Abstract
Abstract 3461
Expansion of CD3+ large granular lymphocytes (T-LGL) can be observed in situations such as viral infection, autoimmune disease, malignant neoplasm, and following allogeneic hematopoietic stem cell transplantation (HSCT). We sought to evaluate in patients treated with allogeneic HSCT incidence, characteristics, and clinical significance of persistent post-transplant T-LGL expansion. In this single center retrospective cohort study, we included all patients seen between January/08 and December/09 in our out-patient clinic for their regular follow-up. In patients with persistent lymphocytosis (>3 G/l for >3months) and an abnormal CD4/CD8 ratio, an extensive immunophenotyping was assessed; in case of an abnormal expansion of T-LGL cells a TCR gene rearrangement was performed. In 14 (7%) out of 215 evaluated patients a T-LGL expansion was diagnosed. Patients' characteristics with and without T-LGL expansion are summarized in Table 1. The median time between HSCT and diagnosis of lymphocytosis was 12 months (1-58). The median lymphocyte count was 4.24 G/l (3.0-26.5). The median duration of lymphocytosis was 29 (4-176) months. In 13/14 cases there was a CD3+/CD8+ immunophenotype, in 1 case was CD3+CD4+. In 5/14 patients a clonal TCR-gene rearrangement was observed. None of the patients presented neutropenia. Mild anemia was observed in 8/14 patients (57%), and thrombocytopenia in 2/14 patients; both changes were most probably not related with the T-LGL expansion. None of the patients had typical clinical signs of a T-LGL leukemia. In the univariate analysis acute GvHD and CMV reactivation were the only variables associated with T-LGL expansion, In the multivariate the relative risk (RR) of CMV reactivation was 5.063 (95%CI: 1.586–16.160; p=0.006) and the RR of acute GvHD grade 2–4 was 2.831 (95%CI: 0.831–9.648; p=0.096).
we detected a T-LGL expansion in 7% of patients after HSCT. No symptoms or clinical signs related to T-LGL leukemia were observed. The T-LGL expansions, even when monoclonal, showed a chronic but indolent course. They have to be considered rather as an expression a chronic stimulation, triggered by causes such CMV reactivation or acute GvHD rather than as a malignant transformation. The question whether a T-LGL expansion plays a GvL role could not be answered in this study due to the small number of patients and the study design.
Characteristics of patients treated with allogeneic HSCT, presenting with or without T-LGL
| . | Total . | With T-LGL expansion . | Without T-LGL expansion . | P-value . |
|---|---|---|---|---|
| N | 215 | 14 | 201 | |
| Median age at HSCT, years (range) | 38.5 (25–64) | 41 (12–68) | 0.835 | |
| Median age at follow up, years (range) | 45 (30–70) | 48(21–69) | 0.519 | |
| Sex | ||||
| - Male | 124 (58%) | 7 (50%) | 117 (58%) | 0.548 |
| - Female | 91 (42%) | 7 (50%) | 84 (42%) | |
| Diagnosis | ||||
| - Malignant hematological diseases | 202 (94%) | 13 (93%) | 189 (94%) | 0.814 |
| - Aplastic anemia | 10 (4%) | 1 (7%) | 9 (4%) | |
| - Autoimmune inborn errors | 3 (2%) | 0 | 3 (2%) | |
| Conditioning | ||||
| - Myeloablative | 174 (84%) | 11 (79%) | 163 (85%) | 0.528 |
| - Reduced intensity conditioning | 32 (16%) | 3 (21%) | 29 (15%) | |
| Total body irradiation | ||||
| - No TBI | 61 (28%) | 3 (21%) | 58 (29%) | 0.551 |
| - With TBI | 154 (72%) | 11 (79%) | 143 (71%) | |
| Donor | ||||
| - Matched sibling | 139 (65%) | 9 (64%) | 130 (65%) | 0.319 |
| - Matched unrelated donor | 63 (29%) | 3 (21%) | 60 (30%) | |
| - Mismatched donor | 10 (5%) | 2 (14%) | 8 (4%) | |
| - Syngeneic sibling | 3 (1%) | 0 | 3 (1%) | |
| Graft | ||||
| - Peripheral blood stem cells | 159 (79%) | 10 (77%) | 149 (79%) | 0.550 |
| - Bone marrow | 43 (21%) | 3 (23%) | 40 (21%) | |
| CMV reactivation | ||||
| - No | 143 (73%) | 5 (36%) | 138 (76%) | 0.001 |
| - Yes | 52 (27%) | 9 (64%) | 43 (24%) | |
| Graft versus host disease (GvHD) | ||||
| - Acute GvHD grade 0-1 | 112 (55%) | 4 (29%) | 111 (57%) | 0.02 |
| - Acute GvHD grade 2-4 | 93 (45%) | 10 (71%) | 83 (43%) | |
| - No chronic GvHD | 62 (29%) | 4 (6%) | 58 (29%) | 0.610 |
| - Chronic GVHD | 150 (71%) | 10 (71%) | 140 (71%) | |
| Remission at control | ||||
| - Complete remission (CR) | 92 (84%) | 13 (93%) | 79 (83%) | 0.350 |
| - Not in CR | 17 (16%) | 1 (7%) | 16 (17%) |
| . | Total . | With T-LGL expansion . | Without T-LGL expansion . | P-value . |
|---|---|---|---|---|
| N | 215 | 14 | 201 | |
| Median age at HSCT, years (range) | 38.5 (25–64) | 41 (12–68) | 0.835 | |
| Median age at follow up, years (range) | 45 (30–70) | 48(21–69) | 0.519 | |
| Sex | ||||
| - Male | 124 (58%) | 7 (50%) | 117 (58%) | 0.548 |
| - Female | 91 (42%) | 7 (50%) | 84 (42%) | |
| Diagnosis | ||||
| - Malignant hematological diseases | 202 (94%) | 13 (93%) | 189 (94%) | 0.814 |
| - Aplastic anemia | 10 (4%) | 1 (7%) | 9 (4%) | |
| - Autoimmune inborn errors | 3 (2%) | 0 | 3 (2%) | |
| Conditioning | ||||
| - Myeloablative | 174 (84%) | 11 (79%) | 163 (85%) | 0.528 |
| - Reduced intensity conditioning | 32 (16%) | 3 (21%) | 29 (15%) | |
| Total body irradiation | ||||
| - No TBI | 61 (28%) | 3 (21%) | 58 (29%) | 0.551 |
| - With TBI | 154 (72%) | 11 (79%) | 143 (71%) | |
| Donor | ||||
| - Matched sibling | 139 (65%) | 9 (64%) | 130 (65%) | 0.319 |
| - Matched unrelated donor | 63 (29%) | 3 (21%) | 60 (30%) | |
| - Mismatched donor | 10 (5%) | 2 (14%) | 8 (4%) | |
| - Syngeneic sibling | 3 (1%) | 0 | 3 (1%) | |
| Graft | ||||
| - Peripheral blood stem cells | 159 (79%) | 10 (77%) | 149 (79%) | 0.550 |
| - Bone marrow | 43 (21%) | 3 (23%) | 40 (21%) | |
| CMV reactivation | ||||
| - No | 143 (73%) | 5 (36%) | 138 (76%) | 0.001 |
| - Yes | 52 (27%) | 9 (64%) | 43 (24%) | |
| Graft versus host disease (GvHD) | ||||
| - Acute GvHD grade 0-1 | 112 (55%) | 4 (29%) | 111 (57%) | 0.02 |
| - Acute GvHD grade 2-4 | 93 (45%) | 10 (71%) | 83 (43%) | |
| - No chronic GvHD | 62 (29%) | 4 (6%) | 58 (29%) | 0.610 |
| - Chronic GVHD | 150 (71%) | 10 (71%) | 140 (71%) | |
| Remission at control | ||||
| - Complete remission (CR) | 92 (84%) | 13 (93%) | 79 (83%) | 0.350 |
| - Not in CR | 17 (16%) | 1 (7%) | 16 (17%) |
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
