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Lubomir Sokol

Publications and source records attributed to Lubomir Sokol.

11 recordsLinked to original sources
PubMed2007

Aggressive T-cell large granular lymphocyte leukemia: a case report and review of the literature.

The majority of patients with T-cell large granular lymphocyte (LGL) leukemia will have an indolent clinical course. Herein, we report a case of an aggressive T-cell LGL leukemia in a previously healthy 42-year-old Caucasian male who presented with acute onset of B-symptoms, hepatosplenomegaly, lymphocytosis, moderate anemia, and thrombocytopenia. Immunophenotypically, the malignant cells co-expressed CD3(+)CD8(+)CD56(+) markers and the T-cell receptor beta (TCR beta) gene demonstrated clonal rearrangement. The patient was treated with an intensive chemotherapeutic regimen (hyper-CVAD) and he achieved a complete remission. A systematic review of all available English literature revealed 12 well-described cases of aggressive T-cell LGL leukemia suggesting that this variant is a new and distinct entity in the spectrum of LGL disorders.

Adult↗
PubMed2006

Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors.

The myelodysplastic syndromes (MDSs) are collections of heterogeneous hematologic diseases characterized by refractory cytopenias as a result of ineffective hematopoiesis. Development of effective treatments has been impeded by limited insights into any unifying pathogenic pathways. We provide evidence that the p38 MAP kinase is constitutively activated or phosphorylated in MDS bone marrows. Such activation is uniformly observed in varied morphologic subtypes of low-risk MDS and correlates with enhanced apoptosis observed in MDS hematopoietic progenitors. Most importantly, pharmacologic inhibition of p38alpha by a novel small molecule inhibitor, SCIO-469, decreases apoptosis in MDS CD34+ progenitors and leads to dose-dependant increases in erythroid and myeloid colony formation. Down-regulation of the dominant p38alpha isoform by siRNA also leads to enhancement of hematopoiesis in MDS bone marrow progenitors in vitro. These data implicate p38 MAPK in the pathobiology of ineffective hematopoiesis in lowrisk MDS and provide a strong rationale for clinical investigation of SCIO-469 in MDS.

Aged↗
PubMed2006

Large granular lymphocyte leukemia.

Clonal disorders of large granular lymphocytes (LGLs) represent a spectrum of biologically distinct lymphoproliferative diseases originating either from mature T cells (CD3+) or natural killer (NK) cells (CD3-). Both subtypes, T-cell and NK-cell LGL leukemia, can manifest as indolent or aggressive disorders. The majority of patients with T-cell LGL leukemia have a clinically indolent course with a median survival time >10 years. Immunosuppressive therapy with low-dose methotrexate, cyclophosphamide, or cyclosporine A can control symptoms and cytopenias in more than 50% of patients, but this approach is not curative. Several cases of an aggressive variant (CD3+ CD56+) of T-cell LGL leukemia with a poor prognosis have also been reported. Aggressive NK-cell LGL leukemia is usually a rapidly progressive disorder associated with Epstein-Barr virus (EBV), with a higher prevalence in Asia and South America. This disease is usually refractory to conventional chemotherapy, with a median survival time of 2 months. Chronic NK-cell leukemia/lymphocytosis is a rare EBV-negative disorder with an indolent clinical course. The malignant origin of this subtype is uncertain because clonality is difficult to determine in LGLs of NK-cell origin.

Algorithms↗
PubMed2006

Developmental therapeutics for myelodysplastic syndromes.

The management strategy for patients with myelodysplastic syndromes (MDS) has evolved from sole reliance on supportive measures to active treatment guided by disease risks. Recent progress in understanding the molecular pathogenesis of MDS has accelerated the discovery of new therapeutic targets, and consequently launched the development of several novel therapeutics that are currently in varied stages of clinical testing. One such agent is lenalidomide, which has shown remarkable effectiveness in the cytogenetically defined subset of MDS with the chromosome 5q31 deletion. The advent of new and effective targeted therapeutics may beneficially affect outcomes of an ever-increasing number of patients with MDS. This discussion summarizes the preliminary results of selected novel therapeutics.

Amifostine↗
PubMed2006

Use of bivalirudin to treat heparin-induced thrombocytopenia in a patient with idiopathic giant-cell myocarditis.

Giant-cell myocarditis (GCM) is a rare, idiopathic disorder of young adults with high rates of morbidity and mortality. We describe a unique case of giant cell myocarditis associated with heparin-induced thrombocytopenia and thrombosis syndrome (HITTS). Our patient responded to therapy with bivalirudin, but later succumbed to complications from multiorgan failure. To our knowledge, this is the first reported case of GCM associated with HITTS, which was treated with bivalirudin (Angiomax; The Medicines Company; Parsippany, NJ).

Adult↗
PubMed2004

Characterization of HTLV envelope seroreactivity in large granular lymphocyte leukemia.

T-cell large granular lymphocyte (T-LGL) leukemia is a rare chronic lymphoproliferative disorder of unknown etiology. We have previously reported that patients with T-LGL leukemia were seroreactive against BA21, a 34 amino acid peptide derived from HTLV-I envelope protein p21. We tested sera from 70 patients with T-LGL leukemia and found that 21/70 (30%) of them were seroreactive against fusion peptide GST-BA21. In control group of healthy blood donors 3/30 (10%) were seroreactive. We synthesized a set of overlapping peptides derived from BA21 and tested them against sera from patients. Only a single peptide (p21 env 417-430) showed reactivity. We then generated multiple fusion peptides consisting of 5-14 amino acid residues derived from this peptide and tested them against patient and control sera. Shortest peptide giving positive seroreactivity was octapeptide P8 (p21 env 418-425). Competitive Western blot assay with use of fusion peptides revealed that the minimal HTLV-I epitope responsible for seroreactivity found in patients with T-LGL leukemia is a decapeptide PP10 (p21 env 417-426). Protein Bank (NCBI) search did not reveal any significant homology between PP10 epitope and known human proteins. These results further define the epitope responsible for HTLV env seroreactivity observed in LGL leukemia.

Amino Acid Sequence↗
PubMed2004

Simultaneous manifestation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL).

We report a unique case of 83-year-old Caucasian male with the initial simultaneous manifestation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). The patient presented with absolute lymphocytosis in the blood, asymptomatic generalized lymphadenopathy, and mild splenomegaly. The diagnosis of CLL was suggested from the blood film, but subsequent flow cytometric (FC) analysis on peripheral blood mononuclear cells (PBMNC) revealed two distinct abnormal clones of mature B cells. A small subpopulation (7%) of lymphoid cells expressed CD20, CD11c, FMC-7, CD103, CD25, and kappa surface light chain, consistent with HCL. The larger subpopulation (75%) of lymphoid cells expressed CD19, CD20, CD23, CD5, and lambda light chain, consistent with CLL. The expression of different immunoglobulin light chains on the circulating CLL (lambda) and HCL (kappa) cells suggested two, independent, malignant B-cell clones. Interestingly, FC analysis of bone marrow (BM) cells done 6 months later revealed bright lambda light chain expression on the HCL cells. Despite administration of several different courses of chemotherapy, the HCL subpopulation was not eliminated from the BM but remained stable between 7% and 10% of total BM lymphoid cells. The CLL, responsible for most of clinical symptoms in our patient, responded to combination chemotherapy with fludarabine and cytoxan, and later to monotherapy with rituximab.

Aged↗
PubMed2003

Large granular lymphocyte leukemia and natural killer cell leukemia/lymphomas.

Natural killer (NK) cell leukemia and lymphoma represent rare conditions with heterogeneity of biologic behavior, prognosis, and responsiveness to therapy. The initial diagnosis of NK-cell malignancies can be difficult because of the lack of immunophenotypic clonality markers, morphologic heterogeneity, and a poor correlation between cytomorphology and prognosis. Therapeutic recommendations for NK-cell malignancies are derived from retrospective studies or case reports. Immature NK-cell malignancies often have aggressive behavior with poor prognosis, despite administration of acute myeloid leukemia or acute lymphocytic leukemia induction chemotherapy. The use of high-dose chemotherapy with stem cell rescue resulted in a prolonged survival in a small series of patients. NK-cell malignancies originating from cells with mature phenotypes form a spectrum of diseases with distinct prognosis. Patients with aggressive NK-cell leukemia invariably die within several months. Nasal and nasal-like NK/T-cell lymphomas with limited stage disease often respond to radiation therapy alone or combination with chemotherapy and radiation therapy, with 5-year disease-free survival rates ranging from 30% to 75%. Patients with T-cell large granular lymphocyte leukemia or chronic NK-cell lymphoproliferative disease of granular lymphocytes can have an indolent clinical course with long survival without therapy. However, approximately 66% of patients with T-cell large granular lymphocyte leukemia require low-dose chemotherapy with methotrexate or cyclophosphamide or immunosuppressive therapy with glucocorticosteroids or cyclosporine A for symptomatic cytopenias during the course of their disease.

Humans↗
PubMed2003

Acute myeloid leukemia mimicking primary testicular neoplasm. Presentation of a case with review of literature.

We describe a new unique case of acute myeloid leukemia (AML) in a 21-yr-old male presenting with abdominal pain, bilateral testicular masses and gynecomastia. Further work-up with computed tomography of the chest, abdomen and pelvis revealed massive retroperitoneal, peripancreatic and mediastinal lymphadenopathy, suggesting primary testicular neoplasm. The patient was subjected to right orchiectomy that showed infiltration of testicular tissue with malignant cells, originally misinterpreted as undifferentiated carcinoma. Immunohistochemistry studies, however, showed these cells to be strongly positive for myeloperoxidase and CD45, indicating a myeloid cell origin. Bone marrow (BM) aspirate and biopsy demonstrated replacement of marrow with immature myeloid cells. Both the morphology and immunophenotype of the blast cells were consistent with AML type M4 (acute myelo-monocytic leukemia), using French-American-British (FAB) classification. The patient received standard induction chemotherapy with cytosine arabinoside (ARA-C) and daunorubicin followed with two cycles of consolidation therapy with high dose ARA-C, which resulted in remission of BM disease and resolution of lymphadenopathy and left testicular masses. After the second cycle of consolidation therapy, the patient developed sepsis that was complicated by refractory disseminated intravascular coagulopathy. He expired with a clinical picture of multiple organ failure. The unique features of this case are presented and the related literature is reviewed.

Abdominal Pain↗
PubMed2002

Turner syndrome associated with acquired von Willebrand disease, primary biliary cirrhosis, and inflammatory bowel disease.

We report a unique case of Turner syndrome associated with acquired von Willebrand disease (AvWD), primary biliary cirrhosis (PBC), and inflammatory bowel disease (IBD). During 7 years of close follow-up, the patient presented with multiple major episodes of upper and lower gastrointestinal bleeding caused by different pathogenic mechanisms, such as IBD, AvWD, gastric varices, and thrombocytopenia. AvWD mimicking familial vWD type III on laboratory testing was most probably triggered by autoimmune mechanism associated with PBC. Therapy of PBC with ursodeoxycholic acid (UDCA) resulted in significant decrease of liver enzymes followed by normalization of vWF and FVIII levels. Portosystemic shunt placement with ligation of gastric varices improved hypersplenism and severe thrombocytopenia and led to clinical stability for more than 24 months. The clinicopathological features of these disorders and of the recurrent bleeding episodes are discussed in the text along with a review of the literature.

Adult↗