HLA-mismatched haploidentical transplantation using low-dose anti-thymocyte globulin (ATG: thymoglobulin)

Hematology. 2017 Apr;22(3):129-135. doi: 10.1080/10245332.2016.1231968. Epub 2016 Dec 1.

Abstract

Objectives: To clarify optimal strategies for human leukocyte antigen (HLA)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT).

Methods: Twelve patients who underwent HSCT from a haploidentical related donor using low-dose thymoglobulin were analyzed retrospectively. Thymoglobulin was added to conditioning regimens at 2.5 mg/kg/day for 2 days (days -4 and -3). Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine and methotrexate.

Results: The median age of the patients was 33 years. Six patients had previous allogeneic HSCT, and HSCT was performed in non-remission for nine patients. All patients but one, who died due to early infection, achieved neutrophil engraftment at a median of 17 days with complete donor-type chimerism. Acute and chronic GVHD were observed in six and five patients, respectively, but no patients died of GVHD-associated complication. No one developed cytomegalovirus disease, but Epstein-Barr virus-related lymphoproliferative disorder was observed in one patient. Long-term survival in remission without immunosuppressive agents are observed in two patients who underwent HSCT in remission, but the majority of patients who underwent HSCT in non-remission experienced disease progression.

Conclusion: Haploidentical HSCT could be performed with thymoglobulin at 5 mg/kg, with the balance between GVHD and relapse rate. The dose reduction of thymoglobulin may be considered for advanced hematological malignancy.

Keywords: Thymoglobulin; allogeneic hematopoietic stem cell transplantation; haploidentical donor; immune reconstitution.

MeSH terms

  • Adolescent
  • Adult
  • Antilymphocyte Serum / administration & dosage*
  • Disease Progression
  • Female
  • Graft Survival
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • HLA Antigens / genetics*
  • HLA Antigens / immunology*
  • Haplotypes*
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transplantation Chimera
  • Transplantation Conditioning* / adverse effects
  • Transplantation Conditioning* / methods
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Antilymphocyte Serum
  • HLA Antigens
  • Immunosuppressive Agents
  • thymoglobulin