Suspected chronic eosinophilic leukemia in a cat treated with toceranib

Abstract

Case summary

A 16-year-old, spayed female domestic shorthair cat was referred to the Schwarzman Animal Medical Center for evaluation of chronic, progressive eosinophilia accompanied by vomiting and weight loss despite normal appetite. Blood smear evaluation revealed immature eosinophils with dysplastic features and occasional giant forms. Abdominal ultrasound identified small-intestinal thickening, a hepatopathy and splenomegaly. Screening for feline leukemia virus, feline immunodeficiency virus and heartworm infection were negative. Chronic eosinophilic leukemia was suspected, although hypereosinophilic syndrome could not be ruled out. At the time of referral, the cat was receiving prednisolone and chlorambucil for suspected small cell gastrointestinal lymphoma, but showed persistent clinical signs and progressive eosinophilia. Chlorambucil was discontinued and toceranib was initiated alongside prednisolone. No adverse effects attributable to toceranib were observed. A partial response, defined as resolution of clinical signs and a 30% reduction in circulating eosinophils, was observed on day 39. A subsequent progression-free survival interval of 4 weeks was achieved. Progressive disease developed on day 75, and given declining quality of life, euthanasia was thereby elected on day 89.

Relevance and novel information

This case report is the first to describe the use of toceranib to treat suspected chronic eosinophilic leukemia, a rare and poorly documented disease process in cats. This novel therapeutic approach is the first publication of a partial response and stable disease in the treatment of suspected chronic eosinophilic leukemia in a cat.

Plain language summary

Suspected Chronic Eosinophilic Leukemia in a Cat Treated with Toceranib

A 16-year-old spayed female cat was referred for chronic progressive vomiting, weight loss, and high eosinophil counts. Bloodwork showed abnormal and immature eosinophils, suggesting chronic eosinophilic leukemia. Ultrasound revealed thickened intestines, along with changes in the liver and spleen. Common infectious causes were ruled out. Chronic eosinophilic leukemia was suspected, although hypereosinophilic syndrome could not be excluded. The cat had previously been treated with prednisolone and chlorambucil for suspected intestinal small cell lymphoma, but showed no improvement. Chlorambucil was stopped, and treatment with toceranib was started alongside prednisolone. The medication was well tolerated. After four weeks, the cat showed a partial response, with improvement in clinical signs and a decrease in eosinophil levels. This response lasted for about one month. By week nine, the disease progressed again. Due to declining quality of life, the cat was euthanized at week ten.

This is the first reported case of using this specific drug (toceranib) to treat suspected chronic eosinophilic leukemia in a cat. This is the first publication to document a partial response to treatment and a progression free survival interval in a cat with suspected chronic eosinophilic leukemia.

Case description

A 16-year-old, female spayed domestic shorthair cat was referred to the Animal Medical Center (AMC) for evaluation of a severe progressive eosinophilia. Mild eosinophilia was detected in 2022 (1.98 K/µl, reference interval 0.17–1.57) and progressed to 10 K/µl by 8 October 2024, coinciding with ptyalism, vomiting and weight loss despite normal appetite, a distended abdomen with thickened intestines and a grade II/VI murmur. Complete blood cell count (CBC) revealed moderate leukocytosis with eosinophilia, neutrophilia, monocytosis and mild normocytic normochromic (NCNC) anemia. Urine was concentrated without proteinuria. Total thyroxine, serum biochemistry and pro-BNP were within normal limits (Table 1).

Table 1.

Complete blood cell count, biochemistry and total thyroid values from 8 October 2024, when clinical signs were first documented

Parameter	Result	RI
Hematocrit (%)	26.9	28.2–52.7
Hemoglobin (g/dl)	8.1	10.3–16.2
Mean corpuscular hemoglobin concentration (g/dl)	30.1	28.5–37.8
White blood cell count (K/µl)	30.2	3.9–19.0
Reticulocyte hemoglobin (pg)	19.4	15.3–22.9
Red blood cell count (M/µl)	4.66	7.12–11.46
Mean corpuscular volume (fl)	58	39–56
Mean corpuscular hemoglobin (pg)	17.4	12.6–16.5
Basophils (/µl)	91	0–100
Eosinophils (/µl)	10,479	90–2180
Lymphocytes (/µl)	1540	850–5850
Monocytes (/µl)	1117	40–530
Neutrophils (/µl)	16,972	2620–15,170
Reticulocytes (K/µl)	19	3–50
Platelet count (K/µl)	330	155–641
Glucose (mg/dl)	153	72–175
Blood urea nitrogen (mg/dl)	25	16–37
Creatinine (mg/dl)	1.0	0.9–2.3
Total protein (g/dl)	7.8	6.3–8.8
Albumin (g/dl)	3.5	2.6–3.9
Globulin (g/dl)	4.3	3.0–5.9
Total bilirubin (mg/dl)	0.2	0.0–0.3
Alkaline phosphatase (U/l)	36	12–59
Alanine aminotransferase (U/l)	47	27–158
Aspartate aminotransferase (U/l)	24	16–67
Gamma-glutamyl transferase (U/l)	1	0–6
Cholesterol (mg/dl)	122	91–305
Calcium (mg/dl)	9.3	8.2–11.2
Phosphorus (mg/dl)	3.3	2.9–6.3
Sodium (mmol/l)	151	147–157
Potassium (mmol/l)	5.0	3.7–5.2
Chloride (mmol/l)	117	114–126
Albumin:globulin ratio	0.8	0.5–1.2
Blood urea nitrogen:creatinine ratio	25.0	–
Creatine kinase (U/l)	122	64–440
Direct bilirubin (mg/dl)	0.1	0.0–0.2
Indirect bilirubin (mg/dl)	0.1	0.0–0.2
Bicarbonate (mmol/l)	20	12–22
Sodium:potassium ratio	30	29–42
Anion gap (mmol/l)	19	12–25
Symmetric dimethylarginine (µg/dl)	13	0–14
Total thyroxine (µg/dl)	2.9	0.8–4.7

Results in bold are outside the reference interval (RI)

Abdominal ultrasound was performed and noted hepatomegaly, hyperechoic hepatopathy, splenomegaly, scant ascites, focal concentric small intestinal thickening and mesenteric lymphadenopathy. Gastrointestinal small cell lymphoma was suspected, prompting empiric treatment with prednisolone (1.6 mg/kg PO q24h) and chlorambucil (0.65 mg/kg PO Monday/Wednesday/Friday).

A moderate progression in eosinophilia (29 K/µl) was seen on 7 December 2024. A repeat ultrasound on 3 January 2025 showed improved intestinal thickening and lymphadenopathy, but persistent hepatosplenomegaly. Cytology of the liver and spleen revealed marked eosinophilic infiltration, with no evidence of mast cell neoplasia or large cell lymphoma. The splenic lymphoid population was mixed but predominantly composed of small lymphocytes.

On 3 June 2025, the eosinophilia progressed to 78 K/µl. Infectious disease testing (feline leukemia virus [FeLV]/feline immunodeficiency virus, heartworm antigen) was negative. Blood smear evaluation revealed a mature eosinophilia with occasional immature forms and dysplastic changes, suggesting chronic eosinophilic leukemia (CEL), hypereosinophilic syndrome (HES) or feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF).

The cat was referred to the AMC Internal Medicine Service. On 13 June 2025, the cat showed ongoing weight loss despite normal appetite. The NCNC anemia was stable and eosinophilia was mildly decreased (Table 2). Serum biochemistry revealed mild hypokalemia and hypophosphatemia. Heartworm antibody testing was negative. Thoracic radiographs revealed mild sternal lymphadenopathy and equivocal cardiomegaly. Abdominal ultrasound showed persistent diffuse small intestinal thickening with focal loss of wall layering, mild jejunal lymphadenopathy, mild splenomegaly and hyperechoic hepatopathy. The absence of a mass and lack of response to steroids and chlorambucil ruled out FGESF.

Table 2.

Serial hematology, alkaline phosphatase and body weight changes over time in relation to concurrent treatment administered in a 16-year-old, spayed female domestic shorthair with suspected chronic eosinophilic leukemia

Date	Eosinophil count (K/µl)	RI (K/µl)	Hematocrit (%)	RI (%)	ALP (U/l)	RI (U/l)	Weight (kg)	Treatment
22 December 2022	1.98*	0.17–1.57	44.1*	28.2–52.7	44	12–59	4.85	None
8 October 2024	10.791 †	0.17–1.57	26.9 †	28.2–52.7	36	12–59	2.9	None
7 December 2024	29.634 †	0.17–1.57	38.9 †	28.2–52.7	33	12–59	3.29	Prednisolone + chlorambucil
3 June 2025	78.051 †	0.17–1.57	27.1 †	28.2–52.7	49	12–59	2.97	Prednisolone + chlorambucil
20 June 2025	44.545 †	0.17–1.57	21.8 †	30.3–52.3	–	12–59	2.8	Prednisolone + chlorambucil
25 July 2025	64.35 †	0.17–1.57	24.1 †	30.3–52.3	–	12–59	2.45	Toceranib + prednisolone
11 August 2025	46.368 †	0.17–1.57	20.1 †	30.3–52.3	60	12–59	2.42	Toceranib + prednisolone
8 September 2025	46.905 †	0.17–1.57	18.5 †	30.3–52.3	44	12–59	2.38	Toceranib + prednisolone
16 September 2025	83.03*	0.17–1.57	22.1*	30.3–52.3	–	–	2.14	Prednisolone

^*Signifies hematology profiles performed on IDEXX Procyte Dx

^†Signifies hematology profiles performed on Sysmex XN QC

ALP = alkaline phosphatase; RI = reference interval

CEL was prioritized over hypereosinophilic syndrome based on the magnitude of eosinophilia and dysplastic changes, and the cat was referred to the AMC Medical Oncology Service. Flow cytometry of peripheral blood was performed but did not add to the understanding of the case.

On 20 June 2025, clinical signs worsened – daily vomiting, diarrhea and ptyalism – despite a normal appetite. Gastrointestinal and bone marrow biopsies were declined. CBC with cytology showed persistent NCNC anemia and hypereosinophilia, with larger immature eosinophils, giant forms and dysplastic changes (Figures 1–4).

Figure 1.

Photomicrograph showing three mature slightly hypogranulated eosinophils and one band eosinophil (arrow) (Wright–Giemsa stain, magnification 50x)

Figure 2.

Photomicrograph depicting dysplastic eosinophils including one giant eosinophil (arrow) and several hypogranulated forms (Wright–Giemsa stain, magnification 100x)

Figure 3.

Photomicrographic evidence of one blast of myeloid origin (arrow) and several eosinophils in various stages of maturation (Wright–Giemsa stain, magnification 100x)

Figure 4.

Photomicrograph showing an eosinophil promyelocyte (arrow), eosinophil bands and hypogranulated mature eosinophils (Wright–Giemsa stain, magnification 100x)

Based on previous findings and clinical signs, empiric treatment for CEL was started with toceranib (2.5 mg/kg PO Monday/Wednesday/Friday) on 4 July 2025 (day 1). Informed consent was obtained for the off-label use of toceranib for the treatment of suspected CEL. The prednisolone dosage was reduced (0.9 mg/kg PO q24h) and chlorambucil was discontinued.

On day 22 (25 July), the cat’s weight had decreased by 12.5% and there was moderate progression of eosinophilia (Table 2); however, vomiting improved to 2–3 times weekly. A gastrointestinal panel revealed severe hypocobalaminemia with normal trypsin-like immunoreactivity, indicating malabsorption. Subcutaneous cyanocobalamin supplementation (250 µg/cat) was started. Mildly elevated pancreatic lipase suggested pancreatitis, possibly secondary to eosinophilic inflammation or toceranib (see Table 3 for results). Alkaline phosphatase (ALP) was mildly elevated, potentially related to pancreatitis or toceranib (Table 2). Other adverse effects of toceranib, including hypertension and proteinuria, were not identified.

Table 3.

Gastrointestinal profile values and reference intervals (RIs) including pancreatic lipase, trypsin-like immunoreactivity, cobalamin and folate

Parameter	Results	RI
Specific feline pancreatic lipase (µg/l)	5.4	0.0–4.4
Trypsin-like immunoreactivity (µg/l)	26.80	12.00–82.00
Cobalamin (ng/l)	<150	276–1425
Folate (µg/l)	16.1	8.9–19.9

Results in bold are outside the RI

A partial response was noted on day 39 (11 August), characterized by a 30% reduction in eosinophils and resolution of gastrointestinal signs. The cat’s weight had stabilized, but the anemia mildly progressed possibly due to chronic disease or primary bone marrow disease.

The eosinophil count, weight and gastrointestinal signs were static on day 67 (8 September), suggesting a progression-free survival (PFS) of 4 weeks. ALP had normalized (see Table 2 for values).

On day 75 (16 September), frequent diarrhea and a 10% reduction in body weight were observed. The anemia had improved, but the eosinophilia had increased to 83 K/µl. Pancreatic lipase was elevated at 29.9 U/l. Since pancreatitis is a known adverse effect of toceranib and there was evidence of progressive disease, therapy was discontinued to assess whether clinical signs would improve.

Clinical signs persisted after cessation of therapy, suggesting progressive disease, and the owners elected humane euthanasia on day 89 (30 September).

Discussion

HES and CEL are rare feline disorders with limited published information. In the largest retrospective study of 312 cats with hypereosinophilia, no cases of CEL were identified. ¹ Consequently, reliable diagnostic criteria to distinguish CEL from HES are lacking. Cytologic features of immaturity, dysplasia and the presence of blasts are often used to differentiate between them.^2–7 However, morphology is not definitive, and some authors propose these two diseases lie on a continuum.^2–6

In humans, HES is an umbrella term for hypereosinophilic conditions, with idiopathic HES considered the closest counterpart in cats. ⁸ HES is defined by persistent hypereosinophilia (⩾1.5 K/µl) and categorized as reactive, neoplastic or idiopathic. ⁸ Once reactive causes have been excluded, organ infiltration and cytogenetic testing can help distinguish between idiopathic HES and CEL. ⁸ CEL represents a clonal eosinophilic proliferation, with less than 20% blasts in circulation. ⁸ Tissue infiltration may occur in CEL but is required for idiopathic HES; without it, the condition is termed ‘HES of unknown significance’. ⁸ Bone marrow evaluation is recommended, as HES shows mature eosinophils, whereas CEL demonstrates dysplastic megakaryocytes, fibrosis and blasts. ⁸

Tumor cytogenetics are vital in human medicine. CEL is defined by the absence of the following mutations and fusion genes: BCR–ABL, PDGFRA, PDGFRB, FGFR1, PCM1/JAK2, ETV6/JAK2 and BCR/JAK2, which are diagnostic for HES caused by myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-eo-TK).^7,8 Analogous feline markers have not been identified, making definitive differentiation challenging. Cytogenetic testing is emerging in veterinary medicine. ⁹

T-cell lymphoma is a cause of reactive HES in cats and humans due to paraneoplastic IL-5 production, which prompts myeloid cell differentiation into eosinophils and acts as an anti-apoptotic and chemotactic factor.^1,8,10,11 T-cell lymphoma has not been shown to cause a paraneoplastic eosinophilia greater than 30,000 K/µl in cats.^1,10,12 Both HES and CEL have been linked to FeLV infection. ¹³

In this case, the eosinophilia had been persistent since 2022 and progressed in 2024; lack of recent anthelmintics left parasitism as a theoretical differential. Progression coincided with gastrointestinal signs and ultrasonographic findings of diffuse small-intestinal thickening with focal loss of wall layering, mild jejunal lymphadenopathy and hepatosplenomegaly. Liver and spleen cytology showed eosinophils, although true infiltration vs blood contamination was unclear.

Eosinophils normally migrate into gastrointestinal tissues but survive for approximately 2 days. ⁵ In disease states, their lifespan can extend up to 2 weeks. ⁵ Eosinophilic infiltration can cause marked clinical signs due to the secretion of cytotoxic granules directly onto their targets, resulting in damage to the regional tissues. ⁵ Involvement of the gastrointestinal tract, liver and spleen has been documented in both HES and CEL.^3,4,14 Ultrasonographic findings were highly suspicious for eosinophilic infiltration, although this could not be confirmed without biopsy.

A blood smear on 3 June 2025 showed occasional dysplastic eosinophils. Two weeks later, the eosinophilia had progressed and cytology demonstrated giant cells, more pronounced dysplasia and immature forms consistent with previous CEL reports.^3,4 This progression, severity and cell morphology increased suspicion for CEL. However, due to client-declined bone marrow biopsy and only one myeloblast cell observed, idiopathic HES could not be ruled out. Ultimately, these diseases are thought to exist on a continuum, both in human and feline medicine. As a result, there are overlapping approaches to treatment.^2–8

This cat initially exhibited an indolent disease course, possibly reflecting transformation from HES of unknown significance to CEL, supporting a disease continuum.^2,6 Progression from chronic inflammation to neoplasia is an established mechanism in other forms of feline oncogenesis. ¹⁵

Glucocorticoids are considered first-line therapy due to suppression of eosinophil activation and survival but have limited long-term efficacy because of resistance. ⁵ Prednisolone (2 mg/kg) was ineffective in a cat with HES presenting with eosinophilic jejunitis and mesenteric lymphadenitis, as vomiting, diarrhea, weight loss and hypereosinophilia continued despite treatment. ¹⁶ Similarly, when prednisone (2 mg/kg) and doxycycline (10 mg/kg/day) were used in a cat with CEL, progressive disease was documented 15 days after initiating treatment, resulting in owner-elected euthanasia. ⁴ In a case of CEL treated with nandrolone decanoate (1 mg/kg IM), the cat deteriorated rapidly and was euthanized. ³

Hydroxyurea combined with prednisolone has been trialed in two cats with HES. ¹⁷ One cat developed disseminated intravascular coagulation and died 10 days after starting hydroxyurea (20–30 mg/kg q24h). ¹⁷ In the second case, hydroxyurea (15 mg/kg q24h) had to be discontinued 24 days into treatment owing to adverse effects, including hematochezia and severe anemia; this cat developed pneumoperitoneum secondary to gastrointestinal perforations from eosinophilic ulcers, prompting euthanasia. ¹⁷

A series of three cats with cutaneous HES reported successful treatment using imatinib (1.25–2 mg/kg q24h) and glucocorticoids without adverse effects. ¹⁸ All three cats showed marked resolution of cutaneous lesions within 2 months of therapy. ¹⁸ In one cat, serial blood work confirmed hematologic remission by week 10. ¹⁸ Long-term follow-up was only available for one cat, in which therapy could not be fully discontinued without relapse; however, this cat remained in remission for 5 years on q48h dosing of imatinib and methylprednisolone. ¹⁸

These findings support tyrosine kinase inhibitors as potential first-line therapy. Imatinib binds to the BCR-ABL domain of the tyrosine kinase receptor, inhibiting its activity.^19–22 In human medicine, imatinib is a first-line therapy for HES, particularly in patients with a FIP1L1-PDGFRA or RHE-PDGFRA fusion gene (F/P fusion), which encodes a constitutively active tyrosine kinase.^19–22 In these patients, even low doses of imatinib induce remission.^19–22 In cases without the F/P fusion gene or unknown F/P fusion status, response rates were in the range of 14–40%.^19–22

Toceranib targets multiple split-kinase domains and was selected over imatinib due to its broader spectrum of activity. ²³ In addition, there is only phase I clinical trial data on the use of imatinib in cats, whereas toceranib is a veterinary drug with more feline safety data.^24–27 Treatment with toceranib resulted in a partial response on day 39 (resolution of gastrointestinal signs and 30% decrease in eosinophilia) with a subsequent PFS of 4 weeks. Treatment was discontinued on day 75 because of progressive disease and pancreatitis.

Conclusions

This case report documents a novel therapeutic approach for suspected CEL. Toceranib with prednisolone was more effective than prior treatment with prednisolone and chlorambucil and previous reports of treatment with nandrolone decanoate and glucocorticoids, with or without hydroxyurea, in CEL and HES.^3,4,16,17 However, long-term remission, such as that reported in HES with imatinib, was not achieved. ¹⁸ Until cytogenetic testing becomes available, tailoring small-molecule inhibitor therapy is not possible. Based on current evidence, toceranib with prednisolone is a reasonable option for suspected CEL.