24 M. R. Grever & P. L. Zinzani
survival following pentostatin was 81%, and the those who relapsed, 75% achieved a second complete
relapse-free survival (RFS) was 67%. Both the response. Therefore, cladribine was highly successful
survival and the RFS were significantly better for in treating the patients with this disease.
patients younger than 55 years of age (p50.0001 In Table II, the overall long-term results of studies
and p¼0.02, respectively). In this trial, patients were with a single purine nucleoside are presented for
not excluded from entry if they had an infection in multiple investigations. Although the overall compete
contrast with the other studies reported with purine remission rates are very similar ranging from 76 to
nucleoside analogs. Despite no upfront exclusion for 98%, the relapse rates are equally comparable
hematological parameters or infection, pentostatin showing that about 30–40% of patients will relapse
was highly effective in changing the natural history of after 5–10 years of follow-up. Else et al. from the
this disease. Royal Marsden recently published their extensive
In 1990, Piro et al. at Scripps Clinic reported the data on both agents [18]. They reviewed 233 patients
remarkable results utilizing a 7-day intravenous treated with either pentostatin (188 patients) or
infusion of cladribine for patients with HCL. This cladribine (45 patients) after a median follow-up of
agent became the ‘treatment of choice’ for front-line 16 years. This group has extensive long-term
therapy because of the reported high complete experience with both agents, and concluded that
remission rate achieved within a single course of there was no significant difference in outcome
therapy. The convenience of this regimen was between the two agents. They estimated that the
attractive and effective. In reviewing the criteria for overall complete response rate was 80%, and the
treatment, these patients clearly had the disease that median RFS was 16 years, in patients who relapse;
required therapy. It is noteworthy that patients with and the second response rates are high and the
an active infection were excluded from these early remissions are quite durable. For those patients still
trials with cladribine. The complete response rate in remission at 5 years, about 25% will relapse by 15
was reported to be*95%, and the long-term results years. Outcomes for patients with recurrence are
from this institution confirmed the durability of these improved with the use of rituximab. Overall, patients
remissions with 7 years of follow-up. The median who are older, more anemic or thrombocytopenic,
first-response duration for 207 assessable patients have extensive splenomegaly or lymphadenopathy,
was 98 months [17]. Thirty-seven percent of patients poor performance scores or previous therapy do
relapsed with a median time to first relapse for all worse. Otherwise, the purine nucleoside analogs have
responders at 42 months. The overall survival was truly transformed the outcome for patients with this
97% at 108 months. Forty-seven patients experi- disease over the past 50 years since its original
enced 58 second malignancies for an observed to description.
expected ratio of second malignancies at 2.03. Of Other investigators have attempted to alter the
course and schedule of cladribine infusion in an
effort to reduce the complications associated with
Table I. HCL intergroup study [3].
myelosuppression. Multiple investigators believe that
Initial Crossover to Initial
the abbreviated administration of cladribine is
Therapy pentostatin pentostatin interferon-a
equally effective and well-tolerated with the more
prolonged 7-day infusion [19]. In addition, studies
Evaluable patients 154 86 159
have been reported showing that the subcutaneous
Complete remission (%) 76 66 11
administration of cladribine can be effective and
HCL, hairy cell leukemia. administered with more convenience than a 7-day
continuous intravenous infusion.
In Table III, the long-term consequences of
Table II. Long-term studies in HCL.
therapy for HCL are enumerated. Immunosuppres-
Study Agent Patients Outcome at 5–10 years
sion with prolonged reduction in CD4 and CD8 cells
Maloisel et al. [8] Pento 238 DFS 68.8%
Johnston et al. [4,14] Pento 28 Remain in CR 56%
Table III. Long-term consequences of therapy for HCL.
Flinn et al. [15] Pento 241 RFS 67%
Jehn et al. [23] CDA 44 Relapse 39% Prolonged period immunosuppression with reduced CD4 and
Zinzani et al. [16] CDA 37 Relapse 27% CD8 cells
Goodman et al. [17] CDA 207 Relapse 37% Most common long-term infection is dermatomal herpes zoster
Chadha et al. [12] CDA 86 PFS 54% Careful assessment of risk for secondary malignancies reveals
either a slight increase in the malignancies or no increase
HCL, hairy cell leukemia; RFS, relapse-free survival; CDA,
related to the treatment
chlorodeoxyadenosine; PFS, progression-free survival; DFS,
disease-free survival; CR, complete remission. HCL, hairy cell leukemia.
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