Abstract

In this study we investigated the correlation between donor chimerism status and disease relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The chimerism of Fluorescence-activated cell sorter (FACS) sorted CD3+T lymphocytes of 153 cases, CD56+CD16+NK lymphocytes of 153 cases and CD19+B lymphocytes of 31 cases with acute B lymphoblastic leukemia (B-ALL) was analyzed post-transplant utilizing polymerase chain reaction amplification of short tandem repeats (PCR-STR). A total of 33 patients (33/153, 21.6%) had recurrent disease. The positive predictive values of declining donor chimerism for hematologic and isolated extramedullary relapse were 58.8% and 10% (P=0.018, Chi-Square). The positive predictive values of declining donor chimerism in BMB, BMT, BMNK and PBB for hematologic relapse were 11.6%, 0%, 0% and 0% under close monitoring in patients with B-ALL. Only the donor chimerism in BMB significantly decreased in the group with hematologic relapse as compared with the group without hematologic relapse (P=0.00, Independent-samples T test) in patients with B-ALL. The median drop of donor chimerism in PBT, BMT, PBNK and BMNK were 0%, 0%, 5.9% and 2.8% one or two weeks prior to hematologic relapse in patients with non-B-ALL. The donor chimerism in PBNK significantly decreased prior to hematologic relapse in the group with hematologic relapse as compared with the group without hematologic relapse (P=0.022, Independent-samples T test).These data suggest donor chimerism of BMB can be used to predict the occurrence of hematologic relapse in patients with B-ALL. Donor chimerism decrease in PBNKwas associated with a somewhat increased risk of hematologic relapse in patients with non-B-ALL. Therefore, our results reveal a more effective path to individually predict for hematologic relapse by dynamic monitoring different cell lineages in different disease.

Highlights

  • Hematopoietic stem cell transplantation is an established treatment for a number of nonmalignant and malignant conditions [1,2,3]

  • One of the most useful tools for monitoring is the assessment of hematopoietic chimerism which occurs after alloHSCT and describes the percentage of donor hematopoietic and lymphoid cells in a transplant recipient [15,16]

  • Our result showed that the hematologic relapse, not isolated extramedullary relapse, can be predicted by chimerism status

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Summary

Introduction

Hematopoietic stem cell transplantation is an established treatment for a number of nonmalignant and malignant conditions [1,2,3]. The relapse rate is still an important problem for patients after allogeneic hematopoietic stem cell transplant (allo-HSCT) [4]. Chimerism analysis offers the possibility of identifying recurrence of underlying disease [8,9]. Detection of chemerism of T cells has been recommended by several guidelines [11], but did not appear to work well for prediction of disease relapse [12]. We analyzed the quantitative chimerism kinetics of 153 consecutive patients who underwent allo-HSCT at Shanghai First People’s Hospital between November 2004 to July 2012. We explore possibilities of prediction of disease relapse by detecting chimerism of subsets of lymphocytes

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