Abstract
Abstract 3318
In the last decade, rituximab has been added to therapeutic plasma exchange (TPE) to treat patients with thrombotic thrombocytopenic purpura (TTP) who appear resistant to TPE. We sought to determine first if rituximab prevented TTP relapse. In addition, if relapse has occurred, we compared the rates of relapse of patients treated with TPE alone with those treated with a combination of TPE and rituximab.
We retrospectively reviewed the medical records of all adult patients treated for TTP between 2003 and 2008 at our institution. TTP was defined as thrombocytopenia, hemolytic anemia and ADAMTS13 activity less than 10% due to an inhibitor. None of the patients had congenital TTP. Patient demographics, laboratory data, treatment characteristics and follow up details were collected from their electronic and apheresis' medical records. Kaplan-Meier curves were drawn for survival and Cox proportional hazards models were applied to look for independent predictors of relapse-free survival (RFS).
A total of 20 patients underwent TPE only (Group 1) as compared to 18 patients who also received rituximab during admission with TTP (Group 2). Table 1 shows that both groups were balanced at baseline for demographic and laboratory data. However, patients in group 2 had longer duration of hospital stay (p<0.0001), underwent more TPE procedures (p<0.0001) and took longer to achieve remission (p<0.0001). The mean follow up in group 1 was 77.5 (±22.4) months and in group 2 was 68.6 (±28.5) months. At follow-up, 5 patients from group 1 relapsed (25%) as compared with 6 patients from group 2 (35%) (p=0.50). The 1-year, 3-year and 5-year RFS rates were 95%, 85% and 74% for group 1, and 94%, 76% and 71%, respectively, for group 2 (p=0.53 using log rank test). On univariate analysis, only age at the time of treatment (p=0.05) and duration of follow-up after treatment (p=0.03) were predictors of relapse. However, on multivariate analysis, no independent predictors of relapse were identified.
Rituximab does not prevent or reduce rates of relapse when used with TPE in patients with TTP. Since rituximab was added to patients later in their TPE course due to delayed response to treatment, it may yet have a role in decreasing the number of TPEs needed to achieve a response if it were started earlier during hospitalization for TTP.
Baseline characteristics, treatment details and follow-up data
| . | TPE only (n=20) . | TPE + Rituximab (n=18) . | p-value . |
|---|---|---|---|
| Race | 0.54 | ||
| White | 3 (15%) | 2 (11%) | |
| African-American | 17 (85%) | 15 (83%) | |
| Asian | 0 | 1 (6%) | |
| Gender (M/F) | 7/13 | 7/11 | 0.80 |
| Age | 38.7 ± 13.3 | 44.1 ± 15.2 | 0.25 |
| Previous therapy | 0.47 | ||
| None | 15 (75%) | 11 (61%) | |
| Corticosteroids | 1 (5%) | 0 | |
| Cytotoxics | 1 (5%) | 1 (6%) | |
| Both | 3 (15%) | 6 (33%) | |
| Creatinine (mg/dL) | 1.65 ± 1.05 | 1.45 ± 0.48 | 0.46 |
| Lactate dehydrogenase (U/L) | 1520 ± 792 | 1309 ± 616 | 0.37 |
| Hemoglobin (g/dL) | 9.1 ± 1.8 | 8.4 ± 1.9 | 0.27 |
| Platelet count (×109/L) | 14.5 ± 6.5 | 15.2 ± 8.3 | 0.78 |
| Fever | 3 (15%) | 4 (23%) | 0.51 |
| Neurological symptoms | 14 (70%) | 9 (60%) | 0.54 |
| ADAMTS13 Inhibitor (units) | 3.1 ± 2.6 | 2.5 ± 2.9 | 0.52 |
| Length of stay (days) | 16.7 ± 10.8 | 37.6 ± 11.3 | <0.0001 |
| No of TPEs | 11 ± 6 | 25 ± 9 | <0.0001 |
| Median no of rituximab doses | Not applicable | 3.5 (1–6) | |
| Immunosuppressive therapy | 0.01 | ||
| None | 4 (21%) | 1 (6%) | |
| Corticosteroids | 11 (58%) | 4 (22%) | |
| Cytotoxics | 0 | 3 (17%) | |
| Both | 4 (21%) | 10 (56%) | |
| Blood stream infection | 3 (15%) | 7 (41%) | 0.07 |
| Time to response (days) | 10.2 ± 8.3 | 28.5 ± 11 | <0.0001 |
| Platelet count at 3 months (×109/L) | 236 ± 32 | 295.13 ± 68 | 0.08 |
| Follow up (months) | 77.5 ± 22.4 | 68.6 ± 28.5 | 0.29 |
| Relapse | 5 (25%) | 6 (35%) | 0.50 |
| . | TPE only (n=20) . | TPE + Rituximab (n=18) . | p-value . |
|---|---|---|---|
| Race | 0.54 | ||
| White | 3 (15%) | 2 (11%) | |
| African-American | 17 (85%) | 15 (83%) | |
| Asian | 0 | 1 (6%) | |
| Gender (M/F) | 7/13 | 7/11 | 0.80 |
| Age | 38.7 ± 13.3 | 44.1 ± 15.2 | 0.25 |
| Previous therapy | 0.47 | ||
| None | 15 (75%) | 11 (61%) | |
| Corticosteroids | 1 (5%) | 0 | |
| Cytotoxics | 1 (5%) | 1 (6%) | |
| Both | 3 (15%) | 6 (33%) | |
| Creatinine (mg/dL) | 1.65 ± 1.05 | 1.45 ± 0.48 | 0.46 |
| Lactate dehydrogenase (U/L) | 1520 ± 792 | 1309 ± 616 | 0.37 |
| Hemoglobin (g/dL) | 9.1 ± 1.8 | 8.4 ± 1.9 | 0.27 |
| Platelet count (×109/L) | 14.5 ± 6.5 | 15.2 ± 8.3 | 0.78 |
| Fever | 3 (15%) | 4 (23%) | 0.51 |
| Neurological symptoms | 14 (70%) | 9 (60%) | 0.54 |
| ADAMTS13 Inhibitor (units) | 3.1 ± 2.6 | 2.5 ± 2.9 | 0.52 |
| Length of stay (days) | 16.7 ± 10.8 | 37.6 ± 11.3 | <0.0001 |
| No of TPEs | 11 ± 6 | 25 ± 9 | <0.0001 |
| Median no of rituximab doses | Not applicable | 3.5 (1–6) | |
| Immunosuppressive therapy | 0.01 | ||
| None | 4 (21%) | 1 (6%) | |
| Corticosteroids | 11 (58%) | 4 (22%) | |
| Cytotoxics | 0 | 3 (17%) | |
| Both | 4 (21%) | 10 (56%) | |
| Blood stream infection | 3 (15%) | 7 (41%) | 0.07 |
| Time to response (days) | 10.2 ± 8.3 | 28.5 ± 11 | <0.0001 |
| Platelet count at 3 months (×109/L) | 236 ± 32 | 295.13 ± 68 | 0.08 |
| Follow up (months) | 77.5 ± 22.4 | 68.6 ± 28.5 | 0.29 |
| Relapse | 5 (25%) | 6 (35%) | 0.50 |
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
