Treatment of myeloid neoplasia with doxorubicin and cytarabine in 11 dogs.

Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) are primary myeloid neoplasms in dogs generally considered to have a poor outcome. In this study, we assessed toxicity, efficacy and outcome of concurrent administration of doxorubicin and cytarabine in 11 dogs with myeloid neoplasia. Bone marrow specimens were reviewed by three pathologists and classified as either MDS (n = 2), high grade MDS/early AML (MDS/AML; n = 4) or AML (n = 5). The median number of treatment cycles was 5 (range 1-9) and resolution of cytopenia was reported in 7 of 11 dogs including 2 dogs with MDS, 2 dogs with MDS/AML, and 3 dogs with AML. The median duration of remission in the seven responders was 344 days (range 109-1428) and the median overall survival for all dogs was 369 days. Adverse events consisted of predominantly low-grade gastrointestinal illness and myelosuppression. Three dogs developed grade V toxicity manifesting with heart failure (n = 2) at 369 and 1170 days after diagnosis and acute gastrointestinal side effects (n =1). Despite a limited sample size, these results suggest that a doxorubicin and cytarabine protocol may be considered as a therapeutic option in dogs with myeloid neoplasia. Protocol safety, in particular regarding myocardial toxicity, and efficacy should be further investigated.

A cat with myelodysplastic syndrome by administration of the methylation inhibitor Azacytidine.

A 5-year-old female cat with nonregenerative anemia and thrombocytopenia was diagnosed with myelodysplastic syndromes (MDS), since peripheral blood and bone marrow (BM) examination revealed various dysplasias and a blast ratio of 19%. Chemotherapy with azacytidine (AZA; 70-35 mg/m2, 3-5 days, three cycles) and treatment with prednisolone, antibiotics, and vitamin K2, and blood transfusion were performed. On day 106, blast cells and dysplasia had decreased in the BM, and the cat remained alive for at least 1,474 days. This report is the first on feline MDS treated with AZA, suggesting appropriate drug dosage, interval and effective combination should be investigated and the pharmacological and cell biological mechanisms needs to be elucidated in the future.

Retrospective study of 152 feline cytological bone marrow examinations: preliminary classification and ranges.

OBJECTIVES: Cytological assessment of the bone marrow is an essential tool for understanding and investigating haematological abnormalities. Sometimes it represents the only way to reach a definitive diagnosis. The purpose of this study was to provide a general overview regarding the prevalence of feline bone marrow disorders encountered in a private European laboratory setting, to classify them and to assess the differential cell counts related to such disorders. METHODS: In total, 152 bone marrow samples were classified using cytological and numerical criteria. The bone marrow cytological examinations were performed after the identification of haematological alterations, such as cytopenias, increased number of cells or suspicion of malignant blood disorders. RESULTS: Of the 152 bone marrow samples evaluated, 71 (46.7%) were classified as hyperplastic, primarily granulocytic and erythroid hyperplasia (50.7% and 45.1%, respectively, of the total hyperplasia); 23 (15.1%) showed dysmyelopoiesis, mainly in the form of myelodysplastic syndrome (39.1% of the total dysmyelopoiesis); 21 (13.8%) had no cytological abnormalities; 17 (11.2%) were malignant blood disorders; 15 (9.9%) had hypoplastic conditions; and two (1.3%) were miscellaneous diseases. Metastatic disease was detected in only two cases (1.3%). Differential cell counts and myeloid-to-erythroid (M:E) ratios were reported for normal, erythroid hypoplastic, erythroid and granulocytic hyperplastic and dysplastic conditions. CONCLUSIONS AND RELEVANCE: This study provides a general overview of the prevalence and incidence of feline bone marrow disorders together with ranges for differential nucleated cell counts and M:E ratios for the various conditions reported.

Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus-negative cat.

A 10-year-old castrated Domestic Short-Haired cat was presented to a primary care veterinarian for a wellness examination and laboratory examination for monitoring of diabetes mellitus. The CBC revealed marked thrombocytosis, leukopenia and macrocytic, normochromic anemia. The cat tested negative for FeLV and feline immunodeficiency virus, but was positive for Mycoplasma haemominutum by PCR. Hematologic abnormalities were not responsive to therapy, so a repeat CBC and a bone marrow aspiration for cytology were performed. Additional blood smear findings included anisocytosis with megaloblastic erythroid precursors, large platelets, eosinophilic myelocytes and metamyelocytes, and rare unidentified blasts. The bone marrow smear was highly cellular, and the cytologic pattern was consistent with myelodysplastic syndrome with an erythroid predominance. At that time, 15% blasts were present. The cat was treated with a vitamin K2 analog, doxycycline, and prednisolone, but without a clinical response. Within 3 months, euthanasia was elected due to declining quality of life, and a necropsy was performed. Postmortem bone marrow smears were highly cellular and dominated by monomorphic blasts of unknown line of origin (52%), persistent marked erythroid and megakaryocytic dysplasia, and ineffective erythropoiesis and granulopoiesis. Immunohistochemical, immunocytochemical, and cytochemical stains resulted in a diagnosis of acute myeloid leukemia of unclassified type. Additional histologic findings included mixed hepatitis with trematode infestation and lymphoplasmacytic interstitial nephritis with fibrosis. The marked thrombocytosis with myelodysplastic syndrome and the FeLV-negative status of this cat were unusual. The difficulty in classifying the myelodysplasia and subsequent leukemia highlights a need for further reporting and characterization of these types of disease.

Diagnosis of secondary dysmyelopoiesis via costochondral rib aspirate in a dog.

OBJECTIVE: To describe a novel bone marrow sampling technique utilized in a dog diagnosed with secondary dysmyelopoiesis. CASE SUMMARY: A 1.5-year-old female spayed Lhasa Apso was treated for generalized seizures, aspiration pneumonia, and severe sepsis. Pertinent history included administration of phenobarbital (2.1 mg/kg PO q 12 h) for the 6 months prior to presentation for suspected idiopathic epilepsy. Initial leukopenia and thrombocytopenia was attributed to underlying sepsis and disseminated intravascular coagulation. Progressive decline in all cell lines (ie, leukopenia, thrombocytopenia, and anemia), along with history of phenobarbital administration, suggested myelodysplastic disease. Bone marrow cytology via serial costochondral rib aspirates confirmed secondary dysmyelopoiesis. Phenobarbital therapy was abruptly discontinued and replaced with alternative anticonvulsant therapy. Complete resolution of the observed leukopenia, thrombocytopenia, and anemia were observed 2 weeks after discontinuation of phenobarbital. NEW OR UNIQUE INFORMATION PROVIDED: Costochondral rib aspirate appears to be a simple, viable method for bone marrow evaluation in dogs. Dysmyelopoiesis is a rare adverse effect of phenobarbital administration that can possess fatal consequences if not quickly recognized. Prompt diagnosis and discontinuation of the inciting drug is imperative to successful case management. Prognosis for return of bone marrow function appears good following drug discontinuation.

Automated analysis of bone marrow aspirates from dogs with haematological disorders.

Automated analysis of bone marrow (BM) aspirates is a useful 'pre-microscopical' screen to identify hypocellular samples and those with potentially abnormal cells. In order to determine whether automated analysis could also be used to identify haemopoietic abnormalities, EDTA-anticoagulated BM aspirates from 43 dogs were analysed using the Advia 2120 instrument. Corresponding Wright-stained BM smears were evaluated microscopically to determine smear quality, cell composition and 500-cell differential counts, and correlation to automated analysis parameters was computed. Leucocyte cytograms generated by the automated analyzer were scrutinized and compared with those of 'normal' BM. Twenty-three neoplastic and 20 non-neoplastic samples were analysed, including samples from 10 cases of acute myeloid leukaemia, four cases of acute lymphocytic leukaemia, four cases of chronic lymphocytic leukaemia, one case of chronic neutrophilic leukaemia, three cases of multiple myeloma, one case of myelodysplastic syndrome, five cases of non-regenerative immune-mediated haemolytic anaemia, one case of immune-mediated neutropenia, three cases of immune-mediated thrombocytopenia, six cases of inflammatory disease, three samples with myelotoxicity and two samples analysed for staging of neoplasia. Automated white blood cell (WBC) counts correlated significantly with smear cellularity, particle cellularity and particle number. There was a significant difference in WBC counts of samples with insufficient versus sufficient particles. Significant correlations between Advia percent neutrophils and microscopical determination of marrow segmented neutrophils/neutrophilic granulocyte reserve, Advia percent lymphocytes and microscopical determination of lymphocytes/rubricytes, Advia percent large unstained cells and microscopical determination of myeloblasts/promyelocytes and between Advia percent eosinophils and manual determination of eosinophils were identified. This suggested that Advia WBC counts may be used to approximate BM sample quality and that Advia differential counts may predict marrow granulocyte reserve and lymphocyte/rubricyte stores. Distinct and consistent alterations in cytogram patterns were observed in cases of acute leukaemia, but were less obvious in chronic leukaemia. Complete automated BM analysis was performed in approximately 2 min, while staining and coverslipping of BM slides required approximately 30 min. Hence, although automated analysis should not supplant microscopical evaluation of BM, it can provide useful ancillary information in a short time and flag potentially inadequate or abnormal samples.

Applicability of 3T body MRI in assessment of nonfocal bone marrow involvement of hematopoietic neoplasia in dogs.

BACKGROUND: The utility of whole body magnetic resonance imaging (MRI) in detecting bone marrow infiltration in dogs with cancer has not been investigated. OBJECTIVES: To assess the feasibility of 3T body MRI for bone marrow assessment in dogs with hematopoietic neoplasia. ANIMALS: Seven dogs with B-cell lymphoma, 3 dogs with myelodysplastic syndrome (MDS), and 2 clinically normal dogs. METHODS: A prospective study of dogs with hematopoetic cancer was conducted using T1W, T2W, In-Phase, Out-of-Phase and STIR pulse sequences of the body excluding the head prior to bone marrow sampling. The relative signal intensity of a midlumbar vertebral body and a midshaft femoral bone marrow was compared by visual and point region of interest analysis to regional skeletal muscle. RESULTS: Similarity of femoral diaphyseal and vertebral body marrow signal intensity to that of skeletal muscle on the Out-of-Phase sequence was useful in distinguishing the 3 dogs with hypercellular marrow because of MDS from the 7 dogs with B-cell lymphoma and from the 2 clinically normal dogs. 1/7 dogs with lymphoma had proven bone marrow involvement but normal cellularity and less than 5% abnormal cells. Unaffected midfemoral marrow had greater signal intensity than skeletal muscle and unaffected vertebral marrow had less signal intensity than skeletal muscle on the Out-of-Phase sequence. CONCLUSIONS AND CLINICAL IMPORTANCE: 3T, Out-of-Phase MR pulse sequence was useful in distinguishing diffuse bone marrow infiltrate (MDS) from minimally or unaffected marrow using skeletal muscle for signal intensity comparison on whole body MRI.

Parenchymal signal intensity in 3-T body MRI of dogs with hematopoietic neoplasia.

We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well.

X-chromosome inactivation pattern analysis for the assessment of cell clonality in cats.

X-chromosome inactivation pattern (XCIP) analysis has been widely used to assess cell clonality in various types of neoplasms in humans. In the present study, a polymerase chain reaction-based feline XCIP analysis using the feline androgen receptor gene was developed. To construct the system of the analysis, polymorphism in CAG tandem repeats within the feline androgen receptor gene was explored using somatic DNAs from 50 male and 103 female cats. CAG tandem repeats in exon 1 of the feline androgen receptor gene were found to be polymorphic, containing 15 to 22 CAG repeats. Of the 103 female cats, 70 (68%) were heterozygous for the number of CAG repeats, indicating the possible usefulness of XCIP analysis in cats. Application of the feline XCIP analysis to 3 feline mammary gland adenocarcinoma cell lines revealed distinctly skewed XCIPs in these cell lines, indicating their clonal origins. Twelve (80%) of the 15 primary tissue/cell samples obtained from cats with various neoplastic diseases showed skewed XCIPs. Moreover, bone marrow samples from 3 cats with myelodysplastic syndrome were also found to have skewed XCIPs. The polymerase chain reaction-based XCIP analysis developed in this study can provide information on cell clonality in female cats, potentially facilitating the differential diagnosis of various disorders in cats.

Abnormal erythroid cell proliferation and myelofibrosis in a cat.

A cat was presented with severe progressive anemia despite marked erythroblastosis. The cat was negative for feline leukemia virus antigen and feline immunodeficiency virus antibody. Bone marrow cytology revealed an excess of erythroid cells with a predominance of prorubricytes and basophilic rubricytes. No response to immunosuppressive therapy was obtained, and a tentative diagnosis of myelodysplastic syndrome was made. The cat showed a partial response to low-dose cytarabine (20 mg/m(2) subcutaneously q24) but died 51 days after the 1st admission. Histopathological examination revealed fibrosis in the bone marrow and marked infiltration of erythroid cells into other organs.

Myelodysplasia in 2 pig-tailed macaques (Macaca nemestrina) associated with retroviral vector-mediated insertional mutagenesis and overexpression of HOXB4.

Gammaretroviral vectors are an efficient means to effect gene therapy. However, genotoxicity from insertion at nonrandom sites can confer a competitive advantage to transduced cells, resulting in clonal proliferation or neoplasia. Six pig-tailed macaques (Macaca nemestrina) underwent total body irradiation and reconstitution with autologous stem cells genetically modified by a gammaretroviral vector overexpressing HOXB4. Two animals were euthanized owing to irradiation- or transplantation-associated toxicity, whereas the other 4 had successful reconstitution. Of the 4 macaques with successful reconstitution, 1 has no long-term follow-up information; 1 was euthanized owing to infection with simian varicella virus infection 18 months post-total body irradiation; and the 2 others are described herein as case Nos. 1 and 2. After being stable for 3 years, case No. 1 developed pancytopenia and petechiation, and after 2 years of stability case No. 2 developed anemia and thrombocytopenia. Despite therapy, the animals deteriorated and were euthanized. Gross findings included emaciation; case No. 1 also had hemorrhage, peritonitis, and cholecystitis. Histologically, bone marrow was hypercellular with predominately blast cells of all hematopoietic lineages, though with myeloid predominance, and with maturation arrest and blast cell dysplasia (myelodysplasia). Myelodysplasia was likely from a combination of insertional mutagenesis by the retroviral vector and overexpression of HOXB4. Consequences of myelodysplasia included the blood dyscrasias and, in case No. 1, hemorrhage, bacterial cholecystitis, hepatitis, and peritonitis.

Prognostic markers for myeloid neoplasms: a comparative review of the literature and goals for future investigation.

Myeloid neoplasms include cancers associated with both rapid (acute myeloid leukemias) and gradual (myelodysplastic syndromes and myeloproliferative neoplasms) disease progression. Percentage of blast cells in marrow is used to separate acute (rapid) from chronic (gradual) and is the most consistently applied prognostic marker in veterinary medicine. However, since there is marked variation in tumor progression within groups, there is a need for more complex schemes to stratify animals into specific risk groups. In people with acute myeloid leukemia (AML), pretreatment karyotyping and molecular genetic analysis have greater utility as prognostic markers than morphologic and immunologic phenotypes. Karyotyping is not available as a prognostic marker for AML in dogs and cats, but progress in molecular genetics has created optimism about the eventual ability of veterinarians to discern conditions potentially responsive to medical intervention. In people with myelodysplastic syndromes (MDS), detailed prognostic scoring systems have been devised that use various combinations of blast cell percentage, hematocrit, platelet counts, unilineal versus multilineal cytopenias and dysplasia, karyotype, gender, age, immunophenotype, transfusion dependence, and colony-forming assays. Predictors of outcome for animals with MDS have been limited to blast cell percentage, anemia versus multilineal cytopenias, and morphologic phenotype. Prognostic markers for myeloproliferative neoplasms (eg, polycythemia vera, essential thrombocythemia) include clinical and hematological factors and in people also include cytogenetics and molecular genetics. Validation of prognostic markers for myeloid neoplasms in animals has been thwarted by the lack of a large case series that requires cooperation across institutions and veterinary specialties. Future progress requires overcoming these barriers.

Myelodysplastic syndromes and acute myeloid leukemia in cats infected with feline leukemia virus clone33 containing a unique long terminal repeat.

Feline leukemia virus (FeLV) clone33 was obtained from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV from other cats with AML, differs from the LTRs of other known FeLV in that it has 3 tandem direct 47-bp repeats in the upstream region of the enhancer (URE). Here, we injected cats with FeLV clone33 and found 41% developed myelodysplastic syndromes (MDS) characterized by peripheral blood cytopenias and dysplastic changes in the bone marrow. Some of the cats with MDS eventually developed AML. The bone marrow of the majority of cats with FeLV clone33 induced MDS produced fewer erythroid and myeloid colonies upon being cultured with erythropoietin or granulocyte-macrophage colony-stimulating factor (GM-SCF) than bone marrow from normal control cats. Furthermore, the bone marrow of some of the cats expressed high-levels of the apoptosis-related genes TNF-alpha and survivin. Analysis of the proviral sequences obtained from 13 cats with naturally occurring MDS reveal they also bear the characteristic URE repeats seen in the LTR of FeLV clone33 and other proviruses from cats with AML. Deletions and mutations within the enhancer elements are frequently observed in naturally occurring MDS as well as AML. These results suggest that FeLV variants that bear URE repeats in their LTR strongly associate with the induction of both MDS and AML in cats.

Blood smear from a cat: features to "dys"cover.

A 4-year-old, spayed female, domestic shorthair cat was presented for lethargy, nonregenerative anemia, and inappetence. Results of a CBC included macrocytic, normochromic, nonregenerative anemia and a glucocorticoid-associated leukogram. On blood smear examination, neutrophils had abnormal features including hyposegmentation and a diffuse chromatin pattern with nuclear filament formation and nuclear blebbing. Microscopic examination of a roll preparation of bone marrow revealed hypolobulated megakaryocytes with asynchronous maturation of nuclei. The granulocytic to erythrocyte (G:E) ratio was 76. Segmented neutrophils had asynchronous maturation and dysplastic features. The entire erythroid lineage was markedly decreased for the degree of anemia and rare dysplastic features were noted in erythroid precursor cells. The interpretation of bone marrow findings was erythroid hypoplasia, megakaryocytic dysplasia, and granulocytic hyperplasia with dysplasia. Histopathologic examination of a bone marrow core sample also revealed myeloid hyperplasia and erythroid hypoplasia. The result of a direct immunofluorescence assay for FeLV performed on the bone marrow roll preparation was positive. A diagnosis of dysmyelopoiesis associated with FeLV infection was made. This case was unique in that the dysplastic changes occurred in cell lines that did not have associated cytopenias. The dysmyelopoiesis most closely resembled myelodysplastic syndrome with refractory cytopenia (MDS-RC); however, secondary dysmyelopoiesis could not be ruled out.

Evaluation of dysmyelopoiesis in cats: 34 cases (1996-2005).

OBJECTIVE: To further classify dysmyelopoiesis as diagnosed by use of a general classification scheme and to determine clinical features and laboratory test results that could be used to differentiate between the various forms of dysmyelopoiesis in cats. DESIGN: Retrospective case series. Sample Population-Bone marrow slides from 34 cats. PROCEDURES: Medical records of cats in which dysmyelopoiesis was diagnosed on the basis of blood and bone marrow analyses from 1996 to 2005 were reviewed. Criteria for inclusion in the study were findings of > 10% dysplastic cells in 1 or more hematologic cell lines in the bone marrow and concurrent cytopenias in the blood. Cats that met these criteria were classified into subcategories of myelodysplastic syndromes or secondary dysmyelopoiesis on the basis of reevaluation of slides. RESULTS: Of 189 bone marrow slides reviewed, 34 (14.9%) had > 10% dysplastic cells in 1 or more cell lines. Cats were subcategorized as having myelodysplastic syndrome with excessive numbers of blast cells (n = 13), myelodysplastic syndrome with refractory cytopenias (8), a variant form of myelodysplastic syndrome (1), and secondary dysmyelopoiesis (12). Findings of dysmyelopoiesis and autoagglutination in cats with myelodysplastic syndrome and in those with immune-mediated anemia complicated differentiating between the 2 conditions. CONCLUSIONS AND CLINICAL RELEVANCE: Differentiating cats with myelodysplastic syndromes from cats with immune-mediated hemolytic anemia was difficult because severe anemia and autoagglutination may be concurrent findings in both conditions. Differentiating between myelodysplastic syndrome with excessive numbers of blast cells and myelodysplastic syndrome with refractory cytopenias was useful in predicting clinical outcome.

Classification of myeloid neoplasms: a comparative review.

Classification of myeloid neoplasms in veterinary medicine was modeled in the early 1990s after French-American-British and National Cancer Institute systems used in human medicine. Recently our physician counterparts, in collaboration with oncologists, constructed a new World Health Organization (WHO) standard. WHO revisions lower the blast threshold from 30% to 20% for diagnosing acute myeloid leukemia (AML) and expand and redefine AML categories. AML is now subdivided into 4 broad groups: 1) AML with recurrent genetic abnormalities, 2) AML with multilineage dysplasia, 3) AML with previous chemotherapy and/or radiation, and 4) AML, not otherwise categorized. AML alphanumeric designations (M1, M2, etc) have been discontinued as numbers of subtypes have increased. The lower blast percentage eliminates one category of myelodysplastic syndrome (MDS): refractory anemia with excess blasts in transformation. A new MDS category was created: refractory cytopenia with multilineage dysplasia (RCMD), with lineage dysplasia assessed using newly defined percentage limits. At least 10% of cells from each of 2 lineages must display atypia for a diagnosis of RCMD. That threshold is 50% for diagnosing AML with multilineage dysplasia. Chronic myelomonocytic leukemia has been removed from the MDS category and included in a new category of diseases that have features of both MDS and chronic leukemia. WHO revisions are a signal to veterinary clinical pathologists to assess the validity of our system, which was built on premises now questioned.

Recognition and classification of dysmyelopoiesis in the dog: a review.

Dysmyelopoiesis is defined as a hematologic disorder characterized by the presence of cytopenias in the blood and dysplastic cells in one or more hematologic cell lines in the blood or bone marrow. The causes of dysmyelopoiesis include acquired mutations in hematopoietic stem cells (i.e., myelodysplastic syndromes [MDSs]), congenital defects in hematopoiesis, and dysmyelopoietic conditions associated with various disease processes, drug treatments, or toxin exposure. Two major subtypes of MDSs (i.e., MDS with refractory cytopenias and MDS with excess myeloblasts) have been described that differ in clinical presentation, response to treatment, and survival time. The most frequently occurring causes of secondary dysmyelopoiesis include immune-mediated hematologic diseases, lymphoid malignancies, and exposure to chemotherapeutic drugs. Differentiation of the various causes of dysmyelopoiesis is essential for establishing an appropriate therapeutic plan and for determining prognosis.

In vitro selective suppression of feline myeloid colony formation is attributable to molecularly cloned strain of feline leukemia virus with unique long terminal repeat.

Molecularly cloned feline leukemia virus (FeLV)-clone 33 (C-33), derived from a cat with acute myelocytic leukemia (AML), was examined to assess its relation to the pathogenesis of AML and myelodysplastic syndrome (MDS). To evaluate in vitro pathogenicity of FeLV C-33, bone marrow colony-forming assay was performed on marrow cells infected with FeLV C-33 or an FeLV subgroup A strain (61E, a molecularly cloned strain with minimal pathogenicity). The myeloid colony-forming activity of feline bone marrow mononuclear cells infected with FeLV C-33 was significantly lower than that of cells infected with 61E. This suggests that FeLV C-33 has myeloid lineage-specific pathogenicity for cats, and that FeLV C-33 infection is useful as an experimental model for investigating pathogenesis of MDS and AML.

New insights into the physiology and treatment of acquired myelodysplastic syndromes and aplastic pancytopenia.

MDS are a diverse group of primary and secondary bone marrow disorders that are characterized by cytopenias in blood, prominent dysplastic features in blood or bone marrow, and normal or hypercellular bone marrow. MDS in cats are typically associated with FeLV infection. Dogs with MDS-RC and MDS-Er seem to respond to erythropoietin administration and have prolonged survival. Dogs with MDS-EB respond poorly to present treatments, and survival is short. Prognosis and probability of progression to acute myelogenous leukemia can be predicted based on the percentage of myeloblasts in bone marrow. Several experimental therapeutic modalities in human beings have been described that may be useful in treating MDS-EB in dogs and cats. Aplastic pancytopenia is a relatively rare disorder in dogs and cats. Causes include Ehrlichia spp, Parvovirus, and FeLV infections; sepsis; chronic renal failure; drug and toxin exposure; and idiopathic causes. Diagnosis is based on identification of multiple cytopenias in the blood and hypoplastic/aplastic bone marrow, with the marrow space replaced by adipose tissue. Treatment and outcome are dependent on determining the underlying cause of the bone marrow failure.