Long‐term follow‐up study of porcine anti‐human thymocyte immunoglobulin therapy combined with cyclosporine for severe aplastic anemia

Abstract

Immunosuppressive therapy with antithymocyte immunoglobulin (ATG) and cyclosporine A is the first treatment option for severe aplastic anemia (SAA) patients without transplantation. Horse ATG is not marketed in China. Because the price of porcine ATG (pATG) is only about one-third of the price of rabbit ATG (rATG), long-term follow-up studies of pATG's efficacy will help provide valuable insights into the treatment of SAA. Retrospective studies were performed to analyze the clinical information of 102 SAA patients treated with pATG and cyclosporine A from 1999 to 2014 in Peking Union Medical College Hospital. The median age was 29 years old (range 12-72). Median follow-up time was 59.6 months (0.2-176.8). The overall response rate was 74.5% (CR 42.1%, PR 32.4%). The recurrence rate was 9.9%. The mortality rate was 16.7%. The median survival time has not been reached, and the 5-year survival rate was 81.8%. Other hematologic abnormalities were observed in 7.8% of patients, including symptomatic PNH, MDS, and AML. Multivariate analysis revealed there was no significant effect on survival by factors such as gender, age, severity of disease, treatment time, and PNH clone (P > 0.05). These data have indicated pATG therapy combined with cyclosporine A has significant long-term efficacy and high overall survival in SAA.

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

“…P-ATG is another preparation, available in China, for clinical use as an immunosuppressive agent, and it is cheaper than R-ATG. One study showed that the drug metabolism curve of P-ATG had an advantage over R-ATG in immunosuppressive therapy; however, the underlying mechanisms were unknown [33]. Results from our hospital (F.K.…”

“…Some studies [33,36] indicated that P-ATG showed similar efficacy and safety profiles to R-ATG in immunosuppressive therapy of acquired SAA. P-ATG could be a suitable alternative preparation for R-ATG with the advantage of lower medical expense.…”

High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2

“…Glyco-humanization refers to removal of the αGal epitopes and conversion of animal-type Neu5Gc/Ac forms of sialic acid into human single type Neu5Ac. The procedure has been initially developed to circumvent problems related to the occurrence of high titers of anti-αGal and anti-Neu5Gc antibodies following administration of anti-T lymphocytes rabbit immunoglobulins, which is potentially causing allergies 42 , serum sickness 28 and a possible “xenosialitis”, a systemic inflammation so far only demonstrated in animal models 11,12 . Although our experiments do not directly address the clinical importance of avoiding anti-αGal/Neu5Gc antibody responses, our data show that “natural” anti-pig antibodies found in human serum are essentially directed against Neu5Gc and that reactivity against rabbit IgG is higher than against pig IgG (Figure 2).…”

“…Although our experiments do not directly address the clinical importance of avoiding anti-αGal/Neu5Gc antibody responses, our data show that “natural” anti-pig antibodies found in human serum are essentially directed against Neu5Gc and that reactivity against rabbit IgG is higher than against pig IgG (Figure 2). These data are of importance in a context where hyperimmune pig immunoglobulins are being used therapeutically to treat aplastic anemia 42,43 and are being developed as an anti-lymphocyte induction treatment in kidney transplantation (NCT 04431219). Glyco-humanized pig immunoglobulins would potentially present, therefore, a safety advantage over rabbit polyclonal antibodies or over immunoglobulins from other species currently in clinical use, such as bovine, horse and goat.…”

Retrospective Comparison of Efficacy and Safety of Rabbit Anti-Thymocyte Globulin and Porcine Anti-Lymphocyte Globulin in Patients With Acquired Aplastic Anemia Undergoing Hematopoietic Stem Cell Transplantation From Matched Sibling Donors

“…The conditioning regimen, graft-versus-host disease (GvHD) prophylaxis, infection prevention, and surveillance followed those in our previous report ( 14 , 15 ). In particular, pALG was prepared using thymic cells (as antigens) introduced in swine and separating anti-lymphocyte serum from the swine (Wuhan Institute of Biological Products Co., Ltd.) ( 11 , 17 ).…”