Achievement of FDG-PET Negativity Does Not Predict Durable Responses in T-Cell Lymphoma.

Abstract Background: T-cell non-Hodgkin’s lymphomas represent approximately 12% of all lymphomas and in general are associated with a worse prognosis compared to their B-cell counterparts. In patients with Hodgkin’s disease and aggressive B-cell lymphoma (18F)fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) represents an important early prognostic tool for predicting outcome. Very little information is available regarding the role of FDG-PET in T-cell lymphoma. Patients and Methods: A total of 20 patients with newly diagnosed and histologically proven T/NK cell lymphomas where staged with both conventional methods and whole-body PET scanning. Patients underwent FDG-PET, concurrently with CT of neck, chest, abdomen, and pelvis within 3 weeks prior to induction treatment, after 2–4 cycles, and after the end of induction. All patients but three received HCVIDDoxil, using pegylated liposomal doxorubicin as a substitute for doxorubicin in the HyerCVAD regimen, alternating with methotrexate and cytarabine. Three patients received the standard CHOP (cyclophosphamide,hydroxydaunomycin, vincristine, prednisone) regimen. According to the International Prognostic Index (IPI), 35% of patients were stratified as low risk, 25% as low/intermediate, 35% as high/intermediate, and 5% as high risk. Baseline scans were strongly positive in all patients. Results: During induction therapy (at 2–4 cycles) FDG-PET became negative in 16 (80%) patients and remained positive in 4 (20%) patients. Twelve out of 16 (75%) patients who were PET negative during induction therapy relapsed, and four out of four (100%) in the PET positive group. Two of the “ early” PET negative patients became positive after 4 cycles. Median progression-free survival was 240 days in the PET negative group and 85 days in the PET positive group (Log-rank p=0.07). Conclusions: In this limited number of patients homogeneously treated with newly diagnosed T cell lymphomas the assessment of metabolic activity by FDG-PET during induction therapy did not predict long-term prognosis.

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Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately?

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.6.725 ◽

1989 ◽

Vol 7 (6) ◽

pp. 725-731 ◽

Cited By ~ 56

Author(s):

A L Cheng ◽

Y C Chen ◽

C H Wang ◽

I J Su ◽

H C Hsieh ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Induction Chemotherapy ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

High Grade ◽

Peripheral T Cell Lymphoma ◽

Laboratory Features ◽

Hodgkin's Lymphomas

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.

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Alemtuzumab in Combination with CHOP and ESHAP as First-Line Treatment in Peripheral T-Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.4740.4740 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4740-4740 ◽

Cited By ~ 3

Author(s):

Tanin Intragumtornchai ◽

Udomsak Bunworasate ◽

Thanyaphong Na Nakorn ◽

Ponlapat Rojnuckarin

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Pneumocystis Carinii ◽

Elevated Serum ◽

T Cell Lymphoma ◽

Newly Diagnosed ◽

Bulky Disease ◽

T Cell Lymphomas ◽

Hodgkin's Lymphomas ◽

Cmv Disease

Abstract Patients diagnosed with peripheral T-cell lymphomas (PTCL) generally had a poorer prognosis compared to B-cell non-Hodgkin’s lymphomas. With conventional treatment, the 5-year overall and failure-free survivals (OS and FFS) were 36% and 23%, respectively (Vose et al, Blood2005;106:abstract 811). Between February 2005 and January 2006, 13 consecutive patients newly diagnosed with PTCL (5, extranodal nasal NK/T-cell lymphoma, 4 subcutaneous panniculitis-like, 3 PTCL, unspecified and 1 enteropathy type) were enrolled. The median age was 44 years (range, 21–56) and male:female was 1.6:1. Fifty-four percent had stage III/IV, 31%, PS 2–3, 69%, B-symptoms, 15%, bulky disease, 46%, > 1 extranodal site, 38%, elevated serum LDH and 39%, aaIPI 2–3. Twenty-three percent had thrombocytopenia. Patients were treated with alemtuzumab 30 mg. sc. D1-3 of cycle 1–5 plus CHOP (day 1 of cycle 1, 3, 5) and ESHAP (day 1 of cycle 2, 4, 6) at 28-day intervals. Valacyclovir 500 mg tid and trimethoprim/sulfamethoxazole were given for prophylaxis of CMV and Pneumocystis carinii infection, respectively. Of the evaluable 10 patients, complete remission was obtained in 8 patients, 1 had partial remission and 1 had CNS progression while on treatment. Infection was a major adverse complication: 54% had CMV reactivation (1 had CMV disease), 54%, febrile neutropenia and 15%, tuberculosis. With a median follow-up time of 8 months, the 2-year OS and FFS were 75% (95%CI, 41–92) and 48% (95%CI, 14–76), respectively. From the standpoint of this result, alemtuzumab in combination with CHOP and ESHAP is an effective front-line therapy for patients newly diagnosed with PTCL.

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The Role of An Early Interim 18 F-FDG PET/CT for Prediction of Outcomes of Patients with Peripheral T Cell Lymphoma

Blood ◽

10.1182/blood.v112.11.5272.5272 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5272-5272

Author(s):

Yoon Hee Choi ◽

Byung Woog Kang ◽

Hyun Soo Hong ◽

Chul Kim ◽

Geundoo Jang ◽

...

Keyword(s):

T Cell ◽

Fdg Pet ◽

Cell Lymphoma ◽

Initial Therapy ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Positive Group ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Background Recent studies have demonstrated that positron emission tomography (PET) performed after one to four cycles of multiagent chemotherapy predicts therapeutic outcome in lymphomas which are mainly diffuse large B cell lymphoma and Hodgkin’s lymphoma. However, interim 2-[18F] fluoro-2-deoxy-D-glucose (FDG) PET/CT has not yet been discussed in peripheral T cell lymphoma. In this study, we investigated the role of an interim 18 F-FDG PET/CT for the prediction of the progression free survival (PFS) and overall survival (OS) in peripheral T cell lymphoma. Patients and methods We retrospectively analyzed the medical records of thirty-three patients with newly diagnosed, initially FDG-avid peripheral T cell lymphoma between 2004 and 2007 (median age of 44 years, 18 peripheral T cell lymphoma, unspecified, 9 anaplastic large cell lymphoma, 6 angioimmunoblastic T cell lymphoma) who underwent 18F-FDG PET/CT after one to four cycles of chemotherapy (interim scan). The maximal response to initial therapy was evaluated using conventional methods. Interim FDG-PET/CT results were correlated to the PFS and OS using Kaplan-Meier survival analysis. Cox regression analyses were performed for independence of prognostic factors. Results The median follow up was 23 months (range, 2–52 months). In the initial therapy, 25 patients achieved CR, 5 patients showed progress and 3 patients died. Interim FDG-PET/CT was negative in 17 patients, positive in 9, and 7 patients showed minimal residual uptake (MRU). The CR rate of initial therapy was 100%, 85% (6/7) and 22% (2/9) in the FDG negative, MRU and positive group, respectively. The estimated 2 year PFS was 88.2% for the negative group, 38.3% for the MRU group, and 0% (median survival of 5.6 months) for the positive group. The log rank test showed strong associations between interim FDG-PET/CT results and PFS (P =0.001) and OS (P <0.001). Also, univariate and multivariate analyses showed that the interim FDG-PET/CT was the only independent factor to predict outcomes among known prognostic factors such as age, elevated lactate dehydrogenase, the number of extranodal disease, stage, performance status (p=0.007). Conclusion Interim FDG PET/CT is an excellent and independent predictor of outcomes of patients with peripheral T cell lymphoma and is suggested to be a useful tool to modify the therapy.

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Expression of Cancer-Testis Antigens in Non-Hodgkin’s Lymphomas

Blood ◽

10.1182/blood.v112.11.5281.5281 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5281-5281

Author(s):

Riguel Jun Inaoka ◽

Gisele W. B. Colleoni ◽

Leina Yukari Etto ◽

Antonio Correa Alves ◽

Marcello Fabiano de Franco ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Lymphoma ◽

Malignant Tumors ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

Ct Antigen ◽

Ct Antigens ◽

Hodgkin's Lymphomas ◽

Cancer Testis

Abstract Cancer-testis (CT) antigens are expressed in a variety of malignant tumors but in normal adult tissues solely in testicular germ cells. Based on this tumor-associated expression pattern, CT antigens are considered valuable targets for immunotherapy. While CT antigens have been studied in many solid tumors, much less is known about their presence in neoplasms of the hematopoetic system such as Non Hodgkin’s Lymphoma (NHL). Aims: To analyze the expression of 10 CT antigens in NHL by immunohistochemistry (IHC) using tissue microarray (TMA) technology, and to correlate its expression with histologic subtypes. Patients and Methods: Formalin-fixed paraffin-embedded tissues of 116 NHL cases dating from June 2003 to June 2007 were retrieved from the archives of the Department of Pathology, Federal University of São Paulo, Brazil. Two TMA blocks were generated comprising three cores/NHL case, as well as positive (testis) and negative (reactive lymph nodes) control tissue cores. The following monoclonal antibodies (mAbs) (to the following antigens) were used for IHC analysis: MA454 (MAGE-A1), M3H67 (MAGE-A3), 57B (MAGE-A4), CT7-33 (CT7/MAGE-C1), CT10#5 (CT10/MAGE-C2), E978 (NY-ESO-1), 219-510-23 (LAGE-1 and NY-ESO-1), #26 (GAGE) and SSX-2#7 (SSX-2). Two observers scored all slides independently and cases with loss of all three punches and/or missing tumor tissue were excluded from analysis. Results: The number of cases which could not be evaluated due to loss of tissue core and/or missing tumor differed, ranging between 8 for mAb #26 to 12 for mAbs MA454, CT10#5 and 219-510-23. 7/116 NHL cases were missing in all slides. 14/109 (12.8%) NHL cases expressed at least one CT antigen: diffuse large B-cell lymphoma (DLBCL) 9/58 (15.5%); anaplastic large cell lymphoma (ALCL) 1/3; follicular lymphoma (FL) 1/10 (10%); lymphoplasmacytic lymphoma (LPL) 1/3; peripheral T-cell lymphoma (PTCL) 1/9 and histiocytic lymphoma (HL) 1/1. No CT antigen expression was present in lymphoblastic lymphoma (5), mantle cell lymphoma (2), small lymphocytic lymphoma (6), marginal zone lymphoma (4), MALT lymphoma (5) and mycosis fungoides (3). The most frequently expressed CT antigens were: GAGE 6/108 (5.5%), NY-ESO-1 5/105 (4.7%), CT7 5/106 (4.7%), MAGE-A1 4/104 (3.8%) and MAGE-A3 4/107 (3.7%). According to cell origin, positivity of CT antigens was more prevalent in B-cell NHL (11/91; 12.1%) than in T-cell NHL (1/15; 6.7%). NY-ESO1 5/91(5.5%) was the most frequently expressed CT in B-cell NHL, followed by GAGE 4/91 (4.4%), MAGE-A1 3/91 (3.3%), MAGE-A3 3/91 (3.3%), CT7 3/91 (3.3%) and LAGE 3/91 (3.3%). The only positive T-cell lymphoma case expressed MAGE-A1 and GAGE. Conclusions: Expression of CT antigens in NHL is limited. In the present TMA-based IHC analysis, only 12% of NHLs express at least one CT antigen, with DLBCL showing the highest incidence and NY-ESO-1 being the most prevalent antigen. In spite of the low incidence, presence of CT antigens could offer the opportunity of vaccine-based immunotherapy in selected cases of NHL.

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Clinicopathological Features of Malignant Lymphoma in JAPAN- Data From the Miyagi Study.

Blood ◽

10.1182/blood.v114.22.4997.4997 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4997-4997

Author(s):

Yukiko Miura ◽

Joji Yamamoto ◽

Katsura Kohata ◽

Kenichi Ishizawa ◽

Ryo Ichinohasama ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Malignant Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Clinicopathological Features ◽

T Cell Lymphoma ◽

Newly Diagnosed ◽

Malignant Lymphomas ◽

Miyagi Prefecture

Abstract Abstract 4997 Background Malignant lymphoma comprises a diverse group of histologic categories. To date, several epidemiological studies in Japan have been reported, however, the data were collected from selected representative institutions, therefore, the results might not reflect the actual incidence and characteristics of malignant lymphoma in Japan. The Miyagi Study is a comprehensive epidemiologic study of malignant lymphoma, including immunologic and genetic information, constructed by a population-based registration system covering Miyagi prefecture, Japan. The population composition by age group and the population growth rate in Miyagi resembles national average figures, therefore, the clinicopathological features of in the Miyagi Study are likely representative of Japan. The purpose of this study was to determine the relative incidences and features of malignant lymphoma subtypes in Japan, compared to that of other countries. Methods A total of 1546 cases of malignant lymphoma newly diagnosed between 2002 and 2008 in Miyagi prefecture, of which the population is about 2.5 million, were enrolled in the Miyagi Study. Clinical and histopathological data including results of flow cytometry(FCM), immunohistochemistry (IHC), G-banding analysis with or without bicolor fluorescence in situ hybridization(FISH), southern blot analysis with or without polymerase chain reaction(PCR) were collected, and analysed. Results The median age of onset was 66 years and the male/female ratio was 1.13. Of the 1546 cases of newly diagnosed malignant lymphoma, 1160 cases (75%) were B-cell lymphomas, 287 cases (19%) were T-cell lymphomas, and only 81 cases (5%) were Hodgkin lymphomas. The most frequent subtype of B-cell lymphoma was diffuse large B-cell lymphoma (DLBCL), accounting for 52% of all B-cell lymphoma cases, followed by follicular lymphoma (FL) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), accounting for 24% and 8% of B-cell lymphoma cases, respectively. The most frequent subtypes of T/NK-cell lymphoma were peripheral T-cell lymphoma, unspecified (PTCLU), angioimmunoblastic T-cell lymphoma(AILT) and adult T-cell lymphoma, accounting for 30%, 15% and 14% of cases, respectively. The relative frequency of malignant lymphoma subtypes was similar to that of Japan reported in 2000 by Lymphoma Study Group of Japanese Pathologists, though there were some differences, such as the high incident rate of FL. There was not a notable time trend in the proportion of FL in B-NHL through 7 years, since it accounted for 20.3% in 2002 and 24.0% in 2008. Within the B-cell lymphoma group, there was a higher frequency of indolent B-cell lymphomas in women (39.8%) compared to men (29.8%). The rates of CD20 and CD22 positivity, as analysed by FCM, were 94.9% and 96.3% in DLBCL, 99.2% and 98.4% in FL, and 98.4% and 100% in MALT lymphoma, respectively. The t(14;18) translocation, a frequent chromosomal abnormality of FL, was present in 63.9% of FL patients, which is less frequent compared with the reports from western countries. De novo CD5+ DLBCL, which is known to have poor outcome, accounted for 21.6% of DLBCL, a frequency higher than previously reported. Conclusions The relative frequency of the subtypes of malignant lymphomas in Miyagi is distinct from that of Western countries and shares some similarities with other Asian countries. In the present study, FL was found to be the second largest subtype of malignant lymphoma, consistent with previous reports that FL is increasing in Far East Asia including Japan, Korea and Taiwan. The results of this study reveal the clinicopathologic characteristics of malignant lymphomas in Japan. Disclosures No relevant conflicts of interest to declare.

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Negative Interim FDG-PET Scan Is Predictive of Superior Outcome in T Cell Lymphoma.

Blood ◽

10.1182/blood.v114.22.1956.1956 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1956-1956 ◽

Cited By ~ 1

Author(s):

Carla Casulo ◽

Andrew D. Zelenetz ◽

Craig H Moskowitz ◽

Steven M. Horwitz

Keyword(s):

T Cell ◽

B Cell ◽

Fdg Pet ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Lymphoma ◽

Large B Cell Lymphoma ◽

T Cell Lymphomas ◽

Pet Scans ◽

Large B Cell

Abstract Abstract 1956 Poster Board I-979 Background: Fluoro-deoxy-glucose positron emission tomography (FDG-PET) is a required staging study for diffuse large B-cell lymphoma and Hodgkin lymphoma. Numerous studies have demonstrated that FDG-PET performed after one to four cycles of multiagent chemotherapy (interim restaging) is predictive of outcome, with relapse rates much higher in patients with positive FDG-PET scans at interim restaging. The prognostic role of FDG-PET in T-cell lymphoma however is unclear and has yet to be well defined. Small retrospective studies have demonstrated FDG-PET avidity of T-cell lymphoma. Our experience confirms that the great majority of patients with mature T or NK lymphomas have FDG-PET avid disease. We hypothesized that the interim FDG-PET (int FDG-PET) may have prognostic importance in patients with T-cell lymphomas as they do in diffuse large B-cell lymphoma and Hodgkin lymphoma. Methods: We reviewed our T-cell lymphoma database to identify patients with mature T or NK lymphomas who had FDG-PET scans as part of complete staging at initial diagnosis as well as repeat PET imaging as part of restaging. Inclusion criteria required FDG-PET avid disease at baseline and treatment administered with curative intent. Results: We reviewed fifty four patients who met the above criteria. Histologies were as follows: peripheral T-cell lymphoma NOS (N=18), angioimmunoblastic T-cell lymphoma (N=5), anaplastic large cell lymphoma ALK-1- (N=15), anaplastic large cell lymphoma ALK-1+ (N=3), and other subtypes (N=13). Patients received a variety of initial chemotherapy regimens including CHOP (N=18), EPOCH (N=6), CHOP/ICE (N=20) or other treatments provided with curative intent. Twenty two patients were consolidated with high dose therapy and either autologous (N=18), or allogeneic (N=4) SCT. Fifty nine percent were PET negative at interim restaging (32/54), 7.4% were positive (4/54), 22 % were not available (12/54), and 11% had equivocal scans (6/54). Median follow up was 17 months. Median PFS for the entire group was 15 months. Median OS for the entire group was 40 months. The median OS of patients with negative int FDG-PET has not been reached, compared to the OS of patients with positive int FDG-PET of 10.2 months (p<.001). Patients with equivocal int FDG-PET had a median OS of 62 months, which was statistically superior to patients with positive int FDG-PET (p=.02). There was no significant difference in median OS in patients with negative versus equivocal int FDG-PET. Similar to what was observed in OS, the median PFS of patients with negative int FDG-PET has not yet been reached, compared to the PFS of patients with a positive int FDG-PET of 4.8 months (p=<.001). Patients with equivocal int FDG-PET had a statistically improved PFS of 16 months when compared to those with a positive int FDG-PET (p<.01). Patients with equivocal int FDG-PET had similar outcomes to patients with a negative int FDG-PET, and superior to those with a positive int FDG-PET, whose results were very poor. Conclusions: In this dataset, interim PET scans are strongly predictive of outcome. Patients with negative int FDG-PET enjoyed significantly longer remissions and better overall survival. Patients with negative int FDG-PET were more likely to receive consolidative therapy, which may contribute to their superior outcomes. This may be a potentially confounding factor. Nonetheless, achievement of a negative int FDG-PET appears to be a reliable predictor of outcome in patients with T-cell lymphomas and may have similar prognostic importance in these patients as they do in diffuse large B-cell lymphoma and Hodgkin lymphoma. It is reasonable to consider int FDG-PET in the restaging of patients with T-cell lymphomas. Disclosures: Zelenetz: Millenium Advisory board: Membership on an entity's Board of Directors or advisory committees. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding.

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