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Donor lymphocyte infusions (DLI) in patients with chronic myeloid leukemia following allogeneic bone marrow
A Bacigalupo1, M Soracco, F Vassallo
1Divisione Ematologia II, Ospedale San Martino, Genova, Italy.
Insights
Donor lymphocyte infusions (DLI) can treat chronic myeloid leukemia (CML) relapse after bone marrow transplant (BMT). Escalating DLI doses may reduce risks of graft-versus-host disease (GVHD) and improve survival.
Area of Science:
- Hematology
- Immunotherapy
- Oncology
Background:
- Allogeneic bone marrow transplant (BMT) is a treatment for chronic myeloid leukemia (CML).
- Relapse of CML post-BMT can occur, necessitating further treatment.
- Donor lymphocyte infusions (DLI) are used to manage relapse post-BMT.
Purpose of the Study:
- To evaluate the efficacy and safety of DLI in CML patients experiencing relapse post-BMT.
- To compare outcomes between patients receiving a large, fixed dose of DLI versus those receiving escalating doses.
- To identify factors influencing the risk of graft-versus-host disease (GVHD) and treatment-related mortality.
Main Methods:
- Retrospective analysis of 18 CML patients treated with DLI between June 1990 and March 1996 for relapse post-BMT.
- Patients were divided into two groups: Group A received a high dose of DLI (>= 1 x 10(8)/kg), and Group B received escalating doses (2 x 10(5) to 2 x 10(8)/kg).
- Outcomes assessed included cytogenetic and hematologic response, incidence of acute GVHD, severe aplasia, treatment-related mortality, and survival rates.
Main Results:
- Acute GVHD occurred in 12 patients, with a higher incidence in patients receiving higher cell doses (37% for >= 1 x 10(8)/kg vs. 14% for escalating doses).
- Treatment-related mortality was higher in Group A (38%) compared to Group B (14%), with deaths primarily linked to high-dose DLI.
- Actuarial 5-year probability of being Philadelphia chromosome (Ph) negative was 69% (46% in Group A, 85% in Group B), and 3-year survival was 38% in Group A and 86% in Group B.
- Significant elevations in serum GPT levels were associated with acute GVHD.
Conclusions:
- DLI is an effective treatment for CML relapse post-BMT, demonstrating long-lasting antileukemic effects.
- The risk of GVHD and treatment-related mortality correlates with the number of infused donor lymphocytes.
- Escalating DLI doses may allow for early identification of side effects and discontinuation of treatment before life-threatening GVHD develops, potentially improving outcomes.
Abstract:
Donor lymphocyte infusions (DLI) were given between June 1990 and March 1996 to 18 patients with chronic myeloid leukemia (CML) for the treatment of cytogenetic (n = 6) or hematologic relapse (n = 12) following an allogeneic bone marrow transplant (BMT). Patients were divided in two groups: patients in group A (n = 8) received a large dose of donor lymphocytes (> or = 1 x 10(8)/kg), whereas patients in group B (n = 10) received escalating numbers of cells (2 x 10(5) up to 2 x 10(8)/kg). The median number of DLI in group A was 2 (range 1-3); the median number of infusions in group B was 7 (range 3-9). Acute GVHD occurred in 12 patients (grades I-III) and was a major cause of death in two. The risk of developing GVHD correlated with the number of cells infused: 37%, 14%, 5% and 0% for DLI with cells > or = 1 x 10(8), 2 x 10(7)/kg, 2 x 10(6)/kg, and 2 x 10(5)/kg, respectively (P = 0.01). Median transaminase levels were found to be significantly increased in patients with, as compared to patients without, acute GVHD (GPT 412 vs 28 IU/l; P = 0.03). Severe aplasia occurred in four and was a contributing cause of death in two patients. Overall, four patients died as a consequence of DLI and all received > 1 x 10(8)/kg cells: the actuarial risk was 38% in group A and 14% in group B (P = 0.1). There were 10 complete and three partial cytogenetic responses: the actuarial probability at 5 years of being Ph negative was 69%: it was 46% for group A and 85% for group B (P = 0.1). The longest patient is now 6 years post-DLI, Ph negative, BCR-ABL negative. The actuarial 3 year survival is 38% in group A and 86% in group B (P = 0.06). The study confirms that DLI post-BMT is not innocuous and that there is a definite long-lasting antileukemic effect in patients with CML. It also suggests that: (1) the risk of developing GVHD correlates with the number of infused cells; (2) that significant elevations of serum GPT levels are associated with GVHD; and (3) that the use of escalating doses of cells may allow the identification of side-effects and discontinuation of infusions before life-threatening GVHD has developed.