Increasing Mixed Chimerism Is an Important Prognostic Factor for Unfavorable Outcome in Children With Acute Lymphoblastic Leukemia After Allogeneic Stem-Cell Transplantation: Possible Role For Pre-Emptive Immunotherapy?

The aim of this study was to analyse the experience of Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in respect to donor lymphocyte infusion procedure. The study included 51 pediatric patients with malignant (45) and non-malignant (6) diseases treated with DLI in the period 1993-2012. The indications for DLI were as follows: (1) increasing recipient chimerism after non-ablative hematopoietic SCT (18 patients); (2) immunomodulation after a reduced intensity conditioning regimen (2 patients); (3) increase in minimal residual disease detection (3 patients); and (4) relapse (28 patients). DLI was carried out at a median of 6 (0.5-79) months after SCT. DLI was administered as either a single-dose (in 19 cases) or in escalating-dose regimens (in 32 cases). The median total dose of CD3-positive T cells was 28.0 (0.1-730.0) × 10 6 /kg body weight. The time for assessment of DLI efficacy ranged from 0 to 70 (median 3) months. At evaluation, 18 patients experienced CR, 3 achieved PR, 19 showed relapse and 11 rejected the graft. DLI was found to be effective in 39% of cases. Complications of the procedure occurred in 18 patients; of these, 2 died. To sum up DLI shows efficacy in a significant percentage of children. Mortality related to the therapy adverse effects is low. However, this method requires standardization.

Section: Discussionsupporting

confidence: 78%

Adoptive therapy with donor lymphocyte infusion after allogenic hematopoietic SCT in pediatric patients

Goździk

Rewucka

Krasowska-Kwiecień

et al. 2014

“…2,8 Serial, quantitative chimerism studies have been recommended for children with ALL after allogeneic HCT to identify those patients at high risk of relapse. 10 In general, analysis of PB cells is more useful than BM cells because lineage-specific chimerism can be determined. 1 Before the advent of FISH and PCR-based studies, the degree of donor engraftment was assessed by conventional karyotype analyses for sex-mismatched donor-recipient pairs, red blood cell phenotyping, or immunoglobulin isotypes.…”

Section: Discussionmentioning

confidence: 99%

Lack of utility of chimerism studies obtained 2–3 months after myeloablative hematopoietic cell transplantation for ALL

Doney

Loken²,

Bryant

et al. 2008

Lineage specific chimerism studies are commonly obtained at several time points after nonmyeloablative haematopoietic cell transplantation to assess the tempo and degree of engraftment, and to monitor graft rejection. For patients who receive myeloablative transplants, the value of frequent chimerism analyses using sensitive molecular techniques is less certain. In this study, a retrospective analysis was performed to assess the transplant outcome of 89 adult patients with acute lymphocytic leukaemia who had chimerism studies of unfractionated bone marrow cells or peripheral blood subsets performed approximately 80 days after transplantation. These patients received unmanipulated, myeloablative transplants using either HLA-identical or HLA-mismatched, related or unrelated donor stem cells. Incomplete donor engraftment was present only in the CD3 + peripheral blood T-cells in a small percentage of patients. There was no correlation of mixed chimerism with transplant outcome. Routine "Day 80" chimerism studies in this group of patients who receive intensive, myeloablative conditioning regimens are not recommended.

“…Frequent analyses of T cell chimerism can help to predict graft rejection, either by PCR analysis of VNTR regions or by flow cytometry of lymphocyte subsets with MoAb against HLA Ags of recipient and donor. 37,38 In case of increasing autologous signals, (1) cessation of immunosuppression and (2) if necessary, low-dose donor lymphocyte infusions are recommended to restore a complete donor chimerism. 38 Moreover, ongoing studies evaluate the role of co-transplanted MSC in the prevention of graft failure.…”

Section: Engraftment and Gvhdmentioning

confidence: 99%

“…37,38 In case of increasing autologous signals, (1) cessation of immunosuppression and (2) if necessary, low-dose donor lymphocyte infusions are recommended to restore a complete donor chimerism. 38 Moreover, ongoing studies evaluate the role of co-transplanted MSC in the prevention of graft failure. 34,39 No rejection occurred in a limited number of patients who received co-transplants of MSC, compared with 15% graft failure in a historical control group.…”

Section: Engraftment and Gvhdmentioning

confidence: 99%

Haploidentical SCT in children: an update and future perspectives

Lang

Handgretinger

2008

Transplantation of haploidentical stem cells has become a well-established approach, which makes a potential donor available for almost all patients. This review focuses on current results and new strategies, especially in pediatric patients with malignant diseases. CD34 þ positive selection was the most common procedure for graft manipulation in the past years, whereas T and B cell depletion is a promising new method. GVHD could herewith be effectively reduced and primary engraftment was reported in 83-100% of patients after transplantation of high stem cell doses. For patients with ALL in remission, diseasefree survival at 3 years ranged between 22 and 48%. TRM, mainly because of viral infections, was improved by the use of reduced-intensity conditioning (which helped to speed up T cell recovery) and by close monitoring of viral loads and prophylactic/preemptive therapy. The role of donor-derived Ag-specific T cells against viral and fungal antigens is currently under investigation. Patients with active disease at the time of transplantation had a poor outcome and several attempts to improve these results are currently evaluated, such as co-infusion of natural killer cells, co-transplantation of MSC, use of new antileukemic drugs and post-transplant immunotherapy.