Primary Intestinal Lymphoma in Rabbits.

Neoplasms of the intestinal tract are uncommon in rabbits and primary lymphoma of the intestinal tract is rare. This case series is the first detailed description of primary intestinal lymphoma in rabbits. We reviewed four cases of primary intestinal lymphoma in rabbits aged 5-9.5 years old with an average age of 7.8 years. Neoplastic cells in three cases were large (8 µm diameter) while one case had intermediate cells (5 µm diameter). Neoplastic lymphocytes were of B-cell lineage and characterized by intense, multifocal, membranous immunoreactivity for CD79a and no immunoreactivity to CD3. Based on the Revised European-American Classification of Lymphoid Neoplasms/World Health Organization classification, three of the cases were consistent with diffuse large B-cell lymphoma and the case with intermediate-sized neoplastic cells was consistent with lymphoblastic lymphoma.

Subleukaemic T-Lymphoblastic Leukaemia in a Horse.

A 20-year-old Dutch Warmblood gelding was referred with clinical signs of anorexia, weight loss, intermittent fever, cough, subcutaneous oedema and exercise intolerance. Haematological examination revealed the presence of blast cells, decreased lymphocytes, mild thrombocytopenia and anaemia but no leucocytosis. Serum analyses detected elevated aspartate aminotransferase and gamma-glutamyl transferase activities and triglyceride concentrations. Twenty-two days after the initial visit, the horse died after showing clinical signs of decreased appetite, increased body temperature, tachypnoea and tachycardia. At necropsy, there was mild splenomegaly but enlarged lymph nodes, masses or nodules were not seen in any organ. Histologically, neoplastic cells were seen in the subcapsular and medullary lymph sinus of the mediastinal, axillary, mesenteric and renal lymph nodes. The bone marrow was densely cellular with numerous large round neoplastic cells that had round nuclei with clear nucleoli and scant cytoplasm. The neoplastic cells were immunopositive for CD3 but negative for CD20, BLA36, CD204, Iba-1, CD204 and granzyme B. Based on these findings, the neoplasm was diagnosed as subleukaemic T-lymphoblastic leukaemia, which, to the best of our knowledge, is the first report of this neoplasm in horses.

Tumor staging in a Beagle dog with concomitant large B-cell lymphoma and T-cell acute lymphoblastic leukemia.

An 8-y-old spayed female Beagle dog was presented with peripheral lymphadenomegaly. Lymph node cytology and flow cytometry led to the diagnosis of large B-cell lymphoma (LBCL). We detected minimal percentages of LBCL cells in peripheral blood and bone marrow samples. However, a monomorphic population of neoplastic cells different from those found in the lymph node was found in the bone marrow. T-cell acute lymphoblastic leukemia was suspected based on flow cytometric immunophenotyping. PCR for antigen receptor rearrangement (PARR) revealed clonal rearrangement of both B-cell and T-cell receptors, and the presence of both neoplastic clones in the lymph node, peripheral blood, and bone marrow. The dog was treated with multi-agent chemotherapy but died 46 d following diagnosis. Tumor staging and patient classification are needed to accurately establish a prognosis and select the most appropriate therapeutic protocol.

Generation and Validation of an Antibody to Canine CD19 for Diagnostic and Future Therapeutic Purposes.

The B-cell coreceptor, CD19 is a transmembrane protein expressed throughout B-cell ontogeny from pro-B cell to plasmablast. It plays an important role in B-cell development and function and is an attractive target for antibody-directed immunotherapies against B-cell malignancies, including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (B-NHL) in humans. With the rapid development of next-generation immunotherapies aimed at improving therapeutic efficacy, there is a pressing need for a clinically relevant, immune-competent, spontaneous animal model to derisk these new approaches and inform human immunotherapy clinical trials. Pet dogs develop spontaneous B-cell malignancies, including B-NHL and leukemias that share comparable oncogenic pathways and similar immunosuppressive features to human B-cell malignancies. Despite treatment with multiagent chemotherapy, durable remissions in canine B-NHL are rare and most dogs succumb to their disease within 1 year of diagnosis. Here we report the development and validation of an anti-canine CD19-targeting monoclonal antibody and its single-chain derivatives, which enable next-generation CD19-targeted immunotherapies to be developed and evaluated in client-owned dogs with spontaneous B-NHL. These future in vivo studies aim to provide important information regarding the safety and therapeutic efficacy of CD19-targeted mono- and combination therapies and identify correlative biomarkers of response that will help to inform human clinical trial design. In addition, development of canine CD19-targeted immunotherapies aims to provide better therapeutic options for pet dogs diagnosed with B-cell malignancies.

Myoclonus and hypercalcemia in a dog with poorly differentiated lymphoproliferative neoplasia.

A 1-year, 8-month-old Rhodesian Ridgeback was presented with obtundation, ambulatory tetraparesis, and myoclonus. Initial clinical findings included ionized hypercalcemia with an apparent marked increase in parathyroid hormone, thrombocytopenia, and nonregenerative anemia. Low numbers of circulating atypical cells were noted on blood film evaluation. Brain magnetic resonance imaging identified an extra-axial contrast enhancing subtentorial lesion, and cerebrospinal fluid (CSF) analysis documented a marked atypical lymphocytic pleocytosis. Flow cytometry performed on the CSF demonstrated expression of only CD45, CD90, and MHC class II, with Pax5 positivity on subsequent immunohistochemistry. The final diagnosis was of B-cell lymphoblastic lymphoma or acute leukemia, given the distribution of disease and the presence of significant bone marrow infiltration alongside an aggressive clinical course. The unusual immunophenotype of the neoplastic cells and hypercalcemia presented antemortem diagnostic challenges, highlighting the need for a multidisciplinary approach and caution in the interpretation of clinical abnormalities in cases with multiple comorbidities.

Clinical and clinicopathological characteristics of acute lymphoblastic leukaemia in six cats.

OBJECTIVES: To investigate the clinical characteristics of feline acute lymphoblastic leukaemia patients diagnosed according to the recent diagnostic criteria for the equivalent canine condition. MATERIALS AND METHODS: The medical records of six cats diagnosed with acute lymphoblastic leukaemia were retrospectively reviewed to extract data on clinicopathological characteristics and outcomes. The lymphoid origin of the tumour cells was confirmed by polymerase chain reaction for antigen receptor gene rearrangement, flow cytometry or immunohistochemistry. RESULTS: Non-specific clinical signs such as lethargy and anorexia were common, and anaemia and thrombocytopenia were also commonly identified. Leucocytosis was observed in four cats and leucopenia was observed in two; the number of lymphoblasts in the peripheral blood samples varied among the cases. Lymphoblasts originated from B-cell lineage in four cats and T-cell lineage in one, and those of another cat were positive for both B-cell marker CD21 and T-cell marker CD8. Five of the six cats were treated with cytotoxic chemotherapy, and a partial response was obtained in two. The median overall survival was 55 days (range: 1 to 115). CLINICAL SIGNIFICANCE: Acute lymphoblastic leukaemia should be considered if lymphoblasts are observed in peripheral blood, even if their number is small. The prognosis for cats that have acute lymphoblastic leukaemia is as poor as that for dogs, and further studies are needed to develop effective treatment.

Dogs with acute myeloid leukemia or lymphoid neoplasms (large cell lymphoma or acute lymphoblastic leukemia) may have indistinguishable mediastinal masses on radiographs.

Acute myeloid leukemia is an uncommon hematopoietic neoplasm of dogs that should be differentiated from lymphoid neoplasms, such as lymphoma, because of different treatment protocols and a worse prognosis. Thoracic radiography is performed frequently in dogs with suspected hematopoietic neoplasia, and detecting a mediastinal mass often prioritizes lymphoma as the most likely diagnosis. However, we have observed a mediastinal mass in several dogs with acute myeloid leukemia and hypothesized that (1) the frequency of a mediastinal mass was higher and (2) the size of the mass was larger in dogs with acute myeloid leukemia compared to dogs with lymphoid neoplasms. In this analytical study (observational, retrospective, and cross-sectional), the sample population included 238 dogs with hematopoietic neoplasia. These dogs were divided into lymphoid (large cell lymphoma, acute lymphoblastic leukemia) and myeloid groups based on standard phenotyping tests. A mediastinal mass was detected during thoracic radiography in 73/218 (33%) and nine of 20 (45%) dogs in the lymphoid and myeloid groups (P = 0.21), respectively. The median size ratio of mediastinal mass to cardiac silhouette was 0.20 and 0.23 in the lymphoid and myeloid groups (P = 0.96), respectively. Additionally, we observed normal thoracic radiographs in 111/218 (51%) dogs in the lymphoid group and nine of 20 (45%) dogs in the myeloid group. In conclusion, acute myeloid leukemia should be considered when a mediastinal mass is detected during radiography in dogs with suspected hematopoietic neoplasia-but the presence or size of a mediastinal mass does not differentiate between myeloid and lymphoid neoplasms.

Lymphoma Classification in Goats.

Lymphoma has been described in individual cases for goats but not systematically characterized in a larger cohort. This study aimed to subtype caprine lymphoma based on topographic and subgross distribution, immunophenotype, and cellular morphology following the World Health Organization classification system for hematopoietic tumors in domestic animals. Fifteen caprine lymphoma cases were assessed with 6 submitted as biopsy and 9 for postmortem examination. Goats were predominantly young adult (median 3 years) and dwarf breeds (Pygmy and Pygora). The sexes were similarly represented. Nuclear size was measured relative to red blood cells (RBCs) and then adjusted for species-specific differences and designated small (<3× RBCs), intermediate (3-4× RBCs), or large (>4× RBCs). Using immunohistochemistry, 11 of 15 (73%) goats had T-cell lymphoma (TCL; CD3 positive, CD79α negative) and 4 of 15 (27%) had B-cell lymphoma (BCL; CD79α positive, CD3 negative). A multicentric distribution was most common. TCL generally involved the thoracic cavity and/or neck, suggestive of thymic origin or homing. TCLs were further classified as lymphoblastic lymphomas (3/11; 27%), large granular lymphocyte lymphoma (1/11; 9%), diffuse small lymphocytic lymphomas (3/11; 27%), or peripheral/mature T-cell lymphoma (PTCL) not otherwise specified (4/11 [36%], of which 3 were high grade and 1 intermediate grade). In 1 goat with PTCL, lymph nodes had either paracortical expansion or diffuse infiltrates suggesting transition from nodular to diffuse PTLC. BCLs were classified as diffuse large B-cell lymphoma (2/4; 50%) or B-cell lymphocytic lymphoma intermediate type (2/4; 50%). In contrast to dogs and horses, lymphomas in goats are predominantly TCL and frequently involve the mediastinum.

Evaluation of CD25-positive cells in relation to the subtypes and prognoses in various lymphoid tumours in dogs.

Interleukin-2 receptor alpha chain (CD25) expression has been reported in human lymphoid tumours and suggested to correlate with the prognosis. In this study, we detected CD25-positive cells in various types of lymphoid tumours in dogs. Immunohistochemical analyses of the tissues from diffuse large B-cell lymphoma (DLBCL) (n = 6), T-zone lymphoma (TZL) (n = 5), and follicular lymphoma (FL) (n = 2) revealed that cells strongly positive for CD25 were observed generally in accordance with lymphoma cell localization. CD25-positive cells were consistently detected in TZL and FL cases; however, the number of CD25-positive cells was variable among DLBCL cases. Furthermore, we evaluated the rate of CD25-positive cells by flow cytometric analysis in 29 dogs with lymphoid malignancies, including high-grade B-cell lymphoma (n = 17), TZL (n = 5), FL (n = 2), cutaneous lymphoma (n=2), and acute lymphoblastic leukaemia (ALL) (n = 3). CD25-positivity in the lymph node cells was significantly higher in dogs with high-grade B-cell lymphoma (mean ± SD, 49.6 ± 31.3%) or TZL (mean ± SD, 80.2 ± 10.0%) than that in healthy dogs (mean ± SD, 9.8 ± 2.8%). In prognostic analysis of 15 cases with high-grade B-cell lymphoma, the progression-free survival was significantly shorter in CD25-high group than that in CD25-low group. The results obtained in this study are useful for subtype differentiation and prognostic analysis of canine lymphomas and future development of molecular-targeted therapy directed at CD25.

Immature T cell neoplasms in three young cattle.

Immature T cell neoplasms in three young Holstein cattle with neoplastic involvement of the thymus are described. Case 1, with a precursor T lymphoblastic leukemia (calf form of leukosis), was an 86-day-old female calf. The leukemia was characterized by replacement of the bone marrow and spleen by leukemia cells, but preservation of epithelial frameworks throughout the thymus. The other two neoplasms were thymic γδ T cell lymphomas, which were observed in a 246-day-old steer (case 2) and a 16-month-old heifer (case 3). Histological examination revealed obliteration of the normal thymic architecture and stromal fibrosis, with the spleen and liver far less severely affected than in case 1. There were cytological differences bewteen the tumors in case 1 and cases 2 and 3. Additionally, WC1 and CD8 were expressed only in the latter. Thus, the leukemia and these lymphomas should be regarded as independent disease entities on the basis of histological and immunohistochemical characteristics.

Retroviral DNA--the silent winner: blood transfusion containing latent feline leukemia provirus causes infection and disease in naïve recipient cats.

BACKGROUND: The feline leukemia virus (FeLV) is a gamma-retrovirus of domestic cats that was discovered half a century ago. Cats that are infected with FeLV may develop a progressive infection resulting in persistent viremia, immunodeficiency, tumors, anemia and death. A significant number of cats mount a protective immune response that suppresses viremia; these cats develop a regressive infection characterized by the absence of viral replication and the presence of low levels of proviral DNA. The biological importance of these latter provirus carriers is largely unknown. RESULTS: Here, we demonstrate that ten cats that received a transfusion of blood from aviremic provirus carriers developed active FeLV infections, some with a progressive outcome and the development of fatal FeLV-associated disease. The infection outcome, disease spectrum and evolution into FeLV-C in one cat mirrored those of natural infection. Two cats developed persistent antigenemia; six cats were transiently antigenemic. Reactivation of infection occurred in some cats. One recipient developed non-regenerative anemia associated with FeLV-C, and four others developed a T-cell lymphoma, one with secondary lymphoblastic leukemia. Five of the ten recipient cats received provirus-positive aviremic blood, whereas the other five received provirus- and viral RNA-positive but aviremic blood. Notably, the cats that received blood containing only proviral DNA exhibited a later onset but graver outcome of FeLV infection than the cats that were transfused with blood containing proviral DNA and viral RNA. Leukocyte counts and cytokine analyses indicated that the immune system of the latter cats reacted quicker and more efficiently. CONCLUSIONS: Our results underline the biological and epidemiological relevance of FeLV provirus carriers and the risk of inadvertent FeLV transmission via blood transfusion and demonstrate the replication capacity of proviral DNA if uncontrolled by the immune system. Our results have implications not only for veterinary medicine, such as the requirement for testing blood donors and blood products for FeLV provirus by sensitive polymerase chain reaction, but are also of general interest by revealing the importance of latent retroviral DNA in infected hosts. When aiming to eliminate a retroviral infection from a population, provirus carriers must be considered.

Properties of cellular and serum forms of thymidine kinase 1 (TK1) in dogs with acute lymphocytic leukemia (ALL) and canine mammary tumors (CMTs): implications for TK1 as a proliferation biomarker.

BACKGROUND: Thymidine kinase 1 (TK1) is a deoxyribonucleic acid (DNA) precursor enzyme and a proliferation biomarker used for prognosis and treatment monitoring of breast cancer in humans. The aim was to determine if serum thymidine kinase 1 (sTK1) activity and sTK1 protein levels in dogs with mammary tumors could be useful in veterinary medicine. RESULTS: Serum samples from 20 healthy dogs and 27 dogs with mammary tumors were analyzed for sTK1 activity, using an [(3)H]-deoxythymidine (dThd) phosphorylation assay, and for sTK1 protein levels by immune affinity/Western blot assay. The molecular forms of sTK1 in acute lymphocytic leukemia (ALL), canine mammary tumor (CMT), and healthy sera were determined by size exclusion chromatography. Mean sTK1 activities in CMT were 1.0 ± 0.36 pmol/min/mL, differing significantly from healthy dogs (mean ± SD = 0.73 ± 0.26 pmol/min/mL). Serum TK1 protein (26 kDa polypeptide) levels were also significantly higher in CMTs compared to healthy dogs (mean ± SD = 28.5 ± 11.4, and 8.5 ± 4 ng/mL, respectively). Cellular TK1 isolated from ALL tumor cells was predominantly a dimer, while the serum TK1 activity eluted as a high molecular weight (MW) oligomer. In analyses of CMT tissue extracts, TK1 activity eluted in two peaks, a minor peak with a high MW oligomer and a major tetramer peak. Western blot analysis of chromatographic fractions showed that cellular TK1 protein in both ALL and CMT dogs, and to some extent serum TK1 from ALL dogs, correlated with activity profiles, but a large fraction of inactive TK1 protein was detected in CMT. CONCLUSIONS: Serum TK1 protein and activity levels were significantly higher in CMT than in healthy dogs. Size exclusion chromatography demonstrated major differences in the molecular forms of sTK1 in ALL, healthy, and CMT dogs, with a large fraction of inactive TK1 protein in CMT. Our results showed that the sTK1 protein assay can differentiate benign tumors (early stage tumors) from healthy more efficiently than sTK1 activity assay. This preliminary data supports that sTK1 protein assay is clinically useful. Further studies are needed to evaluate the diagnostic or prognostic role of serum TK1 protein in CMTs.

Acute lymphoblastic leukemia in a pygmy hippopotamus (Hexaprotodon liberiensis).

A captive, 31-yr-old, intact male pygmy hippopotamus presented with nonspecific signs of weight loss, inappetence, diarrhea, and lethargy. After 5 wk of diagnostic investigation and symptomatic treatment, an acute leukemic process with concurrent polycystic kidney disease was suspected. The animal's condition continued to deteriorate prompting euthanasia. Necropsy, histopathologic, and immunohistochemical examination confirmed acute T-cell lymphoblastic leukemia and polycystic kidneys. Acute T-cell lymphoblastic leukemia has not previously been documented in this species; however, polycystic kidney disease has been reported. This case report adds to the increasing number of pygmy hippopotamuses diagnosed with polycystic kidney disease and describes acute T-cell lymphoblastic leukemia, a previously unreported disease of this species.

Evaluation of tyrosine-kinase receptor c-KIT (c-KIT) mutations, mRNA and protein expression in canine leukemia: might c-KIT represent a therapeutic target?

The tyrosine-kinase receptor c-KIT (c-KIT) plays an important role in proliferation, survival and differentiation of progenitor cells in normal hematopoietic cells. In human hematological malignancies, c-KIT is mostly expressed by progenitor cell neoplasia and seldom by those involving mature cells. Tyrosine kinase inhibitors (TKIs) are actually licensed for the first- and second-line treatment of human hematologic disorders. Aim of the present study was to evaluate c-KIT mRNA and protein expression and complementary DNA (cDNA) mutations in canine leukemia. Eleven acute lymphoblastic leukemia (ALL) and acute undifferentiated leukemia (AUL) and 12 chronic lymphocytic leukemia (CLL) were enrolled in this study. The amounts of c-KIT mRNA and protein were determined, in peripheral blood samples, by using quantitative real time RT-PCR, flow cytometry and immunocytochemistry, respectively. The presence of mutations on c-KIT exons 8-11 and 17 were investigated by cDNA sequencing. Higher amounts of c-KIT mRNA were found in ALL/AUL compared to CLL, and this latter showed a lower pattern of gene expression. Transcriptional data were confirmed at the protein level. No significant gain-of-function mutations were ever observed in both ALL/AUL and CLL. Among canine hematological malignancies, ALL/AUL typically show a very aggressive biological behavior, partly being attributable to the lack of efficacious therapeutic options. The high level of c-KIT expression found in canine ALL/AUL might represent the rationale for using TKIs in future clinical trials.

Linfoma primário de células T no líquido cefalorraquidiano de cão: relato de caso / Characterization of primary t-cell lymphoma (CD3 +) in Csf of a dog: case report

Relata-se o diagnóstico de linfoma primário no sistema nervoso central em um cão Labrador Retrievier, de 10 anos de idade, que apresentava episódios convulsivos, incoordenação nos membros posteriores, head tilt, ataxia e sensibilidade diminuída no lado esquerdo. Constataram-se alterações laterais esquerdas, como ausências de propriocepção e de posicionamento tátil, alterações posteriores nas provas de carrinho de mão e de reação ao pulo e diminuição da extensão da postura e hemilocomoção. No líquido cefalorraquidiano (LCR), houve predomínio de linfócitos atípicos, caracterizados pela presença de anisocitose e anisocariose, nucléolos evidentes e anisonucleose, basofilia e microvacuolização citoplasmáticas, mitoses atípicas e corpúsculos linfoglandulares, compatíveis com linfoma, confirmado pelo exame histológico e imunocitoquímico, o qual revelou origem T, com expressão CD3+ e CD79-. A tomografia computadorizada não foi conclusiva e evidenciou diversas áreas hipodensas e intensificação de contraste na região de sulcos e giros do parênquima encefálico. A coleta do LCR foi essencial na rapidez do diagnóstico definitivo, indicando a natureza rara desta lesão primária.

A primary lymphoma in the central nervous system in a 10 year-old Labrador Retriever presenting seizures, hind limb incoordination, head tilt, ataxia and decreased sensitivity on the left side was reported. Regarding postural reactions, there were changes in the left side such as proprioceptive and tactile positioning defects, and in the posterior reaction tests such as wheelbarrowing and limb hopping, along with a reduction in the extensor postural thrust reaction and hemi-walking response. A cerebrospinal fluid (CSF) analysis showed a predominance of atypical lymphocytes characterized by pleocytosis, marked anisocytosis and anisokaryosis, evident nucleoli and anisonucleosis, cytoplasmic basophilia and microvacuolation, atypical mitotic figures and lymphoglandular bodies. These findings were compatible with lymphoma, which was confirmed by histopathology and immunocytochemistry that showed a T-cell origin, with CD3 + and CD79- expression. A computed tomography scan was inconclusive and showed several hypodense areas and a contrast enhancement in the sulci and gyri region of the brain parenchyma. The CSF analysis was essential for a quicker definitive diagnosis, indicating the nature of this rare primary injury.

Lymphoblastic lymphoma and leukemic blood profile in a red-tail boa (Boa constrictor constrictor) with concurrent inclusion body disease.

An adult male wild-caught true red-tail boa (Boa constrictor constrictor), imported from Surinam, was presented for anorexia, extreme lethargy, and coelomic swelling in the cranial third of the body, in the anatomic location of the thymus. The snake died a few minutes after blood sampling via cardiocentesis. Hematology revealed anemia and extreme leukocytosis (820 × 10(3)/ml) characterized by a predominance (95%) of lymphocytes. Necropsy revealed enlargement of most of the visceral organs. Histology confirmed lymphoblastic lymphoma with a leukemic blood profile and diffuse infiltration of some of the heart, thymus, bone marrow, kidney, spleen, lung, and liver. Several large intracytoplasmic eosinophilic inclusion bodies surrounded by narrow clear "halos" were identified within gastric mucosal cells, proximal and distal convoluted tubule epithelial cells, and splenic cells. The final diagnosis was lymphoblast lymphoma with a leukemic blood profile and concurrent inclusion body disease.

Chemotherapy followed by abdominal cavity irradiation for feline lymphoblastic lymphoma.

Combination chemotherapy is standard care for feline lymphoma, although clinically relevant improvements in remission duration are unlikely to result from manipulations of chemotherapy agents alone. Lymphopoietic tissues generally are sensitive to radiation, and support for chemoradiotherapy as a treatment for lymphoma is found in both humans and dogs. The goal of this prospective pilot study was to determine the normal tissue tolerance to 15 Gy total abdomen fractionated radiation therapy following induction chemotherapy in cats with lymphoblastic lymphoma. Eight cats with lymphoblastic gastrointestinal or multicentric lymphoma confined to the abdominal cavity were treated with a 6-week combination chemotherapy protocol followed 2 weeks later by whole-abdomen radiation therapy consisting of 10 daily fractions of 1.5 Gy. Treatment was well tolerated; renal insufficiency documented in one cat at the start of radiation therapy progressed to stable chronic renal failure. One cat not in complete remission at the time of radiation therapy relapsed 2 weeks later, one cat with multicentric lymphoma relapsed with hepatic large granular lymphoma, and one cat was euthanatized 3 weeks following completion of radiation therapy for other reasons; no evidence of lymphoma or radiation toxicoses was identified on post mortem evaluation. The remaining five cats remain in remission at least 266 days after starting therapy; median remission duration has not been reached (range, > 266 to > 1332 days). Results of this study suggest that 15 Gy total abdomen fractionated radiation therapy after induction chemotherapy is tolerated satisfactorily. This protocol is suitable for further testing to quantify efficacy.

Description of clinical and pathological findings, treatment and outcome of feline large granular lymphocyte lymphoma (1996-2004).

Feline large granular lymphocyte (LGL) lymphoma is an uncommon, morphologically distinct variant of feline lymphoma. Limited information exists in the literature regarding pathological and immunohistochemical descriptions, clinical findings, treatment and survival times. The purpose of this study was to describe clinical features, treatment and outcome in feline LGL lymphoma. Medical records of 45 cats with LGL lymphoma were retrospectively evaluated. Decreased appetite/anorexia, weight loss, lethargy and vomiting were the most commonly reported clinical signs. All cats tested for feline leukaemia virus and feline immunodeficiency virus infection were negative. The mesenteric lymph nodes and small intestine were the most commonly affected organs. One complete response and six partial responses were noted in the 23 cats that received chemotherapy as their initial treatment. Median survival time for cats that were treated was 57 days. Based on these results, feline LGL lymphoma appears to be minimally responsive to chemotherapy and is associated with a grave prognosis.

Changes in C-reactive protein and haptoglobin in dogs with lymphatic neoplasia.

Acute phase proteins (APP) are regarded as a useful diagnostic tool in humans with lymphomas, leukaemias and multiple myeloma. C-reactive protein (CRP) and haptoglobin concentrations were measured in dogs with malignant multicentric (high grade) lymphoma (n=16), acute lymphoblastic leukaemia (ALL) (n=11), chronic lymphocytic leukaemia (CLL) (n=7) and multiple myeloma (n=8). Twenty-five healthy dogs served as controls. Measurements of the CRP plasma concentration were performed using a commercial ELISA and haptoglobin was measured with an assay based on its haemoglobin binding capacity. Global group comparisons using Kruskal-Wallis-test revealed significant group differences for both APPs (P<0.0001). Median CRP concentrations were increased in all groups with neoplastic lymphatic disorders (lymphoma: 37.2mg/L, ALL: 47.8mg/L, CLL: 35.5mg/L, myeloma: 17.6mg/L) compared to controls (1.67mg/L; P<0.001). Compared to the healthy controls (median=0.59g/L), haptoglobin was especially increased in dogs with ALL (6.8g/L, P<0.0001) followed by dogs with malignant lymphoma (3.8g/L, P<0.0001), CLL (3.2g/L, P=0.0008), and multiple myeloma (3.0g/L, P=0.0163). For both APPs, a wide range of values was found in all patient groups. The results indicate that particularly severe and acute lymphatic neoplasia, such as high grade lymphoma and ALL, cause significant acute phase reactions in dogs and must be included in the differential diagnoses of increased blood levels of these APPs.

Serum C-reactive protein concentration as an indicator of remission status in dogs with multicentric lymphoma.

BACKGROUND: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. OBJECTIVE: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. ANIMALS: Twenty-two dogs with untreated multicentric lymphoma. METHODS: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. RESULTS: Before therapy, a statistically significant majority of the dogs (P = .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P < .001). CRP concentrations of dogs in complete remission (median, 1.91; range, 0.2-103) were significantly different (P = .031) from those of dogs with partial remission (median, 2.48; range, 0-89), stable disease (median, 1.77; range, 1.03-42.65), or progressive disease (median, 8.7; range, 0-82.5). There was profound variation of CRP measurements within each dog. CONCLUSIONS: CRP is useful in determining complete remission status after treatment with cytotoxic drugs. However, the individual variation between dogs means CRP concentration is not sufficiently different in other remission states to permit its use in monitoring progression of the disease. Greater reliability in determining remission status might be achieved by combining CRP concentration with other serum markers.