LOPH: a novel chemotherapeutic protocol for feline high-grade multicentric or mediastinal lymphoma, developed in an area endemic for feline leukemia virus

Horta, R.S.; Souza, Luciano Melo de; Sena, Bruna Voltolin de; Almeida, Isabella Oliveira; Jaretta, Tâmara A; Pimenta, Marcos de Mattos; Júnior, Archivaldo Reche

doi:10.1177/1098612x20926893

Cited by 16 publications

(35 citation statements)

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“…Considering the poor prognosis for acute lymphoid leukemias [9] and the patient's retroviral status, treatment was initiated with the LOPH protocol, suggested by Horta et al [17]. This protocol includes lomustine, as a potent agent to induce remission, considering its ineffectiveness in a possible rescue approach in cats with lymphoma, which resulted in a disease-free interval of only 39 days [10].…”

Section: Discussionmentioning

confidence: 99%

“…The LOPH protocol also includes doxorubicin in the induction phase. In underpowered studies, with a small number of cats with lymphoma, doxorubicin promoted longer remission intervals, when included in the induction [17,32] or maintenance protocol [22].…”

Section: Discussionmentioning

confidence: 99%

“…For this, the D-MHC protocol was used, as a modification of the D-MAC protocol [11], considering the greater availability and easier acquisition of doxorubicin, which contributed to a faster initiation of the protocol. Cats have specific polymorphisms in the ABCG2 gene, resulting in the abnormal expression of their transcriptional product, the breast cancer resistance protein (BCRP), related to anthracyclines resistance, with consequent inefficient efflux of their substrates, such as doxorubicin [23], which favors, therefore, the use of this drug in the induction and rescue protocol [17]. The patient presented a new clinical remission, with duration similar to that observed with the first protocol, but there was a novel recurrence with severe pancytopenia, and euthanasia was elected.…”

Section: Discussionmentioning

confidence: 99%

“…With treatment, the febrile condition ceased and the patient's general condition improved, with resolution of lymphocytosis, but with the presence of severe neutropenia (820/µL; Ref: 2500-8500/µL [18]), requiring, again, institution of filgrastim, which allowed, in the following week, the institution of the rescue protocol D-MHC [dexamethasone (Dextar ® ) 8 melphalan (Alkeran ® ) 9 , doxorubicin 4 , and cytarabine 7 ] (Table 1), adapted from the D-MAC protocol, with the replacement of actinomycin-D by doxorubicin 4 Table 1. Chemotherapy protocol for acute leukemia in a domestic cat, for induction it was used the LOPH protocol based on the combination of lomustine, vincristine (Oncovin ® ), prednisolone and doxorubicin (hydroxydaunorubicin) [17] and in a rescue attempt it was used the D-MHC protocol based on the combination of dexamethasone, melphalan, doxorubicin (hydroxydaunorubicin) and cytarabine [11].…”

Section: Casementioning

confidence: 99%

“…A new treatment protocol has been described for multicentric or mediastinal lymphomas in cats with FeLV persistent antigenemia. This protocol, called LOPH, is proposed for an induction phase and consists of the association of Lomustine, Vincristine (Oncovin ® ), Prednisolone and Doxorubicin (Hydroxydaunorubicin), showing good tolerance in cats, with complete response in 81% of cases and an average survival of 214 days, superior to studies with other protocols in populations with high FeLV infection rates [17].…”

Section: Introductionmentioning

confidence: 99%

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LOPH and D-MHC in the Treatment of FeLV Associated Acute Leukemia in a Cat

Horta

Ferreira

Costa

et al. 2021

Acta Scientiae. Vet.

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Background: Bone marrow primary malignancies are denominated leukemias, classified as myeloid or lymphoid, according to the cell lineage, and acute or chronic, according to the cell´s state of maturation. In cats, acute lymphoid leukemia is the most common form, especially in regions endemic for feline leukemia virus and / or feline immunodeficiency virus. A new treatment protocol for lymphomas, called LOPH, has been described for animals with FeLV persistent viremia. This study aimed to report a case of a cat presenting with FeLV associated acute leukemia and treated with the LOPH protocol, and, in the rescue phase, a modification of the D-MAC protocol, denominated D-MHC.Case: A 4-year-old mixed breed intact queen was attended due to lethargy and inappetence. The patient did not present any relevant abnormalities in the clinical exam and complementary exams were performed including complete blood count, biochemical profile, SNAP Feline Triple Test, chest radiographs and abdominal ultrasound. Imaging tests and biochemical values were unremarkable, but the patient presented a reagent result for FeLV and severe leukocytosis due to lymphocytosis. The morphological evaluation of the blood smear revealed the presence of blasts, in a concentration greater than 20% of the nucleated cells, which allowed the characterization of a leukemic state, probably lymphoid. First-line treatment was based on the LOPH protocol, including Lomustine, Vincristine, Prednisoloneand Doxorubicin, in four-week cycles. Nevertheless, during the third cycle, 66 days after the institution of this protocol, the patient presented a febrile condition along with marked leukocytosis due to lymphocytosis, confirming leukemia recurrence. A rescue attempt was performed with a modification of the D-MAC protocol, originally consisting of the combination of dexamethasone, melphalan, actinomycin-D and cytarabine, but with replacement of actinomycin-D by doxorubicin, and therefore nominated D-MHC. After the three cycles there was a return of the febrile condition associated with severe pancytopenia and euthanasia was elected due to poor clinical condition, resulting in a survival time of 124 days. The hematological toxicity of the induction protocol included anemia and neutropenia, with mainly grade I events, but with the occurrence of a grade IV event. The adverse effects of the rescue protocol were similar, but with a greater number of grade IV events.Discussion: FeLV is considered the most lethal retrovirus of the domestic cat, with a major impact on health and life expectancy. Persistent FeLV antigenemia increases the risk of hematopoietic neoplasms in 62.1 times due to a direct insertional mutagenesis. In endemic regions, approximately 70% of cats with acute leukemia have persistent FeLV antigenemia, as the patient in this report. The diagnosis was made through association of retroviral status and the identification of more than 20% of blasts, possibly lymphoblasts, in the blood stream, sparing the need for a myelogram. Considering the poor prognosis for acute lymphoid leukemias and the patient's retroviral status, treatment was initiated with the LOPH protocol, including lomustine, as a potent agent to induce remission, and doxorubicin, which can result in longer remission intervals. After 66 days free of the disease, the patient presented recurrence of the leukemic condition, starting the rescue protocol D-MHC. Remission was again obtained with duration similar to the first protocol, however, on the occasion of a new leukemia recurrence, euthanasia was elected. The treatment adopted for the patient in this report resulted in a longer survival time than reported in other studies. Despite the aggressiveness of the protocols, especially the D-MHC, it was possible to perform it using the monocyte and granulocyte stimulation factor to reverse neutropenia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%