G-CSF Induced Atypical Monocytic Proliferation Mimicking Acute Myelomonocytic Leukemia in Post-Induction Chemotherapy AML Patient
Authors: He Rui Rochelle , Patel-Donnelly Dipti , Kales Arthur N. , Qi Dan Y , Salam Abdus , Nayer Hassan 
Published: October 2019

Abstract
Abstract 4283

Introduction:
Granulocyte colony-stimulating factor (G-CSF) is a major hematopoietic cytokine involved in control of neutrophil production, proliferation and survival.1 Nowadays, recombinant G-CSF is widely used in patients with hematopoietic malignanies receiving chemotherapy to increase leukocyte count.2 Studies have showed that G-CSF use in these settings is safe and does not increase relapse rate.3,4 However, A phenomena called transient atypical monocytosis, or pseudoleukemia, induced by G-CSF administration in AML patients with chemotherapy have been reported.5,6 This entity mimics recurrent/relapsed acute leukemia and causes confusion in pathologic diagnosis and potential problems in clinical management. The case presented in this report is an example of this entity.

Pathology:
A 55-year old male patient presented with leukocytosis and anemia. Peripheral blood smear examination revealed a blast population and monocytosis. Flow cytometry on the blood sample showed 37% blasts with expression of CD33, CD13, CD117, HLA-DR, CD34, CD14, CD15 and CD64. FISH study revealed a chromosomal abnormality of inversion 16. A diagnosis of acute myelomonocytic leukemia was established. The patient was treated with induction chemotherapy and was given Neupogen from day 6 through day 20. Bone marrow examination on the day 14th showed an aplastic marrow. However, examination of the patient’s day 21 bone marrow revealed marked hypercellularity with sheets of large atypical monocytic cells and brisk mitotic figures. These cells showed round to ovoid nuclei, basophilic cytoplasm and prominent nucleoli, morphologically indistinguishable from blastic cells. Immunohistochemical studies confirmed that most of these atypical cells were lysozyme, CD163 and CD68 positive monocytes, some of them were positive for CD117. These findings raised concerns of recurrent/relapsed AML. However, FISH study was negative for inversion 16. These results indicate that the findings in the patient’s day 21 marrow were most likely G-CSF-induced changes. The Neupogen was discontinued soon after. The patient was followed-up with periodic bone marrow examination and FISH study, which showed negative results. Currently, the patient is in complete remission.

Discussion:
We report one case of G-CSF induced atypical monocytic proliferation in an AML patient with induction chemotherapy. The findings could have created diagnostic problems if FISH study data had not available since those atypical cells were morphologically indistinguishable from blastic cells. Studies have shown that administration of recombinant G-CSF induces a rapid and sustained elevation in absolute peripheral neutrophil counts, and its use in leukemic patients during or after induction chemotherapy is safe and does not increase relapse rates.4 G-CSF shortens the transit time of developing granulocytes in bone marrow and accelerates the release of neutrophils that have undergone recent cell division.1 Our case of transient atypical monocytosis and a few similar cases reported in literatures showed an unusual response to G-CSF. This phenomenon was mostly seen in AML-M4, AML-M5 and AML-M3 cases7 and the mechanism is not entirely clear. A possible explanation is that G-CSF does not only act on neutrophils but also acts on progenitor hematopoietic cells including monocytes.8 One problem is that this entity can mimic recurrent AML causing confusion or potential misdiagnosis if clinical information or cytogenetic studies are not available. Therefore, it is important that both clinicians and pathologists be aware of this phenomenon in hematology/oncology settings. Appropriate discontinuation of G-CSF and following-up these patients with morphologic examination and cytogenetic studies is necessary. Meanwhile, a thorough understanding of exogenous G-CSF effects in cancer patients is essential to reduce any potential risks caused by its administration.

Disclosures:
No relevant conflicts of interest to declare.