Prolonged Myelosuppression due to Progressive Bone Marrow Fibrosis in a Patient with Acute Promyelocytic Leukemia

Abstract

A 34-year-old woman was diagnosed with acute promyelocytic leukemia. Chemotherapy was administered following the JALSG APL204 protocol. Induction therapy with all-trans retinoic acid resulted in complete remission on day 49. She developed coccygeal pain from day 18, which spread to the spine and cheekbones and lasted 5 weeks. She had similar bone pain on days 7–10 of the first consolidation therapy and on days 4–12 of the second consolidation therapy. Oral loxoprofen was prescribed for pain relief. On day 33 of the third consolidation, white blood cell and neutrophil counts were 320/μL and 20/μL, respectively. After she developed epigastralgia and hematemesis, she developed septic shock. Gastroendoscopy revealed markedly thickened folds and diffusely damaged mucosa with blood oozing. Computed tomography revealed thickened walls of the antrum and the pylorus. Despite emergency treatments, she died. Bacterial culture of the gastric fluid yielded Enterobacter cloacae and enterococci growth. Collectively, she was diagnosed with phlegmonous gastritis. Retrospective examination of serial bone marrow biopsy specimens demonstrated progressive bone marrow fibrosis, which may have caused prolonged myelosuppression. Thus, evaluation of bone marrow fibrosis by bone marrow biopsy after each treatment cycle might serve as a predictor of persistent myelosuppression induced by chemotherapy.

Can plasma fibrinogen level predict bone marrow fibrosis?

“…The most common malignant diseases in which generalized BMF is seen are chronic idiopathic myelofibrosis (MF), CML, AML, ALL, MDS, lymphomas and metastatic tumors [23]. Non-malignant causes of BMF include endocrine disorders, autoimmune diseases, vitamin D deficiency and infections (HIV, tuberculosis) [1,2,23]. The identification of BMF is vital in some diseases.…”

“…Interleukin (IL)-8, IL-2R and lipocalin-2 are other cytokines that have been suggested to be involved in the pathophysiology of BMF, especially among patients with MF [30]. Genetic studies assessing JAK2 V617, MPL and CALR gene mutations have suggested possible associations with BMF [1]. However, their routine diagnostic value has not been consistent [30].…”

“…Bone marrow fibrosis (BMF) is a histopathological process known for abnormal excess deposition of reticulin or collagen fibers in the BM. A number of malignant and non-malignant conditions and diseases can cause BMF [1,2]. Although, studies have examined whether the severity and type of fibrosis are associated with disease prognosis, the results are inconsistent [2].…”

<p>miR-188-5p Promotes Tumor Growth by Targeting CD2AP Through PI3K/AKT/mTOR Signaling in Children with Acute Promyelocytic Leukemia</p>

“…It has been reported that 10% to 20% of patients with early bleeding had died, and about 60% of patients develop diffuse intravascular coagulation (DIC). 6,7 Therefore, it is of great significance to identify a therapeutic target of pediatric APL patients.…”