Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies
Prophylactic Donor Lymphocyte Infusion After Allo-PBSCT for Patients With Very High-risk Hematologic Malignancies
Unmanipulated allogenic peripheral blood stem cell transplantation (allo-PBSCT) has been an
 established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of
 treatment failure for patients with relapsed/refractory disease or with very high-risk gene
 mutations such as TP53, TET2 and DNMT3a. Donor lymphocyte infusion (DLI) is an option to
 reduce relapse after allo-PBSCT for very high-risk disease without effective targeted
 therapy. In this study, the investigators aimed to compare the safety and efficacy of
 prophylactic DLI with G-CSF-primed peripheral blood progenitors for prevention of relapse
 after allo-PBSCT in patients with very high-risk leukemia/lymphoma.
Conventional DLI has invariably been associated with high rates of severe graft-versus-host
 disease (GVHD) and GVHD-related non-relapse mortality (NRM). Thus, in our previous studies,
 the DLI procedure has been modified to use G-CSF-mobilized peripheral blood stem cells
 (PBSCs) instead of steady-state lymphocytes. G-CSF mobilization results in the modulation of
 the polarization potential of T cells from Th1 to Th2. In addition, T-cell hyporesponsiveness
 is induced via the proliferation of dendritic cell 2 and monocytes and the down-regulation of
 CD28/B7. Furthermore, G-CSF augments NK-T-cell-dependent CD8+ cytotoxicity. These data
 constructed the rationale for the use of G-CSF-primed peripheral blood DLI to reduce
 DLI-associated GVHD and enhance the GVT effect of DLI. To date, there is no effective target
 therapy for acute leukemia with gene mutations such as DNMT3A, TET2 and TP53 and their
 response to chemotherapy and survival even after allogenic stem cell transplantation remains
 poor. Hypomethylating agents were reported to reverse the repression of HLA molecules and
 cancer testis antigens on leukemia cells, rendering them more sensitive to anti-leukemic
 activity mediated by DLI. The use of low-dose decitabine after allogenic stem cell
 transplantation was safe for early hematopoietic reconstitution. Therefore, decitabine was
 planned to be given prior to prophylactic DLI in the current study.
Inclusion Criteria:

 -  disease in the non-remission (NR) state prior to transplantation, including primary
 induction failure, relapse untreated or refractory to reinduction chemotherapy.

 -  achieving CR1 with ≥3 cycles of induction of chemotherapy.

 -  carrying TP53, DNMT3a, TET2 or FLT3-ITD gene mutation.

 Exclusion Criteria:

 -  early relapse, either molecular relapse or hematological relapse.

 -  primary or secondary graft failure.

 -  concomitant uncontrolled disease and/or organ dysfunction (infection, severe heart,
 renal, respiratory or hepatic failure…).