Prognostic Analysis of Early Lymphocyte Recovery in Patients with Advanced Breast Cancer Receiving High-Dose Chemotherapy with an Autologous Hematopoietic Progenitor Cell Transplant

Abstract

Purpose: The purpose of this study was to evaluate the prognostic effect of early posttransplant lymphocyte recovery in patients with advanced breast cancer receiving highdose chemotherapy with autologous hematopoietic progenitor cell transplantation.Experimental Design: We analyzed the effect of the absolute lymphocyte count on day ؉15 posttransplant on freedom from relapse and overall survival in patients with high-risk primary breast cancer or metastatic breast cancer, enrolled between 1990 and 2001 in prospective high-dose chemotherapy trials, using a uniform regimen of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea.Results: Four hundred and seventy-six patients (264 high-risk primary breast cancer and 212 metastatic breast cancer patients) were evaluated at median follow-up of 8 years (range, 1.5-11 years). The disease-free survival and overall survival rates in the high-risk primary breast cancer group were 67% and 70%, respectively. Patients with metastatic breast cancer patients had 21.8% disease-free survival and 31.5% overall survival rates. Day ؉15 absolute lymphocyte count correlated with freedom from relapse (P ‫؍‬ 0.007) and overall survival (P ‫؍‬ 0.04) in the metastatic breast cancer group, but not in the high-risk primary breast cancer group (P ‫؍‬ 0.5 and 0.8, respectively). The prognostic effect of absolute lymphocyte count in metastatic breast cancer was restricted to those patients receiving unmanipulated peripheral blood progenitor cells (P ‫؍‬ 0.04). In contrast, absolute lymphocyte count had no significant effect in those metastatic breast cancer patients receiving bone marrow or a CD34-selected product. In multivariate analyses, the prognostic effect of day ؉15 absolute lymphocyte count in metastatic breast cancer was independent of other predictors, such as disease status, pre-high-dose chemotherapy treatment, number of tumor sites, or HER2.Conclusions: Early lymphocyte recovery is an independent outcome predictor in metastatic breast cancer patients receiving high-dose chemotherapy and an autologous peripheral blood progenitor cell transplant. These observations suggest that immune strategies targeting minimal posttransplant residual disease may prove worthwhile.

Importance of blood graft characteristics in auto-SCT: implications for optimizing mobilization regimens

“…There are several reports suggesting lower risk of relapse and thus better PFS in patients with rapid lymphocyte recovery defined as the Optimizing blood graft content in auto-SCT E Jantunen and S Fruehauf absolute lymphocyte count on day þ 15 after stem-cell infusion. [28][29][30][31][32][33][34][35][36][37][38][39] These studies are summarized in Table 3. The number of lymphocytes within the graft infused seems to have prognostic significance potentially by affecting early lymphocyte recovery.…”

“…62 Several studies suggest that the risk of infectious complications, especially those of viral origin, is increased in patients receiving CD34 þ cell selected grafts, [63][64][65][66] although not all studies have noted this association. 58,67,68 35 NHL 274 ALC-15 independent prognostic factor for PFS and OS Joao 36 NHL/MCL 42 ALC-15 an independent prognostic factor for PFS and OS Tiwari 37 NHL 268 no association with ALC-15 and DFS or OS Porrata 39 NHL 50 NK cell recovery independent predictor for survival Porrata 28 MM 126 ALC-15 associated with better PFS and OS Hiwase 38 MM 119 ALC-30 associated with better PFS and OS Porrata 33 AL 145 ALC-15 independent prognostic factor for PFS and OS Nieto 31 MBC Optimizing blood graft content in auto-SCT E Jantunen and S Fruehauf…”

Prognostic significance of early lymphocyte recovery after post-autografting administration of GM-CSF in non-Hodgkin's lymphoma

“…2 Early lymphocyte recovery measured by an absolute lymphocyte count (ALC) 4500/ml obtained on day 15 post transplant is independently associated with favorable outcomes after autografting for NHL, [3][4][5] multiple myeloma, 3 Hodgkin's disease, 5,6 acute myeloid leukemia 7 and metastatic breast cancer. 8,9 Myeloid growth factors are often administered after hematopoietic cell transplantation to accelerate neutrophil recovery. [10][11][12] In addition to the myeloid effects, GM-CSF affects monocyte and lymphocyte recovery after standard 13 or high-dose chemotherapy; 14 GM-CSF may therefore affect the prognostic significance of early lymphocyte recovery post autografting.…”

Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma

“…[9][10][11] Absolute lymphocyte count (ALC) recovery X500 cells/ ml at day 15 (ALC-15) after ASCT has been reported to be a powerful and independent prognostic factor for clinical outcome in NHL, [12][13][14] Hodgkin lymphoma, 12,15 multiple myeloma (MM), 14 acute myelogenous leukemia, 16 amyloidosis, 17 and breast cancer. 18,19 The fact that the recovery of lymphocytes after ASCT influences survival points toward the clinical presence of an autologous graft-vs-tumor effect, as immune reconstitution after ASCT, may play an important role in the antitumor response.…”