[GUIDELINES FOR DIAGNOSIS AND TREATMENT OF PATIENTS WITH MYELODYSPLASTIC SYNDROME].

Myelodysplastic syndrome Working Group of the Croatian Cooperative Group for Hematologic Diseases (CROHEM), Referral center of the Ministry of Health of the Republic of Croatia for diagnostics and treatment of MDS, as well as the Croatian Society for Haematology of the Croatian Medical Association have made Croatian guidelines for diagnosis and treatment of myelodysplastic syndrome (MDS). MDS is a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplasia, cytopenia and risk of transformation to acute myeloid leukemia (AML). Diagnosis is based on morphological characteristics of hematopoietic cells supplemented with the cytogenetic analysis and bone marrow flow cytometry. Due to great differences in the natural course of the disease, i.e. time to progression to AML and the expected time of survival several scoring systems have been developed to determine the disease risk. The treatment of patients with MDS is based on the risk factors of the disease as well as the individual risk of treatment.

Is there any Role for Splenectomy in Adulthood Onset Chronic Immun e Thrombocytopenia in the Era of TPO Receptors Agonists? A Critic al Overview.

BACKGROUND: Immune thrombocytopenia (ITP) in adulthood is characterized by chronic relapsing course. Despite the efficacious first line treatment (corticosteroid, intravenous immunoglobulin), majority of patients will enter the chronic phase warranting another treatment approach. Until recently, splenectomy performed in ITP chronic phase represented the standard of care with longterm remissions in more than 70% of patients, but it has never been tested in clinical trials. However, with the advances of our understanding of ITP pathophysiology and the shifting focus on megakaryocyte impairment, novel drugs were introduced in the treatment paradigm, mainly trombopoietin receptor agonists (TPO-RAs); romiplostim and eltrombopag. METHODS: These TPO-RAs were tested in randomized controlled trials resulting in adequate platelet response with few side effects and less need for additional therapy leading to approval of corresponding regulatory agencies and wide acceptance by hematological community, but however TPO-RAs must be taken continuously to maintain the response. With their onset, the rate of splenectomy in chronic ITP has diminished in modern era. CONCLUSION: The main aim behind conducting this review is to evaluate the pros and cons of splenectomy compared to TPO-RAs treatment in order to provide the critical overview which may help the practicing clinician in managing often challenging cases of chronic ITP.

Alterations within the Osteo-Hematopoietic Niche in MDS and their Therapeutic Implications.

Hematopoietic and mesenchymal stem and progenitor cells are organized in the osteo-hematopoietic niche, a complex microenvironment ensuring self-renewal and differentiation. Perturbations of the niche architecture, the mutual cellular interactions and signaling pathways disrupt tissue homeostasis resulting in cytopenia and malignant diseases such as myelodysplastic syndromes (MDS), supporting the concept of niche-induced oncogenesis. Analyzing the available treatment options for patients harboring MDS, it becomes evident that many of them specifically modify components of the stem cell niche. Hereby especially compounds inhibiting the TGF-ß superfamily seem to represent a promising novel approach for patients with anemia as a result of ineffective erythropoiesis. Moreover, apart from affecting tumorigenesis, these drugs appear to influence bone structure and function as well as hematopoiesis in elderly MDS patients with a disturbed microarchitecture of the bone marrow. In the present review we will dissect the contribution of components of the stem cell niche for the pathogenesis of MDS and discuss current therapeutic strategies targeting components of the niche, focusing on the modulation of TGF-ß signaling.

[CURRENT APPROACH TO NON-HODGKIN MANTLE CELL LYMPHOMA: LITERATURE REVIEW].

Mantle cell lymphoma (MCL) represents the fourth most common type of non-Hodgkin lymphomas. It is characterized by aggressive course and frequent relapses. The main aim of this review is to evaluate current treatment approach towards this type of lymphoma. In younger patients the chemotherapy including high doses of cytarabine is the gold standard. In case of complete or partial remission, the consolidation with autologous stem cell transplantation is indicated as consolidation approach. In older patients CHOP-R regimen is not the treatment of choice. These patients should be treated with bendamustine in combination with rituximab. In case of complete or partial remission, further therapy with rituximab maintenance as consolidation represents an option. The vast majority of patients with MCL will ultimately relapse which poses a challenge in treatment approach. The approach in relapsed MCL can be divided in two types: chemotherapy or biologic therapy. In young fit patients chemotherapy based on bendamustine and cytarabine is a reasonable option. In patients with comorbidities or poor performance status biologic agents are reasonable options. Ibrutinib, Bruton kinase inhibitor, is characterized by highest overall response rate and the longest duration of response and should be offered to these patients. With the development of novel potent inhibitor of B cell receptor signaling pathway, these agents may become the gold standard in future and introduce the treatment of MCL in "chemo-free"era.

[Wounds in hematology patients]. / Rane kod hematoloskih bolesnika.

Hematology patients can have wounds as part of the initial presentation of the disease, as a result of infection or therapy.Wound therapy is very important and requires multidisciplinary approach of the hematologist, surgeon, dermatologist, and all other medical staff involved in the patient's care. It is very important to provide aseptic care and prevent infections that could complicate the patient's recovery and cure. It is very important to recognize the wound with malignant infiltration because an appropriate chemotherapy can be curative.

Acute graft versus host disease after orthotopic liver transplantation.

Graft versus host disease (GVHD) is an uncommon complication after orthotopic liver transplantation (OLT) with an incidence of 0.1-2%, but an 80-100% mortality rate. Patients can present with skin rashes, diarrhea, and bone marrow aplasia between two to eight weeks after OLT. Diagnosis of GVHD is made based on clinical and histologic evidence, supported by chimerism studies showing donor HLA alleles in the recipient bone marrow or blood. Several therapeutic approaches have been used for the management of GVHD after OLT including increased immunosuppression, decreased immunosuppression, and cellular therapies. However, success rates have been low, and new approaches are needed.

[Extramedullary multiple myeloma of the colon--case presentation and literature review]. / Ekstramedularna infiltracija kolona u bolesnika s multiplim mijelomom--prikaz bolesnika i pregled literature.

Multiple myeloma with gastrointestinal infiltration is rare, and it has been usually described in some case reports or case series. Stomach and small intestine are mostly involved, while large bowell involvement is very rare. Multiple myeloma should be considered in the differential diagnosis of some other diseases of the large bowel associated with weight loss, diarrhoea, malabsorption, frequent lumbar pain, effort intolerance. Colonoscopic biopsy followed by histopathological examination is essential for the diagnosis of multiple myeloma. Multiple myeloma with extramedullary infiltration of the colon has no well defined treatment guideline. Localised infiltration of gastrointestinal tract could be treated by surgical resection, but as these tumors are radiosensitive, radiotherapy has also been used. Chemotherapy with pulsed dexamethasone and afterwards a combination of cyclophosphamide, vincristine, melphalan and prednisone has been described in some case studies. Some patients were treated with other therapies incuding thalidomide, bortezomib, autologous or allogeneic stem cell transplantation. The clinical presentation, diagnosis and therapy may be challenging, so we present a 66-year old patient with extramedullary multiple myeloma of the colon who was treated at our Department.

[Multiple myeloma in a patient with chronic lymphocytic leukemia--case report and literature review]. / Multipli mijelom u bolesnika s dugogodisnjom kronicnom limfocitnom leukemijom--prikaz bolesnika i pregled literature.

The occurrence of B-cell chronic lymphocytic leukemia (B-CLL) and another B-cell neoplasm in the same patient is a rare event and is mostly described in the literature as single case reports. In most cases reported in the literature, CLL was diagnosed several years before multiple myeloma. Some patients were only observed for CLL without therapy, whereas others had already been treated for CLL when the diagnosis of myeloma was established. Some authors came to a conclusion that therapy used for treating CLL can induce some secondary neoplasms, like multiple myeloma. We present a male patient who was diagnosed with multiple myeloma 11 years after B-CLL had been diagnosed. Two hematologic neoplasms in one patient could be a diagnostic problem, but also a therapeutic challenge.

[Acute renal failure as first manifestation of B-CLL]. / Akutno zatajenje bubrega kao prva manifestacija kronicne limfocitne leukemije.

In December 2005, the 55-year-old patient was hospitalized because of acute kidney failure and suspected hemorrhagic fever. The physical examination showed splenomegaly (spleen ultrasound-18 cm in large diameter, and 11 cm by palpation) with thrombocytopenia and anemia. He underwent kidney biopsy which described infiltration of small B cell lymphocytes with positive lambda chains. His bone marrow showed infiltration of atypical lymphocytes, and flow cytometry was typical of B-cell CLL. Patient started therapy with corticosteroids (methylprednisolone 80 mg iv) and continued treatment with prednisone (Decortin 20 mg tablets) and chlorambucil (Leukeran 16 mg tablets) through three days. An addition to therapy lead to an increase in platelet count, creatinine level decline and recovery of renal function was observed. He was treated with 6 cycles of therapy with prednisone and chlorambucil and achieved a satisfactory therapeutic effect with adequate hematologic parameters and less severe splenomegaly. Maintenance therapy was continued with prednison at daily dose of 10 mg. Our patient is one of the amongst previously reported as an example of a rare complication of CLL'with leukemic infiltrate causing acute renal insufficiency. Renal biopsy is necessary to confirm the diagnosis. This complication appears to respond well to a variety of treatments. Our patient achieved complete resolution of renal failure and partial hematological response with combination of chlorambucil and prednisone.

[Billateral pleural effusion as first manifestation of multiple myeloma]. / Bilateralni pleuralni izljev kao prva manifestacija multiplog mijeloma.

Multiple myeloma is clonal malignancy of plasma cells with overproduction of monoclonal antibodies and destruction of bones. Hypercalcemia, anemia and renal disfunction are common manifestations of the disease. Billateral pleural effusion is rare multiple myeloma presentation with unfavorable prognosis so it is important to recognizze it for better diagnostic and therapy approach. 59-year old woman was admitted to Hematology Department with history of severe caugh, dyspnea and left chest pain. Physical examination and chest X-ray showed billateral pleural effusion while cytologic examination of pleural aspirate found plasma cells. Bone marrow examination and skeleton X-ray confirmed diagnosis of multiple myeloma. Serum and urine immunoelectrophoresis detected lambda Bence Jones protein. This case is rare manifestation of multiple myeloma.