A 70-year-old man presented with anemia (hemoglobin, 7.2 g/dL), a neutrophilic leukocytosis (neutrophils, 54 × 10⁹/L), and splenomegaly. The bone marrow showed 100% cellularity, with myeloid hyperplasia and grade 3 fibrosis (panels A-B; hematoxylin and eosin [A] and reticulin [B] stains; original magnification ×400). Myeloproliferative neoplasm mutations were negative. A triple-negative myelofibrosis was diagnosed and ruxolitinib was started. The splenomegaly decreased, but the patient became dependent upon blood transfusions. He was referred for allotransplant. At review, the biopsy showed 10% kappa monotypic plasma cells (panels C-D; kappa and lambda stain; original magnification ×100). Immunoglobulin G kappa (30 g/L) and kappa light chain (1.335 g/L) were found, but no bone lesions, hypercalcemia, or renal insufficiency. A neutrophilic leukemoid reaction caused by ectopic granulocyte colony-stimulating factor (G-CSF)–producing plasma cells was considered, given the high level of G-CSF (375 pg/mL). Such a leukemoid reaction has been described, but not with extensive fibrosis. Bortezomib/thalidomide/dexamethasone was started, but after the third cycle, the disease progressed. After 6 cycles of carfilzomib/cyclophosphamide/dexamethasone, the bone marrow was less cellular (50%-80%) with grade 1 fibrosis and 1% to 2% polytypical plasma cells (panels E-H; hematoxylin and eosin [E], reticulin [F], and kappa and lambda [G-H] stains; original magnification ×400 [E-F] and ×100 [G-H]). The G-CSF level was <8.08 pg/mL.

The patient was consolidated by high-dose melphalan and remains in remission with normal blood counts.