Donor lymphocyte infusion for relapsed hematological malignancies after allogeneic hematopoietic cell transplantation: prognostic relevance of the initial CD3+ T cell dose

Abstract

The impact of donor lymphocyte infusion (DLI) initial cell dose on its outcome is known in patients with chronic myeloid leukemia but limited in patients with other hematological malignancies. In this retrospective study, we evaluated the effect of initial DLI CD3(+) cell dose on graft-versus-host disease (GVHD) and overall survival after DLI given for relapse of any hematological malignancies after allogeneic hematopoietic cell transplantation (HCT) with high- or reduced-intensity conditioning. The cohort included 225 patients. Initial DLI CD3(+) cell dose per kilogram of recipient body weight was ≤ 1 × 10(7) (n = 84; group A), >1.0 to <10 × 10(7) (n = 58; group B), and ≥ 10 × 10(7) (n = 66; group C). The initial cell dose was unknown for the remaining 17 patients. Cumulative incidence rates of GVHD at 12 months after DLI were 21%, 45%, and 55% for groups A, B, and C, respectively. Multivariate analysis showed that initial DLI CD3(+) cell ≥ 10 × 10(7) dose per kilogram is associated with an increased risk of GVHD after DLI (P = .03). Moreover, an initial DLI CD3(+) cell dose of 10 × 10(7) or higher did not decrease the risk of relapse and did not improve overall survival. Thus, these results support the use of less than 10 × 10(7) CD3(+) cell per kilogram as the initial cell dose of DLI for treatment of persistent or recurrent hematological malignancy after HCT.

Figure 1. Outcome after DLI according to DLI cell dose

a. Cumulative incidence of GVHD after DLI according to initial CD3+ cell dose. 12-month cumulative incidence of GVHD for initial DLI cell dose Group A (≤ 1×10⁷ CD3+ cell/kg) was 21%, compared to 45% (P = 0.01) for initial cell dose Group B (> 1×10⁷ – < 10×10⁷ CD3+ cell/kg) and 55% (P < 0.0001) for initial cell dose Group C (≥10×10⁷ CD3+ cell/kg). b. Overall survival after DLI according to initial CD3+ cell dose. 3-year Overall survival were 47% for cell dose A, 45% (P =0.16) for cell dose B, and 32% for cell dose C (P =0.01).

Figure 2. Overall survival after DLI according to initial CD3+ cell dose and disease risk category

Low risk included CML-CP and CLL, MM, low-risk lymphomas. High risk included high risk myeloid malignancies (AML, MDS, CML –AP/BC), myelofibrosis, myeloproliferative disorders, and high risk lymphoid malignancies (ALL, High grade lymphomas (Hodgkin lymphoma, diffuse large B cell lymphoma, transformed non-Hodgkin lymphoma)). a. Low risk category. 1- and 3-year overall survival were 94% and 73% for cell dose A, 67% and 53% for cell dose B and 60% and 55% for cell dose C (P =0.07). b. High risk category. 1- and 3-year overall survival were 47% and 27% for cell dose A, 60% and 42% for cell dose B and 41% and 22% for cell dose C (P =0.35)