocytic lineage. There is growing evidence, that at least two humoral activities affect proliferation of progenitor cells and maturation of its progeny. However, the cytokines that mediate these functionally defined, overlapping activities are not yet precisely known. This review summarizes current understanding of these processes and will discuss the interactions of megakaryocytic cells with the bone marrow microenvironment as well as their role in disorders of hematopoiesis.

Effective hematopoiesis is a multistep phenomenon. It consists in the presence of pluripotent hematopoietic stem cells (HSC), their proliferation and self-maintenance, their differentiation into various committed lineages of specific progenitors, their orderly maturation into functional cells that are released into the circulation in an orderly fashion in response to the body's demand. Increasing numbers of hematopoietic factors are being purified to homogeneity and/or cloned. The availability of sufficient quantities of these regulators promises a new area for research into the physiology and pathophysiology of the hematopoietic system. The purpose of this overview is to consider some newly-developed concepts in the field of hematopoiesis, with regard to regulatory control mechanisms and cellular interactions.