How we manage the patient with hypereosinophilic syndrome?

Hypereosinophilic syndrome (HES) is a group of rare disorders characterized by marked and persistent blood hypereosinophilia and documented as an eosinophilia-attributable organ impairment. Discovery of some novel genetic abnormalities let to the categorization of HES patients into a common group of myeloid and lymphoid neoplasms with eosinophilia and recurrent gene rearrangements: platelet-derived growth factor receptor α and β (PDGFRA/B) and fibroblast growth factor receptor 1 (FGFR1). This classification, however, differs from that one proposed by Working Group for Eosinophilic Disorders in 2012. Namely, HES patients were divided into 3 variants: idiopathic, myeloproliferative (including cases with well-known gene rearrangements) and reactive (including lymphocytic HES). Despite the progress in diagnostic approach, especially in molecular testing, a vast majority of HES cases remain idiopathic. Except the PDGFRA/B-positive patients where tyrosine kinase inhibitor – imatinib mesylate – remains a treatment of choice, the therapy for other HES variants is somehow similar and includes steroids, hydroxyurea and interferon. The PDGFRA/B-positive population has an excellent prognosis with complete hematologic and molecular remissions achieved as 100% and >95% in imatinib-treated patients, respectively. The estimated probability of survival at 20 years for strictly defined idiopathic HES is found to be around 70%. The worst prognosis was demonstrated for cases with chronic eosinophilic leukemia – not otherwise specified and those with FGFR1 rearrangements. This review presents the current state of knowledge on definitions, classifications and treatment of HES in the molecular era

Clinical aspects of prophylaxis and treatment of CNS disease in lymphoma patients

Currently, infiltration of the central nervous system (CNS) in lymphoma patients is an unfavorable prognostic factor contributing to shorter survival. In these cases, immunophenotypisation has become important for evaluation of cerebrospinal fluid cells – especially in the so-called “subclinical form of CNS involvement.” Other methods used in these cases include diagnostic imaging and cytological examination. Therapy protocols, including the prophylactic intrathecal administration of drugs, are used for treatment of some lymphoma subtypes characterized by frequent CNS infiltrations, either at diagnosis or during relapse (lymphoblastic lymphoma/acute lymphoblastic leukemia, Burkitt's lymphoma, diffuse large B cell lymphoma, and lymphoma in HIV+ patients). In current clinical practice, prophylactic irradiation of the CNS is used less frequently. In addition to local treatment of the CNS, systemic therapy with high-dose methotrexate and cytosine arabinoside is recommended. The intrathecal treatment of choice is liposomal cytosine arabinoside or triple therapy: methotrexate, cytarabine, and dexamethasone. Because liposomal cytosine arabinoside has sustained activity in the CSF for 2 weeks, the number of intrathecal administrations necessary to eradicate CNS infiltrations may be reduced.This paper summarizes our current findings and recommendations on the prevention and treatment of CNS involvement in lymphoma patients

Thrombotic complications in Philadelphia-negative myeloproliferative neoplasms

Powikłania zakrzepowe są często obserwowane u chorych z czerwienicą prawdziwą (PV) i nadpłytkowością samoistną (ET) i stanowią główną przyczynę zgonów w tych jednostkach chorobowych. W układzie żylnym mogą się objawiać jako żylna choroba zakrzepowo-zatorowa, często jednak lokalizują się w miejscach nietypowych. W łożysku tętniczym zakrzepy są najczęściej zlokalizowane w naczyniach wieńcowych, w tętnicach krezkowych oraz w tętnicach mózgowia. U chorych z pierwotnym włóknieniem szpiku (PMF) obserwuje się także zwiększone ryzyko powikłań zakrzepowych. W PV/ET/PMF ryzyko jest zwiększone u pacjentów powyżej 60. roku życia oraz po przebytym epizodzie zakrzepowym. Spośród innych analizowanych czynników znaczenie wydają się mieć liczba leukocytów w momencie rozpoznania (u chorych z PV/ET) oraz obecność mutacji JAK2V617F (w PV/ET/PMF). W pracy przedstawiono aktualne poglądy dotyczące czynników sprzyjających występowaniu zakrzepicy, a także omówiono prawdopodobny patomechanizm powikłań.Thrombotic complications are frequently observed in patients with polycythemia vera (PV) and essential thrombocythemia (ET). They remain a main cause of mortality in a majority of above mentionedpatients. In venous system, thrombosis may manifest as venous thromboembolism as well as it may affect veins of unusual locations. In arterial system, it involves coronary, mesenteric and cerebral vessels. Patients with primary myelofi brosis (PMF) were found to have an increased risk of thrombotic complications as well. It was demonstrated that the risk of thrombosis is increased in patients older than 60 years and with a history of thrombotic episode. The other risk factors mayinclude leukocyte count at diagnosis (in PV/ET) and the presence of JAK2V617F point mutation (PV/ET/PMF). Our paper presents the current views on factors infl uencing the development of thrombosis. The probable pathomechanism of thrombosis has also been discussed

Targeted therapy and allogeneic hematopoietic stem cell transplantation may cure patients with acute myeloid leukemia

Acute myeloid leukemia (AML) is a heterogeneous disorder with a diverse prognosis. About 70% of AML patients may achieve complete remission after conventional chemotherapy, but long-term outcome remains unsatisfactory. The development of molecular biology resulted in a better understanding of AML pathogenesis as well as it allowed us the introduction of targeted therapy. However, most AML patients still require the allogeneic hematopoietic stem cell transplantation (alloHSCT) to be cured. The long-term results of alloHSCT for AML depend on a variety of factors including the age at transplant, the presence of well-defined risk factors and disease status at transplant. It seems that the combination of targeted therapy with conventional chemotherapy and subsequent alloHSCT may be a chance for curing a significant proportion of AML patients

Infection-related hemophagocytic lymphohistiocytosis – a case report

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal disorder characterized by abnormal activation of macrophages. It is also characterized by hemophagocytosis in the bone marrow and in the reticuloendothelial system (RES). The most common symptoms are persistent fever, splenomegaly and cytopenia. The probable mechanism of disease is due to hyperinflammation caused by increasing amounts of proinflammatory cytokines. As a consequence numerous metabolic disturbances with multiple organ failure occur. Without a proper treatment this disease may have a fatal outcome. Herein we present a 24-year-old male with HLH who achieved a rapid response to the therapy despite the initial poor overall condition which was associated with an advanced disease stage as well as prolonged diagnostic process

New prognostic factors in chronic lymphocytic leukemia diagnosed using an immunophenotypic method

Chronic lymphocytic leukemia (CLL) is a clonal lymphoproliferative disease which is characterized by proliferation and accumulation in blood, bone marrow and other tissues, small B-derived cells accompanied by coexpression of CD5 antigen. Diagnosis of CLL shall be based on standard criteria, but at the same time in determining the treatment strategies some prognostic factors will be helpful. Some of them are widely known and used, but with the progress of research, looking for new prognostic factors is useful for improving the strategy.Material and MethodsIn 43 patients, previously untreated, studies were performed by flow-cytometry to determine the prevalence of antigen CD49d, CD11c, CD54 on CLL cells. To determine their significance as prognostic factors correlation of their expression with the recognized standard prognostic factors, such as Rai stage, expression of CD38 and ZAP-70 as well as the presence of cytogenetic changes were done.ResultsIn our studies, a positive correlation between the expression of CD38 and CD49d, and ZAP-70 and CD49d on CLL cells were found. It was shown that among patients with CD11c + up 85.7% there were ZAP-70 positive. In addition, a significantly higher incidence of leukemic cells CD49d+ antigen was present in patients in Rai stage III / IV vs. 0/ II. There were no correlations between the number of cells expressing the antigens CD 11c and CD54 and the degree of advancement of Rai and expression of CD38. We also showed no correlation between the expression of CD54 and the expression of ZAP-70 either. In the group of patients CD38 (−), alternatively CD49d (+) and / or CD11c (+) up to 90.9% there were ZAP-70 (+).Conclusions1.Frequency of the incidence of the expression of CD49d correlates with clinical (Rai stage system) and/or risk factors determined by immunophenotype methods (CD38, ZAP-70).2.There is a rationale to continue CD11c antigen estimation as a potential prognostic factor based on our results that 86% of CD11c+ cases presented ZAP-70 positivity.Przewlekła białaczka limfocytowa (PBL) jest klonalną chorobą limfoproliferacyjną charakteryzującą się namnażaniem i nagromadzeniem w krwi, szpiku oraz innych tkankach małych limfocytów B z koekspresją antygenu CD5. O rozpoznaniu PBL decydują standardowe kryteria, natomiast dla ustalenia strategii leczenia pomocne są tzw. czynniki prognostyczne. Niektóre z nich są powszechnie stosowane, ale wraz z postępem badań poszukuje się nowych czynników rokowniczych.Materiał i metodaU 43 pacjentów, uprzednio nieleczonych, metodą cytometrii przepływowej zbadano częstość występowania na komórkach PBL molekuł adhezyjnych CD49d, CD11c, CD54. Dla określenia ich znaczenia, jako czynników prognostycznych, skorelowano ich ekspresję z: stopniem zaawansowania wg Rai, ekspresją CD38 i ZAP-70 oraz aberracjami cytogenetycznymi.Wynikistwierdzono dodatnią korelację pomiędzy ekspresją CD38 i CD49d oraz pomiędzy ZAP-70 i CD49d na komórkach PBL. Wykazano, że 85,7% pacjentów CD11c(+) było ZAP-70(+). Ponadto stwierdzono znamiennie większą częstość występowania na komórkach białaczkowych CD49d w grupie chorych w stadium Rai III/IV vs 0/II. Nie wykazano korelacji pomiędzy liczbą komórek z ekspresją antygenów CD11c i CD54 a stopniem zaawansowania Rai i CD38. Nie wykazano także korelacji pomiędzy ekspresją CD54 a ekspresją ZAP-70. W grupie pacjentów CD38(−) i równocześnie CD49d(+) i/lub CD11c(+) aż 90,9% było ZAP-70(+).Wnioski1.Częstość występowania ekspresji CD49d koreluje z klinicznymi (Rai) i fenotypowymi (CD38, ZAP-70) czynnikami ryzyka.2.Uzasadnionym jest kontynuowanie badań antygenu CD11c jako potencjalnego czynnika prognostycznego, gdyż stwierdzono, że 86% przypadków CD11c+ wykazuje dodatnią ekspresję ZAP-70

Metastasis of solid tumors into bone marrow – Single center experience

Introduction: Metastases of solid tumors to the bone marrow are rarely reported. Clinical manifestation and laboratory findings remain uncharacteristic and lead to misdiagnosis. Detection of bone marrow metastases may have an impact on therapeutic decisions and is usually associated with poor prognosis. Aim: To characterize clinical picture and hematological findings in patients with bone marrow metastasis. Material and methods: We retrospectively reviewed medical records of patients with bone marrow metastases who were primary misdiagnosed with hematological malignancies. Results: Ten patients at median age of 51 years at diagnosis were included. There were following findings on admission: duopenia (n=7), pancytopenia (n=1), anemia (n=1) and skeletal lytic lesions (n=1). The diagnosis of prior cancer was reported in 3 patients and included multiple myeloma, breast cancer and oligoastrocytoma. Clinical manifestations were hepatomegaly (n=4), lymphadenopathy (n=4), skin pallor (n=3), cachexia (n=2) and hemorrhagic diathesis (n=2). Imaging studies revealed diffuse bone lesions (n=5), pulmonary infiltrates (n=2) and liver masses (n=2). Leukoerythroblastosis was demonstrated in 4 cases. Bone marrow aspirate detected the presence of abnormal cell population in 4 patients. In all studied patients a final diagnosis was established by immunohistochemistry of bone marrow biopsy. The following malignancies were detected: prostate adenocarcinoma (n=2), anaplastic microcellular carcinoma of unknown origin (n=2), adenocarcinoma of unknown origin (n=2), Ewing's sarcoma (n=1), breast cancer (n=1), clarocellular renal cancer (n=1) and neuroendocrine tumor (n=1). Nine out of the 10 metastatic patients died shortly after chemotherapy. Conclusions: Unexplained hematological abnormalities should arise the suspicion of bone marrow metastases

Hairy cell leukemia and multiple myeloma: Two distinct entities or a single two-phase disease

Hairy cell leukemia (HCL) and multiple myeloma (MM) originate from mature B-cell and they are characterized by different clinical symptoms and treatment. Their clinical outcome is also different. The introduction of 2-CdA makes HCL a potentially curable disease, but MM still remains incurable despite a therapeutic progress made in the recent years. We report a male patient who simultaneously developed HCL and MM. He was treated with combined therapy including 2-CdA and thalidomide and this approach resulted in complete remission (CR) of HCL and partial response (PR) of his MM. This patient continued MM treatment with CTD regimen (cyclophosphamide, dexamethasone, thalidomide) and he achieved >90% reduction of serum monoclonal protein. The attempt of stem cell collection failed and autologous transplantation has not been performed. Currently, one year off therapy he is remaining in very good PR of his MM and in CR of HCL. The possible explanations for the development of these two disorders have been discussed

An extremely rare lineage switch from T-cell lymphoblastic lymphoma into B-cell acute lymphoblastic leukemia at relapse

Lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) is a neoplasm of precursor B or T-cells. These neoplastic cells may infiltrate bone marrow and peripheral blood (acute lymphoblastic leukemia) or their presence is confined to nodal or extranodal sites with only minimal evidence of blood and bone marrow involvement (lymphoblastic lymphoma). Herein, we report a male patient with infrequent neurological manifestation of T-LBL who failed autologous hematopoietic stem cell transplantation (AHSCT). A lineage switch from T-cell lymphoblastic lymphoma into B-cell acute lymphoblastic leukemia was observed at relapse and this phenomenon has not been described so far. Our case demonstrates difficulties which may occur in diagnosis and treatment of LBL/ALL. It should be underlined that neurological deficits resulting from spinal cord compression may be the first symptom of lymphoma. A switch within the lymphoblastic line may occur but it is an extremely rare finding. Its pathogenesis remains unclear, therefore further studies are highly required

Indolent systemic mastocytosis associated with multiple myeloma: A rare coexistence

Systemic mastocytosis (SM) includes a wide spectrum of clonal disorders characterized by an abnormal growth and accumulation of mast cells. SM may be associated with other hematological neoplasms (SM-AHN) among them the myeloproliferative neoplasms and myelodysplastic syndromes are the most common. The coexistence of SM with lymphoid malignancies has rarely been reported so far. The occurrence of SM associated with multiple myeloma (MM) is extremely rare and its prognosis remains unclear. The treatment of SM-AHM requires an individual approach. We report a male patient diagnosed with indolent SM associated with MM. He did not require the therapy for his SM, but started the treatment against MM. He received the induction regiment consisting of bortezomib, thalidomide and dexamethasone (VTD). After six cycles of VTD he achieved a very good partial response, but refused autologous stem cell transplantation as response consolidation and eventually died of myeloma progression a couple months later. Herein we discuss the likely pathophysiologic mechanisms underlying those two separate entities