Durable Remission of Acute Panmyelosis with Myelofibrosis Following Reduced-Intensity Allogeneic Peripheral Blood Stem Cell Transplantation.
Authors: Park Moo-Rim , Shim Hyeok , Lee Young-Jin 
Published: April 2020

Abstract
Acute panmyelosis with myelofibrosis is a newly defined subtype of acute myeloid leukemia, according to WHO classification. It is a rare, but distinct, disorder. It is characterized by pancytopenia, absence of overt hepatosplenomegaly, and dry tap in bone marrow aspiration. The bone marrow biopsy specimen shows hypercellularity with increased reticulin fibrosis, proliferation of three marrow cell lines with a prominence of megakaryocyte, and blast cells scattered among the trabecular space. The condition is rapidly progressive and eventually fatal. Conventional chemotherapy has not been effective. It has been reported that treatment of 8 patients with high-dose chemotherapy and allogeneic bone marrow transplantation, resolved the marrow fibrosis and induced complete remission, but most of these patients died of transplant-related toxicity and relapse. We report the first case of a patient with acute panmyelosis with myelofibrosis who has successfully undergone allogeneic peripheral blood stem cell transplantation after reduced intensity conditioning.
A 44-year-old male presented with fatigue and dyspnea on exertion. The complete blood cell count showed a hemoglobin level of 4.0 g/dL, WBC count of 2,310/uL with 3% of blasts, a platelet count of 92,000/uL. The peripheral blood smear revealed pancytopenia with leukoerythroblastosis. Bone marrow aspiration was not possible, but the biopsy specimen showed hypercellularity, proliferation of trilineage cell lines (panmyelosis) with extensive myelofibrosis, and clusters of immature cells in the paratrabecular area. On ultrasonographic examination, there was no evidence of hepatosplenomegaly. After remission induction therapy with idarubicine 12 mg/m2 (D1-3) and cytarabine 100 mg/m2 (D1-7), the bone marrow blast count decreased to about 1%, but the marrow fibrosis and pancytopenia were not improved. Two months after diagnosis, G-CSF mobilized peripheral blood stem cells, 7.24x106/kg CD34 positive cells, were transplanted into the patient from his HLA-matched brother, following conditioning with fludarabine 30 mg/m2 for 5 days and intravenous busulfan 3.2 mg/kg for 2 days. GVHD prophylaxis was done with a short course of methotrexate (10mg/m2, D1 and D3), and cyclosporin A. Rapid engraftment occurred and the bone marrow reticulin fibrosis disappeared. But the post-engraftment course was complicated by cytomegalovirus infection at D+35, thrombotic microangiopathy at D+66, and chronic GVHD with increased liver enzyme and oral mucositis. Full-donor chimerism was proved at D+22 by short tandem repeat analysis and maintained for at least 1 year. The patient achieved complete hematological remission. He is alive 16 months after transplantation without any complications. Although the follow-up duration has been short, we speculate that reduced-intensity conditioning allogeneic stem cell transplantation is effective and safer than conventional transplantation for treating a patient with acute panmyelosis with myelofibrosis.