CD34+ selected peripheral blood Stem Cell Boost (SCB) for Poor Graft Function (PGF) or mixed chimerism in pediatric patients, after hematopoietic stem cell transplantation: Results of a retrospective multicenter study

Abstract

Background: PGF is historically associated with high morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods: In this study, we report our multicenter experience on stem cell boost (SCB) for PGF, or incomplete donor engraftment, in 16 pediatric patients. Donors were HLAmatched siblings (n = 4), unrelated donors (n = 11), or haploidentical family members (n = 1). Ten patients had two-lineage cytopenia, 5 had one-lineage cytopenia, and 1 had poor immunological reconstitution together with a low percentage of donor cell engraftment. A median of 6.6x10 6 selected CD34+/Kg was infused after 194 days from allo-HSCT (48-607).Results: In 4 out of 5 patients, one-lineage cytopenia was resolved, while among the 10 patients with two-lineage cytopenia, 4 resolved both cytopenia, 5 resolved onelineage, and one did not respond. All patients reverted their mixed chimera to full donor chimera. OS was 56%, transplant-related mortality (TRM) 32%, and RI 12%.The main causes of failure were related to infections with 4 out of 7 deaths caused by this.Conclusions: SCB may rescue over 50% of patients with PGF after allo-HSCT. An earlier treatment may reduce the infectious complications and improve survival.

CD34 Stem Cell Boost in Pediatric Allogeneic Stem Cell Transplant Recipients: A Case Series and Review of Literature

“…Therefore, these factors likely contributed to their favorable OS at last follow-up. Berger et al found that the majority of deaths occurred within the first 6 months of a SCB [2], consistent with our observation wherein six of the eight deaths occurred within the same timeframe.…”

“…[7,23] In a recent large metanalysis of 209 adults who received a SCB for PGF, the overall pooled ORR, CR and PR were 80%, 72%, and 13%, respectively, but that study did not delineate the type of cytopenia pre-SCB. [6] While the CR rate in our study (29%) is lower than that and those from a few pediatric studies (50-79%) [2,10,12], it is similar to that reported by Mianaridi (36%) [11] and Chandra (25%) [3] (Table 3). Per the latter's report, only 1/3 of patients with MC respond to a SCB.…”

“…A second HCT, on the other hand, has an increased risk of transplant-related mortality (TRM) and morbidity [8,9]. While the current literature mostly focuses on outcomes of SCB post-HCT for PGF in adults [2,3,[10][11][12], there have only been a few pediatric studies that have analyzed outcomes post-SCB in select diseases, such as immunodeficiencies [3] or malignancies [13][14][15]. Therefore, we retrospectively evaluated the efficacy and outcomes of pediatric patients who received a CD34 SCB post-HCT at our center.…”

“…PGF is defined as frequent dependence on blood and/or platelet transfusions and/or growth factors in the absence of other explanations such as disease relapse, drugs or infection [ 1 ]. PGF occurs in 5–27% of patients after initial HCT and is associated with a high mortality rate, most often secondary to infection [ 2 ]. Mixed chimerism is defined as donor chimerism (DC) between 5 and 95% [ 3 ] for both myeloid and lymphoid lineages [ 1 ], and occurs with greater frequency following transplant for non-malignant diseases (NMD) and with the use of reduced intensity (RIC) or non-myeloablative conditioning regimens [ 4 ].…”

CD3/CD19 Depletion for T-cell Reduction of Allogeneic Transplants: Mostly Efficient, but not Robust

“…The disappointing clinical outcomes, with long-term survival rates of not much more than 20% [7], have largely curbed the enthusiasm for allogeneic "naked haplo" transplantation without immediate or delayed co-transplantation of an alloreactivity-attenuated T-cell product [7]. The use of CD34+ selected products is limited to correction of poor graft function following allogeneic hematopoietic stem cell transplantation [13][14][15][16]. In the autologous setting, CD34 selected transplants retain some relevance for tumor cell purging, such as in neuroblastoma [17,18].…”