CD34 Selected Cells for the Treatment of Poor Graft Function after Allogeneic Stem Cell Transplantation

Abstract

Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34(+) cells was 3.4 × 10(6)/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34(+) selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated.

Fresh or Cryopreserved CD34 + -Selected Mobilized Peripheral Blood Stem and Progenitor Cells for the Treatment of Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation

“…It is important to note that the SCB created from cryopreserved products yielded the lowest median CD34 + cell doses; the median CD34 + yield was 61.5% (range 42–95%), 68.5% (range 37–83%), and 28% (range 10–34%) for G-CSF plus plerixafor, G-CSF only, and cryopreserved products, respectively. Other studies have reported no correlation between CD34 + cell dose and PGF response to SCB [16, 17]. …”

The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation

“…This is a question needed to answer in our further study. Some recent reports [20,21] suggest that patients with idiopathic myelofibrosis might have higher incidence of PGF than patients with other underlying disease. However, incidence and pathogenesis were not provided.…”

“…Although some patients received a second infusion of donor cells or even second transplantation, the efficacy was very poor. Some recent studies have shown promising results from treating with a booster of CD34+ cells [20][21][22]; however, we should note that most patients who received the boosted cell infusion had secondary PGF, and we have already demonstrated that primary PGF has significantly worse prognosis than secondary PGF [4]. New therapeutic options are warranted to manage primary PGF on the basis of better understanding of primary PGF.…”

The bone marrow microenvironment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function

“…More recently, Askaa et al, 8 Klyuchnikov et al 9 and Stasia et al 10 reported promising results in treating PGF patients with a CD34 + -selected stem cell boost without further conditioning. However, it should be noted that most patients who received the boosted CD34 + cell infusion had late PGF.…”

“…Nevertheless, the available treatment options for PGF are limited and include the administration of hematopoietic growth factors, a second allo-HSCT, or a CD34 + -selected stem cell boost, among others. 1,[8][9][10] Therefore, obtaining a better understanding of the pathophysiology of PGF promises to guide more effective therapeutic approaches and eventually improve survival.…”