Lubomir Sokol

Moffitt Cancer Center, Tampa, Florida, United States

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Publications (91)398.68 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
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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 · 3.01 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. · 4.24 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 · 2.88 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 · 6.58 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 www.clinicaltrials.gov as #NCT00888927. Copyright © 2015 American Society of Hematology.
    Blood 01/2015; 125(12). DOI:10.1182/blood-2014-09-600924 · 10.43 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 · 3.32 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: 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.
    Cancer control: journal of the Moffitt Cancer Center 10/2014; 21(4):279-289. · 2.66 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5224-5224. DOI:10.1158/1538-7445.AM2014-5224 · 9.28 Impact Factor
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    ABSTRACT: Rosai-Dorfman disease (RDD) is a rare, nonmalignant clinical entity characterized by a group of clinical symptoms and characteristic pathological features.
    Cancer control: journal of the Moffitt Cancer Center 10/2014; 21(4):322-327. · 2.66 Impact Factor
  • Lubomir Sokol
    Cancer control: journal of the Moffitt Cancer Center 10/2014; 21(4):260-261. · 2.66 Impact Factor
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    ABSTRACT: Dendritic and histiocytic cell neoplasms are rare malignancies that make up less than 1% of all neoplasms arising in lymph nodes or soft tissues. These disorders have distinctive disease biology, clinical presentations, pathology, and unique treatment options. Morphology and immunohistochemistry evaluation by a hematopathologist remains key for differentiating between these neoplasms. In this review, we describe tumor biology, clinical features, pathology, and treatment of follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma, indeterminate dendritic cell sarcoma, histiocytic sarcoma, fibroblastic reticular cell tumors, and disseminated juvenile xanthogranuloma.
    Cancer control: journal of the Moffitt Cancer Center 10/2014; 21(4):290-300. · 2.66 Impact Factor
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    ABSTRACT: Primary cutaneous γδ T-cell lymphoma is an extremely rare and aggressive variant of cutaneous lymphoma. Central nervous system (CNS) involvement, a rare finding, and hemophagocytic syndrome are two complications that are commonly fatal. We describe a 58-year-old patient presenting with skin plaque that subsequently developed subcutaneous nodules diagnosed as cutaneous T-cell lymphoma (CTCL), clinically resembling “mycosis fungoides”. The patient was treated with repeat topical radiation therapies but had frequent relapsed disease. Approximately 4.5-years after, the patient presented with 3rd and 6th cranial nerve palsies and was found to have CNS involvement by lymphoma per positron emission tomography—computed tomography (PET/CT) and a biopsy of foramen magnum. Phenotypically, the tumor cells were CD3(+)/CD4(−)/CD8(−)/CD7(+)/CD5(−)/CD30(−)/TCRαβ(−)/TCRγδ(+). Despite aggressive strategies taken, the patient expired three months after the diagnosis of the CNS lesion. A retrospective investigation proved the original CTCL to be γδ T-cell in origin, confirming an indolent cutaneous γδ T-cell lymphoma with eventual CNS manifestation. We present this case to draw attention to the entity, which can occasionally present with misleading histopathologic and clinical features. In addition, we provide a review of the literature to summarize clinical and pathologic features of the reported similar cases.
    Journal of Cutaneous Pathology 10/2014; 41(12). DOI:10.1111/cup.12395 · 1.56 Impact Factor
  • Darcie Deaver · Pedro Horna · Hernani Cualing · Lubomir Sokol
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    ABSTRACT: Kikuchi-Fujimoto disease (KFD) is a rare lymphohistiocytic disorder with an unknown etiopathogenesis. This disease is misdiagnosed as malignant lymphoma in up to one-third of cases and is associated with the development of systemic lupus erythematosus (SLE).
    Cancer control: journal of the Moffitt Cancer Center 10/2014; 21(4):313-321. · 2.66 Impact Factor
  • Ling Zhang · Jun Zhou · Lubomir Sokol
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    ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory/hypercytokinemia syndrome clinicopathologically manifested by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hemophagocytosis.
    Cancer control: journal of the Moffitt Cancer Center 10/2014; 21(4):301-312. · 2.66 Impact Factor
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    ABSTRACT: Histone deacetylase inhibitor romidepsin has demonstrated durable clinical responses and tolerability in patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma (PTCL, CTCL). Selection of novel drug therapies for patients with relapsed/refractory aggressive lymphoma requires not only considerations regarding efficacy but also careful evaluation of toxicities as well as overall clinical benefit. The purpose of this analysis was to examine common adverse events (AEs) reported in pivotal trials of romidepsin in relapsed/refractory PTCL or CTCL and to more clearly define the overall AE profile in these populations. Patients with relapsed/refractory PTCL or CTCL were treated with romidepsin at 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles for up to 6 cycles; patients with at least stable disease could extend therapy until progressive disease or another withdrawal criterion was met. All enrolled patients who received ≥ 1 dose of romidepsin were included in the AE analyses. Overall, safety profiles of common AEs were similar, although patients with relapsed/refractory PTCL had more frequent hematologic toxicities and grade ≥ 3 infections. In both patient populations, the greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during cycles 1–2. Early discontinuations were primarily related to infection, thrombocytopenia, or electrocardiogram abnormalities, confirming the need to closely monitor patients with poor bone marrow reserve or other comorbidities. Despite this, 28% of patients with relapsed/refractory PTCL and 36% of patients with relapsed/refractory CTCL continued on romidepsin treatment for ≥ 6 cycles. This study demonstrates that patients with relapsed/refractory PTCL or CTCL have similar AE profiles with romidepsin treatment, although patients with PTCL experienced more frequent and more severe hematologic toxicities and more frequent grade ≥ 3 infections. The greatest incidence of grade ≥ 3 AEs and the majority of discontinuations due to AEs occurred during treatment cycles 1–2. Extended dosing of romidepsin can be tolerated in responding patients. Trial registration NCT00426764, NCT00106431
    09/2014; 2(1):16. DOI:10.1186/2050-7771-2-16
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    ABSTRACT: Plasmablastic lymphoma (PBL) rarely occurs in the gastrointestinal (GI) tract with limited studies reported. We reviewed the clinical histories and pathology of four patients with GI PBL at our institute and similar case reports published in peer-reviewed journals. In our first case, a 40 year-old human immunodeficiency virus positive male presented with a hemorrhoid-like sensation, and was diagnosed with PBL via biopsy of a rectal mass. The second case involves a 65 year-old healthy male with bloody diarrhea who was found to have PBL in a resected sigmoid mass. The third patient was a 41 year-old male with a history of Crohn's disease who presented with abdominal pain, diarrhea, and weight loss. A small intestinal mass (PBL) was removed. The fourth patient was a 65-year-old male who was found PBL after surgical resection of bowel for his florid Crohn's disease. He later developed secondary acute myeloid leukemia. Clinical outcome was very poor in 3 out of 4 patients as reported in the literature. One patient survived chemotherapy followed by autologous transplant. The prototypical clinical presentation and variations of PBL can help create a more comprehensive differential diagnosis for GI tumors and establish an appropriate therapeutic guideline.

Publication Stats

1k Citations
398.68 Total Impact Points

Institutions

  • 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