Feasibility and outcome of haploidentical SCT in pediatric high-risk hematologic malignancies and Fanconi anemia in Uruguay

Abstract

In total, 17 pediatric patients with hematologic malignancies (n ¼ 14) and Fanconi anemia (FA) (n ¼ 3) underwent haploidentical SCT with T-cell depletion. The patients were conditioned with reduced-intensity regimens, and CYA was used for GVHD prophylaxis. Successful engraftment occurred in 16 patients (94%). One patient failed to achieve a primary engraftment. Another patient rejected the first SCT after 10 weeks and had a successful second transplant. Of all engrafted patients, only one developed severe acute GVHD. Ten patients were alive at a median follow-up of 18 months (range, 5-62 months). The 5-years' OS was 53.8%. The three patients with FA are currently well with full-donor chimerism at 16, 6 and 5 months post transplant, respectively. The OS of 14 patients with high-risk hematologic malignancies was 47.6%. Three patients died as a result of post transplant leukemia relapse. CMV infection, GVHD and organ injury were other causes of mortality. Haploidentical SCT was found to be an alternative feasible treatment in Uruguay for patients who need allogenic transplantation but lack an HLA-identical family donor. It should be considered as an early option in FA patients before transformation or significant exposure to blood products.

New strategies for haploidentical transplantation

“…In a recent update, Pfeiffer et al reported an event-free survival of 51% for children with acute leukemia who were in morphological remission at the time of transplantation (40). A similar promising outcome was recently reported in a pediatric study of haploidentical transplantation using CD3/19-depleted PBSCs from Uruguay (41). It is noteworthy that in this study 3 patients with Fanconi anemia were successfully transplanted from haploidentical donors.…”

Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients

“…There have been several reports on HHCT using CD3-depleted grafts in pediatric patients. 2,[10][11][12][13][14] The Tübingen group reported their experience with CD3/19-depleted HHCT using reduced-intensity conditioning in 38 pediatric patients. 2 The authors reported a primary engraftment rate of 83%, with GR occurring in 17% of patients.…”

“…[10][11][12][13][14] Although all of our patients received GVHD prophylaxis with calcineurin inhibitors and mycophenolate mofetil, the incidences of severe acute and chronic GVHD were acceptable for our partial depletion of T cells.…”

Cyclophosphamide-Based In Vivo T-Cell Depletion for HLA-Haploidentical Transplantation in Fanconi Anemia

“…Unlike other T-cell depletion methods that require expensive, time-consuming, and expertise-driven processing steps such as E-rosette depletion [22] or immunomagnetic bead selection [4, 23, 24], this is a simple, “off the shelf” approach that can be available in transplant centers that do not have access to more technical processing equipment. Although this low-intensity regimen was initially developed to treat medically infirm patients [7, 8] with substantial co-morbidities who had no suitable HLA-matched donors [9–11], we adapted this approach when considering the fragile FA patient who could equally benefit from reduced-dose alkylating agents and low-dose radiation.…”

“…Yabe et al used FLU 150–180 mg/m 2 , CY 40 mg/kg, ATG, and 3–4.5 Gy of thoracoabdominal / TBI for unmanipulated 3/6–6/6 HLA-matched marrow and cord blood grafts [28] . Dufort et al used FLU 160 mg/m 2 , CY 40 mg/kg, ATG, and 4 Gy total lymphoid irradiation followed by T cell-depleted grafts using the Miltenyi CliniMACS system and anti-CD3 antibody OKT3 [23]. MacMillan et al used busulfan 3.2 mg/kg, FLU 140 mg/m 2 , CY 40 mg/kg, and ATG using T cell depleted grafts by either elutriation or CD34 selection with Isolex [19, 29].…”