Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells with a myeloablative regimen for refractory/relapsed hematologic malignancy

Abstract

Human leukocyte antigen haploidentical hematopoietic stem-cell transplantation (haplo-HSCT) is associated with an increased risk of graft failure and severe graft-versus-host disease (GVHD). Mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immunesuppressive effects. We cotransplanted the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs) in 50 people with refractory/relapsed hematologic malignancy undergoing haplo-HSCT with myeloablative conditioning. We observed that all patients given MSCs showed sustained hematopoietic engraftment without any adverse UC-MSC infusion-related reaction. The median times to neutrophil >0.50 × 10(9)/L and platelet >20 × 10(9)/L engraftment were 12.0 and 15.0 days, respectively. We did not observe an increase in severe acute GVHD (aGVHD) and extensive chronic GVHD (cGVHD), too. Grade II-IV aGVHD was observed in 12 of 50 (24.0 %) patients. cGVHD was observed in 17 of 45 (37.7 %) patients and was extensive in 3 patients. Additionally, only five patients (10.0 %) experienced relapse at a median time to progression of 192 days. The probability that patients would attain progression-free survival at 2 years was 66.0 %. The results indicate that this new strategy is effective in improving donor engraftment and reducing severe GVHD, which will provide a feasible option for the therapy of high-risk hematologic malignancy.

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

“…The probability that patients would attain progression-free survival at 2 years was 66.0 %. Our research indicated that MSCs cotransplantation with HSCs is effective in improving donor engraftment and reducing severe GVHD[149]. Meanwhile, our group observed that Patients with severe AA (n=17) received haploidentical HSCT plus MSCs infusion.…”

Novel clinical uses for cord blood derived mesenchymal stromal cells

“…Authors observed no increase in acute or chronic GVHD, with progression-free survival of 66% at 2 years' post-transplant [63]. An additional study is currently accruing at Nanfang Hospital studying the effect of MSCs combined with CB to treat graft failure following autologous stem cell therapy (NCT01763099).…”

Mesenchymal stromal cells for prevention and treatment of graft-versus-host disease

“…At least eight evaluable papers are available [17][18][19][20][21][22][23][24], with three of them [19,20,23] containing a randomized comparison between an arm of MSCtreated patients and a control arm.…”