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M. Else et al.
combination in 18 patients who had been previously treated with one or more lines of pentostatin or cladribine as a single agent.
Patients and methods
This was a retrospective review of the data after treatment was completed and was not a clinical trial. The patients were not treated uniformly: 12 patients received pentostatin and six received cladribine; 14 patients received rituximab concurrently with the purine analog, while four patients received it sequentially, starting 1–2 months after the comple- tion of purine analog therapy (Table I). Patients received between four and eight (median 6.5) intravenous infusions of rituximab at 375 mg/m2. Dosages of pentostatin and cladribine were as previously described [7]. Five patients had received only one previous line of
pentostatin or cladribine as a single agent, while 13 had received between two and six previous lines. In addition, more than half of the patients had received at least one other previous treatment, including a- interferon, splenectomy, and rituximab as a single
agent (Table I). They had a history of relatively poor responses to treatment.Only 50% had achieved a CR after their first-line treatment with a single-agent purine analog and 55% had relapsed by 3 years, compared with a first-line CR rate of 81% and a 3- year relapse rate of 11% in 242 patients in the Royal Marsden Hospital (RMH) HCL series as a whole (see Dearden et al., this issue). However, none of the 18 patients were primary non-responders to purine analogs, compared with 3% of the RMH series as a whole. Thirteen patients were male and five were female. Their median age was 47 years (range 25–66 years) at diagnosis and 60 years (range 32–78 years) at the time they received the combination treatment. The statistical methods used and the definitions of
CR and partial response (PR) were as previously described [7,11]. Minimal residual disease (MRD) was assessed using morphology and immunopheno- typing of peripheral blood and/or bone marrow aspirate and immunohistochemistry of bone marrow trephine biopsies, immunostaining with CD20 and DBA44 antibodies. Disease-free survival was mea- sured from the start of treatment until disease recurrence, censored at the date of latest follow-up
Patient characteristics
Case no. 1
2 3 4 5 6 7 8 9
10 11 12 13 14 15 16 17 18
Age in years at diagnosis (and at combination treatment)
43 (45)
Table I. Summary of patient characteristics, treatment received, and outcomes. Combination treatment
Sex F
No. of previous lines of purine analog therapy
1*
48 (51) M 1 55 (58) M 1* 66 (78) M 1* 49 (67) M 1 25 (32) M 2{ 39 (59) M 2* 40 (52)
52 (56) M 2* 31 (38)
F F
2 2
62 (74) M 2 46 (69) M 2{{x 48 (59) M 2 40 (61) M 3{* 61 (72) 54 (64)
F F
Other previous treatments:
*a-interferon; {splenectomy; {vincristine, cyclophosphamide, and prednisolone; xsingle-agent rituximab.
#Pending further assessment. **Died. s.c., subcutaneous; i.v., intravenous.
3 3
35 (53) M 5* 38 (60) M 6*x
No. of Purine analog
(no. of infusions) Pentostatin (7)
Pentostatin (6) Cladribine s.c. Cladribine s.c. Pentostatin (4) Pentostatin (9) Pentostatin (16) Cladribine i.v. Pentostatin (8) Pentostatin (12) Cladribine s.c. Pentostatin (12) Pentostatin (8) Cladribine s.c. Pentostatin (9) Pentostatin (8) Pentostatin (6) Cladribine i.v.
rituximab infusions
7 4 8 8 4 8 8 6 6 8 8 4 6 4 4 6 7 8
Timing of rituximab Response
Concurrently CR Concurrently CR Sequentially CR Sequentially CR Concurrently CR Concurrently CR Sequentially CR Concurrently CR Concurrently CR Concurrently CR Sequentially CR Concurrently PR Concurrently PR# Concurrently CR Concurrently CR Concurrently CR Concurrently CR Concurrently CR
Results
Time to relapse (or latest follow-up) in months
(77) (54) (50) (48) (29) (83) (76) (68) (38) (28) (26)
10 (34)** (7)
(24) (27) (7) (5)
(49)
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