High-grade T-cell Lymphoma Research Articles

Outcomes and prognostic factors in canine T cell lymphoma treated with lomustine, vincristine, cyclophosphamide, and prednisone chemotherapy

BackgroundThe most common first-line treatment for canine lymphoma is a chemotherapy protocol that includes cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Canine high-grade T-cell lymphoma has been found to have a significantly poorer prognosis than high grade B-cell lymphoma. Several studies have investigated alternative protocols for non-indolent T-cell lymphoma. This retrospective study investigated using a cyclophosphamide, lomustine, vincristine, and prednisone protocol (CLOP) for naïve non-indolent T-cell lymphoma patients.MethodsIn this retrospective study, medical records of dogs treated for non-indolent T-cell lymphoma at a veterinary teaching hospital from 2017 to 2022 were reviewed. Response rate, toxicity, progression-free survival and survival time were calculated. Factors potentially related to prognosis were statistically analyzed.ResultsTwenty-six dogs were included in the study. The median progression-free survival (PFS) time was 166 days (95% CI 119–213). The median overall survival time (OST) for the whole study group was 318 days (95% CI 239–374). Twenty-four dogs experienced gastrointestinal adverse events during the protocol, with 79% of them being grade 1 or 2 as per VCOG-CTCAE v2.ConclusionsThis protocol has shown similar median PFS time and OST compared with previous studies for canine non-indolent T-cell lymphoma treated with CHOP, along with minimal toxicity, and suggests the inclusion of lomustine in first-line chemotherapy protocol against canine non-indolent T-cell lymphoma may be beneficial.

Prognostic role of the updated Kiel classification in canine high-grade T-cell lymphomas.

The aim of this study was to determine and describe the prognostic role of the morphological subtype determined according to the updated Kiel classification in dogs with high-grade T-cell lymphomas (HGTCLs) depending on the treatment applied. The HGTCLs were classified into three subtypes according to the updated Kiel classification: pleomorphic mixed (PM), lymphoblastic lymphoma/acute lymphoblastic leukaemia and plasmacytoid (P). The treatment was divided into a palliative therapy (PlT) group and a chemotherapy (ChT) group. The study was conducted between 2009 and 2017, and it enrolled 58 dogs in which cytomorphological and immunocytochemistry diagnoses were HGTCL. Overall survival (OS) was significantly longer in the ChT group (median OS-4 months, interquartile range [IQR] from 2 to 8 months) than in the PlT group (median OS-6 weeks, IQR from 1 week to 3 months). In the PlT group, PM subtype and glucocorticosteroids (GCSs) treatment proved significantly and independently linked to longer OS and approximately three-fold lower risk of death during the study period (adjusted hazard ratio [HRadj] = 0.26, confidence interval [CI] 95%: 0.08-0.81; p = 0.020 and HRadj = 0.30, CI 95%: 0.11-0.77; p = 0.013, respectively), although due to small group size, precision of estimations was poor (wide CI 95%). In the ChT group, >7 days elapsing between diagnosis and the beginning of chemotherapy and GCS treatment prior to chemotherapy were significantly associated with lower chance of complete remission (CR; p = 0.034 for both); GCS treatment prior to chemotherapy was significantly associated with shorter OS (p = 0.016); chemotherapy based on the modified CHOP protocol was significantly associated with higher chance of CR (p = 0.034) and longer OS (p = 0.039); and CR was significantly linked to longer OS (p = 0.001). The morphological subtype of HGTCL has some prognostic value in dogs treated palliatively (with PM subtype associated with longer OS than P subtype); however, this effect is no longer visible when a dog is treated with chemotherapy.

A case of nerve sheath tumor followed by multicentric high-grade T-cell lymphoma in an African pygmy hedgehog (Atelerix albiventris).

A 3-year-old intact male African pygmy hedgehog was presented at the Teaching Hospital of the Faculty of Veterinary Medicine, University of Belgrade, with a growth on the left side of its abdomen. After clinical examination, the mass was surgically removed, and histopathological findings indicated a nerve sheath tumor. The hedgehog fully recovered after surgery and was euthanized eight months later due to the appearance of multicentric changes in the internal organs. Further necropsy and macroscopic, cytologic, histopathologic, and immunohistochemical findings revealed that the tumor was a multicentric high-grade T-cell lymphoma. This is an unusual case of an African pygmy hedgehog with two different neoplasms - a nerve sheath tumor followed by lymphoma.

Randomised trial evaluating chemotherapy alone or chemotherapy and a novel monoclonal antibody for canine T-cell lymphoma: A multicentre US study.

Canine peripheral nodal T-cell lymphoma is considered chemotherapy resistant and carries a relatively poor prognosis. Prospective evaluations reporting the impact of chemotherapy on progression-free survival (PFS) and overall survival time for dogs with T-cell lymphoma are lacking. This study examined the impact of L-CHOP (L-asparaginase, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy or L-CHOP in combination with AT-005, a US Department of Agriculture-licensed caninised monoclonal antibody, on PFS and response rates in dogs with clinical intermediate- and high-grade peripheral nodal T-cell lymphoma. A prospective, randomised, placebo-controlled, investigator- and owner-blinded, multicentre study was completed. All dogs received a 19-week L-CHOP chemotherapy protocol with randomisation (1:1) into placebo or AT-005 groups. Response was evaluated via the Veterinary Cooperative Oncology Group criteria for canine lymphoma. Forty-nine dogs were enrolled (25 received placebo and 24 received AT-005). Most demographic factors were similar between the two groups, with the exception that more dogs with stage IV and V disease were treated with AT-005 (34% vs. 8%; p = 0.03). Median PFS was 103 days (95% confidence interval [CI], 56-118) in the placebo group versus 64 days (95% CI, 36-118) in the AT-005 group. The overall response rate (ORR) for all dogs was 98% (48 of 49); complete response rate in the placebo group (64%) was not different from the AT-005 group (67%). To the best of the authors' knowledge, this is the first prospective study to document that treatment with L-CHOP chemotherapy, with or without AT-005, may result in a high ORR, but relatively brief PFS in dogs with clinical intermediate- and high-grade T-cell lymphoma.

TCL-525 Salivary Myeloid Sarcoma: A Challenging Diagnosis.

A female in her late 30s from North Africa with no past medical history presented with four months of an expanding left face and neck mass that led to facial disfigurement (Viral screen HIV, HCV & HBV negative, EBV unknown). Ultrasound of the neck showed an enlarged left submandibular salivary gland with increased echogenicity with a surrounding inflammatory process and reactive lymphadenopathy, and no visible stone. Magnetic resonance imaging (MRI) of the neck revealed an infiltrating soft tissue enhancing mass surrounding the left side mandibular body, and it was locally infiltrating the left side submandibular, sublingual salivary gland left parotid, left side masseter muscle, myeloid muscle, and left side medial pterygoid muscle, and prominent bilateral cervical lymphadenopathy. Contrast tomography (CT) of the neck, chest, abdomen, and pelvis was unremarkable apart from cervical lymphadenopathy. Biopsy of the submandibular gland immunohistochemistry (LCA, BCL2, CD7 +VE, & focally for CD3 & CD5, while they are negative for PanCK. CD20, PAX5, CD79a, MUM1.BCL6.CD30, CD2, CD56, & TdT, Ki67 40%) suggested the diagnosis of high-grade T-cell lymphoma. Bone marrow biopsy was normal. The patient received five cycles of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP). A follow-up CT scan and positron emission tomography (PET) scan showed stable disease size and hypermetabolism. Revision of immunohistochemistry was strongly positive for CD45, CD33, CD34, CD43 and CD107, and negative for CD3, CD4, CD8, CD30, CD68, CD11c, CD20, CD79a and MPO. The diagnosis was updated to myeloid sarcoma (granulocytic sarcoma). The patient received 7+3 doxorubicin and cytarabine with impressive results clinically, followed by 3 high-dose cytarabine consolidation. Three months following completion of treatment, facial swelling recurred, and a PET scan showed hypermetabolic activity consistent with recurrence. The patient is undergoing salvage therapy (cytosar & etoposide) in preparation for a bone marrow transplant. We present a challenging case of salivary gland myeloid sarcoma that was initially misdiagnosed as T-cell lymphoma; interestingly, her bone marrow was not involved at the time of diagnosis. A high index of suspicion is warranted in CD3 negative and CD20 negative lymphoma, and expanded immunohistochemistry earlier may improve diagnosis.

Renal lymphoma diagnosed on kidney biopsy presenting as acute kidney injury

Introduction:Renal manifestations associated with hematolymphoid malignancies are known. Primary or secondary involvement of the kidney by lymphomatous infiltration has various clinical presentations. Acute kidney injury is not an uncommon finding in relation to lymphomatous interstitial infiltration proven on kidney biopsy. However, diagnosing it solely on renal biopsy remains a challenge and needs expertise and aid of immunohistochemistry as the prognosis is dismal.Methods:This is a retrospective study of kidney biopsy-proven cases of renal lymphoma presenting with acute kidney injury.Results:The study included 12 patients with ages ranging from 4 to 50 years who presented with serum creatinine ranging 2.1–9.6 mg%. Renal biopsy findings showed interstitial lymphomatous infiltrate. Two cases were diagnosed as primary lymphoma and the other 10 as secondary lymphomas. Among the 12 cases, nine were B-cell non-Hodgkin lymphoma, of which diffuse large B-cell lymphoma was diagnosed in six (50%), low-grade B-cell type in two (16.6%), chronic lymphocytic leukemia in one (8.3%), and three were T-cell-type. Two were acute T-cell lymphoblastic lymphoma and one other was a high-grade T-cell lymphoma. Four patients succumbed. The other four patients are alive; one is on chemotherapy, while two of them are on hemodialysis.Conclusion:Acute kidney injury as a presenting feature with lymphomatous infiltration of renal parenchyma is not uncommon. The patchy involvement makes it challenging on kidney biopsy with definitive diagnosis being made with the help of immunohistochemistry. Appropriate multidisciplinary involvement improves patient outcome.

Hematological and biochemical profiles of canine CD45- T lymphomas are different from other immunophenotypes.

Background:Canine multicentric lymphomas are lymphoproliferative malignancies that have increased in recent decades. The patient’s treatment and prognosis are determined by the grade, histological type, and lymphoma immunophenotyping. Aim:To investigate the paraclinical signs and survival time in canines with different lymphoma immunophenotypes.Methods:Over 2 and a half years, 47 untreated dogs were diagnosed with multicentric lymphoma at the Veterinary School Hospital of Uruguay. The disease was clinically and cytologically diagnosed, and immunophenotyping was determined by flow cytometry. After the immunophenotyping, most of the patients were grouped into the following: B (LB), T aggressive (LTCD45+), or T-zone lymphoma (LTCD45−). The patients’ haematological values, calcemia, lactate dehydrogenase (LDH) levels, and plasmatic electrophoretic profiles were all determined immediately after that. Results:Of all canine lymphomas, 55.3% were B, 31.9% were LTCD45+, and 10.6% were TCD45−. Only 2.2% were classified as nonB/nonT, and survival time differed between groups. Patients with LTCD45− lymphomas had a mean life span of 641 days after diagnosis, followed by LB (166 days) and LTCD45+ (62 days). Red blood cell count, hematocrit, and hemoglobin levels did not differ between groups. However, the LTCD45− group had significantly higher lymphocyte levels than the LTCD45+ and LB groups (p = 0.01 and 0.006, respectively). Levels of albumin, alpha-1, and alpha-2 globulins did not differ between groups. On the other hand, gamma globulins levels in the LTCD45− were higher than in the other lymphoma groups. The presence of hypercalcemia and high plasma LDH levels were associated with patient severity. Only the TCD45+ group had hypercalcemia although both the LB and TCD45+ groups had elevations in LDH activity. Interestingly, there was a direct relationship between high LDH values (greater than 500 IU/l) and lower survival in TCD45+ lymphomas. Conclusion:Survival time and hematological and biochemical patterns differed among canine lymphomas immunophenotypes. Patients of LTCD45− phenotype showed higher lymphocyte counts and gamma globulin levels and more prolonged survival. Serum LDH activity may provide additional prognostic information in high-grade T-cell lymphoma.

Variation of apoptotic and proliferative activity among lymphoma subtypes in dogs: A flow cytometric study

Tumor growth depends on both proliferative and apoptotic rate of neoplastic cells. High proliferation index is a well-known negative prognostic factor in canine lymphomas, whereas little is known about apoptotic activity. We describe proliferative and apoptotic rates in different canine lymphoma subtypes at diagnosis. Flow cytometry (FC) was used to assess the percentage of proliferating cells (Ki67%) and of apoptotic cells (AnnV%) in 128 lymph node (LN) aspirates from dogs with lymphoma. Proliferation/apoptosis ratio (PAR) and turnover index (TI; Ki67% + AnnV%) were then calculated for each case.High-grade B-cell lymphomas showed high values for both Ki67% and AnnV%, low-grade B-cell lymphomas showed low Ki67% and high AnnV%, high-grade T-cell lymphomas showed high Ki67% and low AnnV%, and low-grade T-cell lymphomas showed low levels of both parameters. Lymphoblastic lymphomas had the highest PAR values. High-grade B-cell lymphomas had the highest TI values while small clear cells lymphomas the lowest.The panorama of proliferative and apoptotic activity widely varies among lymphoma subtypes. Our results lay the ground for future clinical and pharmacological studies.

A Case of Multicentric High-Grade T-Cell Lymphoma in a Cat Presenting with Erythematous Patches

A Case of Multicentric High-Grade T-Cell Lymphoma in a Cat Presenting with Erythematous Patches

Primary High-grade Peripheral T-cell Lymphoma of the Testis Clinically Confused With Scrotal Abscess

Testicular T-cell lymphomas are rare and heterogeneous. Their rarity, nonspecific clinical and radiologic features, histomorphologic heterogeneity, and aberrant immunohistochemical expression may impose diagnostic difficulties for clinicians and pathologists. They may mimic germ cell neoplasms, infectious orchitis, and scrotal abscess. We report a case of a high-grade T-cell lymphoma of the testes in an elderly man with uncontrolled diabetes mellitus. It was clinically and radiologically unexpected and was confused with viral or tuberculous orchitis with abscess formation and systemic sepsis.

Comparison of combination l-asparaginase plus CHOP or modified MOPP treatment protocols in dogs with multi-centric T-cell or hypercalcaemic lymphoma.

To compare the progression-free survival of dogs with high-grade T-cell lymphoma treated with either a cyclophosphamide, doxorubicin, vincristine and prednisone-based or a modified mechlorethamine, vincristine, prednisone and procarbazine chemotherapy protocol. In this retrospective study, cases were selected based on histologic or cytologic diagnosis of lymphoma, T-cell phenotype, hypercalcaemia, or both, and no previous chemotherapy for lymphoma. Treatment was not randomly allocated. Seventy-three dogs were included in this study: 50 in the cyclophosphamide, doxorubicin, vincristine and prednisone group and 23 in the mechlorethamine, vincristine, prednisone and procarbazine group. The median progression-free survival was 133 days for dogs in the cyclophosphamide, doxorubicin, vincristine and prednisone group and 97 days for dogs in the mechlorethamine, vincristine, prednisone and procarbazine group. When golden retrievers (n = 16) were evaluated -separately, progression-free survival was longer in the cyclophosphamide, doxorubicin, vincristine and prednisone versus mechlorethamine, vincristine, prednisone and procarbazine treatment group (medianPFS 154 days versus 70.5days, respectively). The progression-free survival time for dogs with multi-centric T-cell lymphoma treated with a modified mechlorethamine, vincristine, prednisone and procarbazine protocol was similar to that of dogs treated with cyclophosphamide, doxorubicin, vincristine and prednisone. Further studies, including those evaluating golden retrievers separately, are needed to confirm these findings.

Breed-associated risks for developing canine lymphoma differ among countries: an European canine lymphoma network study

BackgroundCanine breeds may be considered good animal models for the study of genetic predisposition to cancer, as they represent genetic clusters. From epidemiologic and case collection studies it emerges that some breeds are more likely to develop lymphoma or specific subtypes of lymphoma but available data are variable and geographically inconsistent. This study was born in the context of the European Canine Lymphoma Network with the aim of investigating the breed prevalence of canine lymphoma in different European countries and of investigating possible breed risk of lymphoma overall and/or different lymphoma subtypes.ResultsA total of 1529 canine nodal lymphoma cases and 55,529 control cases from 8 European countries/institutions were retrospectively collected. Odds ratios for lymphoma varied among different countries but Doberman, Rottweiler, boxer and Bernese mountain dogs showed a significant predisposition to lymphoma. In particular, boxers tended to develop T-cell lymphomas (either high- or low-grade) while Rottweilers had a high prevalence of B-cell lymphomas. Labradors were not predisposed to lymphoma overall but tended to develop mainly high-grade T-cell lymphomas. In contrast with previous studies outside of Europe, the European golden retriever population did not show any possible predisposition to lymphoma overall or to specific subtypes such as T-zone lymphoma.ConclusionFurther prospective studies with more precise and consistent subtype identification are needed to confirm our retrospective results and to create the basis for the investigation of possible genes involved in different predispositions.

Loss of CD45 cell surface expression in canine T-zone lymphoma results from reduced gene expression

Canine T-zone lymphoma (TZL) is a peculiar lymphoma subtype characterized by an indolent clinical course and aberrant CD45-negative phenotype, commonly recognized by flow cytometry (FC). Recent studies have described clinical presentation and behavior, but to date the mechanisms behind the loss of CD45 protein expression have never been investigated.The aims of this study were: 1) to confirm the absence of CD45 in canine TZL via the concomitant use of FC and immunohistochemistry with two different sources of antibody; and 2) to investigate the amount of CD45 transcript and the presence of CD45 gene in the neoplastic cells of dogs affected by TZL.57 lymph node aspirates were included in the present study: 40 (70.2%) TZLs, 7 (12.3%) high grade T-cell lymphomas and 10 (17.5%) reactive lymph nodes. Neoplastic cells and normal T-cells were isolated from TZL and reactive lymph nodes, respectively, via cell sorting. Immunohistochemistry was performed on 2 TZL, 2 reactive lymph nodes and 2 Peripheral T-cell Lymphomas. Total RNA and genomic DNA were extracted from lymph-nodes aspirates. Two different quantitative real-time PCR experiments were designed, to determine the amount of the CD45 transcript and of the corresponding gene fragment.All TZL cases were negative for CD45 at immunohistochemistry. CD45 transcript amount was significantly lower in TZL compared to controls (p<0.001). This difference was not significant (p=0.584) for CD45 DNA load, that was similar between TZL and controls. Moreover, CD45 transcript amount was inversely correlated with the percentage of neoplastic cells in each TZL sample (p=0.010).These results confirm that CD45 protein is lacking on cell surface irrespective of the technique and antibody source adopted. This phenotypic aberrancy is apparently due to the absence of gene transcription, as CD45 DNA was present, whereas CD45 transcript was virtually absent in the neoplastic cells. The data here reported support further studies investigating possible factors impairing CD45 gene transcription.

Eerstelijnsbehandeling met CCNU-L(-chloorambucil)-CHOP van honden met een hooggradig multicentrisch of mediastinaal T-cellymfoom

In dit retrospectieve onderzoek werd de ziektevrije- en progressievrije overleving bepaald van chemotherapie-naïeve honden met een hooggradig multicentrisch of mediastinaal T-cellymfoom, behandeld met een eerstelijns-CCNU-L(-chloorambucil)-CHOP-protocol. Van de dertien honden met een multicentrisch lymfoom vertoonde 92,3% een volledige remissie en de mediane ziektevrije- en progressievrije periode was respectievelijk 317 en 256 dagen. Drie honden hadden een mediastinaal lymfoom en vertoonden allemaal een volledige remissie met een mediane ziektevrije- en progressievrije periode van respectievelijk 978 en 1007 dagen. De één- en tweejarige ziektevrije/progressievrije overlevingskans voor honden met de multicentrische vorm was respectievelijk 0,50/0,46 en 0,42/0,38, voor honden met de mediastinale vorm 0,67/0,67. Neutropenie werd gevonden bij 52,9% van de honden, trombocytopenie bij 50% en 56,3% vertoonde een waarschijnlijk door CCNU veroorzaakte nefrotoxiciteit. De conclusie van het onderzoek is dat eerstelijnsbehandeling met CCNU-L(- chloorambucil)-CHOP een positief effect lijkt te hebben op de overlevingstijd van honden met een hooggradig multicentrisch of mediastinaal T-cellymfoom.

Remarkably long overall survival of a 15-month-old Australian shepherd dog with gastric T-cell lymphoma

A 15-month-old female intact Australian shepherd dog was presented with a history of acute, frequent vomiting and progressive lethargy. Only a painful abdomen was detected on physical examination. Laboratory results...

Treatment of T cell lymphoma in dogs

Overall, canine lymphoma remains one of the most chemotherapy-responsive cancers in the dog. In addition to the stage and the substage of disease, T cell phenotype is the most consistently...

A Case of High-grade T-cell Lymphoma With Extensive Involvement of Trachea

A Case of High-grade T-cell Lymphoma With Extensive Involvement of Trachea

Simultaneous occurrence of a CD30 positive/ALK-negative high grade T-cell lymphoma and plasma cell myeloma: Report of a case

Simultaneous occurrences of T-cell and B-cell neoplasms are rare, and etiological relationships between these two malignancies are poorly understood. We report the case of a 76-year-old man who presented with hypercalcemia, multiple skin nodular lesions, fatigue, episodic fever, and night sweats. PET/CT scan showed diffuse skin and subcutaneous fat plane active lesions, supra- and infra- diaphragmatic active lymph nodes, liver and spleen involvement, bone marrow infiltration, and nonspecific bilateral lung nodules. A skin biopsy showed a high grade CD30-positive/ALK-negative T-cell lymphoma. A bone marrow biopsy showed involvement by the same neoplastic cells. Additionally, a monoclonal lambda restricted plasma cell population (15% of marrow elements) was identified, which, in view of an IgA lambda spike in the serum, was consistent with plasma cell myeloma. To the best of our knowledge, this case is the first reported case of a plasma cell neoplasm associated with an aggressive CD30-positive ALK-negative systemic T-cell lymphoma with skin involvement. Reporting such cases is important as it adds to the pool of rare cases of concomitant T-cell neoplasms and plasma cell myelomas, and might help in determining an etiological relationship, if any, between these two hematological malignancies.

Fast Achievement Of a First Metabolic Complete Remission In a Lung Transtplanted Patient With Multiple Comorbidities and a CD30 Positive Anaplastic Large Cell Post-Transplant Lymphoproliferative Disorder (T-PTLD/ALCL) By Treatment With Brentuximab Vedotin Monotherapy

IntroductionPost-Transplant-Lymphoproliferative Disorders are well known known, but rare complications of solid organ or hematologic stem cell transplantations. Incidence after lung-transplantation [LU-TX] is estimated to be ∼ 4.8% (Kremer et al. 2012). Most cases present as B-cell lymphomas (> 90%) and are EBV-associated. The WHO classification discriminates multiple subtypes (early lesions, monomorphic PTLD, polymorphic PTLD & classical Hodgkin lymphoma type PTLD). Treatment options mirror this histologic diversity and range from reduction of immunosuppressive therapy only , to aggressive polychemotherapy, DLI and second transplants. Patient historyIn May 2001 a left sided single LU-TX was performed for high grade bullous emphysema in a then 50 years old male patient. Several episodes of organ rejection required the use of complex immunosuppressive combination therapies, but long-term pulmonary function was preserved and the patient could be tapered to Tacrolimus and low dose steroids for years. Over the years the patient developed multiple severe comorbidities (Diabetes, renal retention, multiple pulmonary embolic events and peripheral thrombosis, as well as cardiac insuffiency and relapsing episodes of pancreatitis). CIRS-G-severity index was 2.7/4 with an ECOG score of 3. In May 2013 the patient developed B-symptoms, cutaneous lesions and a predominantly inguinal and abdominal lymphadenopathy. Histology & StagingA lymph node excision biopsy showed a high grade T-Cell lymphoma (molecular and immunological features are sumarized in Table 1) which could be classified as ALK negative anaplastic large cell lymphoma (ALCL) type PTLD, stage IV BE cutis with additional high risk features (LDH elevation). TreatmentBecause the patient was jugded to be unfit for aggresive polychemotherapy due to multiple comorbidities and his lymphoma was found to be expressing the CD30 antigen strongly and uniformly the anti-CD 30 immunotoxin Brentuximab-Vedotin (BV) was started at 1.8mg/m² every 21 days. B-symptoms disappeared within hours from the first infusion, palpable lymph nodes regressed within 3 weeks, and the patient improved to ECOG 1 in the same period. Furthermore LDH normalized by cycle 2. A PET-CT scan after cycle 3 proved a first complete metabolic remission and the treatment will be continued for 6 cycles. Data on response will be updated at ASH. No clinically relevant toxicities were observed. ConclusionTo our best knowledge this is the 1st report of the successful use of BV in a case of T-PTLD/ALCL after SLU-TX. As this case illustrates Brentuximab-Vedotin is a highly attractive , low toxicity treatment option in patients unfit to undergo aggressive polychemotherapy and can deliver complete responses with undeniable clinical benefit even in very advanced diease. For the rarity of these diseases the performance of a randomized clinical trial comparing BV to standard treatments seems unlikely for the foreseeable future and clinical decisions on treatment allocation have to be made on a case by case basis. We would recommend to at least collect all cases of BV use in PTLD to improve the respective best available evidence.TABLE 1Features of PTLDSubtypeMonomorphicHistologyALCLKi67>90%PositiveCD30 (100%), CD5, CD2, MUM1, EMANegativeCD20, CD117,ALK, Granzyme B, PAX-5, Perforin, KL-1, AE-1, AE-3, Melan-A,CD79, EBV-CISH Disclosures:Off Label Use: Brentuximab Vedotin for PTLD treatment.

Evaluation of tyrosine-kinase receptor c-kit mutations, mRNA and protein expression in canine lymphoma: Might c-kit represent a therapeutic target?

c-kit plays an important role in proliferation, survival and differentiation of hematopoietic progenitor cells. In human hematopoietic malignancies, c-kit is mostly expressed by progenitor cell neoplasms and seldom by mature cell neoplasms. Aim of this study was to evaluate c-kit expression in canine lymphoma. Twenty-five B-cell lymphomas and 21 T-cell lymphomas were enrolled in the study. c-kit mRNA and protein expression was measured in lymph node fine needle aspirates by quantitative real-time RT-PCR, flow cytometry and immunocytochemistry, while the occurrence of KIT mutations on exons 8–11 and 17 was investigated by direct cDNA sequencing. KIT mRNA was amplifiable but below the limit of quantification in 76% of B-cell lymphomas and 33% of T-cell lymphomas. Remaining samples showed a very low expression of KIT, except for some high grade (HG) T-cell lymphomas where a comparatively higher mRNA amount was observed. Transcriptional data were confirmed at the protein level. No gain-of-function mutations were observed. Among canine lymphomas, T-cell lymphoma typically shows an aggressive biological behavior, partly being attributable to the lack of efficacious treatment options, and the evidence of c-kit expression in HG T-cell lymphomas might represent the rationale for its routinely diagnostic evaluation and the use of tyrosine kinase inhibitors in future clinical trials.