Purine Nucleosides

The introduction of the purine nucleosides pentostatin (2-deoxycoformycin) and 2-chlorodeoxyadenosine (2-CdA) revolutionized the management of HCL and raised the possibility of cure. Both of these drugs induce a high percentage of true complete remissions, which are durable in a significant number of patients.12-14 Using the stringent guidelines outlined in the consensus resolution, over 90% of the patients had responses, and those with responses experienced marked improvement in survival. However, using more sophisticated techniques such as flow cytometry and immunohisto-chemistry, up to 50% of the patients in complete remission by standard criteria have minimal residual disease remaining in their bone marrow.1516 The impact of this observation on the outcome of patients is unclear.

Several investigators have examined the remission duration and survival in patients who have negative bone marrows by morphology, but positive bone marrows by immunohistochemistry and flow cytometry.16-18 Tallman et al.16 evaluated 66 patients treated with either pentostatin or 2-CdA, and in complete remission by clinical and morphologic criteria. The estimated 4-year relapse-free survival was 55% in the patients with minimal residual disease by immuno-histochemistry and 88% in the patients without minimal residual disease. Matutes et al.17 evaluated 23 patients after treatment with 2-deoxycoformycin and in complete remission by standard criteria. He reported no difference in relapse rates in the patients with or without minimal residual disease by immunophenotyping of bone marrow or peripheral blood.

For future clinical trials in HCL, it is reasonable to incorporate immunohistochemistry and flow data on the patient's bone marrow, and add a category of complete remission with minimal residual disease by special studies. This will provide us with information on how necessary it is to completely eradicate the hairy cell population, and give us better methods to compare new therapies.

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