Journal List > Korean J Hematol > v.42(3) > 1032727

Kim, Kim, Kim, Kim, Rhee, Bang, Kim, Yoon, Lee, Park, and Kim: Donor Lymphocyte Infusions for Patients with Relapsed Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: a 10-year Experience of Seoul National University Hospital

Abstract

Background:

Donor lymphocyte infusion (DLI) has been established as a salvage therapy for patients with relapsed leukemia after allogeneic hematopoietic stem cell transplantation (HSCT). However, its benefit can be limited by the development of graft-versus-host disease (GVHD) or marrow aplasia.

Methods:

We retrospectively analyzed the data from 39 patients that received DLI for relapsed leukemia after HLA-matched, related HSCT between 1995 and 2005 at Seoul National University Hospital.

Results:

The diagnoses were CML (n=8), AML (n=19) and ALL (n=12). Ten patients had received non-myeloablative HSCT (AML=9, ALL=1). Complete remission after DLI was achieved in 6 (75%) cases with CML, 5 cases (29%) with AML and 5 cases (41%) with ALL. The two-year progression-free survival was 60% in CML patients, but 8.1% in non-CML patients (P=0.01). In addition, better overall survival (OS) was shown in CML patients than in non-CML patients (2-year OS, 68% in CML; 10% in non-CML, P=0.01). The durable remission for more than three years after DLI was confirmed in five patients (one AML patient for 88 months, one ALL patient for 54 months, three CML patients for 38, 47 and 53 months). Acute GVHD (≥Grade II) developed in 14 patients (35.9%). Prolonged marrow aplasia (neutrophil count <500/μL, platelet count <20,000/μL) developed in fourpatients (10.3%).

Conclusion:

DLI was the effective salvage therapy for relapsed CML after allogeneic HSCT, whereas limited effects were shown for AML and ALL with durable remission in only a few patients.

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Fig. 1
Progression free survival after donor lymphocyte infusion. (A) a. Chronic myelocytic leukemia. b. Acute lymphcytic leukemia. c. Acute myelocytic leukemia. (B) a. Chronic myelocytic leukemia. b. non-Chronic myelocytic leukemia.
kjh-42-233f1.tif
Fig. 2
Overall survival after donor lymphocyte infusion. (A) a. Chronic myelocytic leukemia. b. Acute lymphcytic leukemia. c. Acute myelocytic leukemia. (B) a. Chronic myelocytic leukemia. b. non-Chronic myelocytic leukemia.
kjh-42-233f2.tif
Table 1.
Baseline characteristics and donor lymphocyte infusion
  CML AML ALL Ph+ ALL Total
Sex (Male/Female) 6/2 9/10 5/4 2/1 22/17
Age, median (range) 33 (21∼48) 43 (28∼58) 25 (18∼38) 42 (37∼50) 36 (18∼58)
Disease status
  Chronic myelocytic leukemia, chronic/acute 7/1 - - - 7/1
  1st complete remission (CR)/ 1st relapse/2nd CR/refractory - 4/4/3/8 4/3/1/1 0/0/3/0 8/7/7/9
DLI indication
  Relapse from complete chimerism 7 13 7 2 29
  Mixed chimerism 1 3 2 1 7
  Refractory 0 3 0 0 3
Pre-DLI treatment
  None 3 6 1 1 11
  Ara-C+Idarubicin 1 12 0 0 13
  VPD (vincristine Pd daunorubicin)±L-asparaaginase 0 0 8 1 9
  Imatinib/ATRA 4/0 0/1 0 1/0 5/1
Total 8 19 9 3 39

Abbreviations: CML, chronic myelocytic leukemia; AML, acute myelocytic leukemia; ALL, acute lymphocytic leukemia; Ph+ ALL, Philadelphia chromosome positive ALL; ATRA, all-trans retinoic acid; DLI, donor lymphocyte infusion.

Table 2.
Response after DLI and cell dose
  CML AML ALL Ph+ ALL Total
CD3 (×108/kg) 1.4 (0.6∼2.3) 1.0 (0.2∼3.2) 1.7 (0.6∼3.3) 1.2 (0.5∼1.6) 1.3 (0.2∼3.3)
The number of DLI till CR
  1st/2nd/3rd 3/2/1 5/0/0 2/1/0 2/0/0 12/3/1
Complete Remission rate 6/8=75% 5/19=26% 3/9=33.3% 2/3=66.7% 16/39=41.0%
Total 8 19 9 3 39

Abbreviations: See Table 1.

Table 3.
Acut te graft-vers sus-host-disease according to sites
  Skin Liver Gastrointestinal
Stage 1 6 3 8
Stage 2 4 4 1
Stage 3 1 3 0
Stage 4 0 6 0
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