Successful Reduced-Intensity Conditioning (RIC) Allogeneic Transplantation of Peripheral Blood Stem Cells and Bone Marrow Cells in an Advanced Idiopathic Myelofibrosis with Myeloid Myeloaplasia (MMM).
Authors: Jiang Zhisheng , Li Da , Wu Shunjie , Kang Ying , Liu Kun , Lan Xinghao , Yi Wei , Peng Ailing , Ou Yanling , Jiang Linling 
Published: October 2019

No curative therapy available for MMM patients apart from allogeneic hemopoietic cell transplantation(HCT). There are high morbidity and mortality in traditional allogeneic HCT. We have gotten successful RIC allogeneic HCT for a MMM patient. A man, Chinese, 37 yrs. He had anemia and on dependent transfusion and was diagnosed idiopathic MMM according to bone marrow biopsy 7 years ago. He was hospitalized on May 10, 2007. Physical exam showed pale, pencytopenia without hepatosplenomegaly. The result of X-ray on chest and electrocardiography showed anemic cardiac disease. There were some teardrop-shaped red cells on blood. His Hb was 37g/L, WBC 5.9x 109/L, Plt 33x109/L. The total volume of red cell transfusion was about 8400ml. His serum Ferritin elevated 5110 (reference <322) ng/ml. Dry-tap appeared every marrow aspiration. The marrow biopsy with silver staining showed degree 4 reticulin. Received infusion deferoxamine 2.0 a day for 20 days, he underwent allogeneic combination HCT of bone marrow and blood cells from his brother. He had received the ABO major- mismatched (donor A and receptor B), HLA-full matched (HLA-A 02 XX, 11XX; HLA-B 15XX, 46 XX; HLA-DRB1 13XX,15XX) peripheral blood cells [mononuclear cell (CD34+ 8.36x106), and marrow cells (CD34+ 10.45x106)/kg on May 23, and 24, 2007. The conditional regimen consisted of TBI, 200 cGY and FC regimen (Fludarabine 35 mg/M2, cyclophosphamide 60 mg/kg. The level of antibody A in receptor was 1:8, so it was no necessary to move. We moved red cells from bone marrow and remained mononuclear cells for HCT. His graft was at +11d posttransplantation(WBC 5.79x109/L, Plt 24x109/L). He had two infections with high fever and one epilepsy because high serum level of Cyclosporin A (690ng/ml). Complete chimera was observed at +31d after HCT. His Hb was 129g/L, WBC 6.6x109/L, Plt 278x109/L at +76d. There was no dry-tap bone marrow aspiration again. The boiopsy showed myelofibrosis with cellular improving. Current diagnosis is based on morphologic assessment of bone marrow histology for MMM. The typical clinical manifestations includes anemia, dry-tap of bone marrow aspiration, teardrop-shape red cells on blood, silver-staining bone marrow reticular fiber with or without hepatosplenomegaly. Rondelli D reported the 5 of 21 MMM had a palpable spleen. Traditional allogeneic HCT associates significant morbidity and mortality. Rondelli reported RIC allogeneic HCT results in prolong survival in high-risk MMM patients. We performed similar RIC consisted of fludarabine, TBI and cyclophosphamide. His engraftment was faster at +10 days that associated combination transplantion of blood cells and bone marrow cells as we reported before. Pre-transplantation elevated serum ferritin level strongly associated lower overall and disease-free survival. Recently study showed iron overload related posttransplantion liver toxicity such as veno-occlusive disease. We give the patient Desferrin befor and after HCT.