Clinical analysis on granulocyte colony stimulating factor mobilized allogenetic peripheral blood mononuclear cell transfusion for one patient with primary myelofibrosis in fibrosis stage

Abstract

Objective To investigate the safety and efficacy of granulocyte colony stimulating factor mobilized allogenetic peripheral blood mononuclear cell (G-PBMNC) in treatment of patient with primary myelofibrosis (PMF) in fibrosis stage with high risk and unsuitable for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods In March 2016, a case of male PMF patient (age: 70 years old)in fibrosis stage with high risk admitted to Department of Hematology, Affiliated Hospital of Panzhihua University was selected as a research subject. Laboratory and imaging examinations were performed to determine the stage and risk of the disease, combined with his medical history and outpatient examination results. After admission, the patient was treated with danazol, thalidomide and prednisone orally, deep intramuscular injection of deferoxamine, subcutaneous injection of erythropoietin (EPO), and suspended red blood cell infusion. In April 2016, the patient received G-PBMNC from his daughter. General condition and treatment safety of patient were observed, and the blood routine test results, transfusion volume of suspended red blood cell and spleen size were monitored. Relevant examination results, diagnosis, treatment and curative effect of this patient were analyzed retrospectively, and related literature was reviewed. This study protocol was approved by the Ethics Committee of Affiliated Hospital of Panzhihua College (No. 11 of the Ethics Examination in 2015), and informed consent was obtained from participant. Results ① After admitted, results of blood routine examination showed that white blood cell count was 2.0×109/L, red blood cell count was 1.5×1012/L, hemoglobin (Hb) value was 39.0 g/L, platelet count was 23.0×109/L, ratio of primitive cells in peripheral blood was 2%. Serum EPO value was more than 774 mIU/mL, and ferritin value was more than 2 250 μg/L. No specimens were taken from the bone marrow puncture. Result of bone X ray radiography showed bone sclerosis. Result of upper abdomen color Doppler ultrasound showed splenomegaly and slight hepatomegaly. The patient was diagnosed as PMF in fibrosis stage with high risk. ② A total of 140 mL of G-PBMNC suspension was isolated from the donor, and transfused to the patient after separation and counting. Number of mononuclear cell (MNC) and CD34+ cell were 3.0×108/kg and 1.6×106/kg, respectively, and acute graft versus host disease (aGVHD) did not develop 1 months after G-PBMNC infusion. ③ Most of the blood routine examination indexes of the patient showed an upward trend after G-PBMNC infusion. 1 and 11 months after G-PBMNC infusion, median white blood cell counts of the patient were 4.0×109/L (3.1×109/L-4.6×109/L) and 3.6×109/L (2.7×109/L-4.0×109/L), and were higher than that of 1.8×109/L (1.3×109/L-2.3×109/L) before G-PBMNC infusion. 8 and 13 months after infusion, median values of Hb were 69.7 g/L (59.2-82.5 g/L) and 70.5 g/L (61.3-84.1 g/L), and were higher than that of 46.8 g/L (33.5-60.3 g/L) before infusion. 6, 11 and 12 months after infusion, median platelet count were 36.5×109/L (22.6×109/L-43.6×109/L), 41.0 ×109/L (29.9 ×109/L-56.7 ×109/L) and 39.0×109/L (25.7×109/L-50.3×109/L), and were also higher than that of 14.0×109/L (7.2×109/L-18.5×109/L) before infusion . ④ Within one month before G-PBMNC infusion, a total of 12 U of suspended red blood cells were transfused; while one month after G-PBMNC infusion, amount of suspended red blood cell infusion decreased to 6.5 U. 3-4 months after infusion, transfusion volume of suspended red blood cell decreased to 1.5 U. 11 months after G-PBMNC infusion, transfusion volume of suspended red blood cell was only 3.5 U, and the patient did not receive blood transfusion for one month. ⑤ There was no progressive enlargement of spleen after infusion of G-PBMNC. Conclusions G-PBMNC could safely improve the routine blood test indexes of PMF patients in fibrosis stage with high risk and reduce the dependence of blood transfusion, so G-PBMNC could be a safe and effective treatment option for fibrotic PMF patients in no condition to allo-HSCT. But this conclusion is limited to the clinical analysis of a single case, and it requires large sample, multi-center, randomized controlled trials for further study and verification. Key words: Allogeneic cells; Transplantation, homologous; Hematopoietic stem cells; Primary myelofibrosis; Therapeutics