Bone marrow involvement as initial presentation of CD8 cytotoxic peripheral T-cell lymphoma with CD20 coexpression and relatively indolent clinical course

Abstract Background: Blood eosinophilia results either from autonomous expansion of a myeloid stem/progenitor cell, or as a response to cytokines that promote growth and differentiation of eosinophil progenitors. A subset of patients with hypereosinophilic syndrome/idiopathic eosinophilia (HES/IE) display abnormal T-cell immunophenotype and/or clonal rearrangements of the T-cell receptor (TCR), operationally assigned the term “lymphocyte variant” HES/IE. Information on the prevalence, FIP1L1-PDGFRA status, and clinical course of such patients is limited. Methods: Consecutive patients with eosinophilia were identified by querying our institutional electronic database from 1995 to 2004. Clonal rearrangements of the γchain of the TCR were identified by polymerase chain reaction followed by gel electrophoresis in all cases, and confirmed by Southern Blot analysis of the gene coding for the β chain of the TCR, using standard methods. FIP1L1-PDGFRA was screened by fluorescence in situ hybridization. Results: We studied a total of 205 consecutive patients with eosinophilia defined as an absolute eosinophil count (AEC) of > 600/μL, who also had a bone marrow study performed. Of these, TCR gene rearrangements studies were performed in 99 patients (AEC range of 650 to 38,000/μL) including 3 children and 96 adults (age range 18 to 88 years; 58 males). Among these 99 patients, 14 (~14%) had a demonstrable T-cell clone in peripheral blood, bone marrow aspirate, lymph node, and/or skin. Six of the 14 patients with a demonstrable T-cell clone were found to have a concurrent T-cell malignancy at the time of evaluation including T-cell large granular lymphocytic (T-LGL) leukemia - 1 case and peripheral T-cell lymphoma - 5 cases. The other 8 (~8%) patients otherwise fulfilled the working diagnosis of “lymphocyte variant” HES/IE (median AEC=2045/μL, range 720/μL to 9600/μL). The median duration of eosinophilic prodrome, prior to identification of the occult T-cell clone was 5 years (range 3 months to 11 years), and virtually all had dominant skin involvement presenting as dermatitis (5 cases) or episodic angioedema with eosinophilia (EAE) (2 cases). Five of 7 patients tested had an elevated serum IgE level, and a similar proportion displayed an abnormal T-cell immunophenotype (most commonly, aberrant CD5 and/or CD7 expression). Six of the 8 patients with an occult T-cell clone were evaluated for FIP1L1-PDGFRA and tested negative. Two patients were effectively treated with low-dose oral cyclophosphamide or methotrexate (follow-up duration of 3+ and 6+ years, respectively) whereas imatinib treatment was ineffective in another 2 patients. Two patients (25%) transformed into cutaneous T-cell lymphoma after 3 to 8 years of eosinophilic prodrome. Conclusion: The current study suggests that the presence of a T-cell clone in idiopathic eosinophilia is a marker/harbinger of a primarily skin-based peripheral T-cell lymphoma that responds to T cell-directed therapy but not imatinib therapy, which is consistent with the absence of FIP1L1-PDGFRA in such cases.

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Tissue Is the Issue: Accuracy of PET Imaging to Detect Bone Marrow Clearance in Patients with Peripheral T-Cell Lymphoma

Blood ◽

10.1182/blood.v126.23.3947.3947 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3947-3947

Author(s):

Anthony Q Pham ◽

Stephen Broski ◽

Thomas M. Habermann ◽

Dragan Jevremovic ◽

Gregory Wiseman ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

T Cell Lymphoma ◽

Pet Scan ◽

Ct Scans ◽

Peripheral T Cell Lymphoma ◽

Pet Ct ◽

Pet Scans

Abstract INTRODUCTION: Adult mature T- and NK-cell neoplasms are a heterogeneous group of aggressive lymphomas comprising approximately 10% to 20% of all non-Hodgkin lymphomas (NHL) with an estimated 5-year overall survival of 40%. Staging and treatment strategies are guided by malignant involvement on PET/CT scan and bone marrow (BM) biopsy. The Lugano Criteria, established in 2014, suggested that focal FDG uptake within the bone marrow was highly sensitive for both Hodgkin (HL) and diffuse large B-cell lymphoma (DLBCL) potentially obviating the need for a bone marrow biopsy if no lesions were seen. Limited data exist regarding the sensitivity of PET for BM involvement in T-cell lymphoma. This study compares PET/CT scans and repeat BM biopsy in patients who have undergone treatment for peripheral T-cell lymphomas (PTCL) by evaluating BM avidity on PET scans. METHODS: This is a single institution study using the Mayo Clinic Lymphoma Database between January 1, 2001 and January 1, 2015. We retrospectively identified all patients with a diagnosis of PTCL, biopsy proven BM involvement at diagnosis, and a concomitant PET for staging. Patients were then reviewed to assess completion of induction therapy and availability of both PET/CT and bone marrow results post-therapy. Evaluation for concordance and discordant BM involvement were then determined using BM biopsy as the gold standard. RESULTS: Sixteen patients had both PET/CT and BM biopsy after completing induction therapy. Median age at diagnosis was 63 years (range 34-72) and 69% were male. PTCL subtype was peripheral T-cell lymphoma, not otherwise specified in seven patients; ALK negative anaplastic large cell lymphoma in one patient; and angioimmunoblastic in 8 patients. Pre-treatment PET/CT scans demonstrated eight patients (50%) with false negative scans. Post-treatment biopsy results demonstrated that ten (62.5%) had biopsy proven residual bone marrow involvement after induction. Eight patients (50%) were found to have BM biopsy proven disease with a negative PET scan. Two patients (12.5%) had both positive BM biopsy and PET scans; 5 patients (31.3%) had negative BM biopsies and PET scans. One patient (6.25%) had a negative BM biopsy, but had a PET scan that revealed positive disease. This patient was considered to have had a false positive PET scan and indeed has remained in remission since April 2009 without any further relapse or treatment. Sensitivity of PET for BM involvement was very poor at 20% (2/10) with a specificity of 50% (2/4) (Table 1 and 2). CONCLUSIONS: This study in PTCL indicates that PET scans at the completion of therapy have a 50% false negative rate. These patients should not be assumed to have negative bone marrow involvement based solely on PET/CT scans. A bone marrow biopsy at the end of therapy is necessary in PTCL patients to confirm complete response. Table 1. Bone Marrow Involvement Pre-Therapy PET Scan Imaging PET Negative PET Positive Total Patients Bone Marrow Negative NA NA NA Bone Marrow Positive 8 8 16 Total Patients 8 (50%) 8 (50%) 16 Abbreviations: NA, not applicable. The study defined that all patients had to have a positive bone marrow at baseline to be eligible for the study. Table 2. Bone Marrow Involvement PET Negative PET Positive Total Patients Bone Marrow Negative 4 2 6 (37.5%) Bone Marrow Positive 8 2 10 (62.5%) Total Patients 12 (75%) 4 (25%) 16 Table 1 and 2. Involvement of bone marrow with peripheral T-cell lymphoma based on evaluation by PET scans versus bone marrow biopsy. Disclosures Maurer: Kite Pharma: Research Funding.

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Analysis of Prognostic Factors for Survival in 75 Chinese Patients with Peripheral T-Cell Lymphoma (PTCL)

Blood ◽

10.1182/blood.v120.21.4852.4852 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4852-4852

Author(s):

Yue Han ◽

Jia Ruan ◽

Qian Zhu ◽

Xiaochen Chen ◽

Shixiang Zhao ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

T Cell Lymphoma ◽

Chinese Patients ◽

Peripheral T Cell Lymphoma ◽

Ki 67 ◽

Term Survival ◽

Β2 Microglobulin

Abstract Abstract 4852 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor clinical outcomes. The aim of this retrospective study was to correlate the clinical characteristics, risk factors, and treatment methods with overall survial in 75 Chinese patients with PTCL. Methods: Retrospective chart review was conducted to identify patients with newly diagnosed PTCL who were treated at our center from April 2004 to November 2011. Clinical information including demographics, histology, treatment, and survival were collected. Probability of overall survival was estimated using the Kaplan-Meier method. Univariate analysis and log rank test were used to correlate survival with prognostic variables. SPSS1 program (version 7.0) was used for statistic analysis. Results: A total of 75 patients were identified. The median age was 48 years (range 18–73), and M:F ratio was 2:1. Histologic subtypes included PTCL-not-otherwise specified (PTCL-NOS) (n=37, 49.3%), natural killer/T-cell lymphoma (NK/TCL) (n=25, 33.3%), anaplastic large cell lymphoma (ALCL) (n=11, 14.7%), and angioimmunoblastic T-cell lymphomas (AITL) (n=2, 2.7%). The induction chemotherapy consisted primarily of CHOP (n=49, 65.3%), hyperCVAD (n=12, 75%) and SMILE (n=4, 5.3%). Fifty-nine patients (79%) received chemotherapy alone, while 16 patients (21%) received additional autologous hematopoietic stem cell transplantation (HSCT). Of all the patients, overall survial (OS) at 5-year and 3-year were 41.5% and 64.1%, respectively. The 5-year OS was significantly better (P<0.05) in patients who 1) were less than 60 years (46.8% vs 24.5%, comparing to those older than 60); 2) had normal LDH (74.6% vs 24.2%, comparing to high LDH; 3) had IPI score ≤2 (46.5% vs 22.4%, comparing to IPI score>2); 4) had HSCT (80% vs 30.8%, comparing to those receiving chemothrapy only). OS at 5-year for patients treated with chemotherapy alone was lower with CHOP compared to more intensive regimens (28.7 vs 71.3%, P<0.05). Meanwhile, OS at 5-year was higher in patients treated with etoposide containing chemotherapy (60% vs 27.4%, P<0.05). The 3-year OS was higher (P<0.05) in those with 1) normal β2-microglobulin (92.9% vs 49.3%, comparing to elevated β2-microglobulin), 2) Ki-67<10% (86.2% vs 47%, comparing to Ki-67≥10%), 3) PIT score ≤2 (70% vs 28.6%, comparing to PIT score>2). In addition, failure to achieve complete remission after chemotherapy and bone marrow involvement were correlated to poor survival. Conclusion: Chinese patients with PTCL have heterogeneous and generally poor outcomes. Bone marrow involvement, older age, elevated LDH, high β2-microglobulin, Ki-67≥10%, IPI >2 and PIT >2 were associated with inferior survival. Intensive chemotherapy and HSCT may improve the long-term survival of PTCL. Disclosures: No relevant conflicts of interest to declare.

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Bone Marrow Involvement by Peripheral T-cell Lymphoma, Not Otherwise Specified

Pathology Case Reviews ◽

10.1097/pcr.0b013e31825aa5f5 ◽

2012 ◽

Vol 17 (3) ◽

pp. 125-129

Author(s):

Ellen Flatley ◽

Guang Fan

Keyword(s):

Bone Marrow ◽

T Cell ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Not Otherwise Specified

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Peripheral T-cell Lymphoma, NOS With Epstein-Barr Virus Positivity in an Elderly Patient With Myelodysplastic Syndrome: An Autopsy Case Report

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.178 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S81-S81

Author(s):

J Lanceta ◽

W Xue ◽

M Hurford ◽

H Wu

Keyword(s):

Bone Marrow ◽

T Cells ◽

Lymph Node ◽

T Cell ◽

Epstein Barr Virus ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Barr Virus ◽

Epstein Barr

Abstract Casestudy Epstein-Barr virus (EBV)-associated peripheral T-cell lymphomas are a group of aggressive neoplasms with a geographic predilection for South America and Asia, but are very rare in Western populations. Results We report a case of a 74-year-old Caucasian female who presented with pancytopenia and B symptoms with EBV-IgG detected on admission. Past medical history included: ITP, chronic urticaria, and recently diagnosed myelodysplastic syndrome (MDS) on bone marrow biopsy one month prior to admission. Excisional biopsies of an enlarged right neck lymph node (repeated within 6 months) and right axillary lymph node five years ago were negative for a lymphoproliferative disorder at the time. Repeated bone marrow biopsy, performed during the current admission, confirmed the diagnosis of MDS, with scattered T-cells without aberrant immunophenotype. Despite aggressive treatment from multiple specialties, the patient deteriorated and expired four weeks later from complications of MDS. At autopsy, there was diffuse lymphadenopathy involving the mediastinum, axilla, pelvis and peripancreatic fat. Lymph node sections demonstrated nodal architecture effacement by diffuse, vaguely nodular lymphoid infiltrates. Histologically, the infiltrates were composed of medium to large lymphocytes with round to slight irregular nuclei, rare Reed-Sternberg-like multinucleated cells, clumped chromatin, and indistinct nucleoli. Individual cell necrosis was abundant with mitotic figures readily identifiable. Immunohistochemistry revealed CD2+ CD3+ neoplastic T-cells that co-express MUM1 and a subset of CD30, while negative for CD4, CD5, CD8, CD56, ALK1, and TDT. EBV-encoded RNA in-situ hybridization was focally positive. The final postmortem diagnosis was peripheral T-cell lymphoma, not otherwise specified (NOS), with focal EBV positivity. Conclusion Co-existence of a de-novo MDS and non-Hodgkin lymphoma without any prior chemotherapeutic exposure is a highly unusual finding, although MDS-like presentations can occur with EBV-associated lymphomas. Peripheral T-cell lymphoma, NOS is an aggressive lymphoma and EBV positivity has been found correlated with a poor prognosis. This case demonstrates how postmortem examination remains an important tool in clinical- pathological correlation and highlights the potential pathogenetic role EBV plays in MDS and T-cell lymphoma.

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Bone marrow transplantation for peripheral T-cell lymphoma in children and adolescents

Blood ◽

10.1182/blood.v80.11.2938.2938 ◽

1992 ◽

Vol 80 (11) ◽

pp. 2938-2942 ◽

Cited By ~ 21

Author(s):

BG Gordon ◽

PI Warkentin ◽

DD Weisenburger ◽

JM Vose ◽

WG Sanger ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

T Cell ◽

Phase I ◽

Children And Adolescents ◽

Marrow Transplantation ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

The Other ◽

Peripheral T Cell Lymphoma

Abstract We report nine children with relapsed (n = 8) or high-risk (n = 1) peripheral T-cell lymphoma (PTCL) who underwent autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16. The median age of these patients at time of BMT was 6.5 years (range 2.5 years to 14 years). Three were transplanted with active disease after failing salvage chemotherapy. Of the other six, one was transplanted in first complete remission (CR) and five in second or subsequent CR. Of these nine patients, eight are free of disease a median of 25 months after BMT (range, 6 to 48 months), with an estimated 2-year relapse-free survival (RFS) of 89%. Six of these eight patients have been followed for 12 or more months after BMT, and in each their current remission exceeds their longest previous remission duration. The toxicity of the TT/TBI +/- VP-16 regimens was significant but manageable, predominantly consisting of severe mucositis. For a comparison, we reviewed retrospective data on the six additional children and adolescents with PTCL who underwent BMT during the 3-year period preceding this phase I/II study. The median age at BMT of these six patients was 19 years (range 15.5 years to 20 years). These patients were prepared for BMT with a variety of other regimens. One had no response to BMT and the other five relapsed at 1.5 to 5 months after BMT (median, 3 months) with an RFS of 0%. Our data suggest that thioTEPA plus TBI, with or without VP-16, is an effective preparative regimen for BMT for young patients with relapsed or high-stage PTCL and leads to prolonged RFS.

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