Cotransplantation of haploidentical hematopoietic stem cells and allogeneic bone marrow-derived mesenchymal stromal cells as a first-line treatment in very severe aplastic anemia patients with refractory infections

Eur J Haematol. 2018 Jun;100(6):624-629. doi: 10.1111/ejh.13060. Epub 2018 Apr 25.

Abstract

Objectives: In patients with very severe aplastic anemia (VSAA), neutropenia is prolonged and persistent, resulting in refractory overwhelming infections. Hematopoiesis recovery is urgently needed.

Methods: Six patients with de novo VSAA lacking HLA-identical sibling donors and those who experienced refractory infections underwent haploidentical related donor (HRD) hematopoietic stem cell transplantation (HSCT) as a first-line therapy. The conditioning regimen consisted of busulfan, cyclophosphamide, and rabbit antithymocyte globulin. Culture-expanded allogeneic bone marrow-derived mesenchymal stromal cells were infused on day 0 and day +14.

Results: From diagnosis to HSCT, 6 patients experienced a total of 28 episodes of persistent fever, and the median number was 4 (range, 3-7). All cases developed major bacterial infections and invasive pulmonary fungal infection pre-HSCT. The median time from diagnosis to HSCT was 2 months (range, 1-3.5 months). All patients achieved sustained, full donor chimerism, and the median time of myeloid recovery and platelet engraftment was 13 days (range, 9-19 days) and 15.5 days (range, 10-23 days), respectively. One patient died of aGVHD, and 5 patients are alive after a median follow-up of 21 months (range 17-40.5).

Conclusions: Upfront HRD-HSCT may be a safe and promising choice for patients with VSAA in critical situations without suitably matched donors.

Keywords: haploidentical hematopoietic stem cell transplantation; mesenchymal stromal cell; refractory infection; severe aplastic anemia.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Aplastic / complications
  • Anemia, Aplastic / diagnosis*
  • Anemia, Aplastic / therapy*
  • Biomarkers
  • Combined Modality Therapy
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Infections / diagnosis
  • Infections / etiology
  • Male
  • Mesenchymal Stem Cell Transplantation* / adverse effects
  • Severity of Illness Index
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers