Early lymphocyte recovery is an important determinant of outcome following allogeneic transplantation with CD34+ selected graft and limited T-cell addback

Abstract

Summary:We evaluated the outcome of 29 patients (age 22-60 years), who received a CD34+selected related (n ¼ 16) or unrelated graft (n ¼ 13) with limited T-cell addback (TCAB) (median 5.9 Â 10 4 /kg) following full-intensity conditioning for haematological malignancies. In all, 16 patients (55%) had either advanced disease or previous transplants. The cumulative incidences of grade 2-4 acute GVHD were 15.4 and 19.2% and that for chronic extensive GVHD were 35 and 37% in related and unrelated graft recipients, respectively. The strongest predictor of nonrelapse mortality and overall survival was the absolute lymphocyte count (ALC) at 30 days; patients with ALCo0.35 Â 10 9 /l having an NRM and OS of 59.2 and 24.7%, compared to 10 and 90% in those with a higher ALC. Patients with acute leukaemia had poorer survival and this was associated with a lower ALC as well. Thus, TCAB with a CD34+ selected graft resulted in a comparable outcome in both older and younger patients, but the survival was strongly influenced by early lymphocyte recovery.

Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia

“…The cutoff of 0.3 Â 10 9 per liter was chosen as a mid value based on previous adult published literature. [8][9][10][11][12]21 When days 21 or 30 fell on a weekend or there was no differential count available, the ALC 1-2 days prior and 1-2 days post days 21 or 30 were taken into account. Patients with a low white cell count that did not allow differential counts or those with nonengraftment at days 21 or 30 were classified to be in the o0.3 Â 10 9 per liter groups.…”

“…[5][6][7] Previous studies have shown that delayed lymphocyte recovery post-allogeneic HSCT is associated with increased risk of relapse in acute myelogenous and lymphoid leukemia in adults. [8][9][10][11][12] The clinical induction of GVL effect offers a new approach for patients who relapse post-HSCT. 13 This has most commonly been as donor lymphocyte infusion (DLI), and several reports have demonstrated long-term survival with this approach.…”

T-cell reconstitution and expansion after hematopoietic stem cell transplantation: ‘T’ it up!

“…9 Recent studies suggest that higher absolute lymphocyte counts shortly after SCT correlates with improved DFS and/ or overall survival. [10][11][12][13][14] The rate of immune reconstitution in patients with ovarian cancer after high-dose chemotherapy is an independent marker of time to progression, 15 and this may be related to the recent finding that immunosurveillance as assessed by the presence of tumor infiltrating lymphocytes (TILs) at the time of diagnosis is a strong predictor of disease-free survival in ovarian cancer. 16 It is likely that rapid recovery of T-cell function after SCT is critical for protection against infections and to promote graft-versustumor (GVT) activity.…”

Evaluation of BM cytomorphology after allo-SCT in patients with AML

“…The results of correlations performed in this analysis are too weak to allow for any hypothesis (Supplementary Table S1). As is the case for the causal analysis of delayed lymphocyte and neutrophil recovery, [34][35][36] we cannot comment whether, for example, hypocellularity is a matter of increased destruction or decreased production of haematopoietic stem cells and progenitors. Yet, if the trend of a decreased peripheral blood leukocyte count associated with hypocellular BM smears that we observed held true, these phenomena might well be dependent.…”

“…33 A prognostic value has been attributed to quantitative lymphocyte and neutrophil recovery, especially for myeloid neoplasia after allogeneic SCT. [34][35][36] Attempts are made to diagnose 2,3 and treat 11,12 incipient relapse based on parameters such as NPM1 mutations, 7,9,10,37,38 WT1 overexpression [37][38][39][40] and donor-patient chimaerism [41][42][43] or combinations of those. 13 Yet, apart from chimaerism, those methods are frequently available for a limited set of patients (for example, NPM1 mutations).…”