Lubomir Sokol

Moffitt Cancer Center, Tampa, Florida, United States

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Publications (102)435.69 Total impact

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    ABSTRACT: Secondary syphilis has been known since the late 19th century as the great imitator; however, some experts now regard cutaneous lymphoma as the great imitator of skin disease. Either disease, at times an equally fastidious diagnosis, has reported to mimic each other even. It is thus vital to consider these possibilities when presented with a patient demonstrating peculiar skin lesions. No other manifestation of secondary syphilis may pose such quandary as a rare case of rupioid syphilis impersonating cutaneous lymphoma. We present such a case, of a 36-year-old HIV positive male, misdiagnosed with aggressive cutaneous lymphoma, actually exhibiting rupioid syphilis thought secondary to immune reconstitution inflammatory syndrome (IRIS).
    Mediterranean Journal of Hematology and Infectious Diseases 12/2015; 7(1):e2015026. DOI:10.4084/MJHID.2015.026
  • Oluwatobi Ohiole Ozoya · Lubomir Sokol · Samir Dalia ·
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    ABSTRACT: Epstein Barr Virus (EBV) is a common gamma herpes virus with a high prevalence in adults worldwide. Infection is mostly latent in affected individuals. EBV has been linked mostly with lymphoid malignancies but its association with epithelial and other non-lymphoid malignancies has also been described. In this review, we describe current knowledge about the pathogenesis of EBV-related malignancies and evaluate their therapeutic options and outcomes. Current and prospective novel preventive options are also critically reviewed.
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    ABSTRACT: P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to -2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome.
    Oncotarget 09/2015; 15. DOI:10.18632/oncotarget.5255 · 6.36 Impact Factor
  • Samir Dalia · Kelli Dunker · Lubomir Sokol · Rahul Mhaskar ·
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    ABSTRACT: Multiple myeloma (MM) and Hodgkin lymphoma (HL) are common hematological malignancies. There is conflicting data on the potential role of hepatitis B virus (HBV) infection and developing MM or HL. The main aim of this study is to evaluate the association of HBV seropositivity and HL or MM through a meta-analysis of epidemiological studies A literature search through March 2015 found 10 studies that evaluated the association between HBV and MM or HL. Meta-analysis was calculated as an odds ratio (OR). Our analysis showed an OR of developing MM of 1.41 (P=0.03) and an OR of developing HL of 1.54 (P=0.03) in patients with HBV seropositivity. Our results did not change based on study design, quality of studies and use of HBV seropositivity to determine HBV status. Our results suggest that HBV seropositivity increases the risk of developing MM and HL. Further research is needed to confirm these findings.
    Leukemia research 09/2015; DOI:10.1016/j.leukres.2015.09.008 · 2.35 Impact Factor
  • Samir Dalia · Yaman Suleiman · David W Croy · Lubomir Sokol ·
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    ABSTRACT: Background: Hepatitis B virus (HBV) has been associated with the development of non-Hodgkin lymphoma (NHL) and can be reactivated in patients being treated for NHL. Methods: Articles published between 2000 and 2015 that discussed an association between NHL and HBV, mechanisms of HBV induction of NHL, and HBV reactivation in patients with NHL were reviewed and the results compiled to help health care professionals better understand the risk of developing NHL in HBV-seropositive individuals, describe potential etiologies by which HBV infection may lead to lymphomagenesis, and highlight the recent medical literature with respect to the reactivation of HBV in the setting of NHL. Results: An association exists between HBV infection and NHL development. Immunosuppression due to HBV, chronic viral stimulation, and dysregulation of the immune system are possible ways in which lymphoma can develop in patients with HBV infection. All patients being treated with anti-CD20 antibodies or those from or living in HBV-endemic regions should be tested for hepatitis B surface antigen, core antibody, and surface antibody prior to initiating therapy. HBV DNA polymerase chain reaction (PCR) may also be useful in certain cases. Among HBV-seropositive patients or those with detectable HBV DNA, prophylaxis with an antiviral agent should be initiated for 1 year after NHL therapy. HBV DNA PCR monitoring should be undertaken each month during the course of treatment and every 3 months after treatment for a 1-year duration. Conclusions: Health care professionals should become more comfortable treating these high-risk patients with NHL as they become more informed about potential lymphomagenesis and the reactivation of HBV.
    Cancer control: journal of the Moffitt Cancer Center 09/2015; 22(3):360-365. · 3.50 Impact Factor
  • Megan Melody · Bijal Shah · Lubomir Sokol · Celeste Bello · Julio Chavez ·

  • Christa Roe · Rami Komrokji · Ling Zhang · Samantha Price · Lubomir Sokol ·

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    ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening syndrome of excessive immune activation and an inflammatory cytokine storm leading to multiple organ failure. We report our experience in a large tertiary referral center on HLH in the setting of hematologic malignancies and describe responses to therapy and outcomes. Seventeen cases of HLH were included in which the most common underlying diagnosis was aggressive lymphoma (n = 7). The median time from diagnosis of primary hematologic condition to HLH was 3.1 months. The most common presenting features were fever (n = 15), splenomegaly (n = 13), and transaminitis (n = 14). The mean serum ferritin level was 21,000 ng/mL. Fourteen patients demonstrated evidence of hemophagocytosis in bone marrow or other organs. Among all patients, 12 received etoposide, 14 received dexamethasone, and 3 received cyclosporine. Intrathecal chemotherapy was administered to 3 patients. Overall, 7 patients (41%) responded to treatment with clinical and laboratory improvement. The median overall survival (OS) from the time of HLH diagnosis and the primary hematologic diagnosis was 8.4 months and 29.5 months, respectively. The OS was better among patients with HLH with aggressive lymphomas (12 months). Response to treatment was associated with better OS. Recognition of manifestations and prompt diagnosis of HLH are crucial to initiate prompt therapy and improve outcome. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical lymphoma, myeloma & leukemia 06/2015; 15S:S147-S150. DOI:10.1016/j.clml.2015.03.009 · 2.02 Impact Factor
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    ABSTRACT: To assess the ability of flow cytometry (FC) to detect putative neoplastic T-cell subsets on skin shave biopsy (SSB) specimens from patients with mycosis fungoides (MF) and to study the immunophenotype of skin-infiltrating tumor cells in MF. SSB specimens from patients with suspected MF were bisected and submitted for both FC and routine histopathology. Six-dimensional gating strategies were applied to identify putative neoplastic cells, independently from their expected immunophenotype. Aberrant T cells were detected by FC in 18 of 33 SBB specimens, of which all had clinicomorphologic features of MF. Of the remaining 15 SSB specimens, six had clinicomorphologic features of MF and nine were diagnosed with benign inflammatory dermatoses. Unexpectedly, CD26 was aberrantly overexpressed in 11 (73%) and lost in three (20%) of 15 SSB specimens from patients with MF where this antigen was evaluated. Other detected aberrancies included CD3 dim- (13/18 [72%]), CD7 dim- (15/18 [83%]), and CD4-/CD8- (3/18 [17%]). FC is capable of identifying putative neoplastic cells on SSB specimens from patients with MF. Bright homogeneous CD26 expression is a common and previously undescribed immunophenotypic aberrancy on MF skin infiltrates. Copyright© by the American Society for Clinical Pathology.
    American Journal of Clinical Pathology 06/2015; 143(6):785-96. DOI:10.1309/AJCPWE2HBFCGDIDS · 2.51 Impact Factor

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    ABSTRACT: Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease, which are managed in the same way. The advent of novel monoclonal antibodies (ofatumumab and obinutuzumab) led to the development of effective chemoimmunotherapy regimens. The recently approved small molecule kinase inhibitors (ibrutinib and idelalisib) are effective treatment options for CLL in elderly patients with decreased tolerance for aggressive regimens and in patients with poor prognostic features who do not benefit from conventional chemoimmunotherapy regimens. This portion of the NCCN Guidelines for Non-Hodgkin's Lymphomas describes the recent specific to the incorporation of recently approved targeted therapies for the management of patients with newly diagnosed and relapsed or refractory CLL/SLL. Copyright © 2015 by the National Comprehensive Cancer Network.
    Journal of the National Comprehensive Cancer Network: JNCCN 03/2015; 13(3):326-62. · 4.18 Impact Factor
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    ABSTRACT: Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progression-free survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P=0.05). These findings comprise the largest MDS R72P SNP analysis.
    Blood Cancer Journal 03/2015; 5(3):e291. DOI:10.1038/bcj.2015.11 · 3.47 Impact Factor
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    ABSTRACT: For patients with peripheral T-cell lymphoma (PTCL), the value of (18)fluoro-deoxyglucose positron emission tomography (FDG-PET) scans for assessing prognosis and response to treatment remains unclear. The utility of FDG-PET, in addition to conventional radiology, was examined as a planned exploratory endpoint in the pivotal phase 2 trial of romidepsin for the treatment of relapsed/refractory PTCL. Patients received romidepsin at a dose of 14 mg/m(2) on days 1, 8, and 15 of 28-day cycles. The primary endpoint was the rate of confirmed/unconfirmed complete response (CR/CRu) as assessed by International Workshop Criteria (IWC) using conventional radiology. For the exploratory PET endpoint, patients with at least baseline FDG-PET scans were assessed by IWC+PET criteria. Of 130 patients, 110 had baseline FDG-PET scans, and 105 were PET positive at baseline. Use of IWC+PET criteria increased the objective response rate to 30% compared with 26% by conventional radiology. Durations of response were well differentiated by both conventional radiology response criteria (CR/CRu vs partial response [PR], P=.0001) and PET status (negative vs positive, P<.0001). Patients who achieved CR/CRu had prolonged progression-free survival (PFS, median 25.9 months) compared with other response groups (P=.0007). Patients who achieved PR or stable disease (SD) had similar PFS (median 7.2 and 6.3 months, respectively, P=.6427). When grouping PR and SD patients by PET status, patients with PET-negative vs PET-positive disease had median PFS of 18.2 vs 7.1 months (P=.0923) CONCLUSIONS: Routine use of FDG-PET does not obviate conventional staging, but may aid in determining prognosis and refine response assessments for patients with PTCL, particularly for those who do not achieve CR/CRu by conventional staging. The optimal way to incorporate FDG-PET scans for patients with PTCL remains to be determined. NCT00426764. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
    Annals of Oncology 01/2015; 26(4). DOI:10.1093/annonc/mdv010 · 7.04 Impact Factor
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    ABSTRACT: This phase 1/2 study evaluated the efficacy of mogamulizumab, a defucosylated, humanized, anti-CCR4 monoclonal antibody, in 41 pre-treated patients with cutaneous T-cell lymphoma (CTCL). No dose-limiting toxicity was observed and the maximum tolerated dose was not reached in phase 1 after IV infusion of mogamulizumab (0.1, 0.3, and 1.0 mg/kg) once weekly for 4 weeks followed by a 2-week observation. In phase 2, patients were dosed with 1.0 mg/kg mogamulizumab according to the same schedule for the first course followed by infusion every 2 weeks during subsequent courses until disease progression. The most frequent treatment-emergent adverse events were nausea (31.0%), chills (23.8%), headache (21.4%), and infusion-related reaction (21.4%); the majority of events were grade 1/2. There were no significant hematologic effects. Among 38 evaluable patients, the overall response rate was 36.8%: 47.1% in Sézary syndrome (n = 17) and 28.6% in mycosis fungoides (n = 21). Eighteen of 19 (94.7%) patients with ≥B1 blood involvement had a response in blood, including 11 complete responses. Given the safety and efficacy of mogamulizumab, phase 3 investigation of mogamulizumab is warranted in CTCL patients. This trial was registered at as #NCT00888927. Copyright © 2015 American Society of Hematology.
    Blood 01/2015; 125(12). DOI:10.1182/blood-2014-09-600924 · 10.45 Impact Factor
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    ABSTRACT: Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS). Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR) signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size). Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q) MDS.
    PLoS ONE 12/2014; 9(12):e114249. DOI:10.1371/journal.pone.0114249 · 3.23 Impact Factor
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    ABSTRACT: Malignant bone lymphoma can be classified as primary (PBL) or secondary (SBL) bone lymphoma. However, the clinico-pathological characteristics and prognostic factors of PBL versus SBL have not yet been well defined. Whether lymphoma with multifocal bone involvement should be considered as stage IV PBL or SBL still remain controversial throughout the literature. In this study, we retrospectively reviewed 127 patients with bone lymphoma diagnosed from1998 to 2013 at the Moffitt Cancer Center. Patients were classified as PBL (81 cases) and SBL (46 cases) using the 2013 WHO Classification of Bone/Soft Tissue Tumors and PBL patients were further subdivided into: 1) PBL with unifocal bone disease (uPBL, 46 cases), 2) PBL with multifocal bone involvement (mPBL, 35 cases). Patient characteristics, survival, and prognostic factors were analyzed. Diffuse large B-cell lymphoma (DLBCL) was the most common histological subtype in all three groups (37/46 of uPBL, 23/35 of mPBL, 23/46 of SBL). B symptoms, lymph node involvement, and bone marrow involvement were found to be more common in mPB-DLBCL and SB-DLBCL groups than in the uPB-DLBCL group. Femur was found to be the most common affected site in uPB-DLBCL patients, while spine was most commonly involved in the other two groups. Survival analysis indicated that uPBL-DLBCL patients had a significantly better progression-free survival (PFS) and overall survival (OS) than those in the other two groups (P < 0.05). We also found by univariate analysis that multifocality, and stage IV were significantly poor prognostic factors for both PFS and OS in PBL patients. Using multivariate analysis, multifocality remained an independent prognostic factor for both PFS and OS (P = 0.0117, RR: 3.789, 95% CI: 1.275-11.256). Overall, our results suggest that mPBL is more similar to SBL in characteristics and survival rather than uPBL, and thus should be better classified and treated as SBL.
    BMC Cancer 12/2014; 14(1):900. DOI:10.1186/1471-2407-14-900 · 3.36 Impact Factor
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    ABSTRACT: Neoplasms of histiocytic and dendritic cells are rare disorders of the lymph node and soft tissues. Because of this rarity, the corresponding biology, prognosis and terminologies are still being better defined and hence historically, these disorders pose clinical and diagnostic challenges. These disorders include Langerhans cell histiocytosis (LCH), histiocytic sarcoma (HS), follicular dendritic cell sarcoma (FDCS), interdigtating cell sarcoma (IDCS), indeterminate cell sarcoma (INDCS), and fibroblastic reticular cell tumors (FRCT). In order to gain a better understanding of the biology, diagnosis, and treatment in these rare disorders we reviewed our cases of these neoplasms over the last twenty five years and the pertinent literature in each of these rare neoplasms. Cases of histiocytic and dendritic cell neoplasms diagnosed between 1989-2014 were identified using our institutional database. Thirty two cases were included in this analysis and were comprised of the following: Langerhans cell histiocytosis (20/32), histiocytic sarcoma (6/32), follicular dendritic cell sarcoma (2/32), interdigitating dendritic cell sarcoma (2/32), indeterminate dendritic cell sarcoma (1/32), and fibroblastic reticular cell tumor (1/32). Median overall survival was not reached in cases with LCH and showed 52 months in cases with HS, 12 months in cases with FDCS, 58 months in cases with IDCS, 13 months in the case of INDCS, and 51 months in the case of FRCT. The majority of patients had surgical resection as initial treatment (n = 18). Five patients had recurrent disease. We conclude that histiocytic and dendritic cell neoplasms are very rare and perplexing disorders that should be diagnosed with a combination of judicious morphology review and a battery of immunohistochemistry to rule out mimics such as carcinoma, lymphoma, neuroendocrine tumors and to better sub-classify these difficult to diagnose lesions. The mainstay of treatment for localized disease remains surgical resection and the role of adjuvant therapy is unclear. In patients with multiple areas of involvement, treatment at tertiary care centers with multimodality treatment is likely needed. Accurate subset diagnosis will contribute to better data as well as treatment outcomes analysis of these rare disorders of adult patients in the future.
    Cancers 12/2014; 6(4):2275-2295. DOI:10.3390/cancers6042275
  • Wasif Riaz · Ling Zhang · Pedro Horna · Lubomir Sokol ·
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    ABSTRACT: Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. Most patients with BPDCN have skin lesions and simultaneous involvement of the peripheral blood, bone marrow, and lymph nodes. Methods: A search of PubMed and Medline was conducted for English-written articles relating to BPDCN, CD4(+)CD56(+) hematodermic neoplasm, and blastic natural killer cell lymphoma. Data regarding diagnosis, prognosis, and treatment were analyzed. Results: BPDCN is derived from precursor plasmacytoid dendritic cells. The diagnosis of BPDCN is based on the characteristic cytology and immunophenotype of malignant cells coexpressing CD4, CD56, CD123, blood dendritic cell antigens 2 and 4, and CD2AP markers. Multiple chromosomal abnormalities and gene mutations previously reported in patients with myeloid and selected lymphoid neoplasms were identified in approximately 60% of patients with BPDCN. Prospectively controlled studies to guide treatment decisions are lacking. The overall response rate with aggressive acute lymphoblastic leukemia-type induction regimens was as high as 90%, but the durability of response was short. Median survival rates ranged between 12 and 16 months. Patients with relapsed disease may respond to L-asparaginase-containing regimens. Allogeneic hematopoietic stem cell transplantation, particularly when performed during the first remission, may produce durable remissions in selected adults. Conclusions: BPDCN is a rare aggressive disease that typically affects elderly patients. The most commonly affected nonhematopoietic organ is the skin. Although BPDCN is initially sensitive to conventional chemotherapy regimens, this response is relatively short and long-term prognosis is poor. In the near future, novel targeted therapies may improve outcomes for patients with BPDCN.
    Cancer control: journal of the Moffitt Cancer Center 10/2014; 21(4):279-289. · 3.50 Impact Factor

Publication Stats

1k Citations
435.69 Total Impact Points


  • 2005-2015
    • Moffitt Cancer Center
      • Program in Blood and Marrow Transplantation
      Tampa, Florida, United States
  • 2003-2014
    • University of South Florida
      Tampa, Florida, United States
  • 2010
    • CUNY Graduate Center
      New York City, New York, United States
  • 2007
    • The University of Arizona
      Tucson, Arizona, United States
    • Penn State Hershey Medical Center and Penn State College of Medicine
      • Cancer Institute
      Hershey, Pennsylvania, United States